| 1995 | Folia Pharm. Univ. Carol. 19 | Pag. 7—8 |
Luděk Jahodář (jahodar@faf.cuni.cz)
Dean of Pharmaceutical faculty
It is a great honour for me, as the third dean in the history of the Faculty of Pharmacy, Charles University, Hradec Králové, to have the opportunity to review and to evaluate the first twenty-five years of its growth and maturation.
At the very beginning there was discontent among Czech pharmacists with the situation of pharmaceutical graduate studies in Czechoslovakia. The only existing faculty in Bratislava, established under a government directive, was not able to satisfy both the demands for pharmacists and lacked the professional esteem and sense of unity, which had traditionally been developed at the Charles University in Prague and, in the 1950s, at Masaryk University in Brno. During the years 1967—69, it was possible to express wishes in a louder and more concrete way, and the establishment of the federative state returned the faculty to the territory of the Czech Lands. After an intensive search for a location (Olomouc, Brno, Jihlava, Opava), thanks to definite provisions of material from the regional authorities, this honour was gained by the historical town of Czech queens, Hradec Králové, which thus became the second centre of Charles University (there already existed a Charles University Faculty of Medicine). Our thanks are due to all those in the Faculty headed by Prof. J. Květina who managed to establish the Faculty in this difficult period. It is obvious that the teachers of that time were mainly the Czechs who had left the Bratislava Faculty and teachers released by the Faculty of Medicine. Thanks for their understanding of our problems and their help in overcoming them are also due to the Faculty of Medicine, College of Education in Hradec Králové and the College of Chemical Technology in Pardubice as well as the Faculty of Pharmacy in Bratislava. A very creative group of teachers was formed, which managed to overcome the initial obstacles and gradually to realize their vision of the Faculty. In 1973 the Faculty obtained its first building where it was possible, though in provisional conditions, to concentrate nearly all teaching activities, and the Garden of Medicinal Plants, library and other facilities began to be built.
The first graduates in 1974 showed the pharmaceutical profession that the new Faculty really worked and the Faculty had the opportunity to enlarge the Faculty staff with new graduates educated according to the conceptions of the founders. The second half of the 1970s witnessed intsense enthusiasm for the completion of the second building. Both teachers and undergraduates actively participated in their construction and furnishing. At the same time, all teaching and research activities appropriate to a university were carried out properly: the Faculty organized masters and doctoral postgraduate courses, successfully defended research projects, presented scientific publications and original textbooks. The Faculty became known in Central and Eastern Europe. In that period and particularly in the 1980s a number of international agreements about cooperation in research and teaching were concluded, and undergraduates went abroad for short periods of practical training and teachers for research fellowships. Though the then political conditions were unfavourable to opening doors to the “West”, occasionelly people managed to get through the “Iron Curtain”, mainly to the Scandinavian states.
The curricula of the Hradec Králové Faculty were always compatible with those of of the Bratislava Faculty, but they were never identical. Very soon the final state examination was abolished and state exams were distributed within the course. In the 1980s, the three-branch courses of study were introduced: the graduates of the two five-year courses became specialists in either clinical or technological pharmacy, and there was a four-year course for general pharmacists who were expected to work in local pharmacies. Now it is arguable that these tactics which aimed to preserve the five-year courses of pharmacy were premature and whether a good idea was rejected by people who were in practice, unprepared for it, or whether the idea was slightly misguided. At present, there is a five-year course of pharmaceutical studies with internal differentiation. The undergraduate can form his or her individual professional profile by selecting from a choice of compulsory subjects, as well as having other optional subjects. In any case, the profile of the graduate is more universal now, while at the same time preserving high professional qualities in the branch of pharmacy in which the graduate wants to practise. The course formulated in this way seems to suit the present demands of the profession better and is completely comparable with those in the countries of the European Community.
November of 1989 found the Faculty preparing to celebrate the 20th anniversary of its existence and the hectic time, with its visions of new possibilities, released flood-gates of human wishes as well as minor and major acrimonies, and did not provide a good background for the celebrations, and thus they did not take place. Docent Vladimír Semecký, who took over the leadership of the Faculty in this uneasy time, faced a difficult task of adapting the Faculty to the new social conditions. The present-day Faculty, calmly and deliberately efficient, vindicates his approach. Its position in the complex of 16 faculties of Charles University is firm, and is supported by a systematic increase in the qualifications of the teaching staff, accreditation for the habilitation of docents and the appointment of professors, and postgraduate courses in eleven doctoral specializations. The Faculty is successful in competitions for grants and attracts attention from European universities wishing to participate in research. Both teachers and undergraduates make use of the possibilities of the present open Europe.
In the 25th year of its existence, the Faculty is a unique, well-conceived part of the university, ready to defend its incorporation in the famous Charles University in the evaluation procedures which are to follow, and prepared to provide the pharmaceutical services and other branches of pharmacy and health service with up to two hundred well-qualified graduates every year. Thanks for all this are due to all academic dignitaries and heads of departments who carried the main weight of responsibility for the development of the Faculty as well as to all others who were its active members including the graduates and the present students. It will be great satisfaction both for me and for all teachers, when we will meet with the graduates who will perphaps simply, but proudly declare their relationship to their alma mater. It will evidence the credit of the Faculty, which is the greatest award for us.
| 1995 | Folia Pharm. Univ. Carol. 19 | Pag. 9—11 |
Part LXXIII in the series “Antituberculotics”
Karel Waisser1 (waisser@faf.cuni.cz), Marie Jozová1, Želmíra Odlerová2
1Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové
2Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic
In the work appropriate 2-phenylbenzothiazoles were prepared by the oxidation of thiobenzanilides in this way: by the oxidation of thiobenzanilide 2-phenylbenzothiazole (1), by the oxidation of 4'-chlorothiobenzanilide 6-chloro-2-phenylbenzothiazole (2), by the oxidation of 4'-methylthiobenzanilide 6-methyl-2-phenylbenzothiazole (3), and by the oxidation of 4'-methoxythiobenzanilide 6-methoxy-2-phenylbenzothiazole (4). None of the syntetised substances was antimycobacterially active neither to Mycobacterium tuberculosis, nor to Mycobacterium kansasii. We can conclude from the paper that in antituberculously effective derivatives of 2-phenylbenzothiazole described so far 2-phenylbenzothiazole substructural fragment is not a pharmacophore. It concerns the derivatives belonging among antituberculously active amines of benzyl type.
| 1995 | Folia Pharm. Univ. Carol. 19 | Pag. 13—16 |
Karel Waisser1 (waisser@faf.cuni.cz), Želmíra Odlerová2, Wilfried Thiel3
1Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, CZ-50005 Hradec Králové
2Institute for Preventive and Clinical Medicine, SK-83301 Bratislava, Slovakia
3Arzneimittelwerk Dresden, D-01435 Radebeul, Germany
Dithiooxalamide (I) and its N,N-disubstituted (or cyclosubstituted) derivatives II—VIII were tested for their activity against Mycobacterium kansasii, M. avium and M. fortuitum on Šula and Sauton medium. The most active compound in the series studied is dithiooxalamide (I). Structure—activity relationships are briefly discussed for activities against M. avium and M. kansasii measured on Sauton medium. The activity against M. fortuitum is very small. For antimycobacterial data obtained on Šula medium (with proteins), the structure-activity relationships are more complicated.
| 1995 | Folia Pharm. Univ. Carol. 19 | Pag. 17—20 |
Jarmila Vinšová (vinsova@faf.cuni.cz)
Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, Hradec Králové 500 05, Czech Republic
The present study deals with the synthesis of optically active N-isonicotinoyl dipeptide derivatives as potential carriers of tuberculostatic active isoniazid. The appropriate N-isonicotinoyl dipeptide derivatives were prepared by the azide method from the corresponding dipeptide methyl esters and 4-pyridinecarboxylic acid azide. The pyridoyl hydrazides and acids were obtained by standard procedures.
| 1995 | Folia Pharm. Univ. Carol. 19 | Pag. 21—27 |
Alice Lázníčková1 (laznicko@faf.cuni.cz), František Budský2, Milan Lázníček1
1Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
2Nuclear Research Centre, Řež near Prague, Czech Republic
In this work the conditions for 99mTc-labelling of two phosphonate compounds EDTMP (ethylenediamine-N,N,N',N'-tetrakis (methylene phosphonic acid)) and DCHMP (diaminecyclohexane-N,N,N',N'-tetrakis (methylene phsphonic acid)) and their biodistribution in rats were studied for sceletal scintigraphy purposes. Both 99mTc-chelates studied cleared rapidly from the blood and non-osseous tissues and selectively localized in the bone. A significant portion of radioactivity was found also in the kidney due to their glomerular filtration from the blood. 99mTc-DCHMP was shown as alternative bone scintigraphy agent with near biodistribution and complexing ability to other commonly used 99mTc-bone radiopharmaceuticals.
| 1995 | Folia Pharm. Univ. Carol. 19 | Pag. 29—35 |
Milan Lázníček (laznicek@faf.cuni.cz), Jiří Malina, Vít Svačina
Department of Pharmacology, Faculty of Pharmacy, Charles University, Hradec Králové
The effect of lipophilicity on the accumulation of a group of 10 iodine substituted weak organic acids (benzoic, phenylacetic and hippuric acid derivatives) in the renal tissue of rats was studied and compared with that of the blood cell uptake as the model of a different cell type. Whereas the degree of accumulation of the studied compounds into the renal tissue decreased with increasing lipophilicity, the dependence of blood cell uptake of these compounds on lipophilicity was of just opposite character. The rate of renal excretion of model drugs under study was proportional to the degree of their accumulation in the renal tissue.
| 1995 | Folia Pharm. Univ. Carol. 19 | Pag. 37—44 |
Jiří Vlček1 (vlcek@faf.cuni.cz), Zdeněk Fendrich2, Václav Rusek1
1Department of Social and Clinical Pharmacy,
2Department of Pharmacology & Toxicology,
Faculty of Pharmacy, Charles University, Hradec Králové
A brief survey of the history of pharmaceutical education at Charles University since its foundation in the year 1348 is outlined. The teaching of pharmacy continued for centuries with only few re-organizations until 1950 as an associated subject to the teaching of medicine. The education of pharmacy at Charles University was, however, stopped in 1950 not to be continued until 1969 when the first genuine Faculty of Pharmacy was re-established at Charles University again. This faculty, first in the history of pharmacy education, was oriented to the biological character of teaching. During the 24 years of the faculty’s existence a great effort was made to change the meaning of the classes at the faculty toward an education in patient oriented pharmacy. For this reason education of pharmacy was first divided into three branches (a branch of public pharmacy, a branch of clinical pharmacy and a branch of technological pharmacy) which, however, did not prove to be the best for the rapid development of clinical pharmacy and for driving students to the patient’s bed side, because only few, if any, departments of clinical pharmacy were estabished in the pharmaceutical grounds, in actual hospitals, several years ago. Therefore, education of pharmacy was recently re-organised again to be a five year study, without the students branching into different areas of study, with the introduction of other optional topics to enable students to be directed, according to their abilities and interests to the desired branch of pharmaceutical practice. To improve education in patient oriented pharmacy, smooth communication and mutual understanding among pharmacists and physicians who know that they are dependent on one another and that their knowledge in pharmacotherapy is highly valuable for the welfare of patients, is highly desirable. Presently, students can be in close contact with physicians, not only those who are members of the genuine staff of the faculty and who participate in the teaching of pharmacology, physiology, and biochemistry, but first and foremost those who are clinicians from hospitals. In addition, chief physicians from the departments of internal medicine deliver their lectures from pharmacotherapy to students, as well as to the intersted staff of teachers, and consequently students can take part in at the rounds of the wards in hospitals. This close collaboration between physicians and pharmacists definitely contributes to the attraction of interested students to clinical pharmacy and to the establishment of new departments of clinical pharmacy in the future.
| 1995 | Folia Pharm. Univ. Carol. 19 | Pag. 45—55 |
Petr Jílek1 (jilek@faf.cuni.cz), Jan Krejsek2, Milana Kšírová1
1Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové
22nd Department of Medicine, School of Medicine, Charles University, Hradec Králové
Lymphokine activated cells (LAK) are promissing agent in adoptive immunotherapy of tumors. Immunotherapy at all is based on the stimulation of effectors of anticancer immunity. Some cytokines have good stimulatory activity in this point of wiev, but, when applicated systemically, they exhibit severe side effects. Cytotoxic cells can be stimulated in vitro (after removing from patient’s blood) and then reinfused back with reduced doses of cytokines and with lower risk of toxicity. Many different procedures for preparation of LAK cells have been developed, but the basic principles are generally identical:
The peripheral blood mononuclear cells (PBMC) are obtained by leukapheresis and then used for the generation of LAK cells. Recombinant IL-2 (rIL-2) have been usually used for the stimulation of precursor cells. Various cultivation media are used, mainly it is RPMI 1640 in different modifications with or without serum. Also other serumfree media are recommended. The optimal conditions for the cultivation of LAK cells are: plastic bags, atmosphere with 5% carbondioxide, temperature 37°C, time of incubation 3—5 days. It is also possible to cultivate LAK cells for the longer period (till 14 days) in highly effective systems. The sufficient amount of LAK cells (1010—1011) is necessary for the achievement of the clinical effect. Regarding these data, the adoptive immunotherapy is predestined mainly for the patients without previous cytoreductive therapy. The assessment of cytotoxic activity in vitro, cell viability and sterility before re-infusion is obligatory.
The therapeutic regimens include the application of IL-2 several days before the leukapheresis. The higher amount of precursors of LAK cells is obtainable after the cessation of IL-2. The leukaphereses are performed on the 5 consequent days and precursors of LAK cells are cultivated for 35 days. LAK cells are re-infused to the patient together with rIL-2, which is necessary for in vivo proliferation and lifetime prolongation of transferred cells (LAK/IL-2 therapy).
The best results of LAK/IL-2 therapy have been achieved in patients suffering from renal cell carcinoma and malignant melanoma.
| 1995 | Folia Pharm. Univ. Carol. 19 | Pag. 57—62 |
Jiří Gabriel1, Naďa Zimová2, Ivan Němec2, Karel Waisser3 (waisser@faf.cuni.cz), Alexandr Hrabálek3
1Microbiological Institute, Academy of Sciences of the Czech Republic, Prague
2Department of Analytical Chemistry, Faculty of Natural Science, Charles University, Prague, Czech Republic
3Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
The basic chromatographic study of a new 1-phenyl-5-mercaptotetrazole derivatives was performed using a silica column with chloroform—acetonitrile (containing 1% of acetic acid) mobile phase. The optimal composition of mobile phase for 1-(4-bromophenyl)-5-mercaptotetrazole, compound with the best thyreostatic activity from other derivatives, was chloroform : acetonitrile 92.5 : 7.5. The detection limit of 1-(4-bromophenyl)-5-mercaptotetrazole, 2 ng (injection 1 µl), was established.
| 1995 | Folia Pharm. Univ. Carol. 19 | Pag. 63—78 |
Miloslava Netopilová (netopilo@faf.cuni.cz), Jaroslav Dršata
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
MPA induces two types of generalised epileptic seizures in rodents: the minimal clonic seizure and the major tonic-clonic seizure. The compound is a convulsive agent with very rapid action. The convulsive dose and seizure latency does not differ in the individual species.
After systemic MPA administration, GABA concentration in most brain regions decreases, which is considered to be the cause of the seizure by most authors. It is raised by inhibition of GAD in the nerve tissue. In vitro MPA was found to be a competitive inhibitor of this enzyme.
Several authors consider it unprobable that such a rapid development of seizures could be caused solely by mere inhibition of synthesis of one inhibitory neurotransmitter. Direct inhibitory effect of MPA on GABA release, which was observed in in vitro experiments with tissue slices, may participate in the rapid onset of seizures, too. On the other hand, no influence of MPA on synaptosomal GABA transport has been observed. According to some authors, also excitatory amino acids take part in the development of convulsions after MPA.
| 1995 | Folia Pharm. Univ. Carol. 19 | Pag. 79—82 |
Karel Waisser (waisser@faf.cuni.cz),
Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University
The paper analyses the relationships between the structure and antimycotic activity of 2-alkylthio-6-aminobenzothiazoles. Hydrophobic fragmental constants f were used as the structural parameter, and the minimum inhibition concentration (in the case of Penicillium cyclopium) or ED50 (in the case of Candida albicans) served as the measure of activity. The relationships under study were found to be strongly dependent on the species of the microorganisms studied. Whereas the relationship in the case of Candida albicans is similar to the relationship between the structure and antimycobacterial activity in the group of substances uder study, the optimum of activity against Penicillium cyclopium can be expected at a much lower hydrophobicity of alkyls in the alkylthio group.
| 1995 | Folia Pharm. Univ. Carol. 19 | Pag. 83—90 |
Part IX in the series of reviews “Compounds with antituberculous activity”
Karel Waisser (waisser@faf.cuni.cz),
Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové
Quantitative structure—activity studies of potential antituberculotics have been reviewed. The potential antituberculotics under QSAR study can been divided into several groups. In some cases the correlation with electronic parameters are described (Table 1). In the second group, activity increases with a growth in hydrophobicity (Table 4). In the third group, the relationships between activity and hydrophobicity are parabolic (Table 2). In the fourth group, there are no correlations between activity and hydrophobicity of whole molecules, nevertheless in some cases the activity correlates with the local hydrophobic parameters (Table 3). This should be taken to imply that there are no general values of “ideal hydrophobicity” for antituberculous action in vitro. The paper about “ideal hydrophobicity” of gram-negative and gram-positive bacteries has to be revised.
| 1995 | Folia Pharm. Univ. Carol. 19 | Pag. 91—99 |
František Trejtnar (trejtfr@faf.cuni.cz),
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Hradec Králové
An optimalized methodical arrangement for testing of enzymuria in rats was used in this study to asses the diagnostic value of urinary excretion of selected enzymes with different localization in renal tubules for detection of gentamicin-induced kidney damage. For this purpose, changes of excretion of two brush border enzymes, alaninaminopeptidase (AAP) and gamma-glutamyl-transferase (GGT), and a lysosomal enzyme, N-acetyl-beta-D-glucosaminidase (NAG), were studied during eight-day administration of gentamicine in nephrotoxic doses (40 and 80 mg/kg/day). The rate of enzymuria was compared to changes of other parameters of renal function such as creatinine and urea excretion. The increase of urinary excretion of AAP and GGT was characterized by a rapid appearance (the 2nd day after the start of treatment) and not distinct gradation with continuing nephrotoxine administration. Excretion of lysosomal NAG was clearly dose-dependent and was marked by a progressive rise up to the end of treatment indicating cummulative intensification of renal damage. Elevated enzymuria indicated gentamicine-induced dysfunction with a greater sensitivity than impairment of creatinine or urea excretion. A normalization of increased AAP and GGT excretion after higher dosage of gentamicin was preceded by a marked decrease below control values. This finding could give evidence for a limited character of enzyme sources and their subsequent exhaustion by excessive washing into urine during previous damage to tubular cells. Determination of excretion values of all of studied urinary enzymes can be used as an early marker of acute tubulotoxicity. NAG is the best indicator of the development of aminoglycoside renal damage.
| 1995 | Folia Pharm. Univ. Carol. 19 | Pag. 101—129 |
(Abstract of Papers)
Lubomír Opletal (opletal@faf.cuni.cz),
Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Hradec Králové
The complete text contains abstracts of 61 contributions in oral section and of 15 in poster section.
| 1996 | Folia Pharm. Univ. Carol. 20 | Pag. 7—17 |
Daria Kučová, Stanislav Ďoubal (doubal@faf.cuni.cz),
Department of Biophysics and Physical Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové
Growth factors are low molecular weight peptides which are produced in an organism under normal as well as pathological conditions. Under their influence, variety of responses occur — differentiation, stimulation of function, changes of shape, locomotion, proliferation, apoptosis. They affect every disease characterized by tissue damage and repair, as well as the processes of ageing and neoplastic transformation.
In this paper the following growth factors are reviewed: platelet-derived growth factor, epidermal growth factor, transforming growth factors alpha and beta, and acidic and basic fibroblast growth factors, from the point of view of their actual or potential therapeutic significance.
We see the main clinical promises in possible influencing the process of wound healing by growth factors as they regulate all important phases of this process. At present time, therapeutical use of most of the mentioned growth factors is in the phase of successful clinical trials.
Transforming growth factors and basic fibroblast growth factor are closely connected with tumour growth and their diagnostic and/or prognostic value is promising. Use of specific antibodies against these growth factors means another possibility for the treatment of malignant diseases.
Biological therapy with growth factors represents qualitatively new approach in therapy of many diseases. They are going to be a new class of drugs with great future perspectives.
| 1996 | Folia Pharm. Univ. Carol. 20 | Pag. 19—30 |
Eva Kvasničková (kvasnice@faf.cuni.cz), Alice Riegrová, Ivo M. Hais
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové
Flumecinol is a drug used as barbital-type inducer of enzymes which oxygenate and conjugate some xenobiotics. In the present study its inducing effect on pethidine O-demethylase and amidopyrin demethylase, not on aniline hydroxylase, has been demonstrated in rats. Flumecinol inhibits the former two enzymes, does not inhibit aniline hydroxylase. The inhibition of pethidine demethylase and amidopyrin demethylase has been shown to be competitive. The finding of Grossman (1985) oral communication that flumecinol decreases hepatotoxicity of aflatoxin AFB1 has prompted this study, but our results do not suggest that their observation could be explaine by the inhibition of haemoprotein P-450-dependent enzymes which toxicate aflatoxins to their epoxides, since the moderate inhibition of some oxygenases observed here does not affect the “toxicating” enzymes. It can be speculated that hepatotoxicity of aflatoxin B1 could have been reduced by induction of O-demethylating and conjugating enzymes.
| 1996 | Folia Pharm. Univ. Carol. 20 | Pag. 31—34 |
Karel Waisser1 (waisser@faf.cuni.cz), Nestor Houngbedji1, Jaroslav Dršata1, Wilfried Thiel2, Roland Mayer3
1Faculté de Pharmacie, Université Charles, Hradec Králové, République Tchéque
2Arzneimittelwerk Dresden, Radebeul, Allemagne
3Université Technique Dresden, Allemagne
Quantitative Chemical Structure—Hepatotoxicity Relationship of Dithiooxalamides
In a group of antituberculously effective derivatives of dithiooxalamide studied with a prospect of the develepment of novel antituberculous agents, hepatotoxity was found to correlate with the values of RM from chromatography an thin layers of octadecylsilanized silica gel. Hepatotoxicity was evaluated by the activity of alaninamino transferase in blood serum.
| 1996 | Folia Pharm. Univ. Carol. 20 | Pag. 35—48 |
Hana Müllerová1 (mullero@faf.cuni.cz), Jiří Vlček2, Michal Strnad3
1,2Department of Social and Clinical Pharmacy, Faculty of Pharmacy, Charles University, Hradec Králové
3Outpatient Clinic, Internal Medicine, Hradec Králové
Background — Venotropic drugs (or vasoprotectives, venoprotectives, vasoactive substances and venotonics) are mainly plant-derived substances used for treatment of chronic venous insufficiency. Their treatment efficiency is often considered problematic. To clarify this uncertainty, a meta-analysis of clinical trials performed with some chosen venotropic drugs was conducted.
Methods — As data sources the Medline database from 1980 through 1993 was used, for the terms — venous insufficiency, drug therapy and the Bibliographia Medica Čechoslovaca 1980 through 1992 for the term — venotonika. The results of various tests — venous plethysmography, leg circumference and subjective symptoms scored by patients used to evaluate venous insufficiency and their possible changes after treatment with selected vasoprotective drugs were followed up.
Results — Because of considerable inconsistency of clinical studies the numbers of patients whose objective and subjective parameters were influenced by Verum treatment in comparison with patients who were not influenced by Verum were only evaluated. Venotropic drugs, except dihydroergotamine, showed certain treatment effects.
Conclusion — Some venotropic drugs exerted positive effects on subjective and objective parameters in chronic venous insufficiency, but more well-designed clinical trials must be performed to demostrate their long-term efficacy.
| 1996 | Folia Pharm. Univ. Carol. 20 | Pag. 49—52 |
Karel Waisser1 (waisser@faf.cuni.cz), Jiří Kuneš1, Alexandr Hrabálek1, Jiří Gabriel2
1Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
2Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
On examining hydrophobicity of compounds by means of HPLC aqueous methanolic or aqueous acetone solutions are predominantly employed as mobile phases. Several different concentrations of solvents in water are used. The found values capacity factors of compounds under study are then extrapolated to zero concentrations of solvents in water. In the present study of bis(1-aryltetrazole-5-yl)disulfides, acetonitrile with small portions of water was used. Yet the logarithm of extrapolated values of capacity factors still correlated with hydrophobic substituent constants and it could be used in the analysis of relationships between the structure and antimycobacterial activity of the compounds under study.
| 1996 | Folia Pharm. Univ. Carol. 20 | Pag. 53—57 |
Karel Waisser1 (waisser@faf.cuni.cz), Věra Klimešová1, Vladimír Buchta2
1Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
2Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
Fourteen compounds of the group of 2-alkylthio-4-pyridinecarbothioamides was evaluated against four strains of fungi, Candida albicans, Candida glabrata, Trichosporon beigelii, and Aspergillus fumigatus. As the present authors wanted to describe the structure—antifungal activity quantitatively, the minimim inhibitory concentrations were determined in molar concentrations. In the group of compounds under study, some derivatives with a significant anti-Candida affect have been found. Only very low activity against A. fumigatus was found.
Antifungal activity of the compounds under study increases with the growth of hydrophobicity of the alkyl in the alkylthiogroup up to a certain lenght of the alkyl. In both goups of Candidae it is the octyl, in T. beigelii the most effective compounds contained a hexyl and heptyl in the alkylthio group. A futher lengthening of the alkyl results in a steep decrease or even loss of activity. The relation between hydrophobicity of alkyls and antifungal activity in the case of compounds with a lengthened alkyl chain up to the most effective compound can be expressed by linear dependence. Regression coefficients in the above-mentioned equations are very similar to each other in the case of both Candida strains. The benzyl derivative is ussualy more effective than it can be assumed from the calculation from the above-mentioned equations, and the cyclohexyl derivative is less effective. The present authors think that the structure group under study can be of importance in the development of chemotherapeutic agents against mycoses produced by Candidae.
| 1996 | Folia Pharm. Univ. Carol. 20 | Pag. 59—62 |
Karel Waisser1 (waisser@faf.cuni.cz), Věra Klimešová1, Želmíra Odlerová2
1Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
2Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic
On the basis of the study of the relationships between the structure and antimycobacterial acitivity in the group of 2-alkylthio-4-pyridinecarbothioamides it has been demonstrated that the relationships between their structure and antimycobacterial activity against atypical strains (Mycobacterium kansasii, Mycobacterium avium, Mycobacterium fortuitum) are strongly dependent on the strain of the pertinent mycobacteria.
| 1996 | Folia Pharm. Univ. Carol. 20 | Pag. 63—66 |
Věra Klimešová1 (klimeso@faf.cuni.cz), Karel Waisser1, Vladimír Buchta2, Želmíra Odlerová3
1Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
2Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
3Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic
2-Mercapto-4-pyridinecarbonitrile and a group of eleven 2-alkylthio-4-pyridinecarbonitriles were tested for their antimycobacterial activity against M. tuberculosis, M. kansasii, M. avium and M. fortuitum. The activity against M. fortuitum is very small. The activity of 2-mercapto-4-pyridinecarbonitrile and 2-hexylthio-4-pyridinecarbonitrile against atypical strains was higher than the activity of isoniazide and ethionamide.
| 1996 | Folia Pharm. Univ. Carol. 20 | Pag. 67—75 |
Jaroslav Sochor1 (sochor@faf.cuni.cz), Jiří Klimeš1, Jiří Sedláček2
1Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy, Charles University, Hradec Králové
2Department of Pathological Physiology, Faculty of Medicine, Charles University, Hradec Králové
Drug levels of sodium salicylate, acetylsalicylic acid, ibuprofen and kebuzone were determined in the whole blood. Simultaneously, the distribution of the above mentioned drugs between erythrocytes and plasma was observed. An HPLC method for their analysis in samples of the whole blood, erythrocytes and plasma has been developed. These samples, after their suitable treatment, were analysed on reversed-phase columns, detected at ultraviolet spectra and the antirheumatics were quantified using the internal standards. The levels of salicylic acid, acetylsalicylic acid, ibuprofen, kebuzone and their possible metabolites were investigated in laboratory rabbits in 2-hour pharmacokinetic studies.
| 1996 | Folia Pharm. Univ. Carol. 20 | Pag. 77—85 |
Jarmila Vinšová1 (vinsova@faf.cuni.cz), Karel Kosař2, Evžen Kasafírek3, Antonín Šturc3, Jiří Taimr3
1Department of Inorganic and Organic Chemistry, and
2Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
3Research Institute for Pharmacy and Biochemistry, Kouřimská 17, Prague, Czech Republic
Spirocyclic cyclodipeptides of the general formula cyclo(A-B) where A is L(D) amino acid (Gly, Ala, Ser, Leu, Val, Pgl, Phe) and B is r-1-amino-t-3-methyl-1-cyclohexanecarboxylic acid, were prepared; the aim was to determine how the substitution of methyl in position 3 of the cyclohexane circle would influence the inhibition of the proliferative activity of the caudal morphogenetic system (CMS) of chick embryos. Spirocyclic cyclodipeptides 1(a-l) have been prepared by cyclization of the corresponding linear dipeptide methyl esters 2(a-l) which were obtained by condensation of protected amino acids by DCCI method. The results of CHEST I tests show a lower activity in the series tested, as compared with the derivatives without methyl in position 3 of the cyclohexyl ring. A significant retardation of growth has been shown only by cyclo(D-Val-3-Me-Ach).
| 1996 | Folia Pharm. Univ. Carol. 20 | Pag. 87—101 |
Vladimír Buchta1 (buchta@faf.cuni.cz), Miloš Otčenášek2
1Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, 501 65 Hradec Králové
2Institute of Experimental Biopharmaceutics, Joint Scientific Center of Czech Academy of Sciences and PRO.MED. CS, Heyrovského 1207, 500 02 Hradec Králové, Czech Republic
There has been a surge in the importance of in vitro antifungal susceptibility testing during the last twenty years. This results from the increasing incidence of fungal infections and the development of new antimycotic drugs. The tests are a part of the screening and evaluation of compounds of potential interest. At a clinical level, in vitro tests enable the monitoring of the concentrations of antifungals in body fluids and can provide clinicians with useful information that would facilitate the choice of an appropriate therapeutic regimen for the treatment of mycoses. Unfortunately, most of the methods are unstandardised and give results that are not always reliable in the prediction of a clinical response. Problems of the standardisation and reproducibility of antifungal susceptibility tests arise from a number of factors affecting the test results. The main sources of discrepancies between in vitro and in vivo results are inadequate in vitro test systems; the pharmacological profile of the antifungal drug in question; the immunological status of the patient in question; and the exertion of subinhibitory concentrations of some antimycotics on pathogenic fungi, including their interference with fungal virulence mechanisms. Currently used methods are presented and discussed with emphasis on interpretation and clinical relevance of in vitro test results.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 7—14 |
Milan Lázníček (laznicek@faf.cuni.cz), Olga Jindrová, Ivana Hamplová
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
A comparison of lidocaine pharmacokinetics in mice, rats, guinea-pigs, rabbits, and man was made in this paper. Species differences exist in plasma protein binding; in animals 10 to 30 % of lidocaine is bound to plasma proteins whereas in man about 85 % of the drug is protein-bound. Also a certain degree of correlation was found between the free lidocaine fraction in plasma and both the distribution volume of the central compartment and the distribution volume at steady-state. As to elimination, a linear relationship in log-log scale was proposed between the value of lidocaine plasma clearance and body weight across all five mammalian species investigated. Considering the fact that lidocaine is highly extracted by the liver, only small interspecies differences in the ratios of lidocaine clearance-to-liver blood flow were found.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 15—20 |
Pavla Žáčková1, Jiří Vlček2 (vlcek@faf.cuni.cz), Zdeněk Zadák4, Hubert Žáček3
1Institut für Pharmakologie und Toxikologie,
2Institut für Soziale und Klinische Pharmazie
3Institut für Pharmazeutische Technologie, Pharmazeutische Fakultät der Karls-Universität, Hradec Králové
4Gerontologisch-metabolische Klinik im Fakultätskrankenhaus, Hradec Králové, Tschechische Republik
Acute Toxicity of Sodium Humate
The purpose of this work was to access the acute toxicity of sodium humate obtained from home materials within the scope of its preclinic testing.
The acute toxicity was determined on the basis of probit method on two animal species (mice, rats) of both sex. Besides the calculation of LD50, dissection was carried out on the selected dead animals, and histologic study was performed on lung, kidney, liver and spleen in the the surviving ones.
The LD50 (in mg.kg-1) was found to be 108 and 106 in mice and 62 and 73 in rats, males and females respectively. The course of intoxication was more rapid in mice than it was in rats. In the acute stage of intoxication, lung, liver and kidney were congested and the cause of death of the animals might be heart failure.
The acute toxicity of sodium humate of home origin is identical with that of foreign products and therefore is possible to take into consideration its therapeutic use in human and/or veterinary medicine.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 21—27 |
Hubert Žáček1, Pavla Žáčková2 (zackova@faf.cuni.cz)
1Institut für Pharmazeutische Technologie
2Institut für Pharmakologie und Toxikologie, Pharmazeutische Fakultät der Karls-Universität, Hradec Králové, Tschechische Republik
Artificial Intelligence in Pharmaceutical Technology
A new way of explanation of the general principles of the idea of artificial intelligence is described on the example of the preparation of a simple emulsion. This explanation makes no difference between the concept of artificial intelligence and that of expert systems. Some disadvantages and/or merits of artificial intelligence as compared with natural intelligence are given.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 29—34 |
Jiří Vlček1, Zdeněk Fendrich2 (fendrich@faf.cuni.cz)
1Department of Social & Clinical Pharmacy
2Department of Pharmacology & Toxicology, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
The choice of a drug for therapeutic intervention is a rather sensitive matter. In most cases it is not always possible to make the drug be effective only in the sense of healing the disease for which it was administered, but it may concomitantly influence other physiological or pathological processes in the organism. Therefore, it is often necessary to choose a compromise between the required and adverse effects of any drug may depend on many factors, such as the actual state of the organism for wich the drug was aimed, the choice of the correct dosage regimen, environmental factors, taking other drugs, and others. All these factors should always be taken into account. All the factors therefore form the content of the information, which arises mostly in pharmacological and pharmacoepidemiological research. The present authors tried to establish the boundaries of the individual disciplines and the reliability of information. Pharmacology is a fundamental discipline examining the effect of a drug, its mechanisms of action, and relationship to the drug dose. Pharmacoepidemiology is a new science which is based on the knowledge of pharmacology. However, pharmacoepidemiolgy advances further and triesto proceeds from the models used in pharmacology to the analysis of data which arise directly in the therapeutic process. This advantage is, however, balanced by the disadvantage in the sense of higher sensitivity in the development of false conclusions. It is therefore necessary to regularly analyse these faults as an integral part of epidemiological research. Only statistical grounding, or collaboration with a statistician is not sufficient for pharmacoepidemiological analyses, but the application of the fundamental principles of pharmacology, physiology and sociology are also absolutely essential.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 35—41 |
Ilona Bečková1 (beckova@faf.cuni.cz), Michael Vanžura1, Ladislav Bortlík2, Peter Višňovský1, Zdeněk Fendrich1
1Department of Pharmacology & Toxicology, Faculty of Pharmacy, Charles University
2Division of Health, Regional Department, Hradec Králové, Czech Republic
The attitudes towards drug dependence and experiences with abused drugs were examined in 140 students who studied pharmacy in the 3rd year (1996) at the Faculty of Pharmacy, Charles University, Hradec Králové. A standard questionnaire used by the authorities in Czech Republic for this purpose was used. According to obtained results, the students indicated their information about abused drugs as very good. The opinions concerning legalization of abused drugs were not consistent (with a marked minority of those supporting the full legality). Most of the students did not know whether they can obtain or buy the drugs directly at the Faculty of Pharmacy, Charles University. Nevertheless, marihuana and/or other abused drugs were offered to about a half of the students questioned. The experience with marihuana and hashish was reported by 34.3 % of students. The experience with Alnagon® and other drugs inducing possible dependence (hypnotic and anxiolytic agents, etc.) was positively answered by 11 % of students. The results were discussed in comparison with those obtained in other schools of the East Bohemian Region.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 43—51 |
Barbora Szotáková (szotako@faf.cuni.cz), Vladimír Wsól, Eva Kvasničková
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, 500 05 Hradec Králové, Czech Republic
In order to study the metabolism of oracine, a potential cytostatic drug, in vitro methods for preparing oracine metabolites (substrate concentration, incubation period, selection of coenzymes, aerobic and anaerobic incubation), conditions for extracting non-metabolised substrate and of its metabolites from various biological samples (enzyme incubates, urine and faeces samples from experimental animals administered with oracine) as well as methods for their chromatographic separation and detection (TLC and HPLC) have been developed and optimised. Three oxidised metabolites and a product of oracine reduction have been detected in vitro and compared with the in vivo metabolites.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 53—64 |
Petr Solich (solich@faf.cuni.cz),
Department of Analytical Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
The present paper is an abridgement of the present author’s dissertation on the basis of which he has obtained his associate professor degree. It summarizes the author’s research on the development and application of the method of flow injection analysis (FIA) in the field of the analysis of pharmaceuticals and biologically active compounds. The individual original papers resulted from the research of the State Research Task VIII-8-2/9-1 entitled “Instrumental Methods of the Analysis of Pharmaceuticals and Biologically Significant Compounds” investigated at the Faculty of Pharmacy, Charles University, Hradec Králové, under the supervision of Prof. RNDr. R. Karlíček, DrSc., in 1985—1989, and from the present author’s research of the grants “Automated Analytical System for the Determination of Content Uniformity of Pharmaceuticals” (Charles University Grant Agency 35/1993), “Development of Flow-Injection Analysis Used for the Determination of Low Content of Drugs and Biologically Active Compounds” (Charles University Grant Agency 23/1995) and “Development of Flow Methods for Dissolution Studies of Formulations” (Charles University Grant Agency 203/1996), and recently within the framework of the author’s direct research cooperation with Prof. M. A. Koupparis at the University of Athens, Greece.
The present paper includes papers dealing with the application of FIA in a strictly pharmaceutical field, i. e. in the determination of the content of active ingredients in mass-produced pharmaceutical preparations, including both the determination of the total content and, in a number of cases, of the content uniformity as a picture of the distribution of the active ingredient in the individual tablets of the pharmaceutical preparation. It also includes papers which make use of FIA method for the analysis of biologically active compounds. The published papers contribute to a wider application of FIA method in the field of pharmaceutical analysis, which is in agreement with the trends in the world, where in recent years the number of published papers in the very field of combination of FIA method and pharmaceutical analysis has been considerably increased. It can be expected that particularly the methods making use of the flow fluorimetric detection, immobilized enzymes, preconcentration, absorption to the solid phase, and in recent years also biosensors will be applied in thi s field in an ever-increasing extent.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 65—68 |
Karel Waisser1 (waisser@faf.cuni.cz), Vladimír Buchta2, Miloš Macháček1, Wilfried Thiel3, Roland Mayer4
1Department of Inorganic and Organic Chemistry and
2Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
3Arzneimittelwerk Dresden, D-01435 Radebeul, Germany
4Technische Universität Dresden, D-01069 Dresden, Germany
Dithiooxalamide, its N,N-disubstituted derivatives, and dithiooxalmorpholide were tested against Candida albicans, C. tropicalis, C. krusei, C. glabrata, Trichosporon beigelii, Trichophyton mentagrophytes, Aspergillus fumigatus, and Absidia corymbifera. Only the dermatophyte T. mentagrophytes was susceptible to the compounds tested with the MIC range of 125 to 1000 µM. The activity of N,N-disubstituted dithiooxalamides against it correlates well with their activity against both Mycobacterium tuberculosis and M. kansasii.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 69—81 |
Karel Waisser1 (waisser@faf.cuni.cz), Jana Hladůvková1, Alexandr Hrabálek1, Věra Klimešová1, Lenka Kubicová1, Jiří Kuneš1, Karel Palát Jr.1, Miloš Macháček1, Jarmila Vinšová1, Vladimír Buchta2, Petr Jílek2, Želmíra Odlerová3
1Department of Inorganic and Organic Chemistry and
2Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
3Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic
The relationships between the structure and antimycotic and antimycobacterial activity in several groups of compounds (salicylanilides and their analogues, e. g. 3-aryl-2H-1,3-benzoxazine-2,4(3H)-diones; compounds containing a thiocarbonyl group, e. g. thiobenzamides, thiobenzanilides, dithio-oxalamides; compounds containing an alkylthio group bound to an electron-deficient carbon atom, e. g. 2-alkylthio-benzothiazoles, 1-aryl-5-alkylthiotetrazoles; disulfides with an atom of sulfur bound to an electron-deficient carbon atom, e. g. bis(1-aryl-5-tetrazolyl)disulfides; and aromatic and heterocyclic amidrazones) were studied. Compounds containing combination of two pharmacophore groups, e. g. 2-alkylthio-4-pyridinecarbothioamides and [1,3]dithiolo[4,5-c][1,2]dithiole-3-thiones, were also included.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 83—88 |
Jarmila Vinšová1 (vinsova@faf.cuni.cz), Karel Waisser1, Želmíra Odlerová2
1Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
2Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic
The present study deals with the synthesis of optically active N-pyridoyl (picolinoyl, nicotinoyl) dipeptide derivatives and screening of their in vitro activity against Mycobacterium tuberculosis H37Rv. The synthesized dipeptides include methyl esters, hydrazides, hydrazones and dipeptides bearing a C-terminal free carboxyl group. The antimycobacterial effects were evaluated with the use of semisynthetic liquid substrate by Šula (ÚSOL, Prague), Youman’s and synthetic Sauton’s medium. The most active 3-pyridoyl-glycyl-L-valine methyl ester (8) has been active in an only three times higher minimum inhibitory concentration (MIC 12.3 µmol dm-3) in comparison with INH (MIC 4.1 µmol dm-3).
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 89—94 |
Lubomír Opletal1 (opletal@faf.cuni.cz), Karel Vokáč2, Vladimír Hanuš3, Marie Sovová1, Gerald Blunden4, Asmita Patel4, Christopher G. Dacke4
1Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
2Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague
3J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, Prague
4School of Pharmacy and Biomedical Science, University of Portsmouth, St Michael’s Building, White Swan Road, Portsmouth, Hants PO1 2DT, UK
The paper describes a simultaneous quantitative determination of the main components of the ripe seeds of the prospective medicinal plant crown vetch (Coronilla varia L., Fabaceae) — coumarins (scopoletin, daphnoretine, umbelliferon) and cardiotonic glycosides (deglucohyrcanoside, hyrcanoside) — by HPLC and an effective procedure for isolation of cardiotonic glycosides.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 95—99 |
Karel Kosař1, Lubomír Opletal2 (opletal@faf.cuni.cz), Marie Sovová2, Luděk Jahodář2, Christopher G. Dacke3, Gerald Blunden3, Asmita Patel3
1Department of Biological and Medical Sciences and
2Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
3School of Pharmacy and Biomedical Science, University of Portsmouth, St Michael’s Building, White Swan Road, Portsmouth, Hants PO1 2DT, UK
This paper deals with preliminary study of embryotoxicity and potential teratogenicity studies of (-)-epicatechin and (+)-catechin by CHEST (Chick Embryotoxicity Screening Test). It has been found, that these diastereoisomeric compounds do not produce interference with the embryonal developmental processes in doses of order 10-3 M and lower. In contrast, positive controls triamcinolone acetonide (TA) and cyclo(glycyl-L-leucyl) (CGL) are embryotoxic and teratogenic in the same concentrantion (10-3 M and lower).
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 101—107 |
Hana Müllerová (mullero@faf.cuni.cz), Jiří Vlček
Department of Social and Clinical Pharmacy, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
A new regional Drug Information Centre (DIC) as a part of university was established in October 1994. The aims of the centre are as follows:
The present contribution summarises professional activities of the centre two years after the establishment. 167 questions were received. The questions were mainly asked by pharmacists (35 %) and physicians from the hospital (29 %), other health-care professionals were in minority. The scopes of questions most frequently asked include side effects (17.4 %), general properties of active substances (13.8 %), availability of a drug on the market (13.2 %), interactions (9.6 %), dosage (9.6 %) and indications / contraindications (9.6 %). Cost of the service included mainly administrative charges and phone / mail expenses.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 109—114 |
Jana Kotlářová (kotlaro@faf.cuni.cz), Stanislava Hartlová, Věra Klemerová, Olga Jirková
Department of Social and Clinical Pharmacy, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
This study highlights opinions of the pharmacists who graduated at the Faculty of Pharmacy, Charles University in Hradec Králové on the individual extemporaneous preparation of drugs. The collection involved the views of the 192 pharmacists (40 men and 152 women), who graduated from the Faculty of Pharmacy of Charles University in Hradec Králové. The majority of pharmacists think that extemporaneous compounding of drugs is appropriate to the pharmacy and will remain in pharmacies in the future.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 115—117 |
Vilma Estela Henriquez Perez (vlcek@faf.cuni.cz)
Department of Social and Clinical Pharmacy, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
Self-medication has become an essential aspect of healthcare. The over the counter drugs (OTC) are now available for a lot of diseases, and their number will drastically increase in the future. I as pharmacist endeavour to describe the main roles and responsibilities of the principal elements concern in this matter.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 119—126 |
Michal Uher, Olga Rajniaková
Department of Organic Chemistry, Technical University, Bratislava, Slovak Republic
In nature, the quantity of gamma-pyranone derivatives is small, which is compensated by the enormous number of naturally occurring chromones (flavones, isoflavones, flavanones). All the compounds with gamma-pyranone skeleton form an important group of six-member heterocycles in the chemistry of naturally occurring compounds. Currently, the attention being paid to the synthetic utility of these oxygen heterocycles is not proportional to their importance, but there is hope, that the situation will change in the near future.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 127—134 |
František Šeršeň, Katarína Kráľová (kralova@fns.uniba.sk)
Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Bratislava, Slovak Republic
A great number of organic compounds were investigated from the point of view of their effects upon photosynthetic processes in spinach chloroplasts and algae. For all studied compounds and mode of action in photosynthetic electron transport chain were determined. The studied compounds were mainly amphiphilic molecules (surfactants and phenylcarbamates) and some heterocyclic compounds as well. The effect of several compounds on chlorophyll production in algae and green parts the site of higher plants was studied.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 135—140 |
Milan Mokrý (mokry@faf.cuni.cz), Jiří Klimeš
Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
HPLC with electrochemical detection was used to study acid hydrolysis of sulfisoxazole. The chromatographic conditions were elaborated on the reversed phase C18 with a mixture of methanol and water (40:60; v/v) adjusted to pH 4.0 with perchloric acid as the mobile phase. The order of the reaction was determined; for the temperatures at which stability was examined the rate constants as well as the value of energy of activation were calculated. The identity of degradation products was verified by hydrodynamics voltammograms.
| 1998 | Folia Pharm. Univ. Carol. 21—22 | Pag. 141—148 |
Ivo Hais was born on July 5, 1918 in Prague. He studied at the Faculty of Medicine, Charles University, Prague, from 1937 to 1939 when the Czech universities were closed. During this involuntary interruption, he attended a two-year course of chemistry and technology at a Prague polytechnic school. He was also employed in the laboratory of clinical pathology headed by Prof. Richard Foit at the Bulovka Hospital. He worked as a chemist in the B. Fragner chemical and pharmaceutical factory at Dolní Měcholupy where he was first in charge of the department producing injections. He then worked under Dr. Zdeněk Mansfeld, expert in pharmaceutical chemistry, and under the biochemist Dr. J. V. Koštíř, a pioneer of chromatographic and photometric methods and later Professor of Biochemistry at the Charles University, who decisively influenced I. Hais’ subsequent research line. Hais also belonged to the research group of K. Wiesner et al. who were the first to prepare penicillin in our country. After the war, Hais continued to study medicine, during which time he worked in the laboratories of the 3rd Department of Medicine (headed by Prof. Jos. Charvát) and of the 1st Department of Surgery (headed by Prof. A. Jirásek).
After taking his degree in 1947 after a short stay in the Department of Biology of the SPOFA Research and Control Institute (VKÚ), where he worked under Dr. E. Knobloch, he was awarded a SPOFA scholarship at the Department of Biochemistry, University College, London, headed by Prof. F. G. Young. He realised the importance of paper chromatography for medicine (under the influence of Dr. C. E. Dent), biochemistry and analytical chemistry. The interest in this technique determined his further scientific and publication activities. After his return home in 1948, he acquainted Czech chemists and biologists with paper chromatography and through this efforts, this method spread rapidly in Czech scientific institutes.
While working in the VKÚ Department of Pharmacology, he also served as honorary lecturer at the Department of Pharmacology, Charles University Faculty of Medicine. He greatly developed his scientific activities and supervised the work of students of the Faculty of Science preparing their theses in biochemistry. He remained faithful to the subjects he then took up, either continuing or resuming work on them in later years. They include the metabolism and side effects of the anticoagulant Pelentan, urinary amino acids under various conditions, the photolysis of riboflavin.
When VKÚ was reorganised into the Research Institute for Pharmacy and Biochemistry (VÚFB) in 1951, I. Hais became head of its Department of Physiological Chemistry. The common denominator of most of his studies was the biochemistry of drugs, mainly the research of their fate in the organism and some of their effects. His group was chiefly concerned with anticoagulants, chloramphenicol, sulphonamides and drugs affecting the nervous system. In the study of these problems, he used chromatographic and radioisotope methods. In collaboration with the staff of the Department of Sports Medicine, Charles University Faculty of General Medicine, he demonstrated the presence of urocanic acid in sweat, thus paving the way for further investigation of this acid and for the verification of A. Ženíček’s hypothesis of its sunscreen effect in the epidermis.
He continued the study of urocanic acid when he became Head of the Department of Chemistry and Biochemistry, Charles University Faculty of Medicine at Hradec Králové (1961), and summed up most of his results in his Docent’s Thesis (1965). His research subjects were then extended to the study of the wax of the Harderian gland, to the study of the effect of various factors, such as ionising radiation, on the fate of drugs and the activity of enzymes and also to the establishment of changes in urinary excretion of indolylacryloylglycine under different conditions. During his tenure of the Fellowship of the International Atomic Energy Agency in 1962, he participated in the study of the mitochondrial cholesterol degradation in N. B. Myant’s MRC laboratory in London.
He refused to accept Soviet occupation of Czechoslovakia in 1968 and the “normalization” that followed. He was therefore expelled from the Medical Faculty. Since 1970 he was allowed to work at the new Faculty of Pharmacy in Hradec Králové as a research worker of the Department of Biochemical Sciences but not allowed to teach. After the political changes in 1989 was rehabilitated and appointed University Professor (1990).
Research group of Prof. Hais was concerned with xenobiochemical research and the application of chromatographic methods. During last years, as a pensioner, he worked at the Biochemical Department as a consultant of his younger collaborators.
In addition to more than 150 original scientific works, Ivo Hais wrote or edited a number of reviews, chapters of textbooks and chromatography monographs. Among the latter, “Paper Chromatography” edited by I. Hais and K. Macek, appeared in 9 editions (in Czech, German, Russian, Hungarian, Rumanian and English). This monograph became one of the chief reference book of biochemistry. His membership of the Editorial Board of the Journal of Chromatography (since 1959) was connected with his participation in various bibliographic projects on chromatography and in international symposia. He was one of the founders of the Czechoslovak Biochemical Society and for several periods of office served in its Committee. He has been active in the Chromatography Section of the Czechoslovak Chemical Society.
Prof. Hais generously and patiently passed on his expert knowledge and experience to all who were interested. What was more, Prof. Hais’ personality combined a remarkable stock of knowledge in biological and chemical disciplines with linguistic talents (he spoke several languages fluently) and with a broad outlook in culture and social sciences. In both the Research Institute for Pharmacy and Biochemistry and the Faculty of Pharmacy, he promoted the foundation of amateur visual arts groups. He displayed specimens of his paintings, drawings, graphic art and sculptures in a one-man retrospective exhibitions. His efforts in literary sphere were less known. He was talented swimmer taking part in swimming competitions in his youth. He favoured for years skiing and hiking, enjoying the pleasure of movement, keeping fit and setting an example for his colleagues and students. He was biking daily to the Faculty up to his last days.
The sudden and unexpected death of Prof. Hais on the 25th of October 1996 made his colleagues and friends truly sad.
Original papers
1988
Vančurová I., Mělka M., Křepelka J., Nobilis M., Kvasničková E., Beneš M., Hais I. M., Skládaná M., Kejhová I., Pokorná S., Reichlová R.: N-oxidy derivátů 5-(dialkoamino)alkoxy-7-oxo-7H-benzo[c]fluorenu a způsob jejich výroby. Autorské osvědčení vynálezu 239413, Praha 1988, str. 1—3
1989
Dršata J., Přibová M., Hais I. M.: Inhibice dekarboxylasy aromatických aminokyselin protizánětlivými látkami flobufenem a kyselinou 2,4-difluorbifenyl-4-yloctovou. Českoslov. Farm. 38, 1989, 407—410
1990
Hais I. M., Nobilis M., Kvasničková E.: Evaluation of photometric high-performance liquid chromatographic data for the determination of benflurone metabolites in biological materials with and without concomitant use of standard. J. Chromatogr. 500, 1990, 643—653
Nobilis M., Vančurová I., Křepelka J., Mělka M., Lyčka A., Jirman J., Kvasničková E., Hais I. M., Miko M.: Polohové izomery x-hydroxy-5-(dimethylmanoethoxy)-7-oxo-7H-benzo[c]fluorenu. Autorské osvědčení vynálezu 267519, Praha 1990, str. 1—3
1991
Nobilis M., Kvasničková E., Šroler A., Hais I. M.: Elimination of benflurone and its metabolites in the faeces and urine of rats. Drug Metab. Drug Interact. 9, 1991, 220—226
Kvasničková E., Hais I. M., Nobilis M.: Relationship between NADH and NADPH as cosubstrates of N-oxidation of the cytostatic benflurone by FMO. In: Progress in Pharmacology and Clinical Pharmacology, ed. Hlavica P., Vol. 8, Gustav Fischer Verlag, Stuttgart, New York, 1991, p. 137—146
Dršata J., Hais I. M., Maloň P.: Interaction of Z-4,4-bis(4-ethylphenyl)-2,3-dibromo-2-butenoic acid with aminotransferases: Changes in absorption and circular dichroism spectra. Drug Metab. Drug Interact. 9 (1991) 255—268
1992
Drandarov K., Kvasničková E., Hais I. M.: Biotransformation of the sympathomimetic tetraminol in vitro. Arch. Pharm. 323, 1992, 589—561
1993
Drandarov K., Hais I. M.: Thin-layer chromatography of the positional isomers of some 1,2,3,4-tetrahydro-2-naphtol and 3-amino-1,2,3,4-tetrahydro-2-naphtol derivatives. J. Chromatogr. 628, 1993, 103
Marklová E., Klein I., Hais I. M.: Urinary excretion of indolylacryloylglycine, indolylacetic and 5-hydroxyindolylacetic acids in burn patients. Sbor. Vědec. Prací LF UK Hradec Králové 36, 1993, č. 4—5, str. 299—303
1994
Kvasničková E., Hais I. M.: Flavinové monooxygenázy, mechanismus jejich účinku a substrátová specifita. Česká a Slovenská Farm. 53, 1994, 315—319
Kvasničková E., Nobilis M., Šroler A., Wsól V., Hais I.M.: In vitro and in vivo biotransformation ot two potential cytostatic drugs. In: In vitro and Ex vivo Test Systems to Rationalize Drug Design and Delivery, Crommelin D., Couvreur P., Duchéne D. (eds.), Edition de Santé, Paris, 1994, pp. 331—335
Kvasničková E., Wsól V., Szotáková B., Trejtnar F., Hais I. M.: Enzymic and chromatographic characterization of the in vitro and in vivo metabolites of the potential cytostaic oracine, Eur. J. Pharm. Sci. 2, 1994, 175
Hais I. M.: Český farmaceutický výzkum v době II. světové války a po ní. Vzpomínky pozorovatele. Příspěvky k historii československého chemického průmyslu 22, 1994, 64—97
1995
Kvasničková E., Riegrová A., Hais I. M.: Inhibition of microsomal monooxygenases by the enzyme inductor flumecinol. Folia Pharm. Univ. Carol. 20, 1995,
1996
Kvasničková E., Šroler A., Nobilis M., Wsól V., Machala M., Vortel V., Brejcha A., Hais I. M.: Activities of some biotransformation enzymes in the course of experimental pancreatitis. Chem. Listy 90, 1996, 743—744
Wsól V., Kvasničková E., Szotáková B., Hais I. M.: High-performance liquid chromatograhphic assay for the separation and characterization of metabolites of the potential cytostatic drug oracine. J. Chromatogr. 681, 1996, 169—175
Wsól V., Fell A. F., Kvasničková E., Hais I. M.: Separation of the stereoisomers of the main metabolite of a non-steroidal anitinflammatory drug flobufen by chiral HPLC. J. Chromatogr. 1996 (in press)
Short Communication and Contribution to Proceedings
1988
Kvasničková E., Popelková I., Hais I. M.: Interaction between haemoprotein-P-450 dependent monooxygenases and the cytostatic benflurone. 14th International Congress of Biochemistry, Prague 1988, Abstracts p. 486
Nobilis M., Hais I. M., Kvasničková E., Koruna I., Repka M., Lyčka A., Jirman J.: Physicochemical and enzymic approaches in the study of biotransformation of drugs. 14th International Congress of Biochemistry, Prague 1988, Abstracts p. 598
Šroler A., Kvasničková E., Hais I. M.: Activity of MFO system in male rats with experimental induced acute and protracted pancreatic lesion. 14th International Congress of Biochemistry, Prague 1988, Abstracts p. 599
Hais I. M., Kvasničková E., Nobilis M., Šroler A., Lyčka A., Jirman J.: Structure—retention relationships in characterization of drug metabolites. Benflurone and some other examples. 10th Intern. Sympos. Biomed. Applications of Chromatogr. and Electrophoresis, Žinkovy, 26.—29. 6. 1988, Abstracts p. A-13
Dršata J., Hais I. M.: The inhibition of aminotransferases by Z-2,3-dibromo-4,4-bis(4-ethylphenyl)-2-butenoic acid. Time course and changes in absorption spectra of enzymes. 14th International Congress of Biochemistry, Prague 1988, Abstracts p. 132
Veselá J., Dršata J., Hais I. M.: The influence of the cytostatic benflurone on the activity of ornithine decarboxylase of the rat liver regenerating after partial hepatectoctomy. 14th International Congress of Biochemistry, Prague 1988, p. 71
1989
Kvasničková E., Šroler A., Nobilis M., Hais I. M.: Biotransformace Hyrkanosidu in vitro. Konference Možnosti terapeutického a hospodářského využití čičorky pestré (Coronilla varia L.) v Československu, Hradec Králové 22. 6. 1989, Abstrakta str. 22
Kvasničková E., Riegrová A., Hais I. M.: Kinetics of the inhibition of microsomal monooxygenases by the enzyme inductor flumecinol. 3rd European Symposium of Foreign Compounds Metabolism, London 1989, Abstracts p. 92.
Kvasničková E., Hais I. M., Nobilis M.: Relationship between NADH and NADPH as cosubstrates of the N-oxidation of the cytostatic benflurone catalyzed by FMO. 4th International Symposium on the Biological Oxidation of Nitrogen in Organic Molecules, Munich 1989, Abstracts p. 46
Veselá J., Dršata J., Hais I. M.: Ornithindekarboxylasa jako marker nástupu proliferace po parciální hepatektomii u potkana. Sborník XIX. Máj. Hepatol. Dnů — Celoštát. Zjazd Českoslov. Hepatol. Spol. Nový Smokovec 1989, 17.—19. 5.
1990
Kvasničková E., Hais I. M., Nobilis M.: Vztah mezi NADH a NADPH při oxidaci terciárního aminu flavinovými monooxygenasami (FMO). XVI. Xenobiochemické symposium, Domažlice 1990, Abstrakta str. 27
Šroler A., Štyndl M., Nobilis M., Skopec M., Sedlmayer P., Pakostová A., Kvasničková E., Hais I. M.: Vliv experimantální pankreatitidy na aktivitu enzymů mikrosomální frakce a hepatocytů pokusných zvířat. XVI. Xenobiochemické symposium, Domažlice 1990, Abstrakta str. 6
Kvasničková E., Hais I. M., Nobilis M., Peřina M., Sova J.: N-oxidace dvou strukturně analogických terciárních aminů flavinovými monooxygenasami. XII. Celostátní biochemický sjezd, Bratislava 1990, Abstrakta str. F-34
1991
Nobilis M., Kvasničková E., Šroler A., Müllerová M., Hais I. M.: Identifikace metabolitů antidepresiva moxyfetinu HPLC analýzou a mnohokanálovou UV detekcí. XVII. Xenobiochemické symposium, Hradec Králové 1991, Abstrakta str. 20
Dršata J., Hais I. M., Maloň P.: Interakce aminotransferas s kyselinou Z-4,4-bis(4-ethylfenyl)-2,3-dibrom-2-butenovou: Změny UV-VIS a CD-spekter. XVII. Xenobiochemické symposium, Hradec Králové 1991, Abstrakta str. 27
Kvasničková E., Nobilis M., Šroler A., Müllerová M., Štyndl M., Hais I. M.: Biotransformace potenciálního antidepresiva moxyfetinu in vitro. XVII. Xenobiochemické symposium, Hradec Králové 1991, Abstrakta str. 19
1992
Šroler A., Wsól V., Kvasničková E., Hais I. M.: In vitro a in vivo biotransformace látky VÚFB 16956 — potenciálního cytostatika. XIII. Celostátní biochemické dny, České Budějovice 1992, Abstrakta str. 26
1993
Kvasničková E., Nobilis M., Šroler A., Wsól V., Hais I. M.: In vitro and in vivo biotransformation of two potential cytostatic drugs. European Symposium on In Vitro and Ex Vivo Test Systems to Rationalize Drug Design and Delivery, Paris 1993, Abstracts p. 28
Kvasničková E., Hais I. M.: Flavinové monoxygenasy — substrátová specifita a mechanismus jejich katalysy. 14. Biochemický sjezd, Brno 1993, Abstrakta str. 114
Kvasničková E., Hais I. M., Nobilis M.: NADH preference při N-oxidaci terciárního aminu flavinovými monooxygenasami. 14. Biochemický sjezd, Brno 1993, Abstrakta str. 117
1994
Kvasničková E., Wsól V., Szotáková B., Trejtnar F., Hais I. M.: Enzymic and chromatographic characterization of the in vitro and in vivo metabolites of the potential cytostatic oracine. 2nd European Congress of Pharmaceutical Sciences, Berlin 1994, Abstracts p. 175
Wsól V., Kvasničková E., Šroler A., Szotáková B., Hais I. M.: Kvantitativní zastoupení dvou hlavních metabolitů potenciálního cytostatika oracinu u různých druhů laboratorních zvířat. XVIII. Xenobiochemické symposium, Brno 1994, Abstrakta str. 43
Kvasničková E., Buchta V., Wsól V., Nobilis M., Šroler A., Szotáková B., Hais I. M.: Mikroorganismy — model pro studium metabolismu léčiv. XVIII. Xenobiochemické symposium, Brno 1994, Abstrakta str. 23
1995
Kvasničková E., Szotáková B., Wsól V., Skálová L., Trejtnar F., Kuchař M., Hais I. M.: Metabolic transformation of the potential non-steroid antiinflammatory drug flobufene, their localization and interspecies comparison. European Conference on Specificity and Variability in Drug Metabolism, Besanson 1995. Abstracts p. 43
Wsól V., Clark B. J., Kvasničková E., Hais I. M.: The separation of optically active metabolites of potential cytostatic drugs using HPLC. European Conference on Specificity and Variability in Drug Metabolism, Besanson 1995, Abstract p. 48
Wsól V., Kvasničková E., Szotáková B., Hais I. M.: High performance liquid chromatographic assay for the separation and characterization of metabolites of the potential cytostatic drug oracine. 13th International Symposium on Biomedical Application of Chromatography and Electrophoresis, Prague, Czech Republic, 1995, p. P59
Kvasničková E., Wsól V., Szotáková B., Skálová L., Hais I. M.: Metabolické studie potenciálního cytostatika oracinu v podmínkách in vitro a in vivo. XIV. Biochemické dny, Bratislava 1995, Abstrakta str. 136
1996
Wsól V., Kvasničková E., Hais I. M., Fell A. F.: Enantiomeric resolution of a novel NSAID, flobufen, and its principal metabolite by HPLC. 8th International Symposium on Chiral Discrimination, Edinburgh 1996, Abstracts p. 68
Kvasničková E., Šroler A., Nobilis M., Wsól V., Machala M., Vortel V., Brejcha A., Hais I. M.: Activities of some biotransformation enzymes in the course of experimental pancreatitis. XV. Biochemický sjezd, Olomouc 1996, Sborník příspěvků str. 743—744
Books
1991
Devínsky F., Hais I. M., Kvasničková E. (eds.): Drug Metabolism and Drug Interactions, Freund Publishing House (U. K.) Ltd., London, England, 1991, 98 pp.
J. Dršata, E. Kvasničková
| 1998 | Folia Pharm. Univ. Carol. 23 | Pag. 7—13 |
Marie Pospíšilová1 (pospisim@faf.cuni.cz), Jiřina Spilková2
1Department of Analytical Chemistry,
2Department of Pharmacognosy,
Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
The system for the rapid analysis of quercetin has been established using capillary isotachophoresis. Under the conditions employed, authentic quercetin examined was clearly separated into a sharp zone. The following operational system has been used: 5 mmol l-1 HCl + 10 mmol l-1 Tris (pH 8.06) as LE and 10 mmol l-1 Glycine + Ba2+ as TE. The effective mobility of quercetin was given. This technique seems to be useful for the determination of quercetin in the range 40 to 400 µg ml-1 (r = 0.9996). The proposed method is acceptably time efficient and can be used for quality control of authentic quercetin in pharmaceutical analysis.
| 1998 | Folia Pharm. Univ. Carol. 23 | Pag. 15—20 |
Jiřina Dušková1 (duskova@faf.cuni.cz), Jaroslav Dušek2
1Department of Pharmaceutical Botany and Ecology,
2Department of Pharmacognosy
Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
Newly developed 3-allyl-6-nitro-2-benzothiazolinone (ANB) growth regulator was tested either added to a medium alone or in combination with kinetin (K). Lactic acid was tested at the same time. The influence of these substances on the growth, morphogennic activity and production of secondary metabolites in tissue cultures Arctostaphylos uva-ursi, Coronilla varia, Datura meteloides, Leuzea carthamoides, Rhodiola rosea and Rheum palmatum was studied. ANB (0.02; 0.0002 mg.l-1) and both its combinations with kinetin (0.1 mg.l-1) showed statistically significantly higher growth of fresh weight in comparison with the control only at the Leuzea carthamoides culture. The Rheum palmatum culture showed statistically significantly higher growth only at higher concentration of ANB in combination with kinetin. Lactic acid induced statistically significantly higher growths at the Datura meteloides (10.0 mg.l-1) and Rhodiola rosea (in all tested concentrations) cultures. The influence of both regulators on morphogennic activity proved to be ineffective at the cultures we tested with the only exception of the Leuzea carthamoides culture. At this culture little deformed buds were formed due to the influence of ANB. The influence of ANB on the production of secondary metabolites proved to be positive only at the Rheum palmatum culture. When it was present, cultures contained increased amount of flavonoids and anthraquinones in the medium.
| 1998 | Folia Pharm. Univ. Carol. 23 | Pag. 21—25 |
Hubert Žáček, Marie Musilová (musilova@faf.cuni.cz),
Department of Pharmaceutical Technology, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
A study of softening and melting temperatures of ternary mixtures which contained hardened sun-flower oil, cacao oil and neutral fat was undertaken. The design of pertinent experiments was based on relevant Gibbs concentration triangles. Zones conforming to pharmacopoeial requirements were determined.
| 1998 | Folia Pharm. Univ. Carol. 23 | Pag. 27—32 |
Hubert Žáček, Marie Musilová (musilova@faf.cuni.cz),
Department of Pharmaceutical Technology, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
A Contribution to Penetrometric Testing of Ointment Preparations
It is shown that strict differentiation must be made between rheometric measurements carried out on several samples of one and the same ointment preparation and analogous measurements performed repeatedly on a single sample of such preparation. In the latter instance, the phenomenon of „rheeologic memory“ is proved which can have several consequences in the preparation of ointments. It is also shown that the coefficient of determination (square of the correlation coefficient) is a very good measure of the efficiency of penetrometric data.
| 1998 | Folia Pharm. Univ. Carol. 23 | Pag. 33—38 |
Marie Musilová (musilova@faf.cuni.cz), Milan Řehula, Marta Čermáková, Hubert Žáček
Department of Pharmaceutical Technology, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
The Effect of Eucalyptus Oil on the Consistence of Suppository Bases
The effect of eucalyptus oil on the content of solid and liquid parts in hydrophobic suppository base Adeps neutralis was studied by dilatometric method. After addition of eucalyptus oil, the original hard fat became more plastic. More pregnant than for melting temperature was the shifting of softening temperature. For critical temperatures beneath 30 °C, bad consistence can be expected. Liquid parts for concentrations higher than corresponds to the content of eucalyptus oil appear red at temperatures beneath 20 °C, namely for bases with higher melting temperature.
| 1998 | Folia Pharm. Univ. Carol. 23 | Pag. 39—44 |
Alice Lázníčková (laznicko@faf.cuni.cz), Josef Dolejš
Department of Biophysics and Physical Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
The binding of radiolabelled ortho-iodohippurate to bovine serum albumin was studied by equilibrium dialysis at 24 °C. The free drug fraction was dependent on total ortho-iodohippurate concentration. The association constants to primary and secondary binding sites were calculated by non-linear itterative regression analysis. The analysis consisted of computing free and bound ortho-iodohippurate for a range from 10-5 to 10-2 mol/l. One primary binding site with association constant K1 = 3.96×10-3 l/mol and approximatelly four low affinity binding sites (K2 = 0.0774 l/mol) were calculated. This finding is in agreement with general notion of two types of the binding sites on albumin molecule for the binding of acidic drugs.
| 1998 | Folia Pharm. Univ. Carol. 23 | Pag. 45—50 |
Vladimír Kubíček (kubicek@faf.cuni.cz)
Department of Biophysics and Physical Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
The determination of calibration constants of the differential gas permeameter for the measurements of permeation and diffusion of permanent gases in polymer membranes is described. The succesful use of this method is demonstrated by the results of the differential permeameter calibration for CO2, N2 and O2 at four different temperatures.
| 1998 | Folia Pharm. Univ. Carol. 23 | Pag. 51—58 |
Martin Doležal1 (dolezalm@faf.cuni.cz), Jiří Hartl1, Jana Krinková1, Želmíra Odlerová2
1Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
2Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic
Positive influence of amidation or alkylation in position 5 of the pyrazine nucleus on antimycobacterial activity was confirmed. Secondary amines are more active than tertiary amines. The influence of free hydrogen atom is significant for the spread of the activity against the atypical mycobacterial strains. In the series of aromatic derivatives the positive effect on the spread of the activity against atypical mycobacterial strains showed the substitution by some polar group, particularly by phenolic hydroxyl group. The antimycobacterial activity of prepared compounds is mostly influenced by the presence of the thioamidic moiety. The most active compound of this series was 3-anilino-5-cyanopyrazine-2-carboxamide (MIC = 12.5 µg ml-1). The value of optimal hydrophobicity (log P between 2.00 and 3.00) in the series of studied compounds was determined. These values of log P are higher than the one for PZA which is lower than zero. Calculation or prediction of values partition coefficients of prepared compounds is helpful in searching for new active structures and can be used during optimalization their properties.
| 1998 | Folia Pharm. Univ. Carol. 23 | Pag. 59—66 |
Karel Waisser (waisser@faf.cuni.cz), Lenka Kubicová, Hynek Dostál
Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
The previous parts of the present authors’ series of review papers presented a survey of studies connected with biological activity of salicylanilides, thiosalicylanilides, derivatives of 3-aryl-2H,4H-benz[e][1,3]oxazine-2,4-dione and benzanilides. To complete the overall survey, it was to publish similar information on thiobenzanilides, which was the aim of the present review paper. It follows from the analysis that thiobenzanilides have hitherto been studied in a much smaller extent than other compounds similar to salicylanilides and their research is far from complete. They have been reported to show general antibacterial activity, antimycobacterial activity, antifungal activity, insecticidal activity and herbicidal activity. Because of their biological effects, some thiobenzanilides have been patented. Their research, however, is far from being complete and it can be said that we can expect a constant flow of new papers about them in the near future.
| 1999 | Folia Pharm. Univ. Carol. 24 | Pag. 7—12 |
Alice Lázníčková1 (laznicko@faf.cuni.cz), Mathew L. Thakur2
1Charles University in Prague, Faculty of Pharmacy, Hradec Králové, Czech Republic
2Thomas Jefferson University Hospital, Philadelphia, USA
Labelling of RC-160, a somatostatin receptor specific octapeptide, with 99mTc and 125I was studied. For radiolabelling of RC-160 with 99mTc the direct method based on reduction of disulphide groups of the peptide by ascorbate to sulfhydryls (strong binding groups for technetium) was used. For labelling of RC-160 with 125I, either chloramine-T or iodogen methods were employed. Even if RC-160 can be directly labelled with both radionuclides, the purification of the product is necessary to achieve high radiochemical purity. The labelling procedures are difficult as they require special skills which are not available in every radiopharmacy unit, and they are also time consuming and therefore unsuitable for routine investigation.
| 1999 | Folia Pharm. Univ. Carol. 24 | Pag. 13—18 |
Ludmila Melicharová (melichao@faf.cuni.cz), Milan Lázníček, František Trejtnar
Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy, Hradec Králové, Czech Republic
The comparison of liver handling of two model drugs, namely sulfobromophtalein (BSP) and 99mTc-Br-HIDA, aimed in the evaluation of their advantages and limitations in the use as markers of hepatobiliary function was made by employing perfused rat liver preparations. Regardless to their high binding to plasma proteins, both agents were intensively eliminated by the hepatobiliary system. The higher rate of elimination (higher extraction ratio and higher liver clearance value) for 99mTc-Br-HIDA was found when compared to BSP. Bile clerarance values slightly incresed with time (for 90 min of the experiment) for both compounds under study. Extraction ratio values for BSP slightly increased with time. However, a significant decrease of extraction ratio values at the latest time intervals for 99mTc-Br-HIDA was determined. Both agents can serve as markers of intensity of hepatobiliary excretion in perfused rat liver preparations. If radiometric detection is accessible, the use of 99mTc-Br-HIDA makes the determination very easy. In other cases, BSP can be routinely used for this purpose.
| 1999 | Folia Pharm. Univ. Carol. 24 | Pag. 19—27 |
Ilona Bečková (beckova@faf.cuni.cz), Martina Mlynářová, Zdeněk Fendrich, Peter Višňovský
Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy, Hradec Králové, Czech Republic
As it is evident from the present study, habit formers are not a problem of the majority of university students. However, a certain part of students have their own experience with soft drugs and only a minority of students have experience even with hard drugs, which is not, however, an alarming state. It can be concluded that university students are not the most threatened group in this sense5. According to the comparison of the development of the collection, most students already come to the university with their own experience with habit formers and only a smaller part of respondents examine drugs while studying at the university.
| 1999 | Folia Pharm. Univ. Carol. 24 | Pag. 29—32 |
Veronika Opletalová1 (opletalo@faf.cuni.cz), Jiří Hartl1, Camille Domonhedo1, Asmita Patel2
1Department of Pharmaceutical Chemistry and Drug Control, Charles University in Prague, Faculty of Pharmacy, Hradec Králové, Czech Republic
2School of Pharmacy and Biomedical Science, University of Portsmouth, Portsmouth, United Kingdom
Homolytic acetylation of 2-pyrazinecarbonitrile using pyruvic acid as a source of acetyl radical was studied. 5-Acetyl-2-pyrazinecarbonitrile was obtained as the main product. The yield ranged from 5 to 30 % depending on reaction conditions.
| 1999 | Folia Pharm. Univ. Carol. 24 | Pag. 33—39 |
Marie Musilová (musilova@faf.cuni.cz), Milan Řehula, Hubert Žáček, Alice Kaločová
Institut für Pharmazeutische Technologie, Karls-Universität Prag, Pharmazeutische Fakultät, Hradec Králové, Tschechische Republik
Eleven various mixtures of suppository bases Witepsol H 15 and Witepsol E 75 were prepared. These mixtures were characterized by the time of total deformation of the suppositories and by the content of the solid phase which corresponded to the temperature of carrying out the testing of deformation. It was found that the pharmacopoeial requirements are not satisfied in samples for which the content of the solid phase in the suppository base is greater than 26 %. The tolerable temperature zone of the testing of the time of total deformation, i. e. ± 0.5 °C, is too large at the temperature of the mean of the corresponding zone 37 °C.
| 1999 | Folia Pharm. Univ. Carol. 24 | Pag. 41—47 |
Karel Waisser1 (waisser@faf.cuni.cz), Rainer Beckert2, Milan Šlosárek3, Jiří Janota3, Rüdiger Faust4
1Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy, Hradec Králové, Czech Republic
2Institute of Organic and Macromolecular Chemistry, Friedrich Schiller University, D-07743 Jena, Germany
3Institute of Public Health, Prague, Czech Republic
4Institute of Pharmaceutical Chemistry, University of Heidelberg, D-69120 Heidelberg, Germany
In conjunction with our previous work directed towards the study of compounds containing the oxalamidine pharmacophore, the structure of 2,3-dianilinoquinoxaline was subjected to modifications. The replacement of the six-membered heterocycle for a five-membered one as well as the replacement of the aniline nitrogen atom for the ethynyl moiety and the replacement of the chinoxaline ring for the benzotriazine one resulted in obtaining compounds with no activity. Upon replacing the aniline substructural fragment for both the morpholinyl and pyrrolidinyl moiety (similarly, in position 2 for chlorine, and in position 3 for these heterocyclic substituents), and replacing the quinoxaline heterocycle for benzo[a]pyrazol, the activity of the compounds was reduced. In conclusion, the modifications leading to derivatives the structures of which are substantially different from that of the lead compound are not suitable for further consideration.
| 1999 | Folia Pharm. Univ. Carol. 24 | Pag. 49—53 |
Karel Waisser1 (waisser@faf.cuni.cz), Karel Palát Jr.1, Jiří Kuneš1, Želmíra Odlerová2
1Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy, Hradec Králové, Czech Republic
2Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic
This paper aims at determining whether the mechanism of action of several groups of new potential antituberculotics developed at the Faculty of Pharmacy, Charles University, Hradec Králové, is related to the processes in the cell wall of mycobacteria. A simple test for the estimation of the loss of bacterial acidoresistance has been employed in this study. It has been found that the acidoresistance of Mycobacterium tuberculosis is completely lost upon exposure to two new potential antituberculotics, 2-benzothiazolcarboxamide 6, and 3-(4-tolyl)-1,2-dihydroquinoxaline-2-thione 7. It is possible to conclude that the mechanism of their action consists in the intervention into the formation of the cell wall.
| 1999 | Folia Pharm. Univ. Carol. 24 | Pag. 55—78 |
Jana Klečáková (klecako@faf.cuni.cz), Luděk Jahodář
Department of Pharmaceutical Botany and Ecology, Charles University in Prague, Faculty of Pharmacy, Hradec Králové, Czech Republic
The aim of this work is to provide useful information in tabelar form for pharmacists who are working in community and hospital pharmacy and for other biologists. This paper was inspired by the recognition that the level of contemporary knowledge of biologically active substances produced by plants is not very high even some health service workers (include pharmacists). The table is constructed, so that to provide information on scientific names of toxic plants (the plants are arranged by botanical systematics), their metabolites producing toxic and / or adverse effects, symptoms of intoxication and treatment of that. The part of “Notes” provides completing data of the genus or species.
| 1999 | Folia Pharm. Univ. Carol. 24 | Pag. 79—108 |
(Abstract of Papers)
Lubomír Opletal (opletal@faf.cuni.cz)
Department of Pharmaceutical Botany and Ecology, Charles University in Prague, Faculty of Pharmacy, Hradec Králové, Czech Republic
The complete text contains abstracts of 38 lectures and of 16 contributions in poster section.
| 2000 | Folia Pharm. Univ. Carol. 25 | Pag. 7—13 |
David Mendl, Milan Lázníček (laznicek@faf.cuni.cz)
Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Interactions of cyclosporin A with components of the central distribution compartment (plasma proteins and blood cells) were determined in four animal species, namely man, bovine, rabbit and rat. It was demonstrated that cyclosporin A is very strongly bound to plasma proteins (98 — 99 %) and also to blood cells in their suspension (92 — 97 %) in all species. In interspecies comparison, significant differences in distribution of the cyclosporin A in the whole blood were determined. While about three quarters of amount of cyclosporin A were distributed to blood cells and one quarter of the drug was bound to plasma proteins in man, that for rabbit was nearly inverse. Ultrafiltration method by using Centrex UF-0.5 Filters 10 KMWCO (Schleicher and Schuel) gave comparable results of plasma protein binding in comparison with equlibrium dialysis. Advantage of ultrafiltration against the standard method of equilibrium dialysis is above all determination speed (6 minutes vs. 4 hours).
| 2000 | Folia Pharm. Univ. Carol. 25 | Pag. 15—19 |
Martin Doležal (dolezalm@faf.cuni.cz), Jiří Hartl, Miroslav Miletín
Department of Pharmaceutical Chemistry and Drug Control, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Condensation of chlorides of substituted pyrazine-2-carboxylic acids with ring substituted anilines yielded a series of 12 anilides of 6-chloropyrazine-2-carboxylic, 5-(1,1-dimethylethyl)pyrazine-2-carboxylic or 6-chloro-5-(1,1-dimethylethyl)pyrazine-2-carboxylic acids. Products were tested for their antimycobacterial activity. The structure—activity relationships were studied. The values of hydrophobicity in the series of studied compounds were determined. Three of the tested compounds were quite active in vitro against M. tuberculosis (> 50% inhibition). 6-Chloro-5-(1,1-dimethylethyl)pyrazine-2-carboxylic acid 4-hydroxy-anilide (97% inhibition) was the most active compound. The activity dropped or disappeared either at the compounds with lower lipophilicity (log P > 2.00) or at the compounds with higher lipophilicity parameters (log P < 3.80).
| 2000 | Folia Pharm. Univ. Carol. 25 | Pag. 21—33 |
Veronika Opletalová (opletalo@faf.cuni.cz), Pavla Řičičářová, Daniel Šedivý, Dana Meltrová, Jarmila Křiváková
Department of Pharmaceutical Chemistry and Drug Control, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Chalcones exert various biological activities, e. g. antibacterial, including antimycobacterial, antifungal, antiviral, antiprotozoal, antioxidative, antiinflammatory, gastroprotective and antineoplastic. The review gives some examples of biologically active chalcones and their heterocyclic analogues.
| 2000 | Folia Pharm. Univ. Carol. 25 | Pag. 35—43 |
Stanislav Ďoubal (doubal@faf.cuni.cz),
Department of Biophysics and Physical Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Mechanical behavior many biological materials correspond to the behavior of so called visco-elastic body. These materials can not be categorized simply as solids or liquids. The mechanical behavior of this type of materials has partially elastic and partially plastic (viscose) character. Skin, cell walls, numerous structures of internal organs and many other materials belong to this category.
The tools, derived from the theories of solids and liquids, are not adequate for the description of mechanic behavior of such materials. General methodology of description and quantification of mechanical properties of visco-elastic materials follow from the science of rheology. The primary source of information on mechanical behavior in rheology are rheological characteristics (usually creep curves). According the analysis of creep curves, rheological models of materials may be developed.
The feasible appliance for measurement of creep curves is necessary for the application of this methodology. As device, convenient for measurement of creep curves of biological materials, was not available, we designed the appliance in our laboratory.
The paper presents methodology of the measurement of creep curves of biological materials in vivo as well as in vitro. Further, the methodology of identification and parameter determination of rheological models is presented in the paper.
| 2000 | Folia Pharm. Univ. Carol. 25 | Pag. 45—48 |
Stanislav Ďoubal (doubal@faf.cuni.cz),
Department of Biophysics and Physical Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The universal appliance for measurement of basic rheological characteristics of solids and visco-elastic materials was developed and tested. The apparatus may be applied in biological, medical and pharmaceutical laboratories. The device enables measurement of the following parameters and characteristics: stress-strain curves in case of tension, shear, torsion and pressure load, breaking strengths, elastic modules, ductility and time dependencies of strain on stress (e. g. creep curves). The field of application involves measurements of mechanical characteristics of biological materials as skin, cartilage, vascular walls, bones, hairs, and other materials of similar parameters.
| 2000 | Folia Pharm. Univ. Carol. 25 | Pag. 49—52 |
Karel Waisser (waisser@faf.cuni.cz), Tereza Grófová
Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
This work is an example of the application of the Hansch equations to dealing with the problem of the differences of biological activities against different strains of mycobacteria (M. avium and M. tuberculosis). In the cases presented here (salicylanilides, 6-bromo-3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones, 4-fluorothiobenzamides) the importance of the electronic parameter sigma is showed. General conclusions cannot be made, as it is not possible to find statistically significant relationships for some sets of compounds using this approach.
| 2000 | Folia Pharm. Univ. Carol. 25 | Pag. 53—59 |
Karel Waisser (waisser@faf.cuni.cz), Miloš Macháček
Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The present review paper of our communications aims to show that if the values of separated activities for the molecular fragments (substituents) by Free—Wilson method on the modified substitutional sites correlate with physico-chemical parameters, these correlation can be employed to predict the effects of new, hitherto unconsidered structural modifications. Topliss approaches can be used in a similar way in the modifications of substituents correspond to Topliss approach.
| 2000 | Folia Pharm. Univ. Carol. 25 | Pag. 61—65 |
Vladimír Kubíček (kubicek@faf.cuni.cz)
Department of Biophysics and Physical Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The pK values of some carboxy azo dyes measured by spectrophotometric method were compared with the pK values of the same dyes estimated from A—pH curves. Very good agreement of the measured and the estimated values was reached for the most of the dyes.
| 2000 | Folia Pharm. Univ. Carol. 25 | Pag. 67—72 |
Lenka Kubicová1 (kubicova@faf.cuni.cz), Katarína Kissová2, Karel Waisser1
1Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2Institute of Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Slovak Republic
The inhibition of chlorophyll production in statically cultivated algal suspensions of Chlorella vulgaris by R'-substituted salicylanilides and their 5-nitro, 5-fluoro and 5-bromo analogues has been investigated. The studied compounds showed antialgal effects and the IC50 values of the most active compounds were about 2.4—5.0 µmol dm-3. The antialgal activity of the studied compounds depended on the lipophilicity as well as on the electronic parameter of substituent R2.
| 2000 | Folia Pharm. Univ. Carol. 25 | Pag. 73—80 |
Lenka Kubicová1 (kubicova@faf.cuni.cz), Katarína Kráľová2, Hynek Dostál1, František Šeršeň2, Miloš Macháček1, Karel Waisser1
1Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2Institute of Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Slovak Republic
Substituted 2-amino-N-phenylbenzamides inhibit photosynthetic electron transport in spinach chloroplasts and chlorophyll production in Chlorella vulgaris. The photosynthesis-inhibiting activity of the studied compounds in spinach chloroplasts depends on the sum of Hammett constants of R1 and R2 substiuents, whereas their antialgal activity depends mainly on the lipophilicity of 2-amino-N-phenylbenzamides. The site of action of the compounds with chlorophyll-protein complexes present in photosynthetic centres is the D+ intermediate, i. e. the tyrosine radical in position 161 (TyrD) which is located in D2 protein on the donor side of photosystem (PS) 2. The own core of PS 2 (P 680) and a part of the electron transport chain — at least up to plastoquinone — remain intact.
| 2000 | Folia Pharm. Univ. Carol. 25 | Pag. 81—87 |
Lenka Kubicová (kubicova@faf.cuni.cz), Pavlína Kudelová, Hynek Dostál, Karel Waisser
Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Inhibition of the chlorophyll production in statically cultivated algal suspensions of Chlorella vulgaris by 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones and 3-phenyl-3H-quinazoline-4-ones has been investigated. The IC50 values varied in the range from 11.6—75.0 µmol dm-3 for 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones and in the range from 86.4—147 µmol dm-3 for 3-phenyl-3H-quinazoline-4-ones. The presence of Br substituent in the phenyl moiety of the molecule and also in position 6 of benzoxazine ring was found to be favourable for the antialgal activity of 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones. Some 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones and 3-phenyl-3H-quinazoline-4-ones did not show any antialgal activity due to their very low aqueous solubility. 3-Phenyl-3H-quinazoline-4-ones were tested also for in vitro antimycobacterial activity. Some of these were active against atypical strains of Mycobacteria, but inactive against Mycobacterium tuberculosis.
| 2000 | Folia Pharm. Univ. Carol. 25 | Pag. 89—96 |
Lenka Kubicová1 (kubicova@faf.cuni.cz), Katarína Kráľová2, František Šeršeň2, Jiří Gregor1, Karel Waisser1
1Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2Institute of Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Slovak Republic
The inhibitory activity of 10 substituted salicylanilides (R = H, 4'-CH3, 4'-Br, 4'-OCH3, 4'-Cl, 3',4'-Cl2, 3'-Cl, 3'-NO2, 4'-NO2, 4'-N(CH3)2) on oxygen evolution rate in spinach chloroplasts has been investigated. The IC50 values in the investigated set varied in the range from 4 µmol dm-3 (for R = 3'-Cl) to 339.8 µmol dm-3 (for R = 4'-N(CH3)2). The inhibitory activity of the studied compounds correlates with the hydrophobic parameter pi- and the Hammett constant sigma of the substituents. Using EPR spectroscopy, the intermediate D+, i. e. tyrosine radical situated in position 161 in D2 protein on the donor side of photosystem 2 was identified as the site of action of these compounds in the photosynthetic apparatus of spinach chloroplasts.
| 2000 | Folia Pharm. Univ. Carol. 25 | Pag. 97—103 |
Hubert Žáček1, Václav Rusek2 (rusek@faf.cuni.cz), Pavla Žáčková3, Eva Středová2
1Institut für Pharmazeutischen Technologie,
2Pharmazeutische Museum,
3Institut für Pharmakologie und Toxikologie,
Karls-Universität Prag, Pharmazeutische Fakultät in Hradec Králové, Tschechien
"Galenic" dissertation in the Charles University in Prague in the First Half of the 19th Century
"Galenic" dissertation presented (1841) for disputation at the Charles University in Prague by Georgius Horčička is studied as far as its specific contents are concerned. The dissertation describes a great number of pharmaceutical dosage forms of which many are obsolete, but many of them are used up to the present time. It is probably one of the first dissertation dealing with such subject orentation.
| 2000 | Folia Pharm. Univ. Carol. 25 | Pag. 105—108 |
(Abstract of Papers)
Peter Višňovský (visnovsk@faf.cuni.cz)
Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The complete text contains abstracts of 4 lectures.
| 2000 | Folia Pharm. Univ. Carol. 25 | Pag. 109—111 |
In 1999, Faculty of Pharmacy in Hradec Králové celebrated its 30th anniversary. Pharmaceutical studies have been connected with the Charles University in Prague since the medieval times. However, the University had no faculty specialized in pharmacy. Pharmacists were educated at the Medical Faculty, later also at the Faculty of Arts and Faculty of Science. After the World War II, pharmaceutical education continued in Prague and was newly opened in Brno. The first faculties of pharmacy in the then Czechoslovakia were established in 1952 in Brno and Bratislava. In the period 1960—69 only one faculty of pharmacy existed in Bratislava. Czech pharmacist strived intensively to restore pharmaceutical education in Bohemia. Their effort resulted in establishing Faculty of Pharmacy of Charles University in 1969. Hradec Králové was chosen as a seat of the new faculty.
The celebrations of the jubilee commenced in March 1999 with the 28th Pharmaceutical Ball in the Congress Centre ALDIS in Hradec Králové. On 22th April 1999, Concert of Czech Music took place in the Philharmonic Concert Hall in Hradec Králové. The concert was inaugurated by Prof. Eva Kvasničková, the Dean of the Faculty. Concerto for violoncello, h minor and six parts of Slavonic Dances by Antonín Dvořák were then performed by Michal Kaňka and Philharmonic Orchestra of Hradec Králové conducted by František Vajnar.
Some sport activities were also organized in spring. 24-Hours contest in basketball between mixed teams of the Faculty of Pharmacy in Hradec Králové, and volleyball tournament in which students of pharmacy from Hradec Králové, Brno and Bratislava took part were held in April. International basketball tournament among mixed teams from universities of Berlin, Bratislava, Brno, Franfurkt am Main, Hannover and Hradec Králové took place in May.
Scientific meetings formed an integral part of the celebrations. MUDr. Oldřich Vinař, CSc., an outstanding expert in psychopharmacology, was invited to read a lecture concerning questions of modern psychopharmacology. Scientific Conference of Pharmacy Students took place in April, and the authors of the best contributions participated in the International Scientific Conference of Pharmacy Students together their colleagues from Brno and Bratislava in May. At the beginning of June, 3rd Workshop in Clinical Pharmacy took place in Hradec Králové. It was devoted to the problem of psychic disorders in elderly people. 10th International Conference on Flow Injection Analysis that was held in Prague in June was also organized on occasion of the 30th anniversary of the Faculty. In September, 28th Conference “Synthesis and Analysis of Drugs” and Symposium “Addictive Drugs in the Region of Hradec Králové” were included into the programme of the celebrations. Both events took place in the premises of the Faculty in Hradec Králové. 34th Symposium “History of Pharmacy” was organized as a part of the MEFA exhibition in Brno in November.
The celebrations culminated in autumn. On 8th September, members of the academic community, other employees of the Faculty and guests from both the Czech Republic and abroad took part in the meeting of the Scientific Board in the Great Hall of Carolinum in Prague. The addresses were delivered by Prof. Pavel Klener, the Vice-Chancellor of the Charles University, by Prof. Eva Kvasničková, the present Dean of the Faculty, by Prof. Jaroslav Květina, the first Dean of the Faculty, and by some invited guests. The meeting then continued with the performance of the Philharmonic Quartet from Hradec Králové. On 9th September the foundation-stone of a new pavilion was laid in the Botanical Garden of Medicinal Plants. The garden belongs to the Faculty of Pharmacy, and the new building will include rooms for education and research activities as well as several greenhouses. On 10th September, the exhibition documenting history and development of the Faculty was re-opened in the Gallery on the Bridge that is also a part of the Faculty. The exhibition was originally installed on occasion of the 650th anniversary of the Charles University in 1998. In 1999 it was re-installed especially for the alumni of the Faculty who came to Hradec Králové on 11th September to participate in celebrations. The programme further included discussions, films, and excursions to the Czech Pharmaceutical Museum in Kuks. In the evening all participants (about 800 people alltogether) met at an informal party in the Congress Centre ALDIS. Congress of the Czech Pharmaceutical Chamber was held on 12th September. On 20th October, the performance of N. V. Gogol’s play “Wedding” took place in the Klicpera’s Theatre in Hradec Králové. The celebrations ended on the memorable 17th November, when a organ concert was held in the Holy Spirit Cathedral in Hradec Králové to commemorate not only the 30th anniversary of the Faculty of Pharmacy but also the struggle of Czech students for freedom and democracy in 1939 and 1989.
Faculty of Pharmacy in Hradec Králové is an integral part of the Charles University in Prague. During 30 years of its existence more than 3,600 pharmacists were educated at the Faculty, included 70 from abroad. About 135 students have completed postgraduate (doctoral) studies so far, and 167 people attended so called “Third Age University”, a special course for elderly.
The Faculty has about 240 employees and its structure includes:
The Association of Czech Students of Pharmacy was founded in 1990 and is a member of International Pharmacy Student’s Federation. In 1997, the Association of Alumni and Friends of the Faculty of Pharmacy was established.
The Faculty offers two courses: “Pharmacy” and “Biomedical Analysis”. It is opened to foreign students, too. Research activities are also of a great importance.
RNDr. Veronika Opletalová, Ph. D.
| 2001 | Folia Pharm. Univ. Carol. 26 | Pag. 7—12 |
Martin Doležal1 (dolezalm@faf.cuni.cz), Jiří Hartl1, Vladimír Buchta2
1Department of Pharmaceutical Chemistry and Drug Control,
2Department of Medical and Biological Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Condensation of chlorides of substituted pyrazine-2-carboxylic acids with aminophenols yielded a series of anilides of 6-chloropyrazine-2-carboxylic, 5-(1,1-dimethylethyl)pyrazine-2-carboxylic or 6-chloro-5-(dimethylethyl)pyrazine-2-carboxylic acids. Products were tested for their antifungal activity against eight fungal strains. Some of them exhibited only some moderate activity against Trichophyton mentagrophytes (their MIC values ranged from 125 to 500 µmol.dm-3).
| 2001 | Folia Pharm. Univ. Carol. 26 | Pag. 13—20 |
Martin Doležal1 (dolezalm@faf.cuni.cz), Katarína Kráľová2, František Šeršeň2, Miroslav Miletín1
1Department of Pharmaceutical Chemistry and Drug Control, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Bratislava, Slovak Republic
The site of action of some anilides of pyrazine-2-carboxylic acids in the photosynthetic apparatus of spinach chloroplasts was studied using fluorescence and EPR spectroscopies. It was found that the studied compounds cause quenching of the chlorophyll fluorescence at 685 nm belonging mainly to the pigment—protein complexes in photosystem (PS) 2. The extent of the fluorescence quenching correlated with the effectiveness of the compounds concerning inhibition of oxygen evolution rate (OER) in spinach chloroplasts. Using EPR spectroscopy it was confirmed that the studied anilides interact with the intermediate D+ (TyrD), i. e. with the tyrosine radical, which is situated on the donor side of PS 2 at the 161th position of D1 protein. It was found that the studied compounds inhibit OER not only in the suspension of spinach chloroplasts but also in the suspensions of Chlorella vulgaris. Introducing of Cl substituents into anilide as well as pyrazine moiety of the studied anilides enhanced the effectiveness of OER-inhibiting activity.
| 2001 | Folia Pharm. Univ. Carol. 26 | Pag. 21—26 |
Jana Krinková1 (krinkova@faf.cuni.cz), Martin Doležal1, Jiří Hartl1, Vladimír Buchta2
1Department of Pharmaceutical Chemistry and Drug Control,
2Department of Biological and Medical Sciences,
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Homolytic alkylation of 6-chloropyrazine-2-carbonitrile by alkanoic acids and subsequent partial hydrolysis afforded 5-alkyl-6-chloropyrazine-2-carboxamides, which were converted by Lawesson’s reagent into corresponding thioamides. Products were tested for their in vitro antifungal activity. The structure—activity relationships were studied. Three of the tested compounds, 6-chloro-5-butylpyrazine-2-carbothioamide, 6-chloro-5-isobutylpyrazine-2-carbothioamide, and 6-chloro-5-(1,1-dimethylethyl)-pyrazine-2-carbothioamide, were active in vitro against all eight strains tested (MIC values ranged from 62.5 to 500 µmol.dm-3). Thioamides exerted higher antifungal activity than the corresponding amides. The values of hydrophobicity in the series of studied compounds were determined. The activity dropped or disappeared at the compounds with lower lipophilicity (log P > 2.28). Some interesting correlation between antimycobacterial and antifungal activity was found.
| 2001 | Folia Pharm. Univ. Carol. 26 | Pag. 27—32 |
Miroslav Miletín1 (miletin@faf.cuni.cz), Martin Doležal1, Katarína Kráľová2, František Šeršeň2
1Department of Pharmaceutical Chemistry and Drug Control, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Bratislava, Slovak Republic
The inhibition of oxygen evolution rate (OER) in spinach chloroplasts produced by some anilides of 2-alkylsulfanylpyridine-4-carboxylic acids (I) or 2-chloro-6-alkylsulfanyl-pyridine-4-carboxylic acids (II) was studied. The IC50 values concerning OER-inhibiting activity varied in the range from 4.8 to 69.1 µmol dm-3. At comparable lipophilicity of the compounds the inhibitory activity of I was higher than that of II. The dependence of the OER-inhibiting activity on the lipophilicity of the compounds showed a quasi-parabolic course and the lipophilicity of the most active compounds was about log P = 5.0—5.5. The site of action of the studied compounds in the photosynthetic apparatus of spinach chloroplasts has been investigated using EPR spectroscopy. It was found that I and II interact predominantly with the intermediate D+ (TyrD) and in a pronouncedly less extent also with the intermediate Z+ (TyrZ), i. e. with tyrosine radicals situated on the donor side of photosystem (PS) 2 at the 161st position in D2 and D1 proteins. The intensive interaction of I and II with TyrD which is situated in less polar environment of the thylakoid membranes can be connected with the presence of hydrophobic alkylsulfanyl substituent in their molecules. The results of experiment with the artificial electron donor (diphenylcarbazide) acting in Z+/D+ intermediate showed that also some member of the photosynthetic electron transport chain between Z+/D+ and plastoquinone is partially damaged by I and II.
| 2001 | Folia Pharm. Univ. Carol. 26 | Pag. 33—40 |
Hubert Žáček1, Pavla Žáčková2 (zackova@faf.cuni.cz)
1Institut für Pharmazeutische Technologie,
2Institut für Pharmakologie und Toxikologie,
Karls-Universität Prag, Pharmazeutische Fakultät in Hradec Králové, Tschechien
Homoeopathic Dosage Forms as Seen Cybernetically
Fundamental facts concerning homoeopathy, homoeopathic dosage forms and homoeopathic potentiation are presented and principles of cybernetic system approach to problem solving are described. A general system model for the purposes of optimization of homoeopathic dosage forms is suggested. On the basis of this model, homoeopathic concepts of “image of drug substance” and “potentiation” are criticized and the rationality of homoeopathy is at present considered as doubtful.
| 2001 | Folia Pharm. Univ. Carol. 26 | Pag. 41—45 |
Milan Lázníček1 (laznicek@faf.cuni.cz), Alice Lázníčková1, Sylvie Saivin2, Georges Houin2
1Charles University, Faculty of Pharmacy, Hradec Králové, Czech Republic
2Lab. Pharmacocinétique, Hôpital Rangueil, Toulouse, France
Standard heparin labelled with 123I was injected to rats at two doses, namely 0.30 mg/kg and 6 mg/kg (50 IU/kg and 1000 IU/kg). The distribution of the drug was dose-dependent. The more rapid radioactivity-time decrease in blood in initial time intervals after the lower dose of 125I-heparin was probably connected with the higher liver uptake and not with more rapid kidney elimination, because urine excretion of radioactivity in the first 2 hours after administration was somewhat slower at the dose of 0.3 mg/kg in comparison with the dose of 6 mg/kg. Relatively low radioactivity in bowels and also lower elimination into faeces (less than 3 % of administered radioactivity up to 48 hours after heparin administration in comparison with more than 50 % found in urine) proved that the kidney elimination was the main elimination pathway of heparin (and/or its metabolites) in rats.
| 2001 | Folia Pharm. Univ. Carol. 26 | Pag. 47—52 |
Kateřina Nováková (novakovak@faf.cuni.cz), Milan Lázníček
Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Quantitative evaluation of inflammations of rats is a useful parameter for the evaluation of the efficacy of anti-inflammatory drugs. A suitable model of inflammation is acute sterile inflammation of the rat hind limb induced by the phlogistic agent carrageenan. For this purpose, the present authors set up an the apparatus (a plethysmometer), which makes it possible to measure the volume of inflammation (swelling of the rat foot) with sufficient accuracy. Besides the range of inflammation, the plethysmometer can be used for studies of the evaluation of inflammation. The pathway to acute carrageenan inflammation can be expressed as time—edema dependence.
| 2001 | Folia Pharm. Univ. Carol. 26 | Pag. 53—60 |
Jiří Gasparič (gasparic@faf.cuni.cz)
Department of Biophysics and Physical Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Five modifications of the colour reaction of resorcinol with nitrous acid in acidic media were studied. The coloured reaction products, i. e. dinitrosoresorcinol, its Na salt or alkali salts of nitroresorcinols are formed depending on the reaction conditions used (temperature, acid and reagent concentration, reaction time, substituents). The most sensitive photometric procedure is that resulting in the formation of the Na salt of 2,4-dinitrosoresorcinol, procedures in which alkali salts of 2,4,6-trinitroresorcinol are formed are less accurate. The reaction course and chromogens in the case of 4-n-hexyl- and 2,4,6-tribromoresorcinols were also investigated.
| 2001 | Folia Pharm. Univ. Carol. 26 | Pag. 61—64 |
Karel Waisser1 (waisser@faf.cuni.cz), Vladimír Buchta2, Petra Kubanová2, Želmíra Odlerová3
1Department of Inorganic and Organic Chemistry,
2Department of Biological and Medical Sciences,
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
3Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic
So far antimycobacterial and antifunngal activity of pyridinecarboxyamidrazones was studied, the authors present in vitro antimicrobial effect or amidrazones without pyridine moiety against mycobacteria and human pathogenic fungi. The present paper aims to investigate antimycobacterial and antifungal activity of amidrazone. Amidrazone-substructural fragments could be the antifungal and antimycobacterial pharmacophore of these compounds.
| 2001 | Folia Pharm. Univ. Carol. 26 | Pag. 65—68 |
Karel Waisser1 (waisser@faf.cuni.cz), Rainer Beckert2, Milan Šlosárek3, Jiří Janota3
1Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2Institute of Organic and Macromolecular Chemistry, Friedrich Schiller University, Jena, Germany
3National Institute of Public Health, Prague, Czech Republic
This paper completed the evaluation of structure—antimycobacterial activity relationships of the derivatives of 2,3-dianilinoquinoxaline. The antimycobacterial activity of 2,3-dianilinoquinoxaline is described by regression equations correlating the logarithms of minimum inhibitory concentration with the Hammett constants. The activity of the compounds against M. kansasii and M. avium increases with decreasing electron-accepting properties of the substituents on the phenyl ring. In the case of quantitative structure—antimycobacterial activity relationship against M. intracellulare, an exception was observed. The equation is statistically significant from the values of sigmap -0.17 (methyl). The methoxy derivative (sigmap -0.27) is less active than the methyl derivative. The compounds under study are more active than INH against M. kansasii, M. avium and M. intracellulare, but less active than ciprofloxacin.
| 2001 | Folia Pharm. Univ. Carol. 26 | Pag. 69—73 |
Miloslav Hronek1 (hronek@faf.cuni.cz), Zdeněk Zadák2, Dagmar Solichová2, Pavel Jandík3, Bohuslav Melichar3
1Department of Biological and Medical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Králové
2Department of Metabolic Care and Gerontology, Charles University in Prague, Teaching Hospital in Hradec Králové
3Surgery Department, Charles University in Prague, Teaching Hospital in Hradec Králové, Czech Republic
The results of a study conducted to determine the usefulness of neopterin in comparison with tumor markers (CEA, CA 72-4, AFP, TPA) monitoring in the follow up of patients are reported here. The subject of this study were thirty patients (aged 64 ± 12 years) with colorectal cancer at the time of diagnosis in comparison with thirty control persons (aged 61 ± 11 years) with benign disorders not associated with a systemic inflammatory response. The results revealed significantly increased levels of neopterin in urine and tumor markers in plasma compared to reference group. It has been found correlation between excretion of neopterin and single tumor markers in general evaluation but levels of tumor markers have not been dependent on the staging of colorectal cancer. Thus, we conclude that urine neopterin monitoring can be useful for detection of activity immune responses and depend on staging of colorectal cancer different from tumor markers.
| 2001 | Folia Pharm. Univ. Carol. 26 | Pag. 75—82 |
Lenka Syrovcová, Kateřina Venderová, Peter Višňovský (visnovsk@faf.cuni.cz)
Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The goal of the study was to try to record the number of smokers and alcohol consumers at the Faculty of Pharmacy, Charles University in Hradec Králové at the beginning of the academic year 2000/2001. A standard questionnaire was used. As a target group, there were 150 first- and 103 third-year students. In case of the first-year students, the age ranged between 18 and 26 years (the mean age was 19.3 years), 81 % were females and 19 % males and in the group of the third-year students, their age ranged between 19 and 30 years (the mean age was 20.9 years) and the ratio between males and females was similar to the first-year students.
In both groups, most of the students were non-smokers (70 %); in the first year, there were 6.0 % regular smokers and in the third year it was 2.9 %. 16 % of the students smoke occasionally in the first year of study and 22.3 % in their third year. The students prefer wine; for more than 50 % of the students drinking spirits is exceptional. 18 % of the students first got into contact with alcohol at the age of 15 and 15 % of them at the age of 16. So far, one third of them has never got drunk and about 65 % of the students did not get drunk during the last four weeks; 7 % of the third and first year students got drunk two or three times during this period of time. The financial support of most of the students was more than 50 % had 200 Kč and approximately 20 % 500 Kč per week, so they had more possibilities to buy cigarettes and alcohol.
| 2001 | Folia Pharm. Univ. Carol. 26 | Pag. 83—88 |
Marie Musilová (musilova@faf.cuni.cz), Jana Černá
Department of Pharmaceutical Technology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Determination of the content of solid phases, measurements of the time of deformation and resistance to rupture of suppositories were employed to evaluate the effect of cetyl alcohol on the properties of the suppository base Adeps neutralis.
It has been found that cetyl alcohol can be used to correct the properties of the suppository base Adeps neutralis only in concentrations ranging in a narrow zone around 30 % of the substance in a mixture. Lower concentrations exerted negative effects. The values of parameters under study in these samples were lower than in the base alone. Higher values than Adeps neutralis were found in samples containing more than 30 % of cetyl alcohol. Suppositories with a cetyl alcohol content higher than 40 %, however, were not deformed at body temperature.
| 2001 | Folia Pharm. Univ. Carol. 26 | Pag. 89—92 |
Joshita Djajadisastra1 (djaja@faf.cuni.cz), Alice Lázníčková1, Helmut R. Mäcke2
1Department of Biophysics, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2Department of Nuclear Medicine, Kantonhospital Basel, Switzerland
Binding of three somatostatin receptor-specific peptides, namely 111In-DTPA-octreotide, 111In-DOTA-octreotide and 88Y-DOTA-Tyr3-octreotide, to human, bovine, and rat plasma proteins was determined by equilibrium dialysis at 37 °C and by ultrafiltration at room temperature. It was shown that these somatostatin receptor specific peptides are only slightly bound to plasma proteins (per cent bound < 55 %). Interspecies differences in the degree of binding to plasma proteins are negligible. The ultrafiltration method using cellophane bag gave almost similar results comparing to equilibrium dialysis method, the only disadvantage of this method is the need to a greater amount of plasma. The binding of the receptor-specific peptides under study will exert only small effect on their pharmacokinetics.
| 2001 | Folia Pharm. Univ. Carol. 26 | Pag. 93—97 |
František Trejtnar (trejtfr@faf.cuni.cz)
Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
[131I]-o-iodohippurate (OIH) is one of the most important radiodiagnostic agent using for renal imaging and renal function measurement. In the study, a comparison renal excretion parameters after bolus and infusion administration was studied using the method of the perfused rat kidney. The rat kidney was perfused with Krebs-Henseleit solution containing bovine albumin, washed rat erythrocytes (6 %) and a mixture of aminoacids in a recirculation regimen at a constant arterial pressure. Experiments showed significant differences between renal elimination of OIH in the perfused rat kidney after adding of the drug as bolus dose or infusion into the perfusate. After the bolus dose, renal clearance OIH was rapidly falling during the perfusion interval. Infusion OIH administration resulted in stable clearance values during the perfusion. The OIH clearance lowering during the perfusion was probably caused due to reaching such low concentrations when reabsorption could begin to play a significant role simultaneously with secretion. Renal clearance was several times higher than inulin clearance. OIH was considerably bound to the proteins in the perfusate. An analysis of renal handling showed that the extent of tubular secretion in the perfused rat kidney was more than 90 %.
| 2002 | Folia Pharm. Univ. Carol. 27—28 | Pag. 7—12 |
Karel Waisser (waisser@faf.cuni.cz), Milan Peřina
Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The examples presented in this paper aim to demonstrate that values of physico-chemical (local) parameters of molecular fragments could correlate with the final biological activity. This approach can provide equations, which in their formal aspect resemble of the Hansch but operate with local parameters. The examples presented in the study concern antimycobacterial activity (3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones, 7-benzo[c]fluorenones, hydrindacenes, thioanilides, salicylanilides) that was the principal aim of our research. We are using the locale parameters for the study of another group of compounds now (N-benzylsalicylamides and esters of alkoxysubstituted phenylcarbamoic acid).
| 2002 | Folia Pharm. Univ. Carol. 27—28 | Pag. 13—23 |
Karel Palát Jr.1 (palat@faf.cuni.cz), Vladimír Buchta2, Malcolm F. G. Stevens3
1Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic,
2Department of Biological and Medical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic,
3Cancer Research Laboratories, School of Pharmaceutical Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK
9-Halogenoacridines undergo Suzuki cross-coupling reactions with a range of arylboronic and thienylboronic acids to yield substituted 9-arylacridines and 9-thienylacridines. Resulting compounds were assayed for their antifungal activity.
| 2002 | Folia Pharm. Univ. Carol. 27—28 | Pag. 25—28 |
Karel Palát Jr.1 (palat@faf.cuni.cz), Želmíra Odlerová2
1Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic,
2Institute for Preventive and Clinical Medicine, Bratislava, Slovak Republic
Title compounds were tested for their biological activity against different strains of Mycobacterium. Eight compounds from the series of 32 compounds were active. The highest activity was found at dibenzylester of N-(4-bromophenyl)-N,N''-guanidinedicarboxylate. Its minimal inhibitory concentration against Mycobacterium tuberculosis H37Rv is 125 µmol/l, i. e. only twice larger than MIC of isoniazide and twice smaller than is MIC of ethionamide.
| 2002 | Folia Pharm. Univ. Carol. 27—28 | Pag. 29—33 |
Hans-Martin Dahse1 (hmdahse@pmail.hki-jena.de), Ute Möllmann1, Karel Waisser2 (waisser@faf.cuni.cz), Karel Palát Jr.2, Otakar Bureš2, Pavel Holý2
1Hans Knöll Institute of Natural Products Research, Jena, Germany,
2Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Benzoxazine derivatives are known as potential antimycobacterial agents. The cytotoxicity and the proliferation activity of the selected group of compounds with extremely high antimycobacterial activity were studied. The synthesis of the compounds was not published, yet, because we would like to patent of this group. We have found on the basis of this study that the compounds under the study are cytotoxic and the development of new drugs is very problematic.
| 2002 | Folia Pharm. Univ. Carol. 27—28 | Pag. 35—41 |
Jiří Gasparič1 (gasparic@faf.cuni.cz), Karel Kolář2, Šárka Crhová1, Radomír Hyšpler3, Alena Tichá4, Lidmila Hyšplerová2, Monika Indrová4, Karel Myška2
1Department of Biophysics and Physical Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové,
2Department of Chemistry, Faculty of Education, University of Hradec Králové, Hradec Králové,
3Department of Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Králové,
4Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Pardubice,
Czech Republic
The in vitro fission of D,L-mevalonic acid with 50 % sulphuric acid at 100 °C resulted in the formation of isoprene identified by gas chromatography — mass spectrometry. When the same reaction was performed with D,L-mevalonolactone-2-13C two types of isoprene isomers were distinguished in the mass spectra: isoprene with the 13C carbon atom in position 1 or in the methyl group, resp. These isomers were formed in the ratio 2:1. The experimental results were compared with selected quantum chemical calculations and were found to be in agreement with the common knowledge of dehydration reactions.
| 2002 | Folia Pharm. Univ. Carol. 27—28 | Pag. 43—51 |
Stanislav Ďoubal1 (doubal@faf.cuni.cz), Petr Klemera1, Vladimír Semecký2
1Department of Biophysics and Physical Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic,
2Department of Biological and Medical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The quantitative methodology of assessment of mechanical behavior of visco-elastic materials is of crucial significance, among others for pharmaceutical technology, research in cardiovascular system or for mechanical matching of implants. The mechanical (rheological) properties of visco-elastic materials involve elastic as well as plastic elements. The mechanical behavior of these materials is non-linear in many respects and it is different in cases of static and dynamic loading. Consequently, the satisfactory description of mechanical behavior of biological materials is extremely difficult. The classical approach based on theory of elastic or visco-elastic bodies often fails to provide adequate tools for solution of these problems. The concept of complex mechanical impedance enables more universal and more adequate description of mechanical behavior of this category of materials. The concept of mechanical impedance is analogical to the concept of impedance in theory of electric circuits. The mechanical impedance is complex number defined as ratio between instantaneous complex values of stress and strain in steady state of cyclic dynamic loading. The mechanical impedance enables to calculate the amplitude as well as phase of strain response and solve the problem of mechanical matching. The theory of complex mechanical impedance as well as the methodology of identification of mechanical models of visco-elastic materials is presented in the paper.
| 2002 | Folia Pharm. Univ. Carol. 27—28 | Pag. 53—57 |
Hubert Žáček1, Pavla Žáčková2 (zackova@faf.cuni.cz)
1Department of Pharmaceutical Technology,
2Department of Pharmacology and Toxicology,
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The historical typology of pharmaceutical personalities is considered in which two types are distinguished, i. e., the pragmatic type and the intellectual one. The essences of both types are explained. By the example of Dr. Chem. PhMr. František Kaska (born 1834 in Horažďovice), the intellectual type of pharmaceutical personality is presented. Dr. Kaska was military pharmacist in the expedition corps of the Austrian Maxmilian Habsburg (brother of Franz-Joseph I) to Mexico. He was a highly esteemed personality in the Austrian society in Mexico. In the history of pharmacy, he excelled especially as collector of historically valuable objects which he dedicated to the National Museum in Prague.
| 2002 | Folia Pharm. Univ. Carol. 27—28 | Pag. 59—68 |
Jana Dolejšová (dolejso@faf.cuni.cz), Miroslav Polášek, Rolf Karlíček
Department of Analytical Chemistry, Charles University in Prague, Faculty of Pharmacy, Hradec Králové, Czech Republic
Flow-injection spectrophotometric method for determining »0.2 to 400 mmol · l-1 of dihydroxyphenols (catechol, resorcinol, hydroquinone) and of trihydroxyphenols (pyrogallol, phloroglucinol, 1,2,4-hydroxyhydroquinone) using the analyte oxidation in manganese dioxide or lead dioxide-packed reactors (50 mm × 1.2 mm) with aqueous 10 mmol · l-1 H2SO4 as carrier flow (0.6 ml min-1) has been devised. Active and stable reactors packings were prepared by coating sintered glass particles (diam. 0.4 to 0.5 mm) successively with an epoxide glue and powdered MnO2 or PbO2. At the injected sample volume of 80 µl the relative standard deviation was 1.37 % (n = 10) when determining 1.0 mmol · l-1 of catechol (»8.8 µg in 80 µl of the solution) in prepared solution of the pure substance and the sample throughput was 90 h-1 (in manganese dioxide-packed reactors) or 60 h-1 (in lead dioxide-packed reactors). The method has been applied to the analysis of phenols as bulk substances. The results were in good agreement with those of pharmacopoeial UV spectrophotometric determination.
| 2002 | Folia Pharm. Univ. Carol. 27—28 | Pag. 69—75 |
Josef Jampílek1 (jamp@faf.cuni.cz), Martin Doležal1 (dolezalm@faf.cuni.cz), Hans Peter Deigner2 (hans-peter.deigner@ix.urz.uni-heidelberg.de)
1Department of Pharmaceutical Chemistry and Drug Control, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic,
2Institute for Pharmaceutical Chemistry, University of Heidelberg, D-69120 Heidelberg, Germany
The 4-(methoxycarbonyl)-2-phenyl-4,5-dihydrooxazole formed from (S)-serine provides the basis for a useful synthesis of various types of sphingolipids, sphingomyelins and their unnatural analogues or isosteres. This paper deals with optimization (increase of yields) of synthesis (4S,1'R)-4-(1'-hydroxy-2'-(E)-hexadecenyl)-2-phenyl-4,5-dihydrooxazole, respectively (2S,3R)-sphingosine from (S)-serine via oxazolin methyl ester by Tkaczuk—Thornton method. Two stereoisomers (4S,1'R and 4S,1'S), respectively (2S,3R and 2S,3S) are obtained after the final step of the synthetic pathway, but 4S,1'R epimer of sphingosine oxazoline respectively, subsequently convertion to 2S,3R sphingosine has biological activities (inhibition of the protein kinase C) only. A modification of the mobile phase for separating 4S,1'R and 4S,1'S forms is suggested in this paper.
| 2002 | Folia Pharm. Univ. Carol. 27—28 | Pag. 77—83 |
Ladislava Schröterová1, Eva Kvasničková1 (kvasnice@faf.cuni.cz), Vladimír Geršl2
1Department of Biochemical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic,
2Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Králové, Czech Republic
In this article we have focused on optimization of experimental conditions from the point of view of animal tissues sampling, storage conditions, subsequent processing of the samples, and the determination of enzyme activities in the tissue samples. The results are important from the viewpoint of further investigation of the new lipophilic iron chelates PIH and SIH on the activity of enzymes involved in the metabolism of anthracyclines.
| 2002 | Folia Pharm. Univ. Carol. 27—28 | Pag. 85—89 |
Tomáš Siatka (siatka@faf.cuni.cz), Marie Kašparová, Jaroslav Dušek
Department of Pharmacognosy, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Changes in haemolytic activity of Bellis perennis L. leaves and roots over the course of the year were investigated. Samples were collected at a one-month interval from March to October, haemolytic activity was determined according to the Pharmacopoea Bohemoslovaca IV. Haemolytic activity of leaves as well as roots varies considerably depending on the time of collection during the year. It is low in March, then it increases reaching a maximum in July, after that it declines again.
| 2002 | Folia Pharm. Univ. Carol. 27—28 | Pag. 91—94 |
Hana Holubičková, Michael Vanžura, Peter Višňovský (visnovsk@faf.cuni.cz)
Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy, Hradec Králové, Czech Republic
The authors investigated a group of 150 students entering the first year of Faculty of Pharmacy in Hradec Králové, Charles University in Prague. Based on an anonymous standard questionnaire, the attitudes towards the use of substances of addiction and experience with them were evaluated in 120 women and 30 men. The most frequently used substance was marihuana (taken at least once by 30 % of the investigated group). Less frequently other drugs and medicaments (most of them anxiolytics and hypnosedatives) were given. No experience was noted in case of heroin or toluene. However, 70 % of the questionned did not take any drug in the past time and 47.3 % supposed not to take any substance of abuse in the future.
| 2002 | Folia Pharm. Univ. Carol. 27—28 | Pag. 95—103 |
Petr Nachtigal1, Andrea Gojová1, Martin Kopecký1, Dagmar Solichová2, Petr Ždánský2, Vladimír Semecký1 (semecky@faf.cuni.cz)
1Department of Biological and Medical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic,
2Gerontologic and Metabolic Clinic, Teaching Hospital in Hradec Králové, Czech Republic
In the present study we set up biochemical, immunohistochemical and morphometric methods for studying of atherosclerosis in our laboratory. Rabbits fed (1—3 months) by diet containing 0.4 % of cholesterol showed explicit induction of hypercholesterolemia. We standardized immunohistochemical procedures for the visualisation of the expression of inflammatory cell adhesion molecules VCAM-1, ICAM-1 and for smooth muscle cells and macrophages in atherosclerotic lesions. We applied morphometric and stereological methods for quantification of atherosclerotic lesions. Biochemical, immunohistochemical and morphometric outcomes indicates induction of atherogenic changes in our rabbit model of atherosclerosis. All these methods will be used for further investigation of atherosclerosis in our laboratory.
| 2002 | Folia Pharm. Univ. Carol. 27—28 | Pag. 105—110 |
Marie Musilová (musilova@faf.cuni.cz), Romana Svatošová
Department of Pharmaceutical Technology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
On a model example of cocoa butter, the paper studies the effect of different heating rates of the sample on the values of DSC analysis. Heating rates employed were 1.25 °C/min, 2.5 °C/min, 5 °C/min, and 10 °C/min. The evaluation included T-o, T-f, the maximum, and melting enthalpy. SFI values were calculated and compared with the actual SFI. In dependence on the procedure and heating rate, the found difference in SFI values in the region of melting point amounted up to 64 %. The difference between the values of melting enthalpy was not statistically significant. Higher heating rates of samples cannot be recommended for mutual comparison of SFI in different samples, or for the study of interactions in mixtures.
| 2003 | Folia Pharm. Univ. Carol. 29—30 | Pag. 7—12 |
Jiří Gasparič (gasparic@faf.cuni.cz), Iveta Štanclová
Department of Biophysics and Physical Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Procedures for the spectrophotometric determination of arbutin and hydroquinone and for their detection on chromatograms based on their reaction with nitrous acid were worked out. Dinitroarbutin was found to be the coloured reaction product with arbutin, whereas in the case of hydroquinone p-benzoquinone was found to be the reaction product.
| 2003 | Folia Pharm. Univ. Carol. 29—30 | Pag. 13—16 |
Josef Jampílek1 (jamp@faf.cuni.cz), Martin Doležal1, Jiří Kuneš2
1 Department of Pharmaceutical Chemistry and Drug Control, 2 Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic.
This paper describes formation of 4-iodobutan-1-ol and 4-iodobutyl acetate as by-products of the synthesis of 2-arylpropanoic acid in THF, using TiI4 as the heterogeneous catalyst and LiAlH4, CFCl3. These aliphatic iodo derivatives of THF are formed by means of THF cleaving, which has been used as a solvent. The first derivative is generated by opening THF ring in acid environment in 68 % yield. The mechanism of 4-iodobutyl acetate formation (in 8 % yield) may be a combination of opening THF ring and a rearrangement by means of unreacted TiI4 as the Lewis acid.
| 2003 | Folia Pharm. Univ. Carol. 29—30 | Pag. 17—20 |
Karel Waisser1 (waisser@faf.cuni.cz), Kateřina Dražková1, Pavel Holý1, Karel Palát jr.1, Jarmila Kaustová2 (jarmila.kaustova@khsova.cz)
1 Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2 National Reference Laboratory for Mycobacterium kansasii, Institute of Hygiene, Ostrava, Czech Republic
The antimycobacterial activity of salicylanilides and 3-aryl-2H-1,3-benzoxazin-2,4(3H)-diones correlates. It seems, that the mechanisms of antimycobacterial activity is identical. Salicylanilides and 3-aryl-2H-1,3-benzoxazin-2,4(3H)-diones are probably the inhibitors of the regulation of the bacterial two component systems.
| 2003 | Folia Pharm. Univ. Carol. 29—30 | Pag. 21—33 |
Karel Waisser1 (waisser@faf.cuni.cz), Milan Peřina1, Vladimír Buchta2, Petra Kubanová2
1 Department of Inorganic and Organic Chemistry, 2 Department of Biological and Medical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Structure--antifungal activity relationships were studied in a series of 66 N-benzylsalicylamides substituted on the acyl as well as the benzyl moiety. To describe the quantitative structure--antifungal activity relationships (QSARs), an approach based on the Free-Wilson method and on the combination of the Free-Wilson and Hansch methods was employed (the substituent constants were used in the case of the substituents on the benzyl moiety, indicator parameters were used for the substituents on the acyl moiety). The best substitution on the acyl moiety is with bromine or chlorine. The presence of hydrophobic substituents on the benzyl ring usually increased antifungal activity. The effect of the substituents on the acyl moiety seems to be more complex. The relationships between the antifungal activity and physico-chemical parameters of all substituents could be evaluated exactly only against T. mentagrophytes.
| 2003 | Folia Pharm. Univ. Carol. 29—30 | Pag. 35—38 |
Karel Waisser1 (waisser@faf.cuni.cz), Milan Peřina1, Jarmila Kaustová2 (jarmila.kaustova@khsova.cz)
1 Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2 National Reference Laboratory for Mycobacterium kansasii, Institute of Hygiene, Ostrava, Czech Republic
3-benzyl-2H-1,3-benzoxazine-2,4(3H)-diones can be considered as new group of potential antituberculotics. The disadvantage of the compounds is small water-solubility. They belong to middle active potential antituberculotic and for increase the activity are expecting the QSAR studies, molecular modelling and other synthesis.
| 2003 | Folia Pharm. Univ. Carol. 29—30 | Pag. 39—54 |
Martin Šustr, Dáša Hrnčiarová, Marcela Látalová, Martin Pravda, Lenka Kubicová (kubicova@faf.cuni.cz)
Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The present review paper with 155 references links up with the previous communications reviewed biological activity of salicylanilides, thiosalicylanilides, thiobenzanilides, benzanilides, and other compounds based on the structure of carboxylic acids, and includes the research carried out in recent years. The paper surveys the research of biologically active compounds containing in the molecule the N-substituted (thio)amide group, bonded to aromatic or aliphatic structures or also to some heterocyclic systems. In the last period, a number of articles contributing to the knowledge about antimycobacterial, antibacterial, antifungal, antiviral, anticancer, anti-inflammatory, photosynthesis-inhibiting, and antialgal activity of thiobenzanilides and related compounds (e.g. thiosalicylanilides, dihydroxy and trihydroxybenzamides) have been published.
| 2003 | Folia Pharm. Univ. Carol. 29—30 | Pag. 55—63 |
Jiří Hanusek1 (Jiri.Hanusek@upce.cz), Martin Šustr2, Petra Kubanová3, Vladimír Buchta3, Miloš Sedlák1
1 Department of Organic Chemistry, Faculty of Chemical Technology, University of Pardubice, Czech Republic,
2 Department of Inorganic and Organic Chemistry and 3 Department of Biological and Medical Sciences,
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
This work is focused on the investigation of biological activity for a set of previously prepared 2-aminothiobenzamides, 2-benzoylaminothiobenzamides, 2-phenylquinazolin-4-thiones, 2,2-dimethyl-3-phenylquinazolin-4(1H,3H)-thiones, and 2-methyl-3-phenylquinazolin-4-thiones. In the groups of the open derivatives, the presence of hydrogen at 2-amino group appears to be obviously essential for the antifungal activity. The ring closure to quinazolin-4-thione derivatives mainly led to inactive products. In the groups of 2-benzoylaminothiobenzamides and quinazolin-4-thiones, antialgal and tuberculostatic effects were also tested. The substances having hydrogen at the 2-amino group show higher tuberculostatic activity than the corresponding N-methyl derivatives.
| 2003 | Folia Pharm. Univ. Carol. 29—30 | Pag. 65—70 |
Věra Klimešová (klimeso@faf.cuni.cz), Karel Palát jr. (palat@faf.cuni.cz)
Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The antituberculotic activity of 29 benzimidazole derivatives against M. tuberculosis CNCTC My 331/88 were correlated to their electronic, hydrophobic, and steric parameters. The antituberculotic activity of benzimidazole derivatives is mainly related to the electronic parameters σ and to the quantum-chemical parameters εHOMO. The activity increases with electron withdrawing substituents in the benzyl moiety of studied compounds. The significance of HOMO orbital, revealed in QSAR analysis, can be concluded with mechanism of action. HOMO orbital can play an important role for the interaction of the molecule with the receptor. HOMO orbital is located on sulfur in the sulfanyl group and on the benzimidazole moiety. Atoms with the highest density of this orbital could be the location of the highest reactivity and could react as a nucleophilic reagent. This reasoning confirms earlier pronounced hypothesis about the sulfanyl group as a pharmacophore of the antituberculotic activity.
| 2003 | Folia Pharm. Univ. Carol. 29—30 | Pag. 71—76 |
Alena Kavalírová, Jiří Stöhr, Kateřina Venderová, Peter Višňovský (visnovsk@faf.cuni.cz)
Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
A survey on the awareness about legal and illegal drugs and the consumption of them was conducted in 1.312 students of six different faculties in the Czech Republic. The availability of cannabis and the prevalence rates of its use in university students were investigated. A standardized questionnaire designed by the Health Department of the Regional Office in Hradec Králové was employed for the survey. The average age of respondents was 20.2 years. The number of females was higher (75.4 %) than that of males (24.6 %). Prague students reported the highest availability of marijuana (80.3 %), the smallest one was found at the Faculty of Medicine in Pilsen. The offer of hashish was four fold smaller than that of marijuana. In average, 40.2 % of university students had experience with marijuana and 9.6 % with hashish. Mostly, there was a predominance of the male users over the female ones. The highest experience with marijuana and hashish was found at the 3rd Faculty of Medicine in Prague. Three quarters of marijuana consumers admitted more than one experience with marijuana; 8.5 % of respondents had used marijuana more than twenty times, the males tree fold more than the females.
| 2003 | Folia Pharm. Univ. Carol. 29—30 | Pag. 77—80 |
Hubert Žáček1, Václav Rusek2 (rusek@faf.cuni.cz)
1 Department of Pharmaceutical Technology, 2 Czech Pharmaceutical Museum, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic.
Jaroslav Hladík, who on 12. 04. 2003 would reach the age of 100 years, started his professional career as apothecary in different pharmacies, but after certain interim activities he became a university associate professor for pharmaceutical history, founded a pharmaceutical museum, published papers with subjects from pharmaceutical history, created basis of centralized pharmaceutical book collections, etc. He was successively active in pharmaceutical university institutions in Prague, Brno and Bratislava. Pharmaceutical history was his hobby until his death on 01. 08. 1975. He remains a great positive pharmaceutical personality.
| 2003 | Folia Pharm. Univ. Carol. 29—30 | Pag. 81—85 |
Hubert Žáček
Department of Pharmaceutical Technology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
A very quick and simple method for assessing random variability of data on the basis of their standard deviation is described. The simplification consists in approximation of the standard deviation by the quotient of range and the square root of the number n of observations. The method can be successfully applied in treating samples of n = 3 to n = 12. The relative error in comparison with the standard deviation calculated traditionally is in general > 5 %. A pharmaceutical practical example of application of the suggested new method is described on the basis of quality control of volumes of filling injection ampoules. Of course, the new method has also other possibilities of use (e.g., it can also serve as bridge between statistics and cybernetics).
| 2003 | Folia Pharm. Univ. Carol. 29—30 | Pag. 87—94 |
Zdeňka Šklubalová (sklubalo@faf.cuni.cz)
Department of Pharmaceutical Technology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Since microbial contamination of ophthalmic preparation may induce serious disease of eye, all products intended for use in the eye regardless of form must be sterile. Eye preparations in multi-dose containers should contain suitable antimicrobial agent. However, there are strict constrains on the use of preservatives in the eye preparations as the cornea can be easily damaged by the application of chemical agents. This article reviews adverse ocular effects of preservatives commonly used in eye drops and factors relating their ocular irritation as well as the alternatives to their use.
| 2003 | Folia Pharm. Univ. Carol. 29—30 | Pag. 95—99 |
Marie Musilová (musilova@faf.cuni.cz), Jana Černá
Department of Pharmaceutical Technology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The behaviour of blends of Adeps neutralis and cetyl alcohol which is declared as a substance usable for the correction of the melting point of suppository bases was evaluated by means of DSC. The evaluation included the miscibility of these components, temperatures of the beginnings and ends of temperature changes, temperature maxims of blends, and the content of solid phases at certain temperatures.
It has been found that cetyl alcohol dissolves in Adeps neutralis at concentrations of 10 and 20 %. These concentrations produce a eutectic mixture possessing lower temperature characteristics than those of the base alone. Concentrations of 30 % and higher increase the values of the temperature maximum, and the values of the beginnings of temperature changes are in comparison with Adeps neutralis identical or slightly higher. Blends containing about 30 % of cetyl alcohol could be employed for practical purposes.
| 2003 | Folia Pharm. Univ. Carol. 29—30 | Pag. 101—106 |
Markéta Křenková1, Lubomír Opletal1 (opletal@faf.cuni.cz), Miloslav Sebránek2, Jaroslav Jurenka2
1 Department of Pharmaceutical Botany and Ecology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2 Analytical and Physical Laboratory, Research Institute of Organic Synthesis -- CETA, 533 54 Pardubice-Rybitví, Czech Republic
In the present study, results on the chemical composition of the essential oils hydrodistilled from various parts of Schisandra chinensis (Turcz.) Baill. introduced in Czech Republic are presented. Volatile constituents were analyzed by gas chromatography--mass spectrometry (GC-MS) and showed presence of different principal components in various parts of the plant. Essential oil from cauloms is rich in nerolidol, α-elelmene, α-pinene, 2-tridecanone, 2-undecanone and bornyl acetate. Among volatiles contained in leaves β-elemene, (+)-nerolidol, β-farnesene, γ-cadinene and β-myrcene dominate; it makes its spicy-earthy smell. Prominent components of lemon scenting essential oil in seeds are ylangene, β-chamigrene and β-himachalene.
| 2003 | Folia Pharm. Univ. Carol. 29—30 | Pag. 107—111 |
Jitka Vytlačilová1 (vytlacij@faf.cuni.cz), Vladimír Chobot1, Jana Klečáková1, Luděk Jahodář1, Lubomír Opletal1, Milan Pour2
1 Department of Pharmaceutical Botany and Ecology, 2 Laboratory of Structure and Interactions of Biologically Active Molecules, Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The effect of two natural photosensitizers (E)-1-[5-(hept-5-en-1,3-diynyl)thien-2-yl]ethan-1,2-diol and 8-methoxypsoralen (xanthotoxin) on aquatic worms Tubifex tubifex Müll. (Tubificidae) and UV-A radiation was studied. The activity was evaluated by a stereomicroscope and scanning electron microscope. Deep ruptures of epidermis, sub-dermal bleeding and destruction of whole body segments of the worms could be observed.
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 7—14 |
Hana Klusoňová1 (klusono@faf.cuni.cz), Lenka Spáčilová1, Dana Hurtová1, Peter Višňovský2
1 Department of Biological and Medical Sciences, 2 Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Misuse of illegal addictive substances gets ever more common in our population. A study monitoring the spectrum of such substances takes place at two regional contact centers – KC Laxus in Hradec Králové since June 2003 and KC Haus in Zlín since June 2002. 119 clients filled out a questionnaire, 45 from Laxus and 74 from the Contact Center Haus. Three quarters of the persons using addictive substances in Hradec Králové region are men aged 16 – 40 years. They use most often pervitin (63.4 %) and heroin (19.5 %); Cannabis drugs are those which most frequently play a role of substitutive drugs (46.3 %). Only 3 clients completed a therapy of symptoms resulting from drug misuse. 34.2 % of respondents were treated or are currently treated. As in Hradec region there are the persons of 16 – 36 years, mainly the men (almost ¾), who misuse the drugs in Zlín region. The principal additive drug is pervitin (87.1 %). Almost ½ of the addicts (48.1 %) use cannabis drugs as a substitution. ¼ (24.7 %) of them use ecstasy for the same reason. ¼ of the respondents (28.3 %) mentioned a symptomatic therapy of drug misuse, 27.0 % reported previous or current drug addiction therapy. The study leads to the conclusion about developing situation on our drug scene which is different at individual regions. Continuing observation seems to be advisable.
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 15—20 |
Vladimír Kubíček (kubicek@faf.cuni.cz), Alice Lázníčková
Department of Biophysics and Physical Chemistry, Research Centre LN00B125, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Protein binding of amlodipine enantiomers in human and rat plasma was studied by equilibrium dialysis and achiral HPLC. Binding of amlodipine to plasma proteins of both species was relatively high (> 92 %). Significantly higher binding of S(-) enantiomer in comparison to R(+) one was determined. At the drug concentration of 10 μg/ml the main binding protein for amlodipine in human plasma was albumin. On the other hand, α1-acid glycoprotein was responsible for differences in the protein binding of the individual enantiomers.
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 21—26 |
Alice Lázníčková (laznicko@faf.cuni.cz), Jiří Hofmann, Matěj Syrovátko, Milan Lázníček
Research Centre LN00B125, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Plasma protein binding and distribution to blood cells of a new antiasthmatic drug quinlukast (compound VUFB 19363) was determined in man, bovine and rat. Binding to plasma proteins was higher than 99.5 % for all species under study. No significant interspecies differences in plasma protein binding were determined. The drug was accumulated also in the blood cells; its concentration in the cell compartment markedly exceeded that in water phase. In whole blood the drug was mostly in the form bound to proteins in plasma, the fraction distributed in blood cell compartment being substantially lower (lesser than 5 %).
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 27—32 |
Josef Jampílek, Martin Doležal (dolezalm@faf.cuni.cz), Jiří Kuneš
Research Centre LN00B125, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The syntheses of 5-[2-(quinolin-2-ylmethoxy)benzoyl]pyrazine-2-carboxylic acid and 6-{[4-(quinolin-2-ylmethoxy)phenyl]amino}pyrazine-2-carboxylic acid as new potential antileukotrienic agents have been described. Both target compounds were prepared by means of multisteps synthetic pathways; the synthetic approach, analytical and spectroscopic data of all newly synthesized compounds have been presented. The target acids could not be tested for their anticipated biological activities due to their total insolubility in all solvents.
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 33—40 |
Karel Waisser1 (waisser@faf.cuni.cz), Radek Oswald1, Jiří Kuneš1, Jarmila Kaustová2
1 Department of Inorganic and Organic Chemistry,
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2 Department of Diagnosis Mycobacteria,
Regional Institute of Public Health, Ostrava, Czech Republic
The aim of the present paper is the synthesis and study of antimycobacterial acitivity on new 4-methoxysalicylanilides and 7-methoxy-3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones substituted on the phenyl ring and proof of QSAR prognosis from several previous study. In the group of 7-methoxy-3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones the prognosis failures in the case of substitution phenyl in position 4 by lipophilic alkyls. The previous papers did not described this influence.
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 41—46 |
Karel Waisser1 (waisser@faf.cuni.cz), Kateřina Dražková1, Josef Matyk1, Jiří Kuneš1, Jarmila Kaustová2
1 Department of Inorganic and Organic Chemistry,
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2 Department of Diagnosis Mycobacteria,
Regional Institute of Public Health, Ostrava, Czech Republic
A series of derivatives of substituted N-pyridinyl salicylanimides was synthesized. The compounds were evaluated for in vitro antimycobacterial activity against M. tuberculosis, Mycobacterium avium and two strains of Mycobacterium kansasii. The steric hindrance of amide groups by substituents on rings of pyridine decreases the antimycobacterial activity of N-pyridinylsalicylanilides. Antimycobacterial active from the compounds under study was only N-(3-methylpyridin-2-yl)-4-chlorosalicylamide. N-(3-methylpyridin-2-yl)-4-chlorosalicylamide is against potential pathogenic strains more active as INH. The exception we cannot explain.
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 47—52 |
Karel Waisser1 (waisser@faf.cuni.cz), Kateřina Dražková1, Josef Matyk1, Jiří Kuneš1, Jarmila Kaustová2
1 Department of Inorganic and Organic Chemistry,
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2 Department of Diagnosis Mycobacteria,
Regional Institute of Public Health, Ostrava, Czech Republic
A series of derivatives of substituted N-heteroaryl-5-methyl-salicylamides was synthesized. The heterocyclic moiety formed 2-pyrazinyl-, 3-thiazolyl-, 4-methyl-2-thiazolyl-, 1,2,4-triazol-3-yl, 1,2,4-triazol-4-yl, 5-methyl-3-isoxazolyl-, 2-benzothiazolyl- and 2-benzimidazolyl-. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium avium and two strains of Mycobacterium kansasii. The antimycobacterium activity was very low. In the additional research we have to synthesis analogous derivatives with another substitution in salicylic moiety of molecules.
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 53—58 |
Karel Waisser1 (waisser@faf.cuni.cz), Kateřina Dražková1, Josef Matyk1, Jiří Kuneš1, Jarmila Kaustová2
1 Department of Inorganic and Organic Chemistry,
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2 Department of Diagnosis Mycobacteria,
Regional Institute of Public Health, Ostrava, Czech Republic
A series of derivatives of substituted 5-methyl-N-pyridinyl salicylamides was synthesized. The compounds were evaluated for in vitro antimycobacterial activity against M. tuberculosis, Mycobacterium avium and two strains of Mycobacterium kansasii. The compounds are antimycobacterial inactive. Twenty seven of new compounds were synthesized in our last three papers. From our this and other two our previous paper we concluded: a) In drug design of development of antimycobacterial agents in series of N-heteroarylsalicylamides is necessary eliminate every structure with steric hindrance of amide groups. b) The substitution of salicyl-moiety by methyl in position 5 is necessary eliminate, as well.
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 59—65 |
Hubert Žáček
Department of Pharmaceutical Technology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Cause-selecting control charts are graphic representations of information data time series permitting to find in the studied production process directly the cause of the observed disturbance. These representations are principially equivalent to the classical control charts of the Shewhart type, but on them properly transformed data are registered instead of the original ones. The transformations have the purpose of separation of systematic effects in each operation from those in preceding operations of the same process. The practical use of cause-selecting control charts is almost as simple as that of the traditional Shewhart control charts.
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 67—87 |
Martin Pravda1 (pravda@faf.cuni.cz), Lenka Kubicová1, Ondřej Veselý1, Martin Šustr1, Vladimír Buchta2
1 Department of Inorganic and Organic Chemistry, 2 Department of Biological and Medical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Pharmacotherapy of systemic mycoses brings many unsolved problems, but also new challenges. There are just few triazole compounds (voriconazole, itraconazole, fluconazole), amphotericin B (including forms bound on a lipid carrier) and caspofungin, member of a novel group of echinocandin antimycotics. None of these drugs represent an ideal antimycotic acting against a selective fungal target, and therefore with a broad-spectrum activity and without significant adverse effects. A limited number of effecient and safe antimycotics iniciated the search for new structures with antifungal effect among natural and synthetic compounds, but it also resulted in effort of decreasing the toxicity and improving the pharmacokinetic profile of currently used drugs, e.g. using conjugates with polymers. The present review with 165 references provides an overview of current status and perspectives in the area of systemic antifungal agents.
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 89—96 |
Jana Řimáková (rimakova@faf.cuni.cz), Lenka Tůmová
Department of Pharmacognosy, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The influence of different concentrations of known growth regulators 2,4-dichlorophenoxyacetic acid (2,4-D), α-naphthaleneacetic acid (α-NAA) and a combination of α-NAA and kinetin on the growth and production of secondary metabolites (in particular flavonoids) of Calendula officinalis callus cultures was investigated. The highest growth of a fresh weight in comparison with other tested growth regulators showed α-NAA in concentration 10 mg/l. On the other side the callus culture growth was very slow on α-NAA/K medium in 10/10 mg/l concentration rate. In the experiment the medium containing 2,4-D seemed to be less appropriate for growth regulation than the medium with α-NAA/K in concentration rates 10/0.1 mg/l and 10/1 mg/l. Flavonoids were not detected in callus cultures. The influence of an irradiation length on the growth of callus cultures in medium containing α-NAA (10 mg/l) or 2,4-D (1 mg/l) was also studied. The highest fresh weight growth was observed in the period 16 hours light / 8 hours darkness.
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 97—101 |
Lenka Tůmová1 (tumova@faf.cuni.cz), Eliška Petrů1, Jana Řimáková1, Jiří Tůma2
1 Department of Pharmacognosy,
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2 Department of Biology,
University of Hradec Králové, Faculty of Education, Czech Republic
The tested elicitor – trichloracetic acid influenced the production of flavonoids in Ononis arvensis L. callus and suspension cultures. Maximal increase in the production of flavonoids in callus culture was recorded with the use of trichloracetic acid in a concentration of 6.12 x 10-3 mol L-1 24 hours after application. Flavonoid production was increased by 107 % against control. In suspension culture, the flavonoid content was enhanced in about 105 % 24 hours after treatment with 6.12 x 10-4 mol L-1 of trichloracetic acid.
It seams that both the callus culture and suspension culture of Ononis arvensis are sensitive to trichloracetic acid as an elicitor of flavonoid production. The changes in flavonoid production can be influenced not only by the type of elicitor and elicitation time but also by the elicitor concentration and the type of culture in vitro.
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 103—107 |
Lubomír Opletal1 (opletal@faf.cuni.cz), Markéta Křenková1, Martin Jirkovský1, Vladimír Hanuš2, Viktor Voříšek3, Milan Pour1, Helena Sovová4
1 Department of Pharmaceutical Botany and Ecology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, CZ-500 05 Hradec Králové, Czech Republic
2 J. Heyrovský Institute of Physical Chemistry, The Academy of Sciences of the Czech Republic, Dolejškova 3, CZ-182 23 Prague 8, Czech Republic
3 Faculty Hospital, Institute of Clinical Biochemistry and Diagnostics, Sokolská 581, CZ-500 05 Hradec Králové, Czech Republic
4 Institute of Chemical Process Fundamentals, The Academy of Sciences of the Czech Republic, Rozvojová 135, CZ-165 02 Prague 6, Czech Republic
As a part of systematic phytochemical studies of the vegetative parts of the taxon Schisandra chinensis basic extract from the leaves was prepared and further processed with diethyl ether and n-butanol. Ethereal extract was chromatographed on silica gel, and (E)-cinnamic acid kaempferol and quercetin were obtained as the main components. The compounds were found in this taxon for the first time. Both benzopyrane derivatives are most probably aglycones of flavonoid glycosides contained in n-butanol extract. The contained mixture of flavonoids is highly complex and individual components have not yet been separated in a preparative scale.
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 109—115 |
Marta Chlupáčová1 (chlupacova@faf.cuni.cz), Veronika Opletalová1, Jiří Kuneš2, Katarína Kráľová3
1 Department of Pharmaceutical Chemistry and Drug Control,
2 Department of Inorganic and Organic Chemistry,
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
3 Chemical Institute, Comenius University in Bratislava, Faculty of Science, Slovak Republic
A series of Michael adducts of chalcone with various thiols was prepared in high yields by a novel method. The 1H NMR and 13C NMR spectra were recorded. Effect on the chlorophyll production in Chlorella vulgaris and oxygen evolution rate in spinach chloroplasts was tested.
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 117—121 |
Marie Musilová (musilova@faf.cuni.cz), Petra Pátková
Department of Pharmaceutical Technology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The thermal profile of White wax was examined by differential scanning calorimetry (DSC). The DSC melting, crystallisation, and the subsequent melting curve in the second heating of white wax are reported. Each thermal curve was used to determine four DSC parameters, namely the onset temperature To, offset temperature Tf, peak temperature Tp, and melting enthalpy ΔH. On melting, white wax shows one endothermic peak. It begins to crystallise at a temperature slightly lower than the melting point. Both the crystallisation curve and the melting curve of the subsequent second heating show two peaks. The melting curve in the second heating is more reproducible than the melting curve in the first heating and it does not depend on the initial crystalline state of the sample.
| 2004 | Folia Pharm. Univ. Carol. 31—32 | Pag. 123—134 |
Zdeňka Šklubalová1 (sklubalo@faf.cuni.cz), Ruta Masteiková2
1 Department of Pharmaceutical Technology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2 Department of Pharmaceutics, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic
In situ gelling polymers undergo a rapid phase-change transition from liquid state (sol) to the gel in response to various physical or chemical stimuli. In ocular and injectable drug delivery, in situ gelling systems are intensively investigated since they offer many advantages such as that drug, in a sol state, can be easy mixed with vehicle and administered at the site of application to achieve prolong contact time with tissue and to improve bioavailability of drug. This article reviews the most often studied in situ gelling polymers in aqueous ophthalmic and parenteral preparations.
| 2005 | Folia Pharm. Univ. Carol. 33 | Pag. 7—11 |
Karel Waisser (waisser@faf.cuni.cz), Kateřina Dražková, Josef Matyk, Karel Palát
Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The Free-Wilson approach was used for QSAR study.
The molecules were separated on the heterocyclic and salicyl moieties
of the molecules. The 2-pyridyl moiety increases the antimycobacterial activity
more then the 3- or 4- pyridyl moiety. Substitution of the salicyl moiety
by chlorine in position 4 or 5, and 2-pyridyl moiety by nitro group or
by bromine in position 5 had the strongest influence on the increasis
of antimycobacterial activity.
| 2005 | Folia Pharm. Univ. Carol. 33 | Pag. 13—17 |
Jan Adamec1, Karel Waisser1 (waisser@faf.cuni.cz), Luís Silva2, Vladimír Buchta2
1 Department of Inorganic and Organic Chemistry, 2 Department of Biological and Medical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
The purpose of this study was to investigate the structure--antifungal activity relationships in the group of 19 compounds, derivatives of 1-phenyl-5-benzylsulfanyltetrazoles, in which phenyl in position 1 of tetrazole was substituted in position 4 by chlorine, methyl or methoxy group (or by chlorine in position 3 and 4), and by chlorine, methyl or methoxy group in position 4 of benzyl moiety. The goal of this paper was to study in vitro antifungal activity of antimycobacterial tetrazole against Candida albicans ATCC 44859, Candida tropicalis 156, Candida krusei E28, Candida glabrata 20/I, Trichosporon beigelii 1188, Trichophyton mentagrophytes 445, Aspergillus fumigatus 231, Absidia corymbifera 272. The activity against the eight fungal strains were negligible with the exception of T. mentagrophytes and A. fumigatus. The structure--activity relationships against T. mentagrophytes were determined using the Free-Wilson method, which was further combined with the approach of Hansch.
| 2005 | Folia Pharm. Univ. Carol. 33 | Pag. 19—21 |
Karel Waisser1 (waisser@faf.cuni.cz), Jozef Čižmárik2, Jarmila Kaustová3
1 Department of Inorganic and Organic Chemistry,
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2 Department of Pharmaceutical Chemistry,
Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic
3 Department of Diagnosis Mycobacteria,
Institute of Hygiene, Regional Institute of Public Health, Ostrava, Czech Republic
This work is focused on the investigation of the antimycobacterial activity of quarternary ammonium salts of piperidinylethyl esters of alkoxysubstituted phenylcarbamic acids. The work is a part of the investigation of basic substituted alkyl esters of alkoxysubstituted phenylcarbamic acids. The advantage of compounds is a low toxicity. The antimycobacterial activity of compounds under study was very low (with exception of compound 1b). It seems that the antimycobacterial activity increases with the lipohility. The promising activity of compound 1b indicates that it is an attractive direction of research.
| 2005 | Folia Pharm. Univ. Carol. 33 | Pag. 23—29 |
Josef Jampílek1, Martin Doležal2 (dolezalm@faf.cuni.cz), Lukáš Palek2, Luís Silva3, Vladimír Buchta3
1 Zentiva a. s., U Kabelovny 130, 102 37 Prague, Czech Republic
2 Department of Pharmaceutical Chemistry and Drug Control,
3 Department of Biological and Medical Sciences,
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Three possible regioisomers of 6-chloropyrazine- or 5-chloropyrazine- or 3-chloropyrazine-2-carboxylic acid derivatives were generated by means of novel regioselective synthetic and separating methods, developed at our workplace. These C(6) or C(5) or C(3) chlorinated pyrazine derivatives were consequently coupled with 4- or 3-methoxybenzene-1-thiols in the presence of a heterogeneous copper catalyst. Obtained 6- or 5- or 3-(4-methoxyphenyl)- and 6- or 5- or 3-(3-methoxyphenyl)sulfanylpyrazine-2-carboxylic acid derivatives were tested for their antifungal activity against eight fungal strains. Some of them showed only some moderate activities especially against Trichophyton mentagrophytes and Candida albicans (their MIC values ranged from 31.25 to 500 µmol.dm-3).
| 2005 | Folia Pharm. Univ. Carol. 33 | Pag. 31—43 |
Marta Chlupáčová1 (Marta.Chlupacova@faf.cuni.cz), Veronika Opletalová1, Jiří Kuneš1, Luís Silva1, Vladimír Buchta1, Lenka Dušková1, Katarína Kráľová2
1
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
2
Comenius University in Bratislava, Faculty of Natural Sciences, Slovak Republic
Alkylated derivatives of (E)-3-(3-hydroxyphenyl)-, (E)-3-(4-chlorophenyl)-, (E)-3-phenyl-, (E)-3-(2-hydroxy-5-nitrophenyl)- and (E)-3-furyl-1-pyrazin-2-ylprop-2-en-1-ones were prepared by Claisen-Schmidt condensation of corresponding alkylated acetylpyrazines and aldehydes. The products were evaluated on antimycobacterial, photosynthesis-inhibiting and antifungal activity.
| 2005 | Folia Pharm. Univ. Carol. 33 | Pag. 45—52 |
Hubert Žáček
Department of Pharmaceutical Technology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
A very short introduction into the principles of information theory as part of cybernetics is presented in which the category of information is shown as contradictory to that of energy in physical considerations. Based on previous and present findings of the author, three information-theoretic indices are suggested which are appropriate for characterization of technical merits of quality testing methods. These indices are “information content” and “informing power” and “relative informing power” and they can be used for answering manifold experimental and/or other relevant questions. The application of these indices is more intuitive than the usual simple indication of, e. g., mean, standard deviation, etc.
| 2005 | Folia Pharm. Univ. Carol. 33 | Pag. 53—55 |
Jiřina Dušková1, Luděk Jahodář1, Jaroslav Dušek2
1 Lehrstuhl für Pharmazeutische Botanik und Ökologie und 2 Lehrstuhl für Pharmakognosie Karls-Universität in Prag, Pharmazeutische Fakultät in Hradec Králové, Tschechische Republik
Biotransformation of arbutin and 4-methoxyphenol by in-vitro-cultures
Glycosidic and methylic activities of Bellis perennis, Coronilla varia, Rhodiola rosea, Datura meteloides, Leuzea carthamoides and Bergenia crassifolia were studied. Arbutin and 4-methoxyphenol were added into the medium as the substrates of the above-mentioned process. The transformation of arbutin and 4-methoxyphenol to methylarbutin by the Leuzea carthamoides culture was observed. The transformation of 4-methoxyphenol to arbutin by Leuzea carthamoides and Datura meteloides were very interesting.
| 2005 | Folia Pharm. Univ. Carol. 33 | Pag. 57—65 |
Jana Dolejšová, Miroslav Polášek, Petr Solich, Rolf Karlíček
Department of Analytical Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Flow injection chemiluminescence method for determining ≈ 1--13 µmol.l-1 of trihydroxyphenols (pyrogallol, phloroglucinol and 1,2,4-trihydroxybenzene) using the analyte oxidation in aqueous 0.3 mmol.l-1 KMnO4 containing 0.25 mol.l-1 H2SO4 as reagent stream (flow rate 0.91 ml.min-1) has been devised. Sodim hexametaphosphate (60 mmol.l-1) added to the injected phenol samples increased the intensity of chemiluminescence 1,2,4-trihydroxybenzene 4.5 fold relative to the sample without this enhancer of chemiluminescence. At the injected sample volume of 200 µl, the relative standard deviation (RSD) values of the peak heights was 1.02 % (pyrogallol), 1.43 % (phloroglucinol) and 0.68 % (1,2,4-trihydroxybenzene), n = 10, when injected 5 µmol.l-1 calibration solutions of phenols. The sample throughput was 171 sample.h-1.
The results were in good agreement with those of VIS spectrophotometric (Emerson reaction) determination, as evaluated by the Student t-test. The proposed method has been applied to the analysis of phenols as bulk substances.
| 2005 | Folia Pharm. Univ. Carol. 33 | Pag. 67—75 |
Jana Dolejšová, Miroslav Polášek, Petr Solich, Rolf Karlíček
Department of Analytical Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
Flow injection method with chemiluminescence detection has been devised for determining ≈ 2--8 µmol.l-1 of dihydroxyphenols (catechol, resorcinol, hydroquinone). The samples are made 60 mmol.l-1 in aqueous sodium hexametaphosphate (enhancer of the chemiluminescence) and injected (for 5 s) into a reagent stream (flow rate 0.91 ml.min-1) of 0.25 mol.l-1 H2SO4 containing 0.5 mmol.l-1 KMnO4 (for catechol) or 0.3 mmol.l-1 KMnO4 (for the other phenols) as oxidant. The injected sample volume was 200 µl. The relative standard deviation (RSD) values of the peak heights ranged betwen 1.74 % (resorcinol) and 0.82 % (hydroquinone), n = 10, when injected ≈ 5 µmol.l-1 calibration solutions of the phenols. The method has been applied to the analysis of phenols as bulk substances. The sample throughput was 171 sample.h-1. The results were in good agreement with those of VIS spectrophotometric (Emerson reaction) determination, as evaluated by the Student t-test.
| 2005 | Folia Pharm. Univ. Carol. 33 | Pag. 77—86 |
Zdenka Šklubalová (zdenka.sklubalova@faf.cuni.cz), Zdenek Zatloukal
Department of Pharmaceutical Technology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
An aqueous ophthalmic solution to be instilled as a drop in the lower conjunctival sac of the patient remains the best-accepted dosage form for ocular medication. While for oral liquid preparations the Ph. Eur. describes a test on the dose and the dose uniformity, drop volume or drop weight of eye drops is not specified. Although optimally, drop size smaller than 20 µl is preferred to improve the therapeutic effect of ophthalmic drugs and to decrease adverse systemic effects, commercially available dropper tips generally deliver drops with volumes between 25 and 70 µl. Theoretically, size of eye drop is influenced by three major factors: design and characteristics of the dropper tip and dropper bottle, physico-chemical properties of solution to be dispensed and patient handling the dropper bottle. In this work, by using the 2IV7-3 fractional factorial design, seven factors which could relate size of eye drop were systematically investigated. Dropper tip type, dispensing angle and dispensing rate were found to produce significant effect (p < 0.05). In the other part of study, the influence of significant factors: dropper tip type and dispensing angle on drop volume of the surface-active preservative, benzalkonium chloride (BAC), solutions was investigated in detail. As a result, because rubber dropper tip wetting resulted in a dramatic increase in drop volume which could hardly be foreseen in real drop dispensing, slow dispensing rate drop delivery with use of a plastic dropper tip at dispensing angle of 90° may be recommended. Under those defined dispensing conditions, the variability of the drop volume was expressed with variability coefficient of 3.3 %.
| 2005 | Folia Pharm. Univ. Carol. 33 | Pag. 87—93 |
Marie Musilová, Jitka Gabrielová
Department of Pharmaceutical Technology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic
On measurements by means of DSC, linear regression was demonstrated between the value of the melting point of paracetamol and its concentration in the suppository base. The found values were, nevertheless, lower than those that would correspond to the incorporated amount of paracetamol. The differences in the found and declared concentrations were in less concentrated samples about 2 %, in the samples of higher paracetamol concentrations about 0.5 %.
| 2005 | Folia Pharm. Univ. Carol. 33 | Pag. 95—99 |
Stanislav Ďoubal (doubal@faf.cuni.cz), Petr Klemera
Department of Biophysics, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic.
This paper deals with propagation of pulse wave in viscoelastic tube, with viscose liquid inside. Fundamental partial differential equations describing pulse wave were derived. Further, formulas for phase velocity and damping of wave were derived. Propagation of wave through dividing line between two mechanically different parts of tube was also analyzed. Formulas for reflections and passage were derived.