Showing papers in "Acta Poloniae Pharmaceutica in 2002"

Search of antimicrobial activity of selected non-antibiotic drugs.

Abstract: A variety of pharmaceutical preparations, which are applied in the management of non-infectious diseases, have shown in vitro some antimicrobial activity. These drugs are called "non-antibiotics". The aim of this study was to detect and characterise the antimicrobial activity of non-antibiotic drugs. selected from the preparations analysed during state control performed at the Drug Institute in Poland. Over 160 pharmaceutical preparations were randomly chosen from different groups of drugs. The surveillance study was performed on standard ATCC microbial strains used for drug control: S aureus, E. coil, P. aeruginosa and C. albicans. It was shown that the drugs listed below inhibited growth of at least one of the examined strains:acyclovir (Awirol 5%, cream), alendronate (Alenato 5 mg, tabl.), alverine (Meteospasmyl 20 mg, caps.), butorphanole (Butamidor 10 mg/ml, amp.), clodronate (Sindronat 400 mg, caps), diclofenac (Olfen 75 mg, amp.), emadastine (Emadine 0.05%, eye dr.), etodolac (Febret 200 mg, caps.), fluvastatine (Lescol 40 mg, tabl.), ketamine (Ketamidor 10%, amp.), levocabastine (Histimet 0.5 mg/ml, eye dr.), losartan (Lorista 50 mg, tabl.), matipranolol (Betaman 0.3% eye dr.), mesalazine (Pentasa 1%, susp.), naproxen (Nalgesin 550 mg, tabl.), oxaprosine (Reumax 600 mg, tabl.), oxymethazoline (Nasivin 0.025%, nose dr.), proxymetacaine (Alcaine 0.5%, eye dr.), ribavirin (Rebetol 200 mg, caps.), rutoside with ascorbic acid (Cerutin 20+200 mg, tabl.), sulodexide (Vessel due F, 250 LSU, caps.), tegaserole (Zelmac 50 mg, tabl.), telmisartan (Pritor 20 mg, tabl.), temosolomide (Temodal 100 mg, caps.), ticlopidine (Ticlid 250 mg, tabl.), tolfenamic acid (Migea rapid 200 mg, tabl.), tramadole (Tramundin 100 mg, tabl.), tropicamide (Tropicamidum 1%, eye dr.). Staphylococcus aureus was susceptible to most of the drugs listed above. Ticlopidine showed activity against S. aureus, E. coli and C. albicans (MICs equal to: 0.45; 0.45 and 0.65 mg/ml, respectively). Oxymetazoline showed activity against S. aureus and E. coli (MICs: 0.005 and 0.025 mg/ml, respectively). Pseudomonas aeruginosa was sensitive to alendronate, clondronate, oxaprozine, ribavirin and tramadole (MICs: 10, 63, 60, 3 and 43 mg/ml, respectively).

Flavonoids from lemon balm (Melissa officinalis L., Lamiaceae).

Abstract: Six flavonoids have been isolated from the leaves of lemon balm (Melissa officinalis L., Lamiaceae). Their structures were determined on the basis of spectral data (UV, 1R, 1H NMR, 13C NMR and FAB MS) as luteolin, luteolin 7-O-beta-D-glucopyranoside, apigenin 7-O-beta-D-glucopyranoside, luteolin 7-O-beta-D-glucuronopyranoside, luteolin 3'-O-beta-D-glucuronopyranoside and luteolin 7-O-beta-D-glucopyranoside-3'-Obeta-D-glucuronopyranoside. The last three glycosides have been found in lemon balm for the first time and luteolin 7-O-beta-D-glucopyranoside-3'-O-beta-D-glucuronopyranoside is a new compound found in plants.

Flavonoid compounds in the flowers of Abutilon indicum (L.) Sweet (Malvaceae).

Abstract: Seven flavonoid compounds: luteolin, chrysoeriol, luteolin 7-O-beta-glucopyranoside, chrysoeriol 7-O-beta-glucopyranoside, apigenin 7-O-beta-glucopyranoside, quercetin 3-O-beta-glucopyranoside, quercetin 3-O-alpha-rhamnopyranosyl (1 --> 6)-beta-glucopyranoside, were isolated and identified from the flowers of Abutilon indicum (L.) Sweet (Malvaceae).

Synthesis and tumoricidal activity evaluation of new morin and quercetin sulfonic derivatives.

Abstract: Flavonoids are a group of naturally occurring compounds with interesting medical properties, such as antiinflammatory, antiallergic, antiviral, antibacterial and antitumor activities. In our experiments we were trying to examine the tumoricidal activity of newly synthesized derivatives of two flavonoids: 3,5,7,2',4'-pentahydroxyflavone (morin) and 3,5,7,3',4'-pentahydroxyflavone (quercetin). These derivatives were: natrium salt of morin-5'-sulfonic acid (NaMSA), natrium salt of quercetin-5'-sulfonic acid (NaQSA), complex of Mg2+ with quercetin-5'-sulfonic acid (QSA), complex of iron(II) with QSA. The antitumor activity of these agents was tested in vitro on two cell lines: L1210--murine lymphocytic leukaemia and P-815--murine mastocytoma. Our experiments showed that sulfonic derivatives of these two flavonoids were less potent than the original agents in their cytostatic and cytotoxic activities. However, their solubility in water was greater than that of the original agents and higher culture medium concentration of these derivatives was obtained. The results indicate that the ability of flavonoids to act tumoricidally is reciprocally correlated with their lipophilicity.

Synthesis and anticonvulsant properties of new 1-phenyl and 1-phenylamino-3-phenylpyrrolidine-2,5-dione derivatives.

Abstract: A series of N-aryl and N-aminoaryl 3-phenyl pyrrolidine-2,5-diones were synthesized and tested for anticonvulsant activity in the maximum electroshock seizure (MES) and pentetrazol seizure threshold (sc Met) tests. Structures of the novel compounds were confirmed by elemental and spectral analyses.

Current strategies for anticancer chemoprevention and chemoprotection.

Abstract: Relatively new targets in drug design projects in cancer pharmacology include cytostatic agents, immune system modulators, and angiogenesis inhibitors. Preventive oncology applies pharmacological agents to reverse, retard, or halt progression of neoplastic cells to invasive malignancy. Prevention of cancer, however, can be accomplished through many strategies, including changes in diet and lifestyle. For example, the vast majority of lung cancers (80-90%) can be attributed to cigarette smoking and therefore, the most effective primary preventive strategy for lung cancer is to quit smoking. Chemoprevention through interruption of multistage careinogenesis include different molecular targets. Selective estrogen receptor modulators (SERMs) act as estrogen receptor (ER) agonists. Ligands for the peroxisome proliferator-activated receptor gamma (PPAR-gamma) suppress breast carcinogenesis in experimental models and induce differentiation of human liposarcoma cells. Selective PPAR modulators (SPARMs), by analogy to the SERM concept, are designed to have desired effects on specific genes relevant to carcinogenesis. Enzymatic approach in endocrine-related tumors involve inhibition of aromatase to prevent breast cancer and inhibition of 5-alpha-reductase to prevent prostate cancer. Down-regulation of inflammatory prostaglandin synthesis by inhibition of cyclooxygenase-2 (COX-2). inhibition of the inducible nitric oxide synthase (iNOS), and stimulation of phase II detoxication system, are currently examined in experimental models and clinical trials. Overall, potential targets in preventive strategies to reduce the risk of cancer involve agonists of endocrine receptors, factors down-regulating inflammation, factors inducing programmed cell death (PCD)/apoptosis, enzymatic inhibitors and gene therapy.

Comparative study on the free flavonoid aglycones in herbs of different species of Polygonum L.

Abstract: The flavonoid aglycones were studied in the herbs of the following taxons of the Polygonum L. genus: P. hydropiper L, P. bistorta L., P. aviculare L., P. persicaria L., P. lapathifolium ssp. tomentosum (Schrank) Dans, P. lapathifolium ssp. nodosum (Pers.) Dans, P. amphibium L., P. mite Schrank, P. conolvulus L. (Bilderdykia convolvulus L.) by means of the RP-HPLC method. The content of taxifolin, quercetin, quercetin-3-methyl ether, kaempferol, myritcetin, luteolin, isorhamnetin and rhamnetin were determined.

Further flavonoids from the flowers of Prunus spinosa L.

Abstract: Further seven flavonoids were isolated from the flowers of Prunus spinosa L.: quercetin 3-O-alpha-L-arabinopyranoside, 3-O-alpha-L-rhamnopyranoside, 3-O-beta-D-xylo-pyranoside, and 3-O-beta-glucopyranoside, kaempferol 3,7-di-O-alpha-L-rhamnopyranoside, kaempferol and quercetin 3-O-(4"-beta-D-glucopyranosyl)-alpha-L-rhamnopyranosides. Four of them have been found for the first time in this plant. Structural elucidation was performed by means of chemical and spectral methods (UV, LSI MS, 1D and 2D NMR).

Truxillic and truxinic acids--occurrence in plant kingdom.

Abstract: For some years now there has been a systematic increase in the number of reports on new secondary metaholites of truxillic and truxinic acid derivatives. The paper offers a presentation of existing forms of cyclobutanodicarhoxylic acids in plant kingdom. while considering their stereochemical structure and hiosynthesis. Also presented are some results of research on the pharmacological activity of synthetic and natural derivatives of these compounds. The paper shows additionally the results of search in nature for compounds containing fragments of truxillic and truxinic acids seen against the occurrence of other compounds of cyclobutane derivatives in plant kingdom.

Synthesis of 6-substituted 6H-indolo[2,3-b]quinolines as novel cytotoxic agents and topoisomerase II inhibitors.

Abstract: A systematic investigation into the impact of the substituents introduced into the indolo[2,3-b]quinoline system is described. The findings clearly demonstrate that the compounds bearing a methyl group or a longer aliphatic chain at the N-6 position are inactive against prokaryotic and eukaryotic cells. The introduction of alkyl-amino-alkyl substituent at the N-6 position of indolo[2,3-b]quinoline accounts for the appearance of the antimicrobial and.cytotoxic properties. The cytotoxicity against oral epidermoid carcinoma KB (ID50) is in the range from 2.0 to 9.0 microM, and the antimicrobial activity (MIC) falls between 0.03 and 0.50 mM. The structural relation within 6H-indolo[2,3-b]quinolines, concerning their antimicrobial and cytotoxic activity, corresponds well with their ability to bind DNA and to inhibit topoisomerase II activity.

Investigation of interaction of promethazine with cyclodextrins.

Abstract: The effect of beta-CD and its substituted derivatives (DM-beta-CD and HP-beta-CD) on the solubility and photostability of promethazine was investigated in solution and in the solid state. The soluble complexes of protonated (pH = 6.8) and basic (pH = 10.8) forms of promethazine with CDs were studied using the spectral method. The influence of pH and CD complexation on photostability of PM in solution was followed. It was found that the photochemical decomposition of promethazine (PM) alone and in the presence of CD proceeds according to the first order reaction. It was also established that as well the presence of CD as the acidic medium of reaction increased the photostability of PM in solution. Formation of solid inclusion complexes of PM with CDs was evaluated using FT IR, 13C NMR and DSC methods. The results obtained indicate that independently of the complexation method in the solid state (kneading or heating), the presence of CD decreases the solubility of PM; the reason may be that the phenothiazine ring of PM did not enter into the cavity of beta-CD and its derivatives.

A simple and rapid liquid chromatographic method for the determination of metronidazole and its hydroxymetabolite in plasma and cutaneous microdialysates.

Abstract: A rapid, accurate, simple and low-cost method for quantitative determination of metronidazole and its hydroxymetabolite, in plasma and microdialysate samples, using tinidazole as an internal standard, has been developed. Metronidazole is widely used as a valuable agent for antiprotozoal as well as antibiotic therapy when anaerobic organisms are involved. Separation of the compounds studied was performed on a 120 x 4 mm analytical column, filled with LiChrosorb RP-8, 5 microm, the mobile phase consisted of 0.05 mol/L aqueous solution of potassium dihydrogen phosphate, adjusted to pH = 3.5 with orthophosphoric acid, methanol and acetonitrile (40:2:3. v/v/v). Detection was performed at 320 nm. Intra- and interserial precision was below 4.6% and 7.9%, respectively, for both the compounds studied. The presented method is suitable for pharmacokinetic studies.

Synthesis and some pharmacological properties of 3-(4-phenyl-5-oxo-1,2,4-triazolin-1-ylmethyl)-1,2,4-triazolin-5-thione derivatives.

Abstract: In the reaction of (4-phenyl- or 3,4-diphenyl-5-oxo-1,2,4-triazeolin-1-ylmethyl)-carbohydrazide (IIa, IIb) with isothiocyanates the thiosemicarbazide derivatives [IIIa, b - IXa, b] were obtained. Cyclization of those compounds in the presence of 2% or 10% NaOH led to formation of derivatives with the 1,2,4-triazolin-5-thione system [Xa, b - XV[a, b]. Molecular structure proposed for this group of compounds was confirmed by X-ray structure analysis of Xa and XIVa. Compounds Xa, XIIa and XIVa were investigated pharmacologically for their central properties in mice. It was shown that only compound XIIa produced antinociceptive effects in mice.

Bioavailability factors of isoniazid in fast and slow acetylators, healthy volunteers.

Abstract: The INH metabolism mainly involves acetylation to acetyloisoniazid by a non inducible hepatic enzyme N-acetyltransferase Examples of drugs acetylated by this enzymatic system are: isoniazid, sulphadimidine hydrallazine, dapson and sulphapyridine The rate of acetylation is constant in any individual but varies in different patients People are characterized as rapid or slow acetylators with slow acetylation inherited as an autosomal recessive Heterozygotes have intermediate acetylation rate The article presents comparative study of the bioavailability of INH in fast and slow acetylators in healthy volunteers The results have shown that all compared parameters are significantly different in both groups of acetylators

Comparative evaluation of safety and efficacy of pamidronate and zoledronic acid in multiple myeloma patients (single center experience).

Abstract: Osteolytic bone destruction, caused by the aberrant production and activation of osteoclasts, results in significant morbidity for patients with multiple myeloma (MM). Pamidronate [(3-amino-1-hydroxypropylidene)-1,1-bis-phosphonate] inhibits osteoclastic activity and reduces bone resorption. A potency of zoledronic acid (2-[imidazol-1-yl]-1-hydroxyethylidene-1,1-bisphosphonic acid, a new third generation bisphosphonate, as inhibitor of resorption was 850-fold greater than pamidronate, as was shown in preclinical models of bone resorption. Randomized, double-blind study was conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating myeloma bone disease. Since March 1999 the efficacy and safety of pamidronate and zoledronic acid is evaluated in MM patients all receiving anti-myeloma chemotherapy acc. to VMCP/VBAP alternating regimen. Nine patients with stage III myeloma and osteolytic lesions (3 female, 6 male, median age 57 years, range 52-67, with monoclonal protein: IgG-7, IgA-2) were randomly assigned (1:1:1 ratio) to treatment with either 4 or 8 mg of zoledronic acid via 15-minute intravenous infusion or 90 mg of pamidronate via 2-hour intravenous infusion every 3 to 4 weeks for 12 months. All patients have received 500 mg of calcium supplements and 500 IU of vit.D, orally, once daily, for the duration of administration of study medication. In extension phase of the study (June 2000-April 2002) patients did not received bisphosphonates. In 7 patients 18 cycles of assessed treatment was administered to each of them and one patient received 16 cycles. One patient died after receiving of 12 pamidronate therapy cycles at 11 month of the trial duration (and at 49 month since MM diagnosis and anti-tumour treatment). The patient's death occurred during the progression of plasma cell proliferation due to acute left ventricle cardiac failure. During the 12-month-period of bisphosphonate treatment skeletal related events (SRE) and progression of osteolysis occurred with the same frequency in 3 treatment groups. One patient experienced spinal cord compression and received radiation to bone and 2 patients experienced vertebral fracture. Time from study entry to the first SRE was 304 days in pamidronate and 366 and 392 days in 4 and 8 mg zoledronic acid group, respectively. The skeletal morbidity rate was identical in all treatment groups. Single hypocalcemic events occurred in 2 patients, mild hypertransaminasemia was observed in 3, worsening of renal function parameters in 2 patients (transient in one of them). Muscular pain and fever up to 39 degrees C (transient and self-limiting "flu-like" symptoms) occurred in 6 patients after several or some dozens of hours from study drug administration. Adverse events were similar in nature and frequency with zoledronic acid and pamidronate and were experienced by a similar proportion of patients in each treatment group. Median time of patient's observation duration after completing of administered treatment with zoledronic acid and pamidronate amounts to 20 months. At present actual median survival time of analysed patients since MM diagnosis is 42 months, since the beginning of treatment with pamidronate and zoledronic acid--33 months, and since completing treatment--20 months and is similar in 3 treatment groups. As was shown in our single center study in MM patients the safety and efficacy of pamidronate 90 mg and zoledronic acid 4 mg and 8 mg in monthly i.v. infusion are comparable. Thus the recommended dosage of zoledronic acid is 4 mg administered as a 15 minute i.v. infusion at intervals of 3 to 4 weeks.

Effect of chronic hyperglycemia and vanadate treatment on erythrocyte Na/K-ATpase and Mg-ATpase in streptozotocin diabetic rats.

Abstract: We have studied Na/K-ATPase and Mg-ATPase activities in red blood cells of diabetic rats treated in vivo with sodium vanadate. To our knowledge the effect of in vivo vanadate treatment on these two enzymes has not been studied. Red blood cell Na/K-ATPase plays a central role in the regulation of intra- and extra cellular cation homeostasis. Alteration of this transport enzymes is thought to be linked to several complications of diabetes mellitus: hypertension, nephropathy, peripherical neuropathy and microangiopathy. An Mg2+-dependent ATPase activity located in the erythrocyte membrane appears to be responsible for controlling the smoothing of echinocytic erythrocytes to discocytes and stomatocytes. Our results show that in alloxan diabetes activities of both ATPases are reduced (especially the activity of Na/K-ATPase). Vanadate treatment of normal animals reduced the activities of both enzymes: with 33.08% for Na/K-ATPase and 22.76% for Mg-ATPase. Vanadate treatment of diabetic animals did not affect significantly the inhibition process for Na/K-ATPase. For Mg-ATPase we have obtained a significant cumulative inhibition. These results stand out the different functions and physiologic control mechanism of these two ionic pump in red blood cells.

Flavonoids from some species of genus Scopolia Jacq.

Abstract: Kaempferol 3-O-(2-glucosyl)-galactoside-7-O-glucoside was isolated from the leaves of Scopolia carniolica Jacq. and S. sinensis Hemsl. From the latter taxon as well as kaempferol 3-O-galactoside and 3-O-(2-glucosyl)-galactoside, kaempferol and quercetin 3-O-robinobiosides and quercetin 3-O-sophoroside have been obtained. Moreover, from the leaves of S lurida Dun. kaempferol and quercetin 3-O-glucosides and 3-O-rutinosides were isolated. The structures of compounds have been determined by means of chemical and spectral methods (UV, LSI MS, 1H and 13C NMR, 1H-1H COSY NMR).

Applications of derivative UV spectrophotometry for the determinations of cetirizine dihydrochloride in pharmaceutical preparations.

Abstract: A method for the determination of cetirizine dihydrochloride in pharmaceuticals by first-, second-, third- and fourth- order derivative spectrophotometry is described, using "peak-peak" (P-P), and "peak-zero" (P-0) measurements. The calibration curves are linear within the concentration range of 7.5-22.5 microg ml(-1) for cetirizine dihydrochloride. The procedure is simple, rapid and the results are reliable.

The type of isoniazid acetylation in tuberculosis patients treated at National Tuberculosis and Lung Diseases Research Institute.

Abstract: The research has dealt with types of acetylation in 237 TB patients treated by standard course of chemotherapy with a 300 mg dose of INH at the National Tuberculosis and Lung Diseases Research Institute in Warsaw (NTLDRI). Blood samples were taken before (time 0) and 1, 3, 6 and 24 h after drug administration. Plasma concentrations of isoniazid were determined with biological methods. Two indicators of acetylation rate--I3 and C6 have been used to determine the acetylation type. Majority of the treated patients (68.8%) have shown fast type of INH acetylation. After similar dose of isoniazid different profile of absorption and excretion of the drug and significant differences (p < 0.01) in INH concentrations, acetylation rate and bioavailability between 163 fast and 74 slow acetylators have been observed. In plasma of 38.6% fast acetylators drug concentration 3h after ingestion of the dose did not achieve the concentration of 1 mcg/ml. In plasma of 29.7% slow acetylators, concentrations of INH 6h after ingestion were higher than 2 mcg/ml.

Quantitative structure-activity relationships study of a series of imidazole derivatives as potential new antifungal drugs.

Abstract: The Quantitative Structure-Activity Relationships (QSAR) has been developed to relate antifungal activity against Candida albicans and Rhodotorula glutinis of new imidazole derivatives with their physico-chemical and structural properties. For 265 imidazole derivatives the most significant statistically equations has been obtained with correlation coefficients R=0.800 and R=0.820 in case of activity against Ca. and Rh.g., respectively. The overall antifungal activity has been described by means of size and bulkiness related parameters as well as polar and lipophilic interactions. The significance of lipophilicity in terms of n-octanol/water partition coefficient, ClogP, on antifungal potency against both fungi has been investigated. QSAR equations for different classes of antifungal activity have been obtained. With a very high probability level (92% and 96%) the weak or very weak antifungal potency against C.a. can be determined and thus the number of required experiments can be reduced.

Synthesis and antiproliferative activity in vitro of new 3-substituted aminoisoxazolo[5,4-b]pyridines.

Abstract: The synthesis of 3-aminoisoxazolo[5,4-b]pyridine [III] and of several new 3-substituted aminoisoxazolo[5,4-b]pyridines is described. 3-Aminoisoxazlo[5,4-b]pyridine [III] was subjected to reactions with the acid halides and substituted aromatic aldehydes, leading to the production of the corresponding amides IV-VII, IX, XI-XVI and new tricyclic pyridoisoxazolopyrimidine VIII and Schiff bases XX-XXIV. 4-Chlorobutyroamide IX cyclized into 3-(pyrrolidinon-1-yl)isoxazolo[5,4-b]pyridine [X]. 3-Chloroacetylaminoisoxaxolo[5,4-b]pyridine [V] in reaction with secondary amines gave 3-aminoacetylaminoisoxazolo[5,4-b]pyridines XVII-XIX. The structures of the products II-XXIV were established on the basis of elemental analysis and spectral data IR, 1H NMR and MS. Selected compounds were tested for their antiproliferative activity in vitro. Two of them: 3-chloroacetyl-[V] and 3-2-bromo-propionylaminoisoxazolo[5,4-b]pyridine [VI] revealed cytotoxic activity against the cells of 8 various human or mouse tumor cell lines applied. Their ID50 (inhibitory dose 50%) values are in the range of the international activity criterion for synthetic agents (4 microg/ml).

Estimation of humoral activity of Eleutherococcus senticosus.

Abstract: The aim of the present work was an estimation of the influence of two plant pharmaceutical preparations containing an extract from the root of Eleutherococcus senticosus: Argoeleuter tablets and Immuplant tablets, on the humoral response of immunological system. Experiments were performed with female Balb/c mice six weeks old. In order to reveal the influence of taking preparations, containing an extract from Eleutherococcus senticosus on some elements of the immunological system, three ways of their administration have been compared: before illness, during illness and a combination of both. The obtained results allow formulating the following conclusions: - the pharmaceutical preparations, containing the extract from Eleutherococcus senticosus administered orally, influence on the increase of the level of immunoglobulins comprised in the mice's blood serum, - the pharmaceutical preparations act with different power, not fully dependent on the content of marker of the active substance - eleutheroside E, - dosage of the preparations containing the extract from Eleutherococcus senticosus should not be established basing only on the extract content, - best curative results, measured as the stimulation of humoral response of the organism were obtained when a given preparation was administered therapeutically, even though the combined administration - prophylactically with prolonged administration during illness also is correct.

Flavonoid compounds from Pyrus communis L. flowers.

Abstract: Five flavonoid glycosides: kaempferol 3-O-beta-D-glucopyranoside (IV), isorhamnetin 3-O-beta-D-glucopyranoside (V), isorhamnetin 3-O-beta-D-(6''-O-alpha-L-rhamnopyranosyl)-glucopyranoside (VIII), 8-methoxykaempferol 3-O-beta-D-(2''-O-alpha-D-glucopyranosyl)-glucopyranoside (VI), 8-methoxykaempferol 3-O-beta-D-(2''-O-alpha-L-rhamnopyranosyl)-glucopyranoside (VII) and chlorogenic acid (IX) were isolated from the flowers naturally growing Pyrus communis L. They were identified by chemical and spectroscopic methods.

Naproxen ion-selective electrode and its application to pharmaceutical analysis.

Abstract: An ion-selective membrane electrode was prepared based on ion-pair complex of naproxen with methyltrioctylammonium. Its basic analytical parameters such as: slope characteristics, measuring range, detection limit, response time, life time were determined. The electrode showed Nernstian response from the 10(-1) to 10(-4) mol l(-1) concentration range and 5.5-8.5 pH range, low limit of detection 5 x 10(-5) mol l(-1) and short response time--20s. Selectivity was good over a number of organic and inorganic anions. The electrode was applied for the determination of naproxen tablets in aqueous solutions by the calibration curve method and standard addition method.

Influence of vitamins C and E on cytotoxic activity of adriamycin in chosen cell cultures.

Abstract: Influence of different concentrations of ascorbic acid (vitamin C) and dl-alpha-tocopherol acetate (vitamin E) on in vitro cytotoxic adriamycin activity, in: embryonic human fibroblasts (CLV102), human melanoma cells (ME18) and adriamycin-resistant subline cells (ME18/R), was studied. IC50 value for each compound (compound concentration in the culture medium, for which 50% of cells survive) was determined. Cells' survival after the used agent was examined with trypan blue test. The relationship between different concentrations of vitamin C and toxicity of adriamycin, used at appropriate IC50 concentrations, was expressed for all the examined cells as their survival decrease, being in direct proportion to the concentration increase of this vitamin in the medium. In the case of influence of vitamin E on adriamycin cytotoxicity, the protective effect of this vitamin was observed in the concentration range: from 5 to 300 microg/ml (p < or = 0.0001), as an increase of the examined cell survival for ME18, ME18/R as well as for CLV102, comparing to the control (p=0.05) without this vitamin. Parallelly, a statistically significant survival decrease was observed, if the concentration of vitamin E in the culture medium exceeded 500 microg/ml. Received results showed different, in defined concentration range, effects of the vitamin C or vitamin E activity for adriamycin cytotoxicity. These effects were similar for all the examined cells.

Antioxidative properties of coenzyme Q10 and vitamin E in exposure to xylene and gasoline and their mixture with methanol.

Abstract: Exposure to a mixture of solvents in industry is still a problem particularly in industrial laboratories. In the paint and laquer industry the employees are exposed to xylene (Rx) and gasoline (Rg). The influence of xylene and gasoline or their mixture with methanol on lipid peroxidation was evaluated in the presented paper. Antioxidative properties of CoQ10 or vitamin E were also tested. It was observed that xylene caused an increase of lipid peroxidation measured as a MDA level in all used concentrations, but gasoline only in very high doses. The mixture of xylene with methanol increased significantly MDA level, whereas gasoline with methanol did not influence lipid peroxidation. The character of interaction depends on hydrocarbons dose. CoQ10 and vitamin E are effective antioxidants lowering the increased MDA level caused by xylene, gasoline or their mixture with methanol, however the dose of CoQ10 should be adjusted to the strength of oxidative stress in order to avoid disadvantageous effect. CoQ10 is a more effective antioxidant in exposure to xylene rather than gasoline, but vitamin E acts better in exposure to gasoline decreasing the MDA level.

Effect of various vehicles on diclofenac sodium and indomethacin pharmaceutical availability.

Abstract: The aim of the study was to determine the pharmaceutical availability of various ointment systems containing antirheumatic substances and to establish an optimal system for cutaneous application. Topical application permits elimination or at least reduction of side effects connected with oral administration. Three systems were evaluated: emulsion W/O (ointment), emulsion O/W (cream) and gel, all of them containing diclofenac sodium or indomethacin. The investigated systems are characterized by proper rheological parameters and long physicochemical stability. Studies on diclofenac and indomethacin pharmaceutical availability show a good release of the substances from cream and hydrogel bases, but a very poor release from the ointment base.

Determination of the content of vitamin K, in complex vitamin preparations by the HPLC method.

Abstract: In the present study we tried to use HPLC method to determine the vitamin K1 content in complex vitamin preparations. The reverse phases technique was applied and measurements were made at the wavelength 248 nm. On the base of statistical analysis we can note that conditions for HPLC method used in our work gave us precise and accurate results.

Determination of the content of desmopressin in pharmaceutical preparations by HPLC and validation of the method.

Abstract: The aim of this study was to apply high performance liquid chromatography to the determination of content of desmopressin in pharmaceutical preparations and validation of the method. The satisfactory results have been obtained using a column Luna C 8.5 microm, 100 x 4.6 mm and a mobile phase containing 0.067 M phosphate buffer of pH = 7 and acetonitrile in the proportion 83:17. It has been shown that the elaborated method shows good precision and accuracy and can be applied to the qualitative and quantitative analysis of pharmaceutical preparations containing desmopressin.

The effect of cryoprotectants on the physical properties of large liposomes containing sodium diclofenac.

Abstract: Large liposomes (1-10 microm) containing sodium diclofenac were prepared and lyophilized using lactose or mannitol (7.5% in respect to the lipid content) as cryoprotectants. The physical studies of liposomes were performed during 30 days of storage in a dry or resuspended form. Lyophilization of large liposomes and storage in the dry form at 5 degrees C increases their physical stability. Lactose is a cryoprotectant which does not influence changes of properties of liposomes regarding their size, encapsulation efficacy and release rate. Large liposomes lyophilized in the presence of mannitol tend to increase in size and encapsulation efficacy, but the lipid bilayers are stabilized and less permeable to the drug.