[Effect of chromium enriched fermentation product of barley and brewer's yeast and its combination with rosiglitazone on experimentally induced hyperglycaemia in mice].

INTRODUCTION: In the recent years, herbal preparations have been more used to treat diabetes. Dietetic supplement based on barley and beer yeast enriched with chromium (BBCr) is registered in Serbia as a supplement in the treatment of type 2 diabetes. OBJECTIVE: To investigate the effect of the preparation based on barley and brewer's yeast with chromium (BBCr), rosiglitazone (R) and their combination (BBCr+R) on fasting glycaemia and glycaemia in mice after glucose, adrenalin and alloxan application. METHODS: The animals were divided into three groups: glucose 500 mg/kg (I); adrenalin 0.2 mg/kg (II); and alloxan 100 mg/kg (III) and into subgroups according to the substance they received (BBCr: 750 mg/kg, R: 0.75 mg/kg and BBCr+R). Each animal was its own control in respect of glycaemia before and after the treatment with test substances, except for group III which contained a placebo subgroup. RESULTS: BBCr caused a significant decrease of fasting glycaemia and significant reduction of glycaemia after glucose load compared to the values before treatment (7.4 +/- 0.6 mmol/l vs 9.2 +/- 0.6 mmol/l; p=0.01). R and BBCr+R significantly decreased glycaemia after adrenalin load (R: 8.6 +/- 1.8 mmol/l vs 15.4 +/- 3.2 mmol/l; p=0.004; BBCr+R: 9.6 +/- 2.4 mmol/l vs 15.0 +/- 4.4 mmol/l; p=0.04). After alloxan application the glycaemia was significantly lower in the subgroups treated with BBCr, R and BBCr+R compared to placebo subgroup (10.1 +/- 8.0 mmol/l vs 6.8 +/- 2.7 mmol/l vs 13.5 +/- 9.7 mmol/l vs 24.5 +/- 4.7 mmol/l; p=0.001). CONCLUSION: Pretreatment with BBCr caused a significant reduction of fasting glycaemia and glycaemia after glucose load. Rosiglitazone and BBCr+R caused a significant reduction of glycaemia after adrenalin load. Pretreatment with BBCr, R and BBCr+R prevented the onset of experimental diabetes caused by alloxan, which was confirmed by histological analysis of pancreas tissue.

Hypoglycaemic action of stevioside and а barley and brewer's yeast based preparation in the experimental model on mice.

The aim of this study was to investigate influence of the preparation based on barley and brewer's yeast extracts with chromium (BBCr) and stevioside (S) on fasting glycaemia and glycaemia in mice after glucose, adrenalin and alloxan application. The animals were divided into three groups: glucose 500 mgkg(-1) (I); adrenalin 0.2 mgkg(-1)(II) and alloxan 100 mg kg(-1) (III) and into subgroups according to the substance they received: stevioside 20 mg kg(-1) (I-S, II-S, III-S); BBCr 750 mg kg(-1)(I-BBCr, II-BBCr, III-BBCr) and saline 1 ml/100g (III-placebo). Glycaemia was measured before and after 7-day treatment with stevioside or BBCr in the following conditions: fasting, 30 min after glucose load (I) or 45 min after adrenaline load (II). In group III glycaemia was measured before and after 12-day treatment with S, BBCr or placebo and alloxan application (7th, 8th and 10th days of treatment ). BBCr significantly reduced fasting glycaemia in I and II groups and glycaemia values after the glucose load (I-BBCr: 9.20 ± 0.61 vs. 7.42 ± 0.59 mmol/L, p = 0.01). Stevioside significantly reduced glycaemia after the adrenalin load (II-S: 13.45 ± 0.71 vs. 11.65 ± 1.19 mmol/L; p = 0.03). In the III-BBCr glycaemia values did not indicate the development of alloxan-induced diabetes and were significantly lower than in the III-placebo (8.6 ± 3.16 vs. 18.8 ± 5.53 mmol/L; p < 0.05). In conclusion, BBCr caused a significant decrease of fasting glycaemia, significant reduction of glycaemia after glucose load and prevented onset of alloxan-induced diabetes. Stevioside caused the decrease of adrenalin-induced hyperglycaemia.

Anti-oxidative activity of an aqueous suspension of commercial preparation of the mushroom Coprinus comatus.

In this study the effects of an aqueous suspension of a commercial preparation of the mushroom Coprinus comatus on oxidative stress induced in rats by alloxane and carbon tetrachloride was examined. The effects were estimated from changes in the biochemical parameters (xanthine oxidase, glutathione peroxidase and catalase activity, reduced glutathione content, and extent of lipid peroxidation) of liver homogenate as well as histological changes in the liver of the rats treated with alloxane and carbon tetrachloride. Two screening doses of alloxane sufficient to induce diabetes in rats did not have any significant effect on the examined biochemical parameters of liver homogenate or on the cytoarchitectonics of liver cross-sections. Treatment with carbon tetrachloride resulted in a significant increase in the intensity of lipid peroxidation and peroxydasis activity, as well as with decrease in catalase activity. Certain changes in liver cross sections were detected, such is lymphocyte infiltration of dilated sinusoid capillaries. Administration of Coprinus comatus suspension thus showed antioxidative potential, evidenced by an increase of antioxidative status of liver homogenate and prevention of histological changes in liver cross sections.

Effect of 12-monoketocholic acid on modulation of analgesic action of morphine and tramadol.

This work is concerned with the potential promotive action of 12-monoketocholic acid (12-MKC) on the analgesic effect of morphine and tramadol. The investigation was carried out on laboratory Wistar rats divided into five test groups, each treated with either morphine (2 mg/kg), tramadol (9.6 mg/kg), 12-MKC (2 mg/kg), morphine + 12-MKC, or tramadol + 12-MKC, the control group receiving physiological solution (2 mg/kg). The effect of 12-MKC on the analgesic action of morphine and tramadol was determined by radiation heat method. Morphine and tramadol, given in equimolar doses, did not show significant difference in the degree of analgesia. In combination with morphine, 12-MKC increased significantly the analgesic effect compared with the group treated with morphine alone. However, 12-MKC caused no change in the action of tramadol. The 5-day intravenous application of 12-MKC in combination with the two analgesics caused no changes in the biochemical parameters nor pathohistological changes in the liver parenchyma of tested animals.

Evaluation of statistical power function for various diclofenac bioequivalence trials with different subject numbers.

This study presents application of statistical power function for the t-test and ANOVA F-test on the evaluation of diclofenac bioequivalence in trials with the wide variations in sample sizes (N = 12, 18 and 24). The power function, together with appropriate equations tables and figures, is used to calculate the power of the ANOVA for crossover design, the number of subjects for a given value of power and the minimum detectable difference in treatment means for different pharmacokinetic parameters of the formulations. The power of the trial with a small, sample size (N = 12) to detect 20% differences between diclofenac formulations is shown to be more than 0.9 and almost the same as the power of the trial with a large sample size (N = 24). In all trials for all pharmacokinetic parameters the power to detect 20% difference is shown to be more than 0.8. For the power of 0.8, the needed subject number to detect 20% difference in treatment means is the same or smaller than used and the minimum detectable difference is smaller than 20% in all our trials. This investigation shows that bioequivalence studies with small number of subjects (N = 12) may be quite adequate for valid conclusions.

Effect of aroma and magnum hops extracts and paracetamol on antioxidant liver parameters in mice.

Hop varieties that are mainly grown in Serbia are Magnum (German variety) and Aroma, which is grown only in the Vojvodina region. About the use of hops extracts as an auxiliary remedy there are divergent opinions. Our findings indicate that extracts of Magnum and Aroma varieties, among the others, enhance and prolong the analgesic action of paracetamol. For this reason we undertook a study of the effects of these extracts alone and in combination with paracetamol, along with the action of paracetamol alone, on the activity of the antioxidant enzymes GSHPx, CAT, Px, XOD, GSHR, glutathione content, LPx intensity, as well as activities of AST and ALT. Paracetamol in the dose applied exerted no influence on the investigated parameters and neither did ethanolic extract of Magnum variety. On the other hand, ethanolic extract of Aroma hops caused a significant reduction of GSH content. In combination with paracetamol, extracts of both Magnum and Aroma varieties reduced significantly the LPx intensity, activities of CAT and GSHPx, as well as GSH content in the liver homogenate. A significant increase in the AST value with respect to control was also observed. These findings indicate the disturbance in the functioning of hepatocytes, probably by decelarating metabolism and elimination of paracetamol.

Effect of stevioside and sodium salt of monoketocholic acid on glycemia in normoglycemic and diabetic rats.

This study investigated the effect of a commercial preparation of stevioside and a synthetic compound, sodium salt of monketocholic acid (MKC), administered per os (p.o.) and also adminstered via an osmotic pump, on glycemia in normoglycemic and diabetic Wistar rats. Diabetes was induced with alloxan, 100 mg/kg, i.p. Normoglycemic and diabetic rats were treated p.o. for five days either with physiological solution (1 ml/kg, controls), stevioside (20 mg/kg), MKC (4 mg/kg) and a combination of stevioside (20 mg/kg) and MKC (4 mg/kg). Apart from p.o. adminstration, stevioside and MKC were also administered via a subcutaneously (s.c.) implanted osmotic pump. During treatment and upon termination of the latter, glycemia was measured and the rats that were treated p.o. were subjected to the oral glucose tolerance test (OGTTT) at a dose of 1 g/kg. Following this animals were anesthetized with urethane (0.75 g/kg, i.p.) and killed by cardiopunction to determine C-peptide levels in the serum. In all three groups of normoglycemic rats highest decrease in glucose levels was observed on the fourth day of the experiment. The stevioside + MKC combination showed a stronger hypoglycemic effect compared to individual treatments with stevioside and MKC (3.73:4.80:4.73 mmol/L). In the group of diabetic rats that received both substances via the osmotic pump, the hypoglycemic action was also stronger compared to the individual treatments with stevioside and MKC (16.15:18.89:18.75 mmol/L). The treatment of healthy rats with both substances p.o. caused no statistically significant difference in glycemia, whereas in diabetic rats the combination of stevioside + MKC showed a statistically significant decrease in glycemia compared to control values. In both groups of rats, treatment with stevioside and MKC and their combination prevented an increase in glucose concentrations in the OGTT. Only the administration of stevioside by osmotic pump yielded a statistically significant increase in the concentrations of C-peptide in the serum of healthy rats. Compared to controls, the concentrations of C-peptide in diabetic rats were significantly higher after treatment with either stevioside or its combination with MKC, irrespective of the mode of administration.

Effect of aminophylline on aspirin penetration into the central nervous system in rats.

This study investigated with the effect of aminophylline on the penetration of aspirin through the blood-brain barrier (BBB) into the central nervous system (CNS) in rats. Acetylsalycylic was injected into the right axillary artery, to avoid the drug affecting the peripheral organs before it reached the CNS. The test animals received subcutaneously (s.c.) aminophylline 30 min before aspirin injection, while the control animals received an equimolar dose of physiological solution s.c. At time intervals of 30, 60, 90, 120, and 240 s after aspirin injection, the animals were decapitated and blood samples from the left jugular vein, as well as samples from the brainstem, cerebellum and left and right cerebral hemispheres, were taken to determine aspirin concentrations in all of them by a standard method. It was found that aspirin concentrations in the CNS were even 30 times lower than in the blood, with the concentrations being higher in the brainstem and cerebellum than in the left and right hemispheres. The presence of aminophylline did not alter aspirin concentrations either in the blood or the brain, and therefore did not affect significantly the aspirin penetration through the BBB into the CNS.

Effect of aroma and magnum hops extracts and paracetamol on antioxidant liver parameters in mice.

Hop varieties that are mainly grown in Serbia are Magnum (German variety) and Aroma, which is grown only in the Vojvodina region. About the use of hops extracts as an auxiliary remedy there are divergent opinions. Our findings indicate that extracts of Magnum and Aroma varieties, among the others, enhance and prolong the analgesic action of paracetamol. For this reason we undertook a study of the effects of these extracts alone and in combination with paracetamol, along with the action of paracetamol alone, on the activity of the antioxidant enzymes GSHPx, CAT, Px, XOD, GSHR, glutathione content, LPx intensity, as well as activities of AST and ALT. Paracetamol in the dose applied exerted no influence on the investigated parameters and neither did ethanolic extract of Magnum variety. On the other hand, ethanolic extract of Aroma hops caused a significant reduction of GSH content. In combination with paracetamol, extracts of both Magnum and Aroma varieties reduced significantly the LPx intensity, activities of CAT and GSHPx, as well as GSH content in the liver homogenate. A significant increase in the AST value with respect to control was also observed. These findings indicate the disturbance in the functioning of hepatocytes, probably by decelarating metabolism and elimination of paracetamol.

Diclofenac and ketoprofen liver toxicity in rat.

In the last years there appeared many articles about the adverse influence of non-steroidal anti-inflammatory drugs on the liver and heart. This study is concerned with the influence of the duration of treatment with diclofenac and ketoprofen on the macroscopic and microscopic changes in the liver, lungs, heart, and kidneys in rats. Experiments were carried out on mature Wistar strain rats. Animals of test groups received diclofenac and ketoprofen in a dose of 8 mg/kg/day (equivalent to the therapeutic dose for man) during 7 per os (p.o.) or 28 days intraperitoneally (i.p.), whereas controls received physiological solution p.o. A high morbidity was observed in the animals receiving diclofenac p.o. and somewhat lower in those treated with ketoprofen. On the other hand, the rats got through the 28-day i.p. treatment with both drugs mainly without significant complications. Macroscopic examinations revealed some changes in treated rats: distension of the stomach, ascites, fibrin deposits on the internal organs, lung effusion and the changes in color and structure of the liver. These changes were more frequent in the group of rats receiving diclofenac for the 7 days compared with those that received ketoprofen for the same time. It may be thought that the high mortality and macroscopic changes in the internal organs of experimental animals are a consequence of the microscopic changes in the liver and its lowered function.

Interaction of alcoholic extracts of hops with pentobarbital and diazepam in mice.

The interaction of alcoholic extracts of Magnum, Aroma and wild genotype hops with drugs that lower the activity of the central nervous system (CNS) was studied in mice. Hops drying and preparation of extracts were performed according to standard pharmacological procedures for preparing total alcoholic extracts of medicinal plants, i.e. in a ratio of one part dry herbs to two parts of 70% alcohol, with evaporation to dryness so that the extracts no longer contained any alcohol. The mice received four doses intraperitoneally (i.p.) of 0.5% aqueous solutions of the above-mentioned extracts, which were dissolved in warm physiological solution to make up a 0.5% aqueous solution, 24, 16, 4 and 0.5 hours before pentobarbital (40 mg/kg) or diazepam (3 mg/kg) administration. The hypnotic action of pentobarbital and the effect of diazepam on the coordination of movements (rotating rod method) were measured. It was found that hops extracts influenced the action of the investigated drugs, and that the extracts of the Magnum and Aroma genotypes suppressed the hypnotic action of pentobarbital and diazepam. Tert-butanolic extracts also suppressed the action of these two drugs but to a lesser extent, whereas wild hops extracts did not exert any significant effects compared to controls.

Effect of caffeine on quinidine transport to the central nervous system in rats.

We studied the effect of caffeine on the transport of quinidine through the blood-brain barrier (BBB) to the central nervous system (CNS) in rats. The anesthetized animals received quinidine in the form of a retrograde intra-arterial bolus injection (15 s) into the right axillary artery 30 min after receiving a subcutaneous injection of caffeine (test group) or physiological solution (control group). Rats were decapitated at 30, 60, 90, 120, and 240 s after quinidine administration. Blood samples were taken from the left jugular vein. Upon washing, the brain, was divided into the brainstem, cerebellum, and cerebral hemispheres to determine the quinidine content in each section, using a standard spectrofluorimetric method. Quninidine attained maximal concentrations in the CNS with a latency compared with that in blood; the CNS values were higher. Quinidine kinetics showed two compartments in the CNS, one consisting of the brainstem and cerebellum, in which quinidine concentrations were higher, and the other the cerebral hemispheres. Caffeine caused a significant deceleration of quinidine transition through the BBB to the CNS.

Interaction of alcoholic extracts of hops with cocaine and paracetamol in mice.

This work describes a study of the interaction in the mouse model of alcoholic extracts of hops of Magnum, Aroma and wild genotypes with drugs that have excitatory effect on the cerebral cortex (cocaine) and analgesic action (paracetamol). Hop drying and preparation of the extracts were carried out according to standard pharmacological procedures for preparing total alcoholic extracts of dry herbs, consisting of one part of dry drug and two parts of 70% alcohol. The mice received four doses i.p. of 0.5% aqueous solutions of the above-mentioned extracts (10 ml/kg) 24, 16, 4 and 0.5 h prior to receiving cocaine (25 mg/kg) or paracetamol (80 mg/kg). The parameter investigated was the change in spontaneous motility of mice after combined treatment with the extracts and cocaine/paracetamol compared to control animals that received the same dose of the drug after treatment with physiological solution. Only the ethanolic extract of Magnum hops increased the spontaneous motility of mice, while none of the extracts showed analgesic action as measured by the hot-plate method. In the interaction with cocaine, the extract of Magnum hops suppressed almost completely the action of cocaine compared to controls. Extracts of the other hops also decreased the cocaine-induced locomotor activity of mice, but to a lesser extent. Hop extracts exhibited a significant pharmacological interaction with paracetamol, with the most pronounced increase in analgesic action being found for the ethanolic extract of Aroma hops and the tert-butanolic extract of wild hops.

Interaction of alcoholic extracts of hops with pentobarbital and diazepam in mice.

The interaction of alcoholic extracts of Magnum, Aroma and wild genotype hops with drugs that lower the activity of the central nervous system (CNS) was studied in mice. Hops drying and preparation of extracts were performed according to standard pharmacological procedures for preparing total alcoholic extracts of medicinal plants, i.e. in a ratio of one part dry herbs to two parts of 70% alcohol, with evaporation to dryness so that the extracts no longer contained any alcohol. The mice received four doses intraperitoneally (i.p.) of 0.5% aqueous solutions of the above-mentioned extracts, which were dissolved in warm physiological solution to make up a 0.5% aqueous solution, 24, 16, 4 and 0.5 hours before pentobarbital (40 mg/kg) or diazepam (3 mg/kg) administration. The hypnotic action of pentobarbital and the effect of diazepam on the coordination of movements (rotating rod method) were measured. It was found that hops extracts influenced the action of the investigated drugs, and that the extracts of the Magnum and Aroma genotypes suppressed the hypnotic action of pentobarbital and diazepam. Tert-butanolic extracts also suppressed the action of these two drugs but to a lesser extent, whereas wild hops extracts did not exert any significant effects compared to controls.

Effect of parsley (Petroselinum crispum (Mill.) Nym. ex A.W. Hill, Apiaceae) extracts on some biochemical parameters of oxidative stress in mice treated with CCl(4).

The in vitro and in vivo antioxidant activity of different extracts of leaves and root of parsley (Petroselinum crispum (Mill.) Nym. ex A.W. Hill, Apiaceae) were studied. Free radical scavenging capacity (RSC) was evaluated measuring the scavenging activity on the 2,2-diphenyl-1-picrylhydrazil (DPPH) and OH radicals. Also, the effects on lipid peroxidation (LP) were evaluated. The results obtained showed that all examined extracts act as good scavengers of DPPH and OH radicals and reduce the intensity of LP. The in vivo effects were evaluated on some antioxidant systems (activities of LPx, GSH-Px, Px, CAT and XOD, and GSH content) in the mice liver and blood after treatment with the examined parsley extracts, or in combination with carbon tetrachloride (CCl(4)). On the basis of the results obtained it can be concluded that the examined extracts exhibited a certain protective effect. However, combined treatments with CCl(4) and the examined extracts showed both positive and negative synergism, inducing or suppressing the influence of CCl(4) alone.

Effect of rat pretreatment with aqueous solutions of stevioside and bile acids on the action of certain cardioactive drugs.

The interaction of aqueous solutions of stevioside and bile acids with cardioactive drugs was studied in rats by registering changes in their electrocardiograms (ECG). Wistar rats of both sexes received daily doses of 20 mg/kg (i.p.) of an aqueous solution of stevioside or physiological solution (controls), then were narcotized with urethane and connected to the ECG apparatus for the first recording. The jugular vein was prepared and connected to an infusion pump to administer one of the drugs: adrenaline (0.1 mg/ml), verapamil (2.5 mg/ml) or metoprolol (1 mg/ml) to rats in both groups, while recording their ECGs. In the second part of the study, the animals were treated in the same way but instead of the stevioside solution received a single dose of 4 mg/kg of monoketocholic acid methyl ester (ME) or sodium salt of the same bile acid (MKHNa), 30 minutes before cardioactive drug infusion. The infusion rate of cardioactive drugs was 0.2 ml/min, except for verapamil (0.1 ml/min). The events observed on ECG recordings were the first myocardial reaction to drug infusion, the second longer-lasting reaction (observed as more extended extrasystoles, decrease in intensity of the QRS complex, or changes in heart rate frequency), and toxicity effect. In the control animals, adrenaline induced a decrease in heart rate frequency at a dose of 0.094 mg/kg, while with stevioside-pretreated rats this effect appeared significantly earlier (at a dose of 0.018 mg/kg). No toxic effect of adrenaline was observed, either in control or stevioside-pretreated group. Bile acids caused no changes in myocardial reaction to adrenaline. Only in the group of animals that received MKHNa, a significant decrease in the QRS complex was observed. Finally, the infusion of stevioside to intact animals at doses of 45 and 55 mg/kg caused no significant changes in the ECG patterns. The myocardial reaction to metoprolol remained unchanged in rats of all groups when compared with controls except for a mild decrease in heart rate frequency. Stevioside induced/produced a significant increase in myocardial sensitivity to verapamil, but no toxic effect was observed in any of the cases. A similar conclusion also holds for the interaction with MKHNa, whereas ME caused an increase in the toxicity of verapamil.

Joint effect of commercial preparations of Stevia rebaudiana Bertoni and sodium monoketocholate on glycemia in mice.

A study was made of the combined effect of two commercial products of Stevia rebaudiana Bertoni and sodium monoketocholate (mkc) on blood glucose concentration in mice. One group of animals was treated four days with mkc, 4 mg/kg, s.c., second with 200 mg/kg, i.p., of Stevita (Stevita Co, INC, Arlington, Texas) (stevia), third with 20 mg/kg, i.p., of Clear Steviosides Liquid (Stevita Co, INC, Herbal supplement, Brazil) (stevioside), fourth with the combination of stevia and mkc, and the fifth with stevisode and mkc. Blood glucose concentration was measured before treatment, after the first and fourth dose, as well as after subjecting animals to glucose-tolerance test (500 mg/kg, p.o.) or provoking glycemia by injecting adrenaline (0.2 mg/kg, s.c.). It was found that one dose of stevioside combined with mkc caused a significant increase of glycemia with respect of mkc alone and control (10.80:7.90:8.01). However, when repeated four days, the same pretreatment resulted in a significant decrease of glycemia compared with single-dose pretreatment (10.80:7.20). The increase in glycemia with the mice that received four doses of stevioside and mkc and then were subjected to glucose-tolerance test was significantly lower compared to that in mice that were pretreated four days only with mkc before receiving glucose (6.33:7.80). Analogous difference was observed between the animals given mkc alone and mkc plus stevioside after injecting adrenaline (13.33:10.54). As for the interaction of mkc and stevia it was found that the combined pretreatment yielded lower values of glycemia compared with that measured after treatment with stevia alone (6.40:7.82).

Glucose concentration in the blood of intact and alloxan-treated mice after pretreatment with commercial preparations of Stevia rebaudiana (Bertoni).

The study was concerned with the effect of mice pretreatment with two commercial products of Stevia rebaudiana Bertoni on the blood glucose concentration. One group of mice was pretreated four days with 200 mg/kg of Stevita (Stevita Co, INC, Arlington Texas) (stevia) and the other with 20 mg/kg of Clear Steviosides liquid (Stevita Co, INC, Herbal supplement, Brazil) (stevioside), whereas the animals of control group received at the same time physiological solution. Blood glucose concentration was measured before pretreatment and four days after that. The changes in glucose level were provoked by glucose-tolerance test (500 mg/kg, p.o.) and subcutaneous injection of adrenaline (0.2 mg/kg). The same procedure of measuring blood glucose was applied on the mice with alloxan-induced diabetes mellitus (two doses of 100 mg/kg with a 24-hour interval). Blood glucose levels in mice pretreated with stevia and stevioside were lower compared with control (7.82:6.82:8.01). Also, a smaller increase in this parameter compared to control was registered with pretreated mice in the glucose-tolerance test, pretreatment with stevioside being again more effective (8.68:6.36:5.82). Pretreatment with stevioside caused no significant increase in blood glucose concentration after administering adrenaline, which was not the case with the animals pretreated with stevia and control. Pretreatment with stevia, and to a greater extent with stevioside, protected test animals from the toxic action of alloxan compared with controls.

3Alpha,7alpha-dihydroxy-12-oxo-5beta-cholanate as blood-brain barrier permeator.

The aim of the study was to test the efficacy of 3alpha,7alpha-dihydroxy-12-oxo-5beta-cholanate as a blood-brain barrier (BBB) permeator by examining its effect on quinine uptake into the central nervous system in rats, analgesic action of morphine, and on the sleeping time induced by pentobarbital. The obtained results indicate that sodium 3alpha,7alpha-dihydroxy-12-oxo-5beta-cholanate can be considered as modifier of BBB permeability, as it exhibited a promoting effect in all three tests. In the test of quinine uptake, methyl ester of 3alpha,7alpha-dihydroxy-12-oxo-5beta-cholanoic acid (included in the study for comparison) did not show a promoting effect, which can suggest its specific action.

[Use of antibiotics in general practice and at the Clinic for Infectious Diseases]. / Upotreba antibiotika u opstoj praksi i na klinici za infektivne bolesti.

INTRODUCTION: Optimal pharmacotherapy includes utilization of the right drug, at the right time, right duration of therapy and adequate dosage. This study analyzed utilization of antimicrobial drugs at the Clinic of Infectious Diseases of the Clinical Center Novi Sad and in outpatients of the Outpatient General Service of the Health Center Novi Sad-Liman. MATERIAL AND METHODS: Utilization of anti-infective agents was examined according to Anatomic-Therapeutic-Chemical Classification (group J). Drug utilization data were presented in Defined Daily Doses at the Clinic of Infectious Diseases of the Clinical Center Novi Sad in Defined Daily Doses per 100 bed-days, and in the Outpatient General Service of the Health Center Novi Sad-Liman in Defined Daily Doses/1000 inhabitants per day. RESULTS: At the Clinic of Infectious Diseases of the Clinical Center Novi Sad penicillins susceptible to beta-lactamase were established as most frequently used (39.33%) namely: benzylpenicillin (32.18%), quinolone antibacterial agents, ciprofloxacin (12.44%) and cephalosporins, cephalexin (8.25%). In the Outpatient General Service of the Health Center Novi Sad-Liman most frequently used were extended-spectrum penicillins (24.20%) namely: tetracyclines, doxycycline (18.98%), amoxicillin (18.27%), macrolides, roxithromycin (17.56%). At the Clinic of Infectious Diseases of the Clinical Center Novi Sad the decision on using antibiotics and establishing whether it was bacterial or virus infection in 92.13% cases was made on the basis of following analyses: throat and nasal swabs, urine culture, virus complement-binding reaction. In Outpatient General Service of the Health Center Novi Sad-Liman it was done only in 18.46%. CONCLUSION: Although treatment performed based on clinical picture and experience usually proves to be correct, antibiotic prescription policy should include antibiograms to provide optimal treatment and decrease the degree of resistance. Thus, medicine would be considered an exact science and it should be one of its goals of the 21st century.