Ivan Mikov

Gliclazide reduces MKC intestinal transport in healthy but not diabetic rats

SummaryThe aim is to investigate the influence of the antidiabetic drug gliclazide on the ileal permeation of the semisynthetic bile acid, MKC, in tissues from healthy and diabetic rats. Sixteen Wistar rats (350±50 g) were randomly allocated into four groups (4 rats per group, 8 chambers per rat i.e. n=32) two of which were made diabetic (given alloxan i.v.30 mg/kg). Group 1 was used to measure the permeation of MKC (50 μg/ml) alone (control) while group 2 to measure MKC permeation in the presence of gliclazide (200μg/ml). The diabetic groups 3 (gliclazide) and 4 (MKC+gliclazide) were treated in the same way. Rats were sacrificed and tissues were mounted into the Ussing chamber for the measurement of MKC mucosal to serosal (absorptive) and serosal to mucosal (secretory) fluxes. In healthy tissues, gliclazide reduced MKC absorptive flux (p<0.01) and increased its secretory flux (p<0.01). In diabetic tissues, gliclazide had no effect on either the absorptive or the secretory fluxes of MKC. The lack of effect of gliclazide on MKC permeation in diabetic tissues suggests the absence or suppressed drug transporters. Furthermore, gliclazide inhibition of MKC absorptive flux and induction of MKC secretory flux in healthy tissues may result from the selective inhibition of an efflux drug transporter.

Vitiligo In Children

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Cefotaxime pharmacokinetics after oral application in the form of 3α,7α-dihydroxy-12-keto-5β-cholanate microvesicles in rat

SummaryThe aim of ths study was to investigate the pharmacokinetics of cefotaxime sodium (CEF) pharmacokinetics after oral application in the form of sodium 3α,7α-dihydroxy-12-keto-5β-cholanate (MKC) microvesicles (MV) in rat. Thirty Male Wister rats were divided into six groups (n=5 per group). Groups were treated orally with: i. CEF (15 mg/kg) saline solution (15 mg/kg); ii. CEF (15 mg/kg) saline solution with MKC (2 mg/kg); iii. CEF saline solution mixed with blank microvesicles; iv. CEF (15 mg/kg) encapsulated in microvesicles with saline solution; v. CEF saline solution (15 mg/kg) mixed with blank MKC microvesicules; vi. CEF (15 mg/kg) encapsulated in MKC microvesicules with saline solution. Data were analyzed using noncompartmental model. CEF oral bioavailability was increased twofold when coadministered with MKC and when encapsulated in microvesicles and ninefold when encap-sulated in MKC microvesicles compared to the same CEF dose administered orally as saline solution. The increased bioavailability of CEF resulting from CEF encapsulation in microvesicules with MKC suggests that this formulation can extend the application of CEF from parenteral only to oral application.

Effect of Simultaneous Exposure to Benzene and Ethanol on Urinary Phenol Excretion in Mice

Benzene has been widely used as a solvent, but its use is declining in most developed countries because it is a well established human carcinogen. An association between occupational exposure to benzene and health effects such as aplastic anaemia and leukaemia has been reported in studies of workers in various industries. For many solvent uses benzene has been replaced by other less toxic organic solvents and is considered a toxic impurity in other industrial solvents, but it is still used as a starting material in numerous chemical syntheses. In addition to industrial sources, benzene is present in the environment as a component of cigarette smoke and automobile emissions. Benzene induces hematotoxicity as a result of chronic exposure. Acute exposure to benzene causes neurotoxic and hepatotoxic effects. Toxic effects of benzene, chronic as well as acute, are the consequence of the unknown reactive metabolite produced by cytochrome P-450. Benzene is metabolized mainly by ethanol inducible cytochrome P-4502E1 (CYP2E1) in animal and human liver microsomes. Ethanol is consumed worldwide in tremendous amounts and is an effective inducer of hepatic xenobiotic metabolism, especially involving pathways accomplished by the isoform CYP2E1 of cytochrome P-450. Therefore, whenever xenobiotics that are substrates of CYP2E1, such as many organic solvents, are taken in by an individual who is also chronically consuming ethanol, the accelerated metabolism of these agents has to be considered. In contrast to the long-term consumption of ethanol, which induces the hepatic metabolism of xenobiotics, short-term consumption inhibits their metabolism because of direct competition for CYP2E1. Ethanol, when given to a living body, exerts dual effects on the xenobiotic metabolizing enzymes, i.e., inhibition and stimulation. Which one is more predominant over the other depends on the time that has elapsed after ethanol ingestion. In an early period when ethanol exists in the body in high concentrations, it may preferentially act as an inhibitor . In this study, effect of simultaneous exposure to benzene and ethanol on benzene metabolism in mice were investigated by measuring the concentration of phenol, the main metabolite of benzene.

Hypoglycemic effect of herbicide 2,4-dichlorophenoxyacetic acid (2,4-D).

Herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), a synthetic auxin which promotes uncontrolled plant growth is widely used. The aim of our study was to investigate, using an experimental model, the effect of herbicide 2,4-D on liver function tests, enzyme a amylase and glucose blood level. BALB/C mice were treated i.p. with the herbicide (30 mg/ kg 2,4-D) for four consecutive days. Twenty-four hours after the last injection, the treated and the control animals were weighed and sacrificed for biochemical analysis: haematocrit, glucose blood level, serum activities of enzymes alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, and a amylase, as well as liver reduced glutathione. Herbicide 2,4-D significantly decreased glucose blood level in mice. There were no changes in liver function tests or activity of enzyme a amylase. In this study on mice we confirmed the results obtained in the previous study, which showed a hypoglycemic effect of herbicide 2,4-D on agricultural workers. To elucidate the mechanism of this effect, a further research is needed.

Incidence and outcomes of breech presentation at term in newborns with congenital postural deformities.

The increased incidence of congenital postural deformities among newborns with breech presentation may be associated with causes of breech presentation rather than the presentation itself.

Effect of Simultaneous Exposure to Benzene and Ethanol on Urinary Thioether Excretion

Abstract The toxicity of benzene is not an issue of the past, especially in developing countries. Bone marrow toxicity is demonstrated among workers. In this study, the effect of simultaneous exposure to benzene and ethanol on benzene metabolism in mice was investigated by measuring the excretion of thioethers in urine. Urinary thioether excretion significantly decreased in the mice receiving both benzene and ethanol compared with the animals receiving benzene only. The assay of determining thioethers in urine samples in this study is a simple and low-cost method, thus suitable for routine use, especially in developing countries, not only for benzene, but also for other alkilating agents, which can be found during occupational exposure. Our results suggest that further research is needed to elucidate the mechanisms of decreased urinary excretion of thioether after simultaneous exposure to benzene and ethanol.

The Effect of Aminophylline on Quinidine Passage into the Central Nervous System of Rats

Background and Objective: There is significant interest in mutual influence of substances during their passage into the central nervous system (CNS). Quinidine is a drug which can achieve significant concentration in CNS and cause side effects and aminophylline is a drug with possibility to change distribution of drugs in CNS. Thus the aim of this work was to study the effect of aminophylline on the transition of quinidine through the bloodbrain barrier into the central nervous system. Material and Methods: The experiments were carried out on Wistar rats, which received quinidine in the form of the retrograde intra-arterial bolus injection into the right axillary vein. The control group of animals received subcutaneously physiological solution 30 min before the intra-arterial quinidine application, whereas the test group animals also received subcutaneously aminophylline 30 min before quinidine application. The rats were sacrificed by decapitation in specified time intervals in order to determine quinidine concentration in different parts of CNS. Results: There were no significant changes in serum quinidine levels by comparing the results of experimental group with those of the control group of animals. In all parts of CNS aminophylline pre-treatment caused significant decrease in CNS quinidine concentration. Conclusion: The results suggest that co-administration of aminophylline and quinidine, decreases quinidine concentrations in the CNS of rats.