Prolonged cold storage diminishes the 5-hydroxytryptamine- and potassium chloride-mediated contractions of rat thoracic aorta.

Hypothermic preservation of the organ for transplantation causes vascular damage; therefore, the preservation of vascular function is important for the organs to function correctly after transplantation. The aim of the present study is to evaluate the influence of prolonged cold storage (72 hours) on vascular responses to 5-hydroxytryptamine (5-HT) and potassium chloride (KCl), each of which causes receptor-dependent and receptor-independent contractions, respectively. We also examined the protective roles of superoxide dismutase (SOD), L-arginine, the precursor of nitric oxide, iloprost, a synthetic analogue of prostaglandin I(2) with vasodilator functions, or endothelium removal for vascular responses. Endothelium-intact rings were prepared from the rat thoracic aorta, and stored at 4 degrees C for up to 72 hours in Krebs solution alone or Krebs solution that contains SOD, L-arginine or iloprost. The vascular responses were investigated daily. The Analysis of Variance (ANOVA) followed by Dunn test was used for statistical analysis. Being kept in cold in Krebs solution diminished the vascular responses to 5-HT and KCl. The presence of SOD in Krebs solution successfully prevented the decline in these responses, while iloprost or L-arginine partially restored them. In the endothelium-denuded rings, the 5-HT-induced contraction remained protected after 72 hours, whereas the KCl-induced contraction was partially restored. These results indicate that cold preservation declines the 5-HT and KCl-induced vascular responses, which can be partially prevented by iloprost or L-arginine, and can be restored by endothelium removal or SOD. Therefore, superoxide anion and endothelium-derived factors contribute to the decline in the contracting function of the aorta during prolonged cold storage.

Examination of the rescue effects of folic acid on derangement of the tubo-ovarian ultrastructural architecture caused by methotrexate.

The purpose of this examination was to observe the effects of folic acid (FA) on methotrexate (MTX)-induced derangements in the fallopian tubes. Investigators in this study sought to explore whether MTX-induced dysfunction in the fallopian tubes would be lessened by the addition of FA to MTX treatment. For this study, 18 albino Wistar rats were randomly divided into 6 groups, each of which comprised 3 rats; 0.1 mg/kg FA, 1 mg/kg MTX + 0.1 mg/kg FA, 5 mg/kg MTX + 0.1 mg/kg FA, 1 mg/kg MTX, and 5 mg/kg MTX were given to groups 2, 3, 4, 5,and 6, respectively; group 1 was the control group. After MTX injection, fallop-ian tube samples from all groups were prepared for examination under electron microscopy. The findings observed in groups 1 and 2 were similar. The level of cellular destruction was greater with the higher doses of MTX without FA; in particular, loss of cilia in the epithelium was prominent in groups 5 and 6. However, there was less cellular destruction observed in groups 3 and 4 than in groups 5 and 6. As a result, the addition of FA should not be overlooked, even when a single-dose MTX regimen is chosen for the treatment of patients with unruptured ectopic pregnancy.

The effect of systemic leptin administration on aorta smooth muscle responses in diabetic rats.

Leptin produces effects in central nervous system and peripheral tissues via its specific receptors. Leptin also stimulates nitric oxide release in a concentration-dependent manner. In this study, our aim was to test the hypothesis that whether leptin has a modulatory role on endothelium or smooth muscle function in streptozotocin (STZ)-induced diabetic rats. Wistar-Albino rats were divided into four groups: 1 -- Control, 2 -- Diabetic, 3 -- Control + leptin and 4 -- Diabetic + leptin. Experimental diabetes was produced by intraperitoneal injection of a single dose of STZ (55 mg/kg). Diabetes was determined by increased fasting blood glucose level on the 7th day of the experiment. Leptin (0.1 mg/kg/day) was administered intraperitoneally for 5 days. At the end of the 5th day, thoracic aortas were isolated and phenylephrine (Phe)-induced contractions and acetylcholine (ACh)-induced relaxations of each group were estimated. In diabetic rats, Phe-induced contractility was increased (p < 0.05). Leptin pre-treatment increased the Phe-induced contractility significantly in aortic rings obtained from diabetic rats (p < 0.05). In normal rats, leptin administration produced only a slight and non-significant increase in Phe-induced contractions. Although the relaxant responses were decreased in diabetic rats, leptin administration enhanced the ACh-induced relaxation in both normal and diabetic animals significantly. As a conclusion; chronic leptin pre-treatment caused a significant increase both in Phe-induced contractions and ACh-induced Endothelial-Derived Relaxing Factor (EDRF)/Nitric oxide-mediated relaxations in the aortic rings isolated from streptozotocin-induced diabetic rats. This peptide hormone caused a significant increase in the relaxations obtained by ACh while not inducing a significant alteration in the contractile effect of Phe in control rats.

Effects of dexfenfluramine on serotonin levels of mice ileum, contractility, glutathione and malondialdehyde level.

UNLABELLED: Dexfenfluramine is one of the anorectic drugs that suppresses food intake which acts via inhibition of reuptake of serotonin into brain terminal. Gastrointestinal tract is the main source of peripheral serotonin which is involved in the regulation of gastrointestinal motility. During the use of anorectic drugs, the antioxidant defence is affected especially by reactive oxygen species. The purpose of this study to search: The effect of dexfenfluramine on serotonin levels of ileum and the effect of dexfenfluramine on ileal contractility and oxidative stress. MATERIALS AND METHODS: Twenty-two adult male Swiss-albino mice were divided two groups (1) Control, (2) Dexfenfluramine treated (i.p. twice a day 0.2 mg kg(-1) in 0.2 ml saline solution for 7 days). Animal body weights were recorded at the beginning and at the end of the experimental period. Ileum tissues contractile responses to different concentrations of KCl and acethycholine were recorded on polygraph. In the meantime ileal tissue malondialdehyde, a product of lipid peroxidation, and glutathione, endogenous antioxidant levels were assessed by spectrophotometric methods. Ileal tissue serotonin level determined by immunohistochemical method. Body weights decrease and ileal contractile response of acethycholine increased significantly by dexfenfluramine treatment. Meanwhile, ileum glutathione levels decreased and malondialdehyde levels increased in dexfenfluramine treated group. Immunohistochemical detection showed that ileal serotonin levels increased by dexfenfluramine treatments. As a conclusion, there is a relationship between increased ileal contractility and oxidant status in dexfenfluramine treated animals. These effects can be related by increased serotonin levels which is induced by dexfenfluramine in ileum.

Light and electron microscope examination of the effects of methotrexate on the endosalpinx.

OBJECTIVE: To examine the effects of increasing doses of methotrexate (Mtx) on the fallopian tubes. STUDY DESIGN: The study was carried out on 24 female rats (Albino Wistar type, 250-300 g). The rats were randomly divided into four groups of six. Different doses of Mtx were given to the rats by i.p. injection: 1mg/kg to those in group 1, 5mg/kg in group 2 and 10 mg/kg in group 3. Rats in group 4 received injections of physiological serum only and were treated as the control group. Ten days after the injection, the fallopian tubes of the rats were removed for examination separately by light and electron microscopy (EM) for comparison. RESULTS: Light microscopy showed that in group 1 the surface epithelial cells were normal and the lamina propria was infiltrated by numerous inflammatory cells with a prevalence of polymorphonuclear leucocytes. Findings in groups 2 and 3 were similar: the lamina propria was infiltrated with granulocytes in one specimen from each of the two groups, and granulocytes were also observed among epithelial cells. In the control group all surface structures were found to be in a normal condition. Electron microscopy showed cilial loss in the epithelial cells and central crystolysis in mitochondria in all group 1 specimens. Findings in groups 2 and 3 were similar. The cytoplasm of the epithelial cells seemed to be dense, there was prominent crystolysis (crystalloid formation) in the mitochondria, and vacuolisation (vacuole formation) in the cytoplasm seemed to be augmented. Cilial loss was prominent, and the basal membrane was irregular. Epithelial cell nuclei were in disorder. Lipid granules were observed extensively in epithelial cells. Eosinophils seemed to be dominant in connective tissues below the epithelium. In all control group specimens the epithelium seemed to be normal with all organelles in place; the condition of intercellular junctions, ciliated epithelium and all mitochondria also seemed to be normal, and the basal membrane was observed to be in order. CONCLUSION: In view of these findings, we conclude that the ultrastructural derangements resulting from administration of Mtx in doses in excess of 1mg/kg can cause a reduction in the surface epithelium's ability to make rhythmic lashing movements and can impair the patency of the fallopian tubes. All these disturbances could be involved to some degree in the causation of infertility and recurrent ectopic pregnancy. Therefore, the dosage of Mtx should be limited to use of the lowest effective dose to avoid these adverse effects.

Effect of glycerol on endothelium-derived factors in the vasculature of the rabbit kidney.

1. In the present study, endothelium-derived relaxing factor (EDRF/nitric oxide (NO)), conversion of big endothelin (ET)-1 to endothelin-1 (ET-1) and the role of reactive oxygen species were investigated in kidneys isolated from glycerol (GLY)-pretreated rabbits. 2. Acetylcholine (ACh)-induced vasodilation that is due to the release of EDRF/NO is significantly decreased, whereas big ET-1-induced vasoconstriction was increased in kidneys isolated from GLY-pretreated rabbits. 3. Pretreatment of rabbits with the xanthine oxidase inhibitor allopurinol and the NO precursor L-arginine reversed the inhibition of ACh-induced vasodilation due to GLY and protects the kidney vasculature. 4. Big ET-1, but not ET-1, responses were found to be significantly increased in kidneys isolated from GLY-pretreated rabbits. This increase is attributed to the higher conversion rate of big ET-1 to ET-1 because the ET-converting enzyme (ECE) inhibitor phosphoramidon, at a concentration of 10(-6) mol/L, causes an inhibition in the response to big ET-1 by 52.6% in normal kidneys, whereas this inhibition with the same concentration of phosphoramidon was found to be significantly decreased in kidneys isolated from GLY-pretreated rabbits. 5. The non-selective NO synthase inhibitor N(G)-nitro-L- arginine methyl ester (L-NAME) caused a significant potentiation in the vasoconstrictor response to ET-1 in normal isolated perfused rabbit kidneys. However, L-NAME did not alter the responses to ET-1 in GLY-pretreated kidneys. 6. These results indicate that accumulation of reactive oxygen species causes an inhibition in NO bioavailability. Increased conversion of big ET-1 to ET-1 may also contribute to the mechanism of vascular damage due to GLY.