Nesfatin-1 alleviates extrahepatic cholestatic damage of liver in rats

Obstructive jaundice (OJ) can be defined as cessation of bile flow into the small intestine due to benign or malignant changes. Nesfatin-1, recently discovered anorexigenic peptide derived from nucleobindin-2 in hypothalamic nuclei, was shown to have anti-inflammatory and antiapoptotic effects. This study is aimed to investigate the therapeutic effects of nesfatin-1 on OJ in rats. Twenty-four adult male Wistar-Hannover rats were randomly assigned to three groups: sham (n = 8), control (n = 8), and nesfatin (n = 8). After bile duct ligation, the study groups were treated with saline or nesfatin-1, for 10 days. Afterward, blood and liver tissue samples were obtained for biochemical analyses, measurement of cytokines, determination of the oxidative DNA damage, DNA fragmentation, and histopathologic analyses. Alanine aminotransferase and gamma-glutamyl transferase levels were decreased after the nesfatin treatment; however, these drops were statistically non-significant compared to control group (p = 0.345, p = 0.114). Malondialdehyde levels decreased significantly in nesfatin group compared to control group (p = 0.032). Decreases in interleukin-6 and tumor necrosis factor-a levels from the liver tissue samples were not statistically significant in nesfatin group compared to control group. The level of oxidative DNA damage was lower in nesfatin group, however this result was not statistically significant (p = 0.75). DNA fragmentation results of all groups were similar. Histopathological examination revealed that there was less neutrophil infiltration, edema, bile duct proliferation, hepatocyte necrosis, basement membrane damage, and parenchymal necrosis in nesfatin compared to control group. The nesfatin-1 treatment could alleviate cholestatic liver damage caused by OJ due to its anti-inflammatory and antioxidant effects

Road for understanding cancer stem cells: model cell lines

There is increasing evidence suggesting that stem cells are susceptive to carcinogenesis and, consequently, can be the origin of many cancers. Recently, the neoplastic potential of stem cells has been supported by many groups showing the existence of subpopulations with stem cell characteristics in tumor biopsies such as brain and breast. Evidence supporting the cancer stem cell hypothesis has gained impact due to progress in stem cell biology and development of new models to validate the self-renewal potential of stem cells. Recent evidence on the possible identification of cancer stem cells may offer an opportunity to use these cells as future therapeutic targets. Therefore, model systems in this field have become very important and useful. This review will focus on the state of knowledge on cancer stem cell research, including cell line models for cancer stem cells. The latter will, as models, help us both in the identification and characterization of cancer stem cells and in the further development of therapeutic strategies including tissue engineering

Effect of hormone replacement therapy on plasma lipoproteins and apolipoproteins, endothelial function and myocardial perfusion in postmenopausal women with estrogen receptor-alpha IVS1-397C/C genotype and established coronary artery disease

Effect of hormone replacement (HRT) therapy on plasma lipoproteins and apolipoproteins, endothelial function and myocardial perfusion in postmenopausal women with estrogen receptor-alpha (ER-alpha) IVS1-397 C/C genotype and established coronary artery disease. Background/ Aims: Associations between various ER-a polymorphisms and clinical phenotypes have been studied, including lipid levels and coronary atherosclerosis. We studied 48 postmenopausal women to determine the effect of ER-a IVS1-397 polymorphism on the response to treatment with HRT. Methods: The study had a randomized, double-blind, placebo-controlled and crossover design. Patients were divided into two groups according to ER-alpha IVS1-397 polymorphism: CC genotype (n = 9); CT or TT genotype (n = 39). HRT was given continuously for 4 weeks, with 4-week washout periods between the treatment periods. Brachial artery Doppler and TI-201 scintigraphy were performed at the end of each treatment period. Results: HRT lowered total cholesterol, LDL-c and Apo-B levels from baseline values (all p < 0.05) and to a similar degree in CC and CT/TT genotype patients. HRT increased estradiol, HDL-c and Apo A-1 levels relative to baseline values, but to a greater degree in CC patients (p = 0.04, 0.05 and 0.04 by ANOVA, respectively). HRT increased peak forearm blood flow, brachial artery diameter during reactive hyperemia and endothelium-dependent dilation in both groups, but to a greater degree in CC patients (p = 0.03, 0.03 and 0.04 by ANOVA, respectively). Summed stress and rest scores were also more markedly reduced in CC patients (p = 0.04 and 0.05, respectively). The increase in estradiol levels was strongly correlated with the improvement in endothelium-dependent dilation (r = 0.66, p < 0.01), which in turn showed negative correlation with summed stress (r =-0.62, p < 0.01) and rest scores (r =-0.52, p < 0.05) in the CC genotype group. Conclusion: These data suggest that the improvement in endothelium-dependent dilation and the reduction in perfusion abnormalities by increasing estradiol levels with HRT in postmenopausal women with coronary artery disease may differ with respect to different genotypes, the effect being more prominent in those patients with ER-alpha IVS1-397 CC genotype. Copyright (c) 2006 S. Karger AG, Basel

Faktör V A4070G, Metilentetrahidrofolat redüktaz A1298C ve plazminojen aktivatör inhibitörü-1 4G/5G mutasyonlarının sebebi açıklanamayan gebelik komplikasyonlarındaki sıklığının saptanması ve yorumlanması

Tromboz yatkınlığı, kalıtımla ya da sonradan edinilen etkenlere bağlı olarak gelişen bir bozukluktur. Edinsel etkenlere maruz kalmanın önlenebilirliği ve patofizyolojinin açıklanmasında, çoğu zaman, tek bir grup etkenin yeterli olmaması, özellikle kalıtsal tromboz yatkınlığı ile araştırmaların ön plana çıkmasına neden olmuştur. Gebeliğe bağlı, nedeni açıklanamayan hipertansiyon, preeklampsi, eklampsi, intrauterin gelişme geriliği, intrauterin fötus ölümü, plasenta dekolmanı gibi gebelikle ilişkili komplikasyonlar, anne ve fötus ölüm nedenlerinin önemli bir bölümünü oluşturmaktadır. Bu komplikasyonların gelişiminde endotel işlev bozukluğu, vazokonstriksiyon, plasenta iskemisi ve pıhtılaşma artışının rol oynadığı, bu etkenlerin uterusla plasenta arasındaki dolaşımın yetmezliğine yol açtığı gösterilmiştir. Tromboza yol açan kalıtsal etkenlerden pıhtılaşma ve fibrin yıkım düzeneklerinde yer alan moleküllere ait kusurlar, gebelikle ilişkili bu bozukluklarda araştırılmaktadır. Bu çalışmada, tromboza yatkınlığı arttırdığı düşünülen kalıtsal etkenlerden, pıhtılaşma düzeneği içinde yer alan faktör V, metionin-homosistein döngüsünde görev yapan metilentetrahidrofolat redüktaz enzimi ve fibrin yıkımında düzenleyici görevi yapan plazminojen aktivatör inhibitörü-1 moleküllerine ilişkin kusurların, nedeni açıklanamayan komplikasyonlu ve sağlıklı gebelerdeki sıklığı, klinik ve demografik özelliklerle ilişkisi incelenmiştir. İlerleyen yıllarda, riskli gebeliklerin erken dönemlerinde, kalıtsal tromboz yatkınlığı etkenlerine yönelik koruyucu tedaviler uygulanmasının rutin hale gelebileceği öne sürülmektedir. Bu tip çalışmaların, bu konuya katkı yapması beklenmektedir. The Incidence and Interpretation of Factor V A4070G, Methylenetetrahydrofolate Reductase A1298C, and Plasminogen Activator Inhibitor-1 4G/5G Mutation Rates In Women With Complicated Pregnancies of Unknown Etiology Thrombophilia is a disorder, developing due to acquired or heritable factors. The preventable feature of acquired factors and the inefficiency of solely a group of etiologic causes, raise the importance of reserach on heritable factors of thrombophilia. Pregnancy complications with an unknown cause like pregnancy-induced hypertension, pre-eclampsia / eclampsia, intrauterine foetal death, intrauterine growth retardation and abruptio placentae are the major causes of maternal and foetal morbidity and mortality. Endothelial dysfunction, vasoconstriction, plasental ischemia, and increased coagulation are shown to be associated with the development of these complications by leading to utero-placental insufficiency. The association of defects in coagulation and fibrinolysis are currently being investigated in pregnancy complications with an unknown cause. In this study, in women with healthy and complicated pregnancies, the incidence of the defects of factor V of the coagulation cascade, methylenetetrahydrofolate reductase enzyme in methionine-homocysteine cycle, and plasminogen activator inhibitor-1 in fibrinolysis regulation and their relation to the clinical findins have been analysed. Preventive measures against heritable thrombophilic causes can be applied in management of pregnancies under risk, in the future. Such studies are expected to have additive effect on the knowledge about the subject

Oxytocin or Social Housing Alleviates Local Burn Injury in Rats

Background. Thermal injury may cause distant organ inflammation and multiorgan failure. Oxytocin (OT), a nonapeptide, modulates the immune and inflammatory processes. Materials and Methods. To investigate the effects of oxytocin on burn-induced tissue injury, Sprague-Dawley rats were subjected to a partial thickness burn. Immediately after burn, half of the burned rats were placed single in the cages, while others were caged in groups. All the rats then were treated with either OT (5 mu g/kg, s.c) or saline twice daily for 5 d. The control rats had no burn injury and received no treatments. On day 5, the rats were decapitated, tissue and serum samples were obtained to score the severity of damage and to assay TNF-alpha levels. Results. Burn trauma resulted in oxidative ileal damage, as evidenced by increased apoptotic rate, increased neutrophil recruitment, and enhanced lipid peroxidation. OT treatment depressed the TNF-a level and alleviated dermal degeneration, while attenuating ileal damage. Although a higher degree of skin damage was observed in the animals kept isolated following burn injury, keeping the rats in groups did not affect the level of TNF-a or the severity of dermal or ileal injury, but abolished the burn-induced elevations in ileal lipid peroxidation and myeloperoxidase activity. Moreover, OT treatment reduced the ileal apoptosis when applied to rats housed in groups, while the treatment did not alter apoptotic ratio in the isolated rats. Conclusion. Oxytocin can be considered as a potential agent in treating burn-induced distant organ injury. (C) 2010 Elsevier Inc. All rights reserved

Oxytocin ameliorates skin damage and oxidant gastric injury in rats with thermal trauma

Transient splanchnic vasoconstriction following major burns causes oxidative and/or nitrosative damage in gastrointestinal tissues due to ischemia, which is followed by reperfusion injury. Oxytocin (OT), a hypothalamic nonapeptide, possesses antisecretory and antiulcer effects, facilitates wound healing and is involved in immune and inflammatory processes. To assess the possible protective effect of oxytocin (OT) against burn-induced gastric injury, Sprague-Dawley rats (250-300 g) were randomly divided into three groups as control (n = 8), OT-treated burn (n = 8) and saline-treated burn (n = 8) groups. Under anesthesia, the shaved dorsal skin of rats was exposed to 90 degrees C water for 10 s to induce burn injury covering 30% of total body surface area in a standardized manner. Either oxytocin (5 mu g/kg) or saline was administered subcutaneously immediately after and at 24 h following burn, and the rats were decapitated at 48 h. Serum samples were assayed for TNF-alpha, and stomach was taken for the determination of malondialdehyde (MDA), myeloperoxidase (MPO) activity, DNA fragmentation rate (%) and histopathological examination. MDA and MPO were assayed for products of lipid peroxidation and as an index of tissue neutrophil infiltration, respectively. When compared to control group, burn caused significant increases in gastric MDA and MPO activity and increased microscopic damage scores at 48 h (p < 0.001). Oxytocin treatment reversed the burn-induced elevations in MDA and MPO levels and reduced the gastric damage scores (p < 0.001, p < 0.01), while TNF-alpha levels, which were increased significantly at 48th h after injury (p < 0.001), were abolished with OT treatment (p < 0.001). The results of this study suggest that oxytocin may provide a therapeutic benefit in diminishing burn-induced gastric inflammation by depressing tissue neutrophil infiltration and decreasing the release of inflammatory cytokines, but requires further investigation as a potential therapeutic agent in ameliorating the systemic effects of severe burn. (C) 2007 Elsevier Ltd and ISBI. All rights reserved