Expression of Ghrelin and GHSR-1a in Long Term Diabetic Rat's Kidney

The aim of this work was to study the relative ghrelin and growth hormone secretagogue receptor (GHS-R)1a gene expression in the kidney of long-term diabetic rats. Forty male Wistar albino rats were divided into four groups: C- control group, DI- one month diabetic rats group, DII- two months diabetic rats group, and DIII- three months diabetic rats group. Diabetes was induced by streptozotocin STZ (40mg/kg i.p). The rats were decapitated under ketamine anesthesia and their kidney tissues were removed. Tissue GHS-R mRNA levels, ghrelin expression, and histopathological damage scores were compared. Dilatation in the distal tubules, epithelial desquamation into the lumen of the tubules and transparent tubules showing glycogen vacuolation were observed in all the diabetic groups. Ghrelin immunoreactivity was significantly higher in group DI compared to group C, whereas in groups DII and DIII, ghrelin immunoreactivity was similar with group C. GHSR-1a mRNA level in group DIII was significantly lower than in group C. As a result, ghrelin immunoreactivity increased at the beginning of diabetes; however, with increase in the duration of diabetes ghrelin immunoreactivity approached to the control values. The expression of GHSR-1a mRNA decreased with increase in diabetes duration. It seemed that down-regulation of GHSR-1a contributed to the renal damage induced by long-term diabetes

H2O2'nin daha koroner arter düz kasında gevşetici etki mekanizmaları

Bu in vitro çalışmada, reaktif oksijen türlerinden hidrojen peroksid (H2O2) in dana koroner arterindeki etkileri ve bu etkilerde K+ kanallarının, siklooksijenaz, nitrik oksid sentaz ve Na+,K+'a bağımlı ATPaz enzimlerinin rolü araştırılmıştır. Arterlerden elde edilen şeritler, %95 O2 -%5 CO2 karışımı ile gazlandırılan, 37 °C'de Krebs-Henseleit solüsyonu içeren 25 ml hacminde organ banyosu içine alındı. Endotelli ve endotelsiz dokularda H202'nin bazal tonus üzerine etkisi araştırıldı. Çalışmanın diğer bir bölümünde dokular U46619 (3.10"7M) ile kasıldı ve banyolara kümülatif tarzda H2O2 (10"7 - 10"2M) ilave edildi. Bu prosedür H2O2 ilavesinden önce apamin (İO"6^, karibdotoksin (10"7M), TEA (İOİVİ), glibenklamid (KT^M), indometazin (10"5M), L-NAME (İO"4^ ve uvabain (10"5M) ile 20 dakika süreyle inkübe edilen dokularda tekrarlandı. Her bir gruba bu ajanlardan yalnız biri uygulandı. H2O2 endotelli ve endotelsiz dokuların bazal tonusunu değiştirmedi. U46619 ile kasılan dokularda ise doza bağımlı tarzda gevşeme cevaplan oluşturdu. Endotel tabakası sağlam olan ve apamin, karibdotoksin ve TEA ile inkübe edilen dokularda H2O2 için hesaplanan maksimum gevşeme cevaplan ve pICso değerleri ile endotelsiz (kontrol) dokulardan alınan değerler arasında anlamlı bir fark bulunmadı. Glibenklamid, indometazin, L-NAME ve uvabain ile inkübe edilen dokularda ki değerler ise endotelsiz dokulardan alınan değerlere göre anlamlı olarak farklı idi. Bu sonuçlar H^Oî'nin dana koroner arter düz kasında oluşturduğu gevşeme cevaplarında Katp tipi K+ kanallarının ve ayrıca Na+,K+'a bağımlı ATPaz, siklooksijenaz ve NOS enzimlerinin aktivasyonunun rol oynadığını göstermektedir.In this in vitro study; the effects of H2O2, a reactive oxygene specie, on bovine coronary artery and roles of K+ channels, cyclooxygenase, nitric oxide synthase and Na+-K+-ATPase enzymes on these effects were investigated. Strips from arteries were mounted in 25 ml organ baths containing Krebs-Henseleit Solution at 37 °C aerated with %95 02 and %5 C02. Effects of H202 on basal tone of tissues with and without endothelium were investigated. In an other part of study, tissues were contracted with U46619 (3. 10"7 M) and cumulative H202 (10"7-10*2M) was added to the organ baths. This procedure was repeated on tissues incubated with apamin (lO"6^, charybdotoxin (10"7M), tetraethylammonium (TEA, KT^M), glibenclamide (KT^M), indometasine (10'5M), N^mtro-L-arginine methyl ester (L-NAME, 10"^) and ouabaine (105 M). Each group of tissue was incubated with only one of these agents. H202 did not affect basal tone of tissues with and without endothelium but relaxed tissues contracted with U46619 in concentration dependent manner. In tissues with endothelium and in tissues incubated with apamine, charybdotoxine and tetraethylammonium, Emax values and pICso values of H202 were not different significantly from values obtained from tissues without endothelium (control tissues). However values obtained from tissues incubated with glibenclamide, indometasine, L-NAME and ouabaine were different significantly from values obtained from tissues without endothelium. These results indicate that ATP-sensitive potassium channels and Na+-K+-ATPase, cyclooxygenase and nitric oxide synthase enzymes plays role in the relaxant effects of H202 on bovine coronary artery smooth muscle

Potassium induced dilation in bovine coronary artery involves both inward rectifier potassium channels and Na+/K+ ATPase

Increases in extracellular potassium (K+) concentration (up to 20 mM) cause dilation in some blood vessels. This may be particularly important in myocardial ischemia because in this condition K+ is released from ischemic cells. In this study, we investigated mechanisms of effect of increased K+ concentration on the tone of isolated bovine coronary artery. Bovine coronary arteries were isolated and mounted in organ baths for isometric tension recording. After an equilibration period, arteries were contracted with serotonin (1 mu M). When serotonin contraction reached a steady-state, K+ concentration of organ baths was increased from physiological levels to 10 mM, 14 mM, 18 mM or 22 mM in four groups of the arteries. After a washout period, this procedure was repeated in presence of ouabain, a blocker of Na+/K+ ATPase or a K+ channel blocker (tetraethylammonium, 4-aminopyridine, glibenclamide or barium). Increasing K+ concentration of the organ baths to 10 mM, 14 mM and 18 mM caused dilation in the arteries. Ouabain abolished the dilation and barium (a blocker of inward rectifier K+ channels) inhibited the dilation significantly

Antinociceptive Effect of Mirtazapine in Rats with Diabetic Neuropathy

INTRODUCTION: To evaluate the antinociceptive effect of mirtazapine and the mechanisms mediating this effect in neuropathic pain in rats with diabetes. METHODS: The experiments were performed in Sprague Dawley rats using a hot-plate device. Streptozotocin (STZ) was administered to the rats after taking control measurements. Rats with a blood glucose level of 240 mg/dL or above in the blood specimen obtained from the tail vein 3 days after STZ administration were considered as being diabetic. Three weeks after STZ administration, the hot-plate test was performed. Compared with the control measurements, rats that exhibited >20% decrease in the second hot-plate test measurements were considered to have developed neuropathy. Drugs [mirtazapine, naloxone (opioidergic antagonist), metergoline (serotonergic antagonist), and BRL44408 (adrenergic antagonist)] and drug combinations were administered to those rats that developed neuropathy. After administrating the drugs or drug combinations, the third hot-plate test was performed. RESULTS: Mirtazapine at doses of 10 and 15 mg/kg exhibited a significant antinociceptive effect. Naloxone, metergoline, or BRL44408 alone did not cause an antinociceptive effect. However, combinations of these drugs with mirtazapine (15 mg/kg) significantly decreased the antinociceptive effect of mirtazapine. CONCLUSION: It is suggested that mirtazapine has a significant antinociceptive effect in diabetic neuropathy and that opioidergic, serotonergic, and adrenergic systems have roles to play in this effect

Antinociceptive Effect of Mirtazapine in Rats with Diabetic Neuropathy

Introduction: To evaluate the antinociceptive effect of mirtazapine and the mechanisms mediating this effect in neuropathic pain in rats with diabetes

Protective effect of propolis on methotrexate-induced kidney injury in the rat

Objectives Propolis is a potent antioxidant and a free radical scavenger. Pharmacological induction of heat shock proteins (HSPs) has been investigated for restoring normal cellular function following an injury. In this study, effect of propolis on HSP-70 expression in methotrexate-induced nephrotoxicity and direct preventive effect of propolis in this toxicity were investigated. Material and methods A total of 40 male Wistar albino rats were divided into four groups: Group 1 was the untreated control. On the eighth day of the experiment, groups 2 and 3 received single intraperitoneal injections of methotrexate (MTX) at 20mg/kg. Groups 3 and 4 received 100mg/kg/day propolis (by oral gavage) for 15 d by the first day of the experimental protocol. Then the rats were decapitated under ketamine esthesia and their kidney tissues were removed. HSP-70 expression, apoptosis, and histopathological damage scores were then compared. Results MTX caused epithelial desquamation into the lumen of the tubules, dilatation, and congestion of the peritubular vessels and renal corpuscles with obscure Bowman's space. The number of apoptotic cells (p=0.000) and HSP-70 (p=0.002) expression were increased in group 2. Propolis prevented the rise in number of apoptotic cells (p=0.017), HSP-70 (p=0.000) expression, and improved kidney morphology. Conclusions It was found that methotrexate gives rise to serious damage in the kidney and propolis is a potent antioxidant agent in preventing kidney injury

Acute Respiratory Distress due to Antipsychotic Drugs

We report a 36-year-old male schizophrenic patient who was treated with risperidone for a long time. Because of an acute psychotic reaction, haloperidol, chlorpromazine and olanzapine were administered additionally. After administration of these drugs, he developed acute respiratory distress that caused his death. We discuss the cause of this respiratory distress and conclude that it might be due to acute laryngeal dystonia caused by these antipsychotic drugs. Antipsychotic drug-induced laryngeal dystonia is rarely reported but it is a life threatening side effect. All physicians dealing with antipsychotic drug therapy must be aware of acute laryngeal dystonia, and an antiparkinsonian agent should be administered immediately