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Streptozotocin (STZ) is commonly used to induce diabetes mellitus in experimental animal studies on peripheral diabetic neuropathy (PDN). Animals with STZ model of diabetes commonly develop changes in test stimulus-evoked pain behavior. However, it is still unclear whether rats with STZ model of diabetes have ongoing pain. Here we assessed whether STZ-induced diabetes induces ongoing pain-like behavior in male rats using conditioned place-preference (CPP) paradigm. CPP was tested in the fourth week of diabetes by pairing one chamber of the CPP device with vehicle and another chamber with either pregabalin (an established analgesic; 30 mg/kg i.p.; n = 9) or Chembridge-5861528 (a TRPA1 channel antagonist; 30 mg/kg i.p.; n = 9). After drug-pairings, the animals were allowed to choose which chamber they preferred. Mechanical sensitivity was assessed with monofilaments and chemonociception in the skin by determining mustard oil-induced pain behavior. Diabetic animals developed in two weeks mechanical hypersensitivity that changed into hyposensitivity by the fourth week. Mustard oil-induced sustained pain was reduced by the 4th week. After 4 weeks of diabetes, neither pregabalin nor the TRPA1 antagonist induced a significant overall change in the median CPP, although both drugs significantly reduced median withdrawal responses evoked by noxious mechanical stimulation. Pregabalin-induced CPP, however, had a significant positive correlation with the sustained pain behaviour induced by topical mustard oil. In conclusion, the present results suggest that the response to topical mustard oil may predict ongoing pain-like behavior in the STZ model of diabetes.Sitagliptin (SIT) is an antidiabetic used worldwide to ameliorate the hyperglycemia and insulin insensitivity induced dysmetabolism. In this study, we investigated the effect of sitagliptin and vitamin E on metabolic dysfunction in high-fat diet (HFD) fed rats. Sixty-four male rats were allocated into 8 groups (n = 8) as follow; control, control + vitamin E, control + sitagliptin, control + sitagliptin + vitamin E, HFD, HFD + vitamin E, HFD + sitagliptin and HFD + sitagliptin + vitamin E. Control groups were fed with chow diet for 15 weeks, while HFD groups were fed with HFD for the same duration. Vitamin E and sitagliptin were administered in the last 4 weeks of the study. At the end of the 15th week, body weight, liver weight/body weight ratio, weight gain, glucose, lipid profile, liver enzymes, adiponectin and pro-inflammatory cytokines as interleukin 6 (IL-6), high sensitive C reactive protein (hs-CRP) and tumour necrosis factor-α (TNF-α) were measured. Additionally, gene expressions of senescence marker protein 30 (SMP30), Bcl-2, and Bax were measured. Total antioxidant capacity (TAC) and thiobaribituric acid reactive substances (TBARS) were assayed. HFD increased TBARS, IL-6, hs-CRP and TNF-α significantly and decreased TAC and adiponectin. Sitagliptin produced a comparable result through increasing adiponectin, sitagliptin alone or in combination with vitamin E increased the TAC, and gene expression of SMP30 and Bcl-2 and decreased TBARS with downregulation of the overexpressed Bax. Vitamin E, as a natural antioxidant, ameliorates the oxidative stress with insignificant change in lipid profile and inflammatory cytokine levels. Concomitant sitagliptin and vitamin E reduced the hepatic dysfunction induced by HFD.Conjugated linoleic acids (CLA) have been extensively advertised as dietary supplements to reduce fat and increase muscle mass. However, the role of CLA in glycogen metabolism is still largely unknown. The aim of this study was to assess the effect of CLA on glycogen synthesis in vitro (CCL 136 cell line human) and CLA in vivo (C57BL/6J mice). The materials used were the CCL 136 muscle cell line and muscles of female C57BL/6J mice (n = 52), housed at animal laboratory facility and feed with "MURIGRAN", a standard feed prepared for rodents (Agropol, Poland). Chemically pure fatty acids were added to soybean oil. CLA isomers (c9,t11 CLA, t10,c12 CLA, and as a mixture (11)) were administered with feed. Supplementation in mice started at week 6 of age and lasted for 4 weeks. Methods used in the study were real time- PCR - quantification of gene expression, Western blot glycogen synthase kinase-3 (GSK3α 9) and glycogen synthase (GS) protein, glycogen staining by PAS. Quantitative determination of glycogen by spectrophotometry and intracellular reactive oxygen species was measured the intracellular oxidation of dichloro-dihydro-fluorescein diacetate (DCFH-DA). In vitro data showed that GS and GSK3 expression was lower in cells cultured with different CLAs and a mixture of CLAs. GS gene expression was significantly decreased in cells cultured with c9, t11 CLA (P less then 0.04) and t10, c12 CLA (P less then 0.05) as well as the mixture of both isomers. The GSK3α gene expression was reduced in cells cultured with a mixture of CLA (P less then 0.02), whereas phosphorylation of GSK3α increased in cells cultured with c9, t11 CLA GSK3α (P less then 0.05). In vivo data showed a reduction in the glycogen concentration among mice fed a diet containing t10, c 12 CLA and a mixture of CLA isomers. We conclude that both CLA isomers can affect the synthesis of glycogen in muscle cells through the regulation of GS and GSK3α gene expression.Vitamin K antagonists (VKA) continue to be the standard of long-term anticoagulation. Direct oral anticoagulants(DOAC) are increasingly used. In many trials DOAC were at least as effective as VKA. In this study we evaluate the bleeding profiles, frequencies and etiologies of patients receiving DOAC versus VKA in a real-life setting. All patients presenting with suspected gastrointestinal bleeding (GIB) in the emergency department of the University Hospital Erlangen in one year were enrolled in this study. They were looked up for the intake of either DOAC (dabigatran, rivaroxaban and apixaban) or VKA. The results showed that 406 patients with suspected GIB were admitted to the emergency unit of the University Hospital Erlangen. In 228 of those patients GIB could be verified (56.2%). Fifty four of those patients (23.7%) were administered either VKA or DOAC. In 35 of those 54 patients (64.8%) GIB was classified as 'major bleeding'. Cryptotanshinone order In 27 patients with administration of VKA upper GIB was recorded and lower GIB was detected four times.
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