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Diabetic neuropathy is a common complication of diabetes. It occurs in approximately 10?20% of patients with diabetes, or roughly 40?50% patients with diabetic neuropathy. However, the pathogenesis of diabetic neuropathic pain is still largely unknown. Several animal models have been used to study the underlying mechanisms for this complication. Some commonly used animal models include streptozotocin-induced rat and mouse models, diet/nutrition-induced models, combination of chemically- and nutrition-induced model, Zucker diabetic fatty rat model, type 1 insulinopenic BB/Wor and type 2 hyperinsulinemic diabetic BBZDR/Wor rat models, and transgenic/knock-out models. Even though the manifestations of diabetic neuropathic pain vary from thermal or chemical hyperalgesia, thermal or chemical hypoalgeia, allodynia, to spontaneous pain, some pathogenesis factors are shared among these symptoms. Increased AR activity, oxidative-nitrosative stress, protein kinase C, PARP and ACE activations, C-peptide deficiency, impaired neurotrophism, and proinflammatory responses have been identified in the development of diabetic neuropathic pain. This review discusses selected animal models for diabetic neuropathic pain, as well as some commonly shared pathways in these models.

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Serum neurone-specific enolase (NSE) and S-100 protein are well established as markers of cerebral injury, and have been used as markers of neuronal and glial cell damage, respectively, after cardiac surgery with cardiopulmonary bypass (CPB), but the speed of their increase during CPB has not been studied. Therefore, we have investigated the time course of NSE and S-100 release during and after CPB. We studied 18 adult patients undergoing elective coronary artery bypass grafting (CABG). Standard hypothermic (32 degrees C) pulsatile bypass with membrane oxygenation was used. Blood samples were obtained at induction, before bypass, before rewarming, at the end of rewarming, 10 min, 1 h and 8 h after bypass and 1, 2 and 3 days after surgery. NSE and S-100 were assayed using immunoradiometric assay kits (Sangtec Medical). NSE and S-100 release followed similar time courses. Both increased sharply during bypass, reached peak concentrations at the end of rewarming (mean 25.55 (SEM 2.79) and 1.65 (0.23) microgram litre-1, respectively), had decreased significantly by the end of operation and returned to pre-bypass concentrations by the second day after surgery. No patient developed a major neurological deficit. When using NSE and S-100 assays to study cerebral dysfunction in relation to CPB, postoperative samples miss peak (end-bypass) concentrations, and studies should be designed to include intraoperative samples.

Key WordsInflammatory injury • MicroRNA-146a • C-X-C chemokine receptor type 4 • PI3K/AKT • Wnt/β-catenin Abstract Background/Aims: Osteoarthritis (OA) as a degenerative disease is a major problem in ageing populations. To better understand the molecular mechanisms in the pathogenesis of OA, this study explored the role of microRNA (miR)-146a in the articular chondrocytes. Methods: The articular chondrocyte line ATDC5 was used to simulate inflammatory injury by LPS administration in vitro. Cell viability, apoptosis, mRNA expressions and productions of inflammatory factors were assessed, respectively. Mir-146a and Cxcr4 mRNA expressions were measured by qRT-PCR. Targeting effect of miR-146a on Cxcr4 3'UTR was assessed by luciferase activity analysis. Protein expression levels of CXCR4 and main factors in PI3K/AKT, Wnt/β-catenin signal pathways were measured by western blotting. Results: LPS exposure suppressed cell viability, prompted apoptosis of ATDC5 cells, and stimulated expression and release of inflammatory factors. MiR-146a was upregulated in LPS-induced cells. Overexpression of miR146a further aggravated LPS-induced inflammatory injury, while it was reduced after miR146a was knocked down. CXCR4 expression was negatively regulated by miR-146a. CXCR4 was a direct target of miR-146a and thus involved in regulatory effect of miR-146a on the injured chondrocytes, which was also related with phosphorylation levels of PI3K/AKT and expressions of Wnt/β-catenin signal factors. Conclusion: miR-146a promoted inflammatory response of articular chondrocytes via targeting CXCR4 and suppressing CXCR4 expression. Overexpression of CXCR4 could attenuate the inflammatory injury. Our findings provided novel evidence which might be useful for further studies exploring therapeutic approaches for OA via targeting miR-146a.