BACKGROUND AND PURPOSE: Nicorandil, an ATP‐sensitive potassium (K_ATP) channel opener and nitric oxide donor, is used in the treatment of angina and acute heart failure. Here we investigated the effects of two K_ATP channel openers, nicorandil and cromakalim on ischaemia reperfusion (I‐R) injury in the kidney.EXPERIMENTAL APPROACH: Right nephrectomy was performed in 8‐week‐old male Sprague‐Dawley rats and they were then divided into six groups: control group; I‐R, including 30 min of left renal ischaemia followed by 24 h of reperfusion; I‐R groups plus nicorandil 3 or 10 mg·kg⁻¹ i.p.; and I‐R groups plus cromakalim 100 or 300 µg·kg⁻¹ i.p. After reperfusion, renal function was estimated by serum creatinine (SCr), urinary albumin : creatinine ratio (ACR) and urinary β2‐microglobulin (β2‐MG). Levels of K_ATP channel subtypes were investigated by Western blot. Kidney sections were stained for 4‐hydroxy‐2‐nonenal and 8‐hydroxy‐2′‐deoxyguanosine.KEY RESULTS: Renal I‐R induced significant increases in SCr, ACR and β2‐MG levels compared with the control animals. Treatment with K_ATP channel openers reduced urinary β2‐MG levels, raised by I‐R. Both K_IR6.1 and K_IR6.2 channels were expressed. Expression of K_IR6.2 channels in the I‐R group was lower than in the control group, which was restored to normal by treatment with K_ATP channel openers. Histologically, severe acute tubular damage was observed in the I‐R kidney and this damage was ameliorated by K_ATP channel openers, dose‐dependently.CONCLUSIONS AND IMPLICATIONS: ATP‐sensitive potassium channel openers protected against proximal tubule damage after I‐R injury. Nicorandil could represent a powerful additional component in the treatment of patients undergoing partial nephrectomy or renal transplantation.

Stroke is a major cause of death worldwide, leading to serious disability. Post-ischemic injury, especially in the cerebral ischemia-prone hippocampus, is a serious problem, as it contributes to vascular dementia. Many studies have shown that in the hippocampus, ischemia/reperfusion induces neuronal death through oxidative stress and neuronal zinc (Zn²⁺) dyshomeostasis. Glutathione (GSH) plays an important role in protecting neurons against oxidative stress as a major intracellular antioxidant. In addition, the thiol group of GSH can function as a principal Zn²⁺ chelator for the maintenance of Zn²⁺ homeostasis in neurons. These lines of evidence suggest that neuronal GSH levels could be a key factor in post-stroke neuronal survival. In neurons, excitatory amino acid carrier 1 (EAAC1) is involved in the influx of cysteine, and intracellular cysteine is the rate-limiting substrate for the synthesis of GSH. Recently, several studies have indicated that cysteine uptake through EAAC1 suppresses ischemia-induced neuronal death via the promotion of hippocampal GSH synthesis in ischemic animal models. In this article, we aimed to review and describe the role of GSH in hippocampal neuroprotection after ischemia/reperfusion, focusing on EAAC1.

Microglia, the resident immune cells of the central nervous system, can display a pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype. Arginase (Arg)-1 expressed in interleukin-4 (IL-4)-induced M2 microglia reduces nitric oxide (NO) production by competing with inducible NO synthase for L-arginine, which contributes to the attenuation of brain inflammation. Although previous studies have indicated that brain zinc promotes M1 activation, the effect of zinc on M2 microglial activation remains to be determined. In the present study, murine primary microglia treated with 10 ng mL⁻¹ IL-4 exhibited increased Arg-1 mRNA expression and levels of intracellular free zinc. Chelation of this increased intracellular free zinc by the cell permeable zinc chelator N,N,N′,N′-tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN) aggravated the IL-4-induced mRNA expression and enzymatic activity of Arg-1. However, the cell impermeable zinc chelator CaEDTA had no effect on Arg-1 expression or cytosolic levels of free zinc in IL-4-induced M2-polarized microglia. Furthermore, treatment with IL-4 resulted in upregulation of phagocytic activity in microglia, while administration of TPEN abolished IL-4-induced phagocytic activity. Moreover, this effect was reversed viaL-arginine supplementation. These findings suggest that IL-4 induces an increase in intracellular free zinc in microglia, which may act as a negative regulator of IL-4-induced Arg-1 expression, and that such negative regulation is essential for microglial phagocytic activity.

Combining small-diameter optical-fiber technology and space-division multiplexing employing multicore fiber is a promising method of further increasing the transmission capacity of optical networks. Four-core multicore fibers with a 200-m coating diameter (200-4CFs), which were reduced from 250 m, were fabricated. The 200-4CFs had almost the same characteristics as the 4CFs with a 250-m cladding diameter. The 200-4CFs were ribbonized and cabled. This cabling is the first time a multicore fiber with a 200-m coating has been used. The attenuation increment due to the cabling was compared with that of the 250-m coating diameter. The effective bending radius of the 4CFs in a cable employing intermittently connected ribbons was investigated and found to be smaller than the cable-drum radius. Mechanical and environmental tests were performed and confirmed to satisfy IEC standards. The scalability of a high-fiber-count cable employing 200-4CFs was demonstrated. Finally, the applicability of an automatic splice with core identification by side-view alignment to the 200-4CFs is presented.

Reactivation of hepatitis B virus (HBV) is a serious complication of immunosuppressive therapy and cytotoxic chemotherapy. The optimal duration of HBV-DNA monitoring for at-risk patients depends on the clinical features of reactivation, especially the range of potency from therapies to reactivation. We present a case of very late reactivation after chemotherapy for lymphoma and review previous reports of late reactivation cases. We also underscore the significance of developing an indicator for anti-HBV immunity which can be used to determine the optimal monitoring period.