Aims/hypothesis: Appropriate counter-regulatory hormonal responses are essential for recovery from hypoglycaemia. Although the hypothalamus is known to be involved in these responses, the molecular mechanisms have not been fully elucidated. AMP-activated protein kinase (AMPK) functions as a cellular energy sensor, being activated during energy depletion. As AMPK is expressed in the hypothalamus, an important site of neuroendocrine regulation, the present study was undertaken to determine whether hypothalamic AMPK mediates counter-regulatory responses to hypoglycaemia. Materials and methods: Hypoglycaemia was induced by i.p. injection of regular insulin (6 U/kg) in Sprague-Dawley rats. Hypothalamic AMPK phosphorylation and activities were determined 1 h after i.p. insulin injection. To investigate the role of hypothalamic AMPK activation in mediating counter-regulatory responses, an AMPK inhibitor, compound C, was pre-administered intracerebroventricularly (i.c.v.) or dominant-negative (DN)-AMPK was overexpressed in the hypothalamus before induction of hypoglycaemia. Results: Insulin-induced hypoglycaemia increased hypothalamic AMPK phosphorylation and α2-AMPK activities in rats. The change was significant in the arcuate nucleus/ventromedial hypothalamus (ARC/VMH) and paraventricular nuclei (PVN). Prior i.c.v. administration of compound C attenuated hypoglycaemia-induced increases in plasma concentrations of corticosterone, glucagon and catecholamines, resulting in severe and prolonged hypoglycaemia. ARC/VMH DN-AMPK overexpression impaired early counter-regulation, as evidenced by reduced glucagon and catecholamine responses. In contrast, PVN DN-AMPK overexpression attenuated late counter-regulation and corticosterone responses. Conclusions/ interpretation: Systemic hypoglycaemia causes hypothalamic AMPK activation, which is important for counterregulatory hormonal responses. Our data indicate that hypothalamic AMPK acts as a fuel gauge, sensing the whole-body energy state and regulating not only energy homeostasis but also neuroendocrine functions.

Objective: The object of this study was to investigate the in vivo antioxidant effect of green tea and dosage effect of green tea on antioxidant effect. Design: We tested 10 healthy subjects (aged 23 ± 25 y, ®ve women and ®ve men) with overnight fasting. The total antioxidant capacity of plasma was measured at baseline and 60 min and 120 min after ingestion of 150 ml green tea. Green tea was prepared by infusing 2.5 g of dried green tea leaves for 2 min at 80 C in 150 ml of water. In the second week, they took 300 ml of tea (5.0 g of green tea leaves) and, in the third week, 450 ml of tea (7.5 g of green tea leaves). The total antioxidant capacities of plasma were determined with a Total Antioxidant Kit (Randox Laboratories Ltd, UK) using a Cobas Mira analyser (Roche Diagnostic Systems Inc., Switzerland). The mean intra-assay coef®cient of variation was 1.2%. Results: The total antioxidant capacity of plasma increased by 1.1% at 60 min and 2.1% at 120 min over baseline value in subjects consuming 150 ml of green tea, which was statistically not signi®cant. However, total antioxidant capacity of plasma after consuming 300 ml of green tea showed a signi®cant increase of 7.0% after 60 min and 6.2% after 120 min (P`0.0001), and after consuming 450 ml 12.0% after 60 min and 12.7% after 120 min over baseline value (P`0.0001). Conclusions: Total antioxidant capacity of plasma was signi®cantly increased after taking green tea in amounts of 300 and 450 ml. A positive increment according to green tea dosage was also observed. Sponsorship: This work was funded by the Paci®c Corporation (Korea).

These findings strongly suggest that exposure to phthalate may lead to establishment of endometriosis by enhancing invasive and proliferative activities of endometrial cells.

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Background/Aim: Endothelial dysfunction due to reduced nitric oxide (NO) availability precedes the development of atherosclerosis. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is not only a cause of endothelial dysfunction, but also a predictor of the cardiovascular outcome in end-stage renal disease (ESRD) patients on hemodialysis (HD). α-Lipoic acid (ALA), a strong antioxidant, increases NO-mediated vasodilation in diabetic patients. We investigated whether ALA could decrease the plasma level of ADMA in diabetic ESRD patients on HD. Methods: Fifty patients undergoing HD three times per week were randomized to a treatment group receiving ALA 600 mg/day for 12 weeks or a control group. We measured the plasma levels of cholesterol, albumin, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, hemoglobin A_1c, and ADMA in both groups at baseline and at 12 weeks. Results: In the control group, the levels of total cholesterol, serum albumin, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, hemoglobin A_1c, and ADMA did not change. In the treatment group, the plasma levels of ADMA decreased significantly from a median of 1.68 (range 0.45–3.78) µM to a median of 1.31 (range 0.25–3.19) µM (p = 0.001). Conclusion: Considering that ADMA is an independent risk factor for cardiovascular outcome in ESRD patients, ALA may have the potential of a beneficial effect in them, in part by decreasing the plasma level of ADMA.

Background and Purpose-Early recurrent ischemic lesions (ERILs) on diffusion-weighted imaging after acute ischemic stroke have been suggested as a potential marker of early recurrent stroke. We hypothesized that biomarkers of inflammation or coagulation may be associated with the pathogenesis of ERILs and sought to investigate whether these biomarkers provide prognostic information on the risk of development of ERILs independently of clinical and imaging variables. Methods-This prospective study enrolled 153 consecutive patients with acute ischemic stroke who underwent diffusion-weighted imaging within 24 hours and subsequently at 5 days after onset and whose plasma or serum for biomarkers (C-reactive protein, fibrinogen, D-dimer, tissue plasminogen activator, and plasminogen activator inhibitor-1) were collected within 24 hours of onset. Those receiving thrombolysis or interventional therapy were excluded. ERILs were defined as new ischemic lesions on 5-day diffusion-weighted imaging separate from the index stroke lesions, which were not accompanied by subsequent recanalization. Results-ERILs

The urinary NGAL/urine creatinine ratio may be an early biomarker of AKI in adult patients undergoing LRLT.

The CYP3A5 genotype of the liver is considered to show the most important association with tacrolimus concentrations. Ultimately, genotyping for CYP3A5 may help optimal individualization of immunosuppressive drug therapy for patients undergoing solid organ transplantation.