Endothelial dysfunction is the earliest pathologic alteration in diabetic vascular injury and plays a critical role in the development of atherosclerosis. Plasma levels of adiponectin (APN), a novel vasculoprotective adipocytokine, are significantly reduced in diabetic patients, but its relationship with endothelial dysfunction remains unclear. The present study aims to determine whether APN deficiency may cause endothelial dysfunction and to investigate the involved mechanisms. Vascular rings were made from the aortic vessels of wild type (WT) or APN knockout (APN -/-) mice. Endothelial function, total NO production, eNOS expression/phosphorylation, superoxide production, and peroxynitrite formation were determined. ACh and acidified NaNO 2 (endothelial dependent and independent vasodilators, respectively) caused similar concentration-dependent vasorelaxation in WT vascular rings. APN -/-rings had a normal response to acidified NaNO 2 , but a markedly reduced response to ACh (>50% reduction vs. WT, P<0.01). Both superoxide and peroxynitrite production were increased in APN -/-vessels (P<0.01 vs. WT). Pretreatment with superoxide scavenger Tiron significantly, but incompletely restored vascular vasodilatory response to ACh. In APN -/-vessels, eNOS expression was normal, but NO production and eNOS phosphorylation was significantly reduced (P<0.01 vs. WT). Treatment of APN -/-mice in vivo with the globular domain of adiponectin reduced aortic superoxide production, increased eNOS phosphorylation, and normalized vasodilatory response to ACh. Increased NO inactivation combined with decreased basal NO production contribute to endothelial dysfunction development when there is a paucity of APN production. Interventions directed towards increasing plasma APN levels may improve endothelial function, and reduce cardiovascular complications suffered by diabetic patients. §Address proofs to:

To assess the compliance of treatment, its affecting factors, and reasons for dropout, a questionnaire was mailed to a cohort of 2139 subjects who received sildenafil prescriptions for erectile dysfunction (ED) at our institution from 1999 to 2002. A total of 726 subjects (34%) with a mean age of 67 years answered the questionnaires. The response rate for sildenafil treatment was 67%. Of these sildenafil responders, 43% reported that they continued using sildenafil while 57% did not, in a mean follow-up of 3 years. Common reasons for discontinuation were effect below expectations, high cost, loss of interest in sex, and inconvenience in obtaining sildenafil. The continuers showed a higher rate than the discontinuers (P < 0.05) of having tried other treatments, dose titration, and a dose higher than 50 mg. The discontinuers reported having a lower mean responding dose and improvement score post sildenafil treatment than the continuers. In conclusion, effect below expectations was the leading reason for discontinuation of sildenafil treatment. How ED subjects tried the medication and the adequacy of education in the initial treatment period may impact the compliance of sildenafil treatment.

Thrombosis and its complications are the leading cause of death in patients with diabetes. Metformin, a first-line therapy for type 2 diabetes, is the only drug demonstrated to reduce cardiovascular complications in diabetic patients. However, whether metformin can effectively prevent thrombosis and its potential mechanism of action is unknown. Here we show, metformin prevents both venous and arterial thrombosis with no significant prolonged bleeding time by inhibiting platelet activation and extracellular mitochondrial DNA (mtDNA) release. Specifically, metformin inhibits mitochondrial complex I and thereby protects mitochondrial function, reduces activated platelet-induced mitochondrial hyperpolarization, reactive oxygen species overload and associated membrane damage. In mitochondrial function assays designed to detect amounts of extracellular mtDNA, we found that metformin prevents mtDNA release. This study also demonstrated that mtDNA induces platelet activation through a DC-SIGN dependent pathway. Metformin exemplifies a promising new class of antiplatelet agents that are highly effective at inhibiting platelet activation by decreasing the release of free mtDNA, which induces platelet activation in a DC-SIGN-dependent manner. This study has established a novel therapeutic strategy and molecular target for thrombotic diseases, especially for thrombotic complications of diabetes mellitus.

SummaryBackground and objective To observe the outcomes of AKI following multiple wasp stings.Design, setting, participants, & measurements Eighty-one patients (mean age 6 SD, 45.5614.7 years; 55 men and 26 women; mean Acute Physiology and Chronic Health Evaluation II score, 16.8562.78) with AKI following multiple wasp stings between 1997 and 2011 were retrospectively analyzed. Data on their demographic characteristics, initial modalities of renal replacement therapy (RRT), urine output, serum creatinine, bilirubin, myoglobin, and other variables were collected. Renal outcomes included complete recovery of kidney function, CKD, and death. Subgroup analysis was performed according to initial modality of RRT in the first 48 hours, including continuous veno-venous hemofiltration (CVVH), intermittent hemodialysis (IHD), and CVVH plus plasma exchange (PE).Results Of the 75 patients available for follow-up, 7 (9.3%) died, and 8 (10.7%, all in the IHD group) developed CKD. The average RRT time was 18.268.4 days, and the average kidney function recovery time was 36.0 (29.0, 41.0) days. Subgroup analysis showed no difference in the mortality rates between the CVVH, CVVH + PE, and IHD groups (8.0%, 7.1%, and 11.1%, respectively; P.0.99). The recovery time for kidney function was significantly shorter in the CVVH and CVVH + PE groups than in the IHD group (31.968.5 days, 28.669.4 days, and 41.668.1 days, respectively; P,0.001).Conclusions This is a large case series report on the outcomes of patients with AKI following multiple wasp stings. Most patients survived with complete recovery of their kidney function. Despite the lack of difference in mortality rates, the patients who began RRT with CVVH and CVVH + PE experienced a better and more rapid recovery of kidney function than those initiated with IHD.

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The flesh colour and phenolic metabolism in potato tuber during curing and after cut were investigated. Result indicated that postharvest curing not only changed phenolic metabolism during curing, but also improved fresh-cut colour for 12 days after fresh cut. Significantly lower PAL and higher phenolic content and PPO activities during curing treatment and fresh-cut potatoes were detected compared to the control, which lead to the lower browning in the slices from curing treated potatoes. HPLC analysis revealed that amounts of total phenolics, chlorogenic acid, gallic acid and protocatechuic acid were induced by curing and highly accumulated in the curing treated potatoes. Our results demonstrated that phenolic metabolism played an important role in the control of browning of fresh cut potato after curing.

In March 2013, an influenza outbreak caused by the novel avian-origin H7N9 influenza A virus emerged in eastern China and had caused 43 fatalities by 31 July 2013, although the basis for disease pathogenesis still remains unclear. To assess the immunological and viral factors associated with disease severity, viral RNA and inflammatory cytokines were quantified for 18 H7N9 patients in Shanghai, China. Detailed clinical information was collected and clinical laboratory investigations were performed for all patients. H7N9 infection is characterized by high pharyngeal virus load and frequent detection of viral RNA in blood. High pharyngeal virus load persisted through the first 10 days of antiviral therapy in fatal cases. Genetic characterization of the H7N9 virus revealed an Arg292Lys mutation in the neuraminidase gene associated with oseltamivir-resistance. Pronounced lymphopenia and high chemokine and cytokine levels were observed in H7N9-infected patients, particularly in those where disease was fatal. Serum levels of interleukin-6 (IL-6), IL-8 and macrophage inflammatory protein-1β in our subjects also correlated positively with pharyngeal virus load. Lymphocyte counts <0.5 × 10(9)  cells/L, and serum IL-6 >97 pg/mL, IL-8 >40 pg/mL and C-reactive protein >90 mg/L were identified as being connected with adverse clinical outcome through univariate logistic analysis. Significant survival differences were also observed between patients with serum C-reactive protein <90 mg/L or creatinine <90 μmol/L and those with higher levels. Our data demonstrated that high viral load, and the resulting intense inflammatory responses, played an important role in H7N9 pathogenesis. Though immunomodulatory treatment has potential benefits, the focus of clinical management should be on preventing the intense cytokine response by early diagnosis and effective antiviral treatment.

Closure of live poultry markets was implemented in areas affected by the influenza virus A(H7N9) outbreak in China during winter, 2013–14. Our analysis showed that closing live poultry markets in the most affected cities of Guangdong and Zhejiang provinces was highly effective in reducing the risk for H7N9 infection in humans.