Neutrophil extracellular traps exacerbate coagulation and endothelial damage in patients with essential hypertension and hyperhomocysteinemia.

Patients with essential hypertension (EH) and hyperhomocysteinemia (HHCY) suffer from more increased thrombotic events than those in EH alone. However, the underlying mechanisms for this effect are not well understood. This study hypothesized that neutrophil extracellular trap (NET) releasing may be triggered by HHCY in patients in EH, thereby predisposing them to a more hypercoagulable state. Using a modified-capture enzyme-linked immunosorbent assay (ELISA) method, we observed that cell-free DNA (CF-DNA) and myeloperoxidase DNA (MPO-DNA) in patients With EH and HHCY were significantly higher. The NET formation was also positively correlated with homocysteine levels, neutrophil-lymphocyte ratio (NLR), and hypercoagulable markers (thrombin-antithrombin complex, D-dimers). Furthermore, neutrophils from patients in EH with HHCY were found to be predisposed to amplified NET release when compared to patients in EH without HHCY or CTR. Coagulation function assays showed that NETs in patients With EH and HHCY resulted in a significantly increased ability to generate thrombin and fibrin than in those in EH without HHCY or CTR. These procoagulant effects of NETs in patients With EH and HHCY were markedly inhibited (approximately 70%) by the cleavage of NETs with DNase I. Isolated NETs from patients With EH and HHCY neutrophils also exerted a strong cytotoxic effect on endothelial cells (ECs), converted them to apoptosis. This study revealed a previously unrecognized association between the hypercoagulable state and neutrophils in patients With EH and HHCY. Therefore, blocking NETs may represent a new therapeutic objective for preventing thrombosis in these patients.

Different Na+/K+-ATPase signal pathways was involved in the increase of [Ca2+]i induced by strophanthidin in normal and failing isolated guinea pig ventricular myocytes.

AIM: To determine whether different Na+/K+-ATPase signal transduction pathways have positive inotropic effects on normal ventricular myocytes (NC) and failing ventricular myocytes (FC), and are involved in an increase of [Ca2+]i induced by strophanthidin (Str). METHODS: A guinea pig model of congestive heart failure was made by constricting descending aorta. The left ventricular myocytes were enzymatically isolated. The effects of 25 micromol/L Str with different signal-transducing inhibitors on contractility and the calcium transient of NC or FC from guinea pigs were simultaneously assessed and compared with those in the 25 micromol/L Str-only group by a video-based, motion-edge detection system. RESULTS: Str at 1, 10, and 25 micromol/L in NC and Str at 0.1, 1, 10, and 25 micromol/L) in FC elevated the calcium transient amplitude and increased the positive inotropic effects in a concentration-dependent manner, respectively. At the same concentration, the effects of Str were more potent in FC than in NC. In FC, both the mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS) signal transduction pathway of Na+/K+-ATPase were involved in the increase of the calcium transient induced by Str, but only activation of the MAPK pathway increased the calcium transient in NC. However, only the ROS pathway was involved in positive inotropic effects both in NC and FC. CONCLUSION: The present study suggests that Na+/K+-ATPase signaling pathways involved in the inotropic effects of Str in NC and FC are consistent, and Na+/K+-ATPase signaling pathways involved in the increase of [Ca2+]i by Str in NC and FC are different.

Evaluation on the visual inspection with Lugol's iodine in cervical cancer screening program / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate visual inspection with Lugol's iodine (VILI) in cervical cancer screening program and to provide evidence for designing a cervical cancer screening algorithm in high risk areas of existing low-resource settings to reduce the incidence and mortality of cervical cancer.</p><p><b>METHODS</b>Women in Yangcheng county, Shanxi province were screened with VILI, colposcopy, liquid-based cytology test and human papilloma virus (HPV) DNA test. The efficacy of different screening tests was compared by Youden's index based on the pathology as the gold standard.</p><p><b>RESULTS</b>In the population being screened, the mean age was 40.80 +/- 10.75 years old. Based on pathological findings, 4.35% (32/735) of the subjects had >or= CIN (cervical intraepithelial neoplasia) II. The sensitivity and specificity for the VILI test (>or= positive) were 53.13 and 82.19, while 56.25 and 79.09 were for colposcopy (>or= low grade dysplasia) respectively. Comparing by the Youden's indexs, there was no statistically significant difference (P > 0.05) between VILI and colposcopy. However, statistical significant difference (P < 0.05) was found between VILI and liquid-based cytology test and HPV DNA test. In addition, there was no statistically significant difference (P > 0.05) found between the experienced doctors and the newly-trained doctors working in the field station.</p><p><b>CONCLUSION</b>With low sensitivity when using microscope but low cost of equipments, VILI can be one of the primary screening tests in China's rural area with low-resource settings if the screening frequency is to be increased.</p>