Sperm ubiquitination and DNA fragmentation in men with occupational exposure and varicocele

Assessment of sperm ubiquitination and DNA fragmentation as sperm functional markers are proposed to complement routine semen analysis. This study focuses on the evaluation of these markers in infertile men with varicocele or exposed to occupational background. The results were compared with normozoospermic men. Semen parameters in both groups were lower than those in the control group. Ubiquitination median, as a marker for functionality of the ubiquitin–proteasome system, was also lower in both groups. The ubiquitination median showed a significant positive correlation with motility in both groups, while it showed only a negative correlation with sperm morphology in the varicocele group. DNA fragmentation showed a significant correlation with semen parameters, in total varicocele and also total exposure groups. In conclusion, significant difference of sperm ubiquitination between normal and study groups further validates that sperm ubiquitination as a potential molecular marker for sperm evaluation in addition to routine semen analysis in clinical laboratories.     

Neuropeptide Y Attenuates Stress‐Induced Bone Loss Through Suppression of Noradrenaline Circuits

Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress‐induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress‐induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6‐week restraint, or cold‐stress protocol, Npy‐null mice exhibit three‐fold greater bone loss compared to wild‐type mice, owing to suppression of osteoblast activity. This stress‐protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin‐releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy‐null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy‐null mice blocks the increase in circulating noradrenaline and the stress‐induced bone loss. Thus, NPY protects against excessive stress‐induced bone loss, through Y2 receptor‐mediated modulation of central and peripheral noradrenergic neurons. © 2014 American Society for Bone and Mineral Research.     

Synthesis of thioether derivatives of quinazoline-4-one-2-thione and evaluation of their antiplatelet aggregation activity

A series of 2-(arylmethylthio)-3-phenylquinazolin-4-one derivatives have been synthesized and their antiplatelet aggregation activities were assessed against ADP and arachidonic acid-induced platelet aggregation in human plasma. Among the tested thioethers, derivative 2, 3, 5 and 16 were the most potent compounds with satisfactory IC₅₀ for inhibition of platelet aggregation induced by ADP. Analysis of global physicochemical parameters shows some correlations between activities and molecular volume and also surface area of the studied derivatives.     

Identification of low density lipoprotein as a regulator of Fc receptor-mediated phagocytosis.

Optimal expression of the high-affinity Fc receptor for IgG (FcRI) by the human monocyte cell line U-937 requires the presence of low density lipoprotein (LDL), and neither cholesterol nor high density lipoprotein can provide the component necessary for optimal FcRI expression. Here we show that FcR-mediated phagocytosis also requires LDL. U-937 cells were cultured in medium containing interferon gamma and either fetal calf serum (FCS) or delipidated FCS (DLFCS). The phagocytosis of IgG-coated erythrocytes was measured by a colorimetric assay. U-937 cells cultured in DLFCS medium had less than 16% of the phagocytic activity of cells cultured in normal FCS medium. Phagocytosis of IgG-coated erythrocytes could be inhibited 85% by the addition of murine IgG2a myeloma protein (5 micrograms/ml). U-937 cells cultured in DLFCS medium supplemented with pure cholesterol in ethanol (10 micrograms/ml) had only 30% of the phagocytic activity of cells grown in FCS medium. Addition of very low density lipoprotein (0.2 mg of protein per ml) to DLFCS medium also failed to increase phagocytosis. However, the addition of LDL (0.2 mg of protein per ml) to DLFCS medium restored 90% of the phagocytic activity. Since neither pure cholesterol nor very low density lipoprotein restored normal phagocytic function to U-937 cells despite a normalization of cellular cholesterol content, the restoration of phagocytosis observed with LDL replacement cannot be explained by mere delivery of cholesterol by LDL. Thus, LDL is required for the expression of FcRI and FcR-mediated phagocytosis by U-937 cells and may be an important regulator of phagocytic activity of monocytes and macrophages in vivo.     

A new series of Schiff base derivatives bearing 1,2,3‐triazole: Design,synthesis, molecular docking,and α‐glucosidase inhibition

A series of new Schiff bases bearing 1,2,3‐triazole 12a ? o was designed, synthesized, and evaluated as α‐glucosidase inhibitors. All the synthesized compounds showed promising inhibition against α‐glucosidase and were more potent than the standard drug acarbose. The kinetic study on the most potent compound 12n showed that this compound acted as a competitive α‐glucosidase inhibitor. The docking study revealed that the synthesized compounds interacted with the important residues in the active site of α‐glucosidase.     

The potential role of pretransplant MIBG diagnostic scintigraphy in targeted administration of 131I‐MIBG accompanied by ASCT for high‐risk and relapsed neuroblastoma: A pilot study

MIBG is an effective component in treatment of neuroblastoma. Furthermore, MIBG scintigraphy is an imaging modality in primary assessments. None of the previous studies have evaluated the role of pretransplant MIBG scintigraphy in decision making for neuroblastoma treatment. We selected therapeutic regimen based on pretransplant ¹³¹I‐MIBG scintigraphy. Twenty high‐risk patients were enrolled. On day ?30, patients underwent diagnostic MIBG scintigraphy. Patients were then subdivided into two groups (10 cases in each arm). MIBG‐avid subgroup received MIBG (12 mCi/kg), etoposide (1200 mg/m²), carboplatin (1500 mg/m²), and melphalan (210 mg/m²). Non‐MIBG‐avid subgroup received etoposide (600 mg/m²), carboplatin (1200 mg/m²), and melphalan (150 mg/m²). Patients received CRA after ASCT. Mean age at diagnosis was 42.5 months (range, 17–65) in MIBG‐avid and 38.9 months (range, 18–65) in non‐MIBG‐avid patients. Mean age at diagnosis and transplantation did not reveal significant difference between two subgroups. In MIBG‐avid patients, the three‐yr OS was 66 ± 21%. In MIBG‐non‐avid subgroup, the three‐yr OS was 53 ± 20%. In MIBG‐avid and non‐MIBG‐avid subgroups, the three‐yr EFS were 66 ± 21% and 47 ± 19%, respectively. These findings may suggest an effective role in selecting the therapeutic strategy for pre‐ASCT MIBG scintigraphy in high‐risk neuroblastoma. MIBG‐avid subset may benefit from the combination of therapeutic MIBG and high dose of chemotherapy.     

Placebo effect in burning mouth syndrome: a systematic review

Placebo controls play a critical role in the evaluation of any pharmacotherapy. This review surveys the placebo arm in 12 randomized controlled trials (RCTs) investigating burning mouth syndrome (BMS) and documents a positive placebo response in 6 of them. On average, treatment with placebos produced a response that was 72% as large as the response to active drugs. The lack of homogeneity in the use of placebos adds to the difficulty in comparing results and aggregating data. Future RCTs investigating BMS would benefit from larger sample sizes, adequate follow‐up periods, and use of a standard placebo.     

艾滋病合并隐球菌脑膜炎18例临床分析

目的　提高对艾滋病 (AIDS)合并隐球菌脑膜炎的认识。方法　对赤道几内亚巴塔地区医院 18例AIDS合并隐球菌脑膜炎患者进行临床综合分析。结果　 18例AIDS合并隐球菌脑膜炎患者的临床主要表现为 :发热、剧烈头痛、极度乏力、肢体痛、脑膜刺激征及消瘦与脱水等。脑脊液 (CSF)培养均为新型隐球菌生长 ;涂片及隐球菌多糖荚膜抗原 (ELISA法 )检测的阳性率分别为 77 8% (14/ 18) ,94 4% (17/ 18)。结论　隐球菌脑膜炎为AIDS常见机会性感染及主要致死病因之一。     

Prolonged procoagulant activity on overstretch-injured coronary arteries in pigs

Summary.  This study was designed to assess the time course and nature of the vascular procoagulant response after 1.5-fold balloon overstretch injury of the coronary arteries in pigs. Arteries were excised for chromogenic assay of bound factor (F)Xa and thrombin at 24 h, 3 days, 1 week, or 2 weeks after injury. FXa at the site of injury remained elevated for 1 week (4.9 ± 5.9 µg cm⁻², n  = 10), compared with non-injured control arteries (0.4 ± 0.2 µg cm⁻², n  = 18, P  = 0.00025), while thrombin was increased only at 24 h. Tissue factor protein was abundant in non-injured coronaries (10 ± 6 ng µg⁻¹ total protein, n  = 9) and levels were unchanged by injury (13 ± 11 ng µg⁻¹, n  = 6) or 24-h administration of tissue factor pathway inhibitor (16 ± 6 ng µg⁻¹, n  = 6). Persistent tissue factor-mediated procoagulant activity may explain the need for prolonged anticoagulation to attenuate neointimal formation after balloon-induced coronary injury.