Aspirin intolerance. II. A prospective study in an atopic and normal population

In a prospective study 1,372 patients with asthma and rhinitis and 808 normal individuals were directly questioned about symptoms of intolerance to aspirin. The frequency of aspirin intolerance in our asthmatic group was significantly greater (3.8 per cent) than the frequency in the rhinitis alone group (1.4 per cent) or in our normal group (0.9 per cent). There was no statistical difference of aspirin intolerance between rhinitis alone and our normal individuals. The predominant symptom of aspirin intolerance in our asthmatic group was bronchospasm, while the predominant symptom in our rhinitis alone group was urticaria. In our normal individuals, manifestations of aspirin intolerance were about equally divided between bronchospasm and urticaria. It appears that at least two possible pathogenic mechanisms may be present in aspirin intolerance, one producing bronchospasm and the other resulting in angioedema/urticaria.     

Diaphragm Muscle Surface Electromyography in Patients Submitted to Liver Transplant and Eligible for Extubation

Introduction

Liver disease induces many organic and metabolic changes, leading to malnutrition and weight and muscular function loss. Surface electromyography is an easily applicable, noninvasive study, through which the magnitudes of the peaks on the charts depict voluntary muscle activity.

多囊卵巢综合征患者血清外泌体中miR-184的表达水平及其对卵巢颗粒细胞增殖的影响

目的研究多囊卵巢综合征(PCOS)患者血清外泌体中miR-184的表达水平及其对卵巢细胞颗粒增殖的影响。方法回顾性选取2018年2月至2020年4月期间盘锦辽油宝石花医院收治的60例PCOS患者作为PCOS组,另纳入同期30名健康成年女性作为对照组,提取2组受试者血清外泌体。应用实时荧光定量聚合酶链式反应(qRT-PCR)法检测2组受试者血清外泌体中及人卵巢颗粒细胞KGN和人正常卵巢上皮细胞IOSE80中的miR-184的相对表达。转染miR-184抑制剂的KGN细胞设为miR-184抑制剂组,转染抑制剂对照物的KGN细胞设为对照组,不做任何处理的KGN细胞设为空白组。应用MTT法检测各组KGN细胞的增殖情况,应用平板克隆实验检测各组KGN细胞的克隆形成率。结果PCOS患者血清外泌体中和KGN细胞中的miR-184的相对表达量为4.23±0.49、5.81±0.73,显著高于对照组(1.32±0.21)和IOSE80组细胞(1.19±0.15),差异有统计学意义(P<0.05)。miR-184抑制剂组KGN细胞在24、48、72、96 h的吸光度值分别为0.20±0.05、0.22±0.07、0.26±0.08、0.29±0.07,均显著低于阴性对照组(0.31±0.09、0.52±0.11、0.78±0.12、0.96±0.18)和空白对照组(0.31±0.08、0.53±0.10、0.77±0.14、0.94±0.18),克隆形成率(26.78±5.98)%显著低于阴性对照组[(45.98±4.12)%]和空白对照组[(43.56±4.34)%],差异有统计学意义(P<0.05)。结论PCOS患者血清外泌体和人卵巢颗粒细胞KGN中miR-184呈现高表达,PCOS的发病可能与miR-184促进卵巢颗粒细胞增殖有关。     

Spinal administration of the monoacylglycerol lipase inhibitor JZL184 produces robust inhibitory effects on nociceptive processing and the development of central sensitization in the rat

Background and Purpose

The cannabinoid receptor-mediated analgesic effects of 2-arachidonoylglycerol (2-AG) are limited by monoacylglycerol lipase (MAGL). 4-nitrophenyl 4-[bis (1,3-benzodioxol-5-yl) (hydroxy) methyl] piperidine-1-carboxylate (JZL184) is a potent inhibitor of MAGL in the mouse, though potency is reportedly reduced in the rat. Here we have assessed the effects of spinal inhibition of MAGL with JZL184 on nociceptive processing in rats.

Experimental Approach

In vivo spinal electrophysiological assays in anaesthetized rats were used to determine the effects of spinal administration of JZL184 on spinal nociceptive processing in the presence and absence of hindpaw inflammation. Contributions of CB₁ receptors to these effects was assessed with AM251. Inhibition of 2-oleoylglycerol hydrolytic activity and alterations of 2-AG in the spinal cord after JZL 184 were also assessed.

Key Results

Spinal JZL184 dose-dependently inhibited mechanically evoked responses of wide dynamic range (WDR) neurones in naïve anaesthetized rats, in part via the CB₁ receptor. A single spinal administration of JZL184 abolished inflammation-induced expansion of the receptive fields of spinal WDR neurones. However, neither spinal nor systemic JZL184 altered levels of 2-AG, or 2-oleoylglycerol hydrolytic activity in the spinal cord, although JZL184 displayed robust inhibition of MAGL when incubated with spinal cord tissue in vitro.

Conclusions and Implications

JZL184 exerted robust anti-nociceptive effects at the level of the spinal cord in vivo and inhibited rat spinal cord MAGL activity in vitro. The discordance between in vivo and in vitro assays suggests that localized sites of action of JZL184 produce these profound functional inhibitory effects.

Linked Articles

This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.167.issue-8     

Later Evaluation of Ischemia and Reperfusion by the Pringle Maneuver in Wistar Rats,Demonstrating That Hepatic Lesions Can Be Reversible

Objective

There has been much research on hepatic ischemia and reperfusion by means of short or longer interruption of the portal triad. The aim of this work was to evaluate the mitochondrial respiratory activity and liver histology at 2 different times after the Pringle maneuver.

Down-regulation of microRNA-184 contributes to the development of cyanotic congenital heart diseases

Purpose: We aimed to investigate the roles of miR-184 in adaptation of hypoxic cardiomyocytes, as well as to elucidate the possible mechanisms of miR-184 in the development of cyanotic congenital heart diseases (CHD). Materials and methods: We conducted quantitative real-time polymerase chain reaction (qRT-PCR) to determine the expression of miR-184 in patients with cyanotic cardiac defects. The embryonic rat ventricular myocardial H9c2 cells were transfected with miR-184 inhibitor and negative scramble RNA. Mock group was untreated by anything. We then used MTT assay and in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) to determine whether inhibition of miR-184 in vitro affect cell proliferation and apoptosis under hypoxic conditions. Besides, the expression levels of caspase-3 and caspase-9 in hypoxic H9c2 cells were determined by western blot. Results: MiR-184 was significantly down-regulated in CHD patients with cyanotic cardiac defects. In addition, miR-184 was successfully inhibited in hypoxic H9c2 cells. Moreover, inhibition of miR-184 markedly decreased cell viability and obviously induced apoptosis under hypoxic conditions in vitro. Besides, the expression levels of caspase-3 and caspase-9 in hypoxic H9c2 were significantly increased after miR-184 inhibition. Conclusions: Our findings indicate that inhibition of microRNA-184 may contribute to the development of cyanotic CHD via decreasing proliferation and inducing apoptosis of cardiomyocytes. Moreover, miR-184 inhibition may promote hypoxia-induced apoptosis via activation of caspase-3 and caspase-9. Congenital down-regulation of miR-184 may be a mechanism leading to CHD development.     

心理应激致血浆外泌体miR-184-3p抑制血管内皮细胞增殖、迁移功能的作用分析

目的 探讨心理应激源性血浆外泌体miR-184-3p在调控血管内皮细胞增殖、迁移功能中的作用。方法 （1）将60只6~8周龄C57BL/6雄性小鼠随机分为对照组和心理应激组,每组30只。采用21 d慢性不可预知性心理应激刺激建模。通过行为学实验（旷场实验、高架十字迷宫实验和强迫游泳实验）评价建模效果。提取血浆外泌体进行电镜分析,qPCR检测血浆外泌体miR-184-3p表达水平。（2）体外培养小鼠肺微血管内皮细胞（MPVEC）,分别转染对照组小鼠血浆外泌体（C-EXO组）、心理应激组小鼠血浆外泌体（S-EXO组）、NC mimic组和miR-184-3p mimic组。划痕实验分析细胞迁移情况,EdU染色分析细胞增殖情况。结果 （1）心理应激组小鼠探索行为较对照组显著降低,不动时间显著增加（P<0.01）。电镜分析验证血浆外泌体直径为30~200 nm的双层膜囊泡结构,qPCR证实心理应激组小鼠血浆外泌体中miR-184-3p的表达量显著增加（P<0.05）。（2）细胞实验结果显示S-EXO组细胞迁移和增殖能力较C-EXO组下降（P<0.01）;同时miR-184-3p mimic组细胞增殖和迁移能力较NC mimic组下降（P<0.05）。结论 慢性心理应激源性血浆外泌体可以通过介导miR-184-3p抑制血管内皮细胞的增殖和迁移。