Pharmacological modulation of C‐X‐C motif chemokine receptor 4 influences development of acute respiratory distress syndrome after lung ischaemia–reperfusion injury

Activation of C‐X‐C motif chemokine receptor 4 (CXCR4) has been reported to result in lung protective effects in various experimental models. The effects of pharmacological CXCR4 modulation on the development of acute respiratory distress syndrome (ARDS) after lung injury, however, are unknown. Thus, we studied whether blockade and activation of CXCR4 influences development of ARDS in a unilateral lung ischaemia–reperfusion injury rat model. Anaesthetized, mechanically ventilated animals underwent right lung ischaemia (series 1, 30 minutes; series 2, 60 minutes) followed by reperfusion for 300 minutes. In series 1, animals were treated with vehicle or 0.7 μmol/kg of AMD3100 (CXCR4 antagonist) and in series 2 with vehicle, 0.7 or 3.5 μmol/kg ubiquitin (non‐cognate CXCR4 agonist) within 5 minutes of reperfusion. AMD3100 significantly reduced PaO₂/FiO₂ ratios, converted mild ARDS with vehicle treatment into moderate ARDS (PaO₂/FiO₂ ratio<200) and increased histological lung injury. Ubiquitin dose‐dependently increased PaO₂/FiO₂ ratios, converted moderate‐to‐severe into mild‐to‐moderate ARDS and reduced protein content of bronchoalveolar lavage fluid (BALF). Measurements of cytokine levels (TNFα, IL‐6, IL‐10) in lung homogenates and BALF showed that AMD3100 reduced IL‐10 levels in homogenates from post‐ischaemic lungs, whereas ubiquitin dose‐dependently increased IL‐10 levels in BALF from post‐ischaemic lungs. Our findings establish a cause‐effect relationship for the effects of pharmacological CXCR4 modulation on the development of ARDS after lung ischaemia–reperfusion injury. These data further suggest CXCR4 as a new drug target to reduce the incidence and attenuate the severity of ARDS after lung injury.     

Metabolic syndrome among individuals with heroin use disorders on methadone therapy: Prevalence,characteristics, and related factors

ABSTRACT

Background: Observational studies have reported a high prevalence of obesity and diabetes in subjects on methadone therapy; there are, however, limited data about metabolic syndrome. The aim of the study was to evaluate the prevalence of metabolic syndrome and related factors in individuals with heroin use disorder on methadone therapy. Methods: A cross-sectional study in individuals with heroin use disorder on methadone therapy at a drug abuse outpatient center. Medical examinations and laboratory analyses after a 12-hour overnight fast were recorded. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria. Results: One hundred and twenty-two subjects were included, with a mean age of 46.1 ± 9 years, a median body mass index (BMI) of 25.3 kg/m² (interquartile range [IQR]: 21.2–28), and 77.9% were men. Median exposure to methadone therapy was 13 years (IQR: 5–20). Overweight and obesity were present in 29.5% and 17.2% of the participants, respectively. Metabolic syndrome components were low high-density lipoprotein (HDL) cholesterol (51.6%), hypertriglyceridemia (36.8%), high blood pressure (36.8%), abdominal obesity (27.0%), and raised blood glucose levels (18.0%). Abdominal obesity was more prevalent in women (52% vs. 20%, P = >0.01) and high blood pressure more prevalent in men (41.1% vs. 22.2%, P = .07). Prevalence of metabolic syndrome was 29.5% (95% confidence interval [CI]: 16.6–31.8). In the multivariate logistic regression analysis, BMI (per 1 kg/m² increase odds ratio [OR]: 1.49, 95% CI: 1.27–1.76) and exposure time to methadone therapy (per 5 years of treatment increase OR: 1.38, 95% CI: 1.28–1.48) were associated with metabolic syndrome. Conclusions: Overweight and metabolic syndrome are prevalent findings in individuals with heroin use disorder on methadone therapy. Of specific concern is the association of methadone exposure with metabolic syndrome. Preventive measures and clinical routine screening should be recommended to prevent metabolic syndrome in subjects on methadone therapy.     

Second generation antipsychotic-induced mitochondrial alterations: Implications for increased risk of metabolic syndrome in patients with schizophrenia

Metabolic syndrome (MetS) is seen more frequently in persons with schizophrenia than in the general population, and these metabolic abnormalities are further aggravated by second generation antipsychotic (SGA) drugs. Although the underlying mechanisms responsible for the increased prevalence of MetS among patients under SGA treatment are not well understood, alterations in mitochondria function have been implicated. We performed a comprehensive evaluation of the role of mitochondrial dysfunction in the pathophysiology of drug-induced MetS in schizophrenia. We found a downregulation in genes encoding subunits of the electron transport chain complexes (ETC), enzyme activity, and mitochondrial dynamics in peripheral blood cells from patients at high-risk for MetS. Additionally, we evaluated several markers of energy metabolism in lymphoblastoid cell lines from patients with schizophrenia and controls following exposure to antipsychotics. We found that the high-risk drugs clozapine and olanzapine induced a general down-regulation of genes involved in the ETC, as well as decreased activities of the corresponding enzymes, ATP levels and a significant decrease in all the functional parameters of mitochondrial oxygen consumption in cells from patients and controls. We also observed that the medium-risk SGA quetiapine decreased oxygen consumption and respiratory control ratio in controls and patients. Additionally, clozapine and olanzapine induced a downregulation of Drp1 and Mfn2 both in terms of mRNA and protein levels. Together, these data suggest that an intrinsic defect in multiple components of oxidative metabolism may contribute to the increased prevalence of MetS in patients under treatment with SGAs known to cause risk for MetS.     

奈韦拉平致Stevens Johnson综合征和中毒性表皮坏死松解症的文献分析

摘 要 目的：分析奈韦拉平致Stevens Johnson综合征（SJS）和中毒性表皮坏死松解症（TEN）不良反应发生的特点,为临床用药提供依据。方法：以“奈韦拉平”、“不良反应”、“史蒂文斯 约翰逊综合征”、“中毒性表皮坏死松解症”为中文关键词,以“nevirapine”、“drug adverse reaction”、“stevens johnson syndrome (SJS)”、“toxic epidermal necrolysis (TEN)”为英文主题词,分别检索国内外主要文献数据库,对符合纳入标准的文献,提取患者性别、年龄、原患疾病、药物过敏史、给药剂量、临床表现、出现时间等内容进行统计分析。结果：共筛选出病例报道文献17篇,有效病例21例。奈韦拉平引起的SJS/TEN多发生在50岁以下人群中,以男性居多,住院天数12 d至3个月不等,有3例患者出现了死亡、1例失明。结论：在临床应用中,应重视奈韦拉平引起的SJS和TEN不良反应,注重对患者的用药教育,以减少不良反应发生,确保安全用药。     

新型口服抗凝药治疗急性冠状动脉综合征预后的Meta分析

摘 要 目的：系统性评价新型口服抗凝药（NOACs）用于急性冠状动脉综合征（ACS）患者的安全性和有效性。 方法：计算机检索PubMed、Embase、Medline、The Cochrane Library、SinoMed、WanFang Data、VIP、CNKI、中国临床试验注册中心（www.chictr.org.cn）,收集关于任何NOACs用于ACS的随机对照试验（RCT）。检索时限均为建库至2017年12月。由两位研究员独立筛选文献、提取资料并对纳入研究进行偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果：总计纳入10个RCTs,病例总数为38 882例。Meta分析结果如下：①有效性（总缺血事件发生率）：与抗血小板治疗组比较,加用NOACs组的缺血事件明显减少[RR=0.86,95%CI（0.80,0.93）,P=0.000 2];②安全性（总出血事件发生率）：与抗血小板治疗组比较,加用NOACs组明显增加根据国际血栓与出血学会（International Society on Thrombosis and Haemostasis,ISTH）标准定义的出血事件[RR=2.08,95%CI（1.79,2.41）,P＜0.000 01]和心肌梗死溶栓治疗临床试验（TIMI）定义的出血事件[RR=2.15,95%CI（1.56,2.96）,P＜0.000 01];③不同药物的有效性和安全性：加用希美加群、利伐沙班的缺血事件发生率明显减少,但出血事件发生率明显增加;加用阿哌沙班、达比加群、TAK 442（Letaxaban）、Darexaban的缺血事件发生率未见明显减少。〖HTH〗结论：〖HTK〗与单纯抗血小板药治疗相比,加用NOACs用于ACS能显著减少缺血事件,但明显增加出血事件。与抗血小板治疗组比较,不同NOACs的有效性并不一致。临床实践中应充分评估患者出血和缺血风险,实行个体化给药。     

血府逐瘀胶囊对重度血瘀证患者经皮冠状动脉介入治疗术后氯吡格雷抵抗的调节作用

目的 观察血府逐瘀胶囊联合氯吡格雷治疗氯吡格雷抵抗患者的效果,评价其改善氯吡格雷抵抗作用的效果。方法 经皮冠状动脉介入治疗（PCI）术后氯吡格雷抵抗患者80人,随机分组,分别给予3种药物治疗方案：A组用国产氯吡格雷（泰嘉）加用血府逐瘀胶囊;B组使用进口氯吡格雷（波立维）;C组用国产氯吡格雷（泰嘉）加用西洛他唑,连续3个月,采用血栓弹力图法检测干预后血小板抑制率。并随访患者半年,观察临床不良事件的发生率。结果 治疗3个月后,各组抑制率均有所提高,且均有显著差异（P<0.05）。A组对血小板抑制的有效率达40%,优于C组（33.33%）,与B组相当（40.74%）。对阿司匹林、氯吡格雷均不敏感的患者换用进口波立维对提高血小板抑制效果更佳;仅对氯吡格雷不敏感的患者加用血府逐瘀胶囊对血小板抑制有协同作用。随访半年后发现,联合使用血府逐瘀胶囊的时间延长可能会增强血小板抑制的效果,但并不增加出血及凝血功能异常等风险。结论 血府逐瘀胶囊对提高血小板抑制率有一定的作用,同时对出血风险影响较小。     

美托洛尔对急性冠脉综合征患者急诊经皮冠状动脉介入术后QRS-T转角改变及其临床意义

目的 探讨美托洛尔干预对于急性冠脉综合征(ACS)患者急诊经皮冠状动脉介入术(PCI)术后QRS-T转角改变及其临床意义.方法 连续性纳入120例ACS患者,行急诊PCI手术开通罪犯血管,术后分为美托洛尔组60例和常规治疗组60例.另选取60名年龄相符,非冠心病(CHD)志愿者作为对照组.观察术前和术后额面QRS-T夹角情况与术后1年主要不良心血管事件(MACE)发生率的相关性.结果 ACS患者PCI术前额面QRS-T夹角均明显高于对照组(F=3.565,P=0.01).在急诊PCI后第3天可见美托洛尔组ACS患者额面QRS-T夹角明显回落(75.5±11.6)°vs(52.1±17.4)°,P<0.05.美托洛尔治疗与ACS患者急诊PCI术后额面QRS-T夹角改变(r=0.755,P=0.002)成正相关,而与MACE发生率(r=-0.543,P=0.009)存在负相关.ACS患者急诊PCI术后使用早期加用美托洛尔治疗后可以使MACE发生风险降低25％(P=0.009)、△额面QRS-T夹角(每增加1°)使MACE风险降低9％(P=0.011),而Gensini评分(每增加1分)使MACE发生风险升高45％(P=0.005).结论 ACS患者PCI术后早期应用美托洛尔治疗可以促进额面QRS-T夹角水平回落.额面QRS-T夹角回落幅度与MACE的发生相关.     

服用氯吡格雷或替格瑞洛患者的血小板最大聚集率差异研究

摘 要 目的：研究经皮冠脉介入术（PCI）后服用氯吡格雷的患者与服用替格瑞洛的患者血小板最大聚集率（MAR）的差异和出血情况,为临床使用抗血小板药物提供参考。方法: 选取因急性冠状动脉综合征(ACS)入院行PCI后服用氯吡格雷或者替格瑞洛的患者,在出院前对其MAR值进行检测,随访3个月内出血事件的发生情况,并比较两组患者MAR值以及随访结果的差异。结果: 服用氯吡格雷的患者出院时MAR为（51.1±13.7）%（n=76）,服用替格瑞洛的患者MAR为（32.6±15.7）%（n=76）,两组差异有统计学意义（P<0.001）。随访结果显示氯吡格雷组出血事件低于替格瑞洛组（P<0.05）。结论: 服用替格瑞洛的患者出院后出血的倾向可能比服用氯吡格雷的患者更大。     

临床药师参与老年B型胰岛素抵抗综合征患者的药物治疗1例

摘 要B型胰岛素抵抗综合征是较为罕见的自身免疫性疾病,通常表现为大剂量胰岛素治疗下血糖仍持续偏高。本文介绍了1例临床药师参与的老年B型胰岛素抵抗综合征患者的治疗并进行病例分析。临床药师根据患者基础状况、血糖特点,参考其病理生理变化特点及伴发疾病等因素,全程参与治疗,协助临床医师制定个体化药物治疗方案。临床药师在选择合适的降糖方案的基础上,建议加用糖皮质激素和免疫调节剂,并在治疗过程中对患者进行全面的药学监护。经过治疗后,患者的胰岛素剂量有所减少,血糖较入院前有所改善,说明治疗有效,体现了临床药师的价值。