2型糖尿病脑梗死患者血浆血栓调节蛋白水平及其临床意义

目的：探讨血浆可溶性血栓调节蛋白（soluble thrombomodulin,sTM）与2型糖尿病脑梗死（type 2 diabetes mellitus cerebral infarction,DMCI）的关系及其临床意义。方法：选择2011年12月至2012年8月我科收治的急性脑梗死（acute cerebral infarction,ACO患者60例,其中DMCI患者30例,非2型糖尿病合并脑梗死（non—diabetes mellitus cerebral infarction,NDMCI）患者30例,以及同期健康体检者30例。采用酶联免疫吸附法（ELISA）检测其血浆sTM水平,并按美国国立卫生研究所脑卒中评分（NIHSS）进行临床神经功能缺损评估。结果：（1）与正常对照组相比,DMCI组及NDMCI组患者血浆sTM水平均明显升高,差异有统计学意义fP〈0．01）;（2）DMCI组患者血浆sTM水平和NIHSS评分均较NDMCI组显著升高,差异有统计学意义（P〈0．01）;（3）DMCI组和NDMCI组患者血浆sTM水平与NIHSS评分呈显著正相关,（r=0．785,P〈0．001）。结论：2型糖尿病脑梗死患者血浆sTM水平较正常人群显著升高,且与其神经功能缺损的严重程度呈显著正相关,检测血浆STM水平可有助于评估2型糖尿病合并脑梗死的分期、严重程度及其转归。     

载脂蛋白E基因多态性与2型 糖尿病脑梗死的关系

研究载脂蛋白E (ApoE) 基因多态性与中国东北汉族2型糖尿病合并脑梗死的关系。采用聚合酶链反应－限制性片段长度多态性（PCR-RFLP）技术,检测了208例个体的ApoE基因多态性,其中对照（CON）组69例,2型糖尿病无大血管病变（T2DM）组67例和2型糖尿病合并脑梗死（T2DMCI）组72例;同时测定了其中70例T2DMCI患者的血脂含量。CON组等位基因频率为：ε2 9.6％、ε3 82.4％、ε4 8.1％,基因型频率为：ε2ε3 13.2％、ε3ε367.6％、ε3ε416.2％;T2DM组等位基因频率为：ε2 10.5％、ε3 84.3％、ε4 5.2％,基因型频率为：ε2ε3 19.4％、ε3ε370.1％、ε3ε49％;T2DMCI组等位基因频率为：ε2 11.8％、ε3 84.7％、ε4 3.5％,基因型频率为：ε2ε3 15.2％、ε3ε375％、ε3ε44.2％。3组间等位基因和基因型频率的差异经检验无统计学意义。T2DMCI患者中各基因型之间的血浆总胆固醇 （TC）、甘油三酯 （TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）水平亦无显著性差异。在中国东北汉族人群中,未发现ApoE基因多态性与T2DMCI之间存在关联,亦未发现ApoE基因多态性与T2DMCI患者的TC、TG、 HDL-C和 LDL-C水平之间存在关联。Abstract: In order to explore the association of apolipoprotein E (ApoE) gene polymorphism with cerebral infarction in type 2 diabetic patients of Han nationality in Northeast China , the genotypes of ApoE gene were analyzed by polymerase chain reaction –restriction fragment length polymorphism (PCR-RFLP) in the 208 cases, including 69 cases in control (CON) group and 67 in type 2 diabetes mellitus (T2DM) group as well as 72 in type 2 diabetes mellitus with cerebral infarction (T2DMCI) group. Plasma lipid content in T2DMCI was also detected for 70 cases. The distribution of genotypes in ApoE gene,ε2ε3、ε3ε3 as well asε3ε4 was no significant difference in three groups (ε2ε3 : 13.2％、ε3ε3 : 67.6％、ε3ε4 : 16.2％in CON group;ε2ε3 : 19.4％、ε3ε3: : 70.1％ε3ε4 : 9％in T2DM group;ε2ε3 : 15.2％、ε3ε3 : 75％、ε3ε4 : 4.2％in T2DMCI group).The allele frequencies ofε2、ε3 andε4 were not significantly different in the three groups, either (ε2 : 9.6％、ε3 : 82.4％、ε4 : 8.1％in CON group; ε2 :10.5％、ε3 :84.3％、ε4 : 5.2％in T2DM group; ε2 :11.8％、ε3 :84.7％、ε4 : 3.5％in T2DMCI group). The levels of total cholesterol (TC), tryglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were not significantly different among the different genotypes in T2DMCI group. The study confirmed that the polymorphisms of ApoE gene are neither associated with the T2DMCI, nor with the levels of plasma lipid in T2DMCI.     

犀角地黄汤联合常规治疗对瘀热证急性脑梗死患者临床疗效及对血脂水平的影响

目的：观察犀角地黄汤联合常规疗法治疗瘀热证急性脑梗死（acute cerebral infarction,ACI）的临床效果及对患者血脂水平的影响。方法：前瞻性纳入本院神经内科在2021年1月至2022年12月收治的100例瘀热证型ACI患者,分为对照组和观察组,各50例。给予对照组患者常规内科治疗,在此基础上给予观察组患者加用犀角地黄汤,两组均连续治疗14 d。比较两组患者临床疗效、治疗后改良Rankin量表（m RS）评分以及治疗前后美国国立卫生研究院卒中量表（NIHSS）评分、瘀热证候积分、血清脂蛋白相关磷脂酶A2(Lp-PLA2)、同型半胱氨酸（Hcy）、D-二聚体（DD）、纤维蛋白原（FIB）和血脂[总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）]水平。结果：（1）两组患者治疗结束时的NIHSS评分、瘀热证候评分和m RS评分均显著降低,观察组患者下降幅度更显著（P<0.05）。（2）观察组患者治疗总有效率显著高于对照组（98.00%vs. 92.00%,P<0.05）。（3）治疗结束时,观察组患者血清Lp-...     

降纤酶对急性脑梗死患者血清C 反应蛋白、神经功能缺损及凝血时间的影响

目的:探讨降纤酶对急性脑梗死患者血清C反应蛋白(CRP)、神经功能缺损评分(NIHSS)及凝血时间的影响。方法:将2011年7月至2015年7月医院收治的86例急性脑梗死患者随机分为治疗组和对照组,每组43例。对照组给予常规治疗,治疗组在对照组基础上静脉滴注降纤酶,10U/次,1次/2d,两组患者均治疗2周为1个疗程。比较两组患者治疗前后患者部分凝血活酶时间(APTT)、凝血酶原时间(PT)水平,分别于治疗前、治疗1周、治疗2周检测两组患者血清CRP水平及评价NIHSS评分。结果:治疗组总有效率为88.4%(38/43),对照组为69.8%(30/43),治疗组总有效率显著高于对照组(P0.05)。治疗后,两组患者APTT、PT均较治疗前显著升高,且治疗组治疗后APTT、PT显著高于对照组,异均有统计学意义(P0.05)。治疗后,两组患者NIHSS评分、血清CRP水平均呈降低趋势,治疗后1周、2周两组患者NIHSS评分、血清CRP水平显著低于治疗前(P0.05);治疗组治疗后各时段NIHSS评分、血清CRP水平显著低于同时点对照组(P0.05)。结论:降纤酶能够延长急性脑梗死患者凝血时间,降低血清CRP水平,部分恢复患者神经功能。     

血清CysC、hs-CRP与急性脑梗死分型及并发医院感染的相关性探究

摘要 目的：探究血清胱抑素C（CysC）、超敏C反应蛋白（hs-CRP）与急性脑梗死TOAST分型及并发医院感染的相关性。方法：以2017年9月~2022年9月84例急性脑梗死患者（脑梗死组）及57例健康体检者（对照组）为研究对象，采用免疫比浊法检测受试者血清CysC水平，采用乳胶增强免疫比浊法检测其hs-CRP水平。分析血清CysC、hs-CRP水平与急性脑梗死TOAST分型及并发医院感染的关系。结果：本研究纳入病例中无不明原因性缺血性卒中（SUE）患者，主要包括大动脉粥样硬化型（LAA）患者37例、小动脉闭塞型（SAO）患者12例、心源性栓塞型（CE）患者31例、其他病因明确型缺血性卒中（SOE）患者4例。不同TOAST分型患者的血清CysC、hs-CRP水平对比，存在显著性差异（P<0.05）；CE组血清CysC、hs-CRP水平高于LAA组、SAO组、SOE组，LAA组血清CysC、hs-CRP水平高于SAO组、SOE组，SAO组血清CysC、hs-CRP水平高于SOE组（P<0.05）。根据NIHSS评分将脑梗死患者分为重度组18例、中度组29例、轻度组37例，不同严重程度脑梗死患者的血清CysC、hs-CRP水平均高于对照组，且重度组高于中度组、轻度组（P<0.05）；中度组的血清CysC水平高于轻度组（P<0.05）。血清CysC、hs-CRP水平与脑梗死患者NIHSS评分均呈正相关（P<0.05）。84例脑梗死患者伴发医院感染28例，其中上呼吸道感染13例、肺部感染8例、泌尿系统感染5例、其他2例。感染组中合并糖尿病、有侵入性操作、TOAST分型为CE型的人数比例高于未感染组，NIHSS评分及血清CysC、hs-CRP水平高于未感染组（P<0.05）。侵入性操作、NIHSS评分≥16分、TOAST分型为CE型及CysC、hs-CRP水平升高是急性脑梗死并发感染的危险因素（P<0.05）。结论：CE型急性脑梗死患者血清CysC、hs-CRP水平显著升高，与病情严重程度相关，且侵入性操作、NIHSS评分≥16分、TOAST分型为CE型及CysC、hs-CRP水平升高是急性脑梗死并发感染的危险因素。     

C 反应蛋白、白细胞计数与脑梗死体积及近期预后的关系

目的:研究血清C反应蛋白水平、白细胞计数与急性脑梗死患者的梗死灶体积大小以及预后的关系。方法:检测70例急性脑梗死患者(CI组)、64例腔隙性脑梗死患者(LCI组)和80例健康人(对照组)的血浆CRP水平,并进行白细胞计数。在CI及LCI组人院当天和4周时进行临床神经功能缺损程度评分(NDS)评定以判断预后。结果:CI组血浆CRP水平高于LCI组及对照组(P<0.01),LCI组高于对照组(P<0.01);CI组白细胞计数高于LCI组及对照组(P<0.01),LCI组高于对照组(P<0.05);血浆CRP水平及白细胞计数正常组患者住院4周时显著进步和进步的比率明显高于血浆CRP水平及白细胞计数异常组(均P<0.01),而无变化和死亡的比率明显低于异常组(均P<0.01)。结论:ACI患者血浆CRP水平和白细胞计数均明显升高;脑梗死急性期血清CRP水平、白细胞计数可能与脑梗死患者梗死体积大小以及近期预后有密切的关系。     

依达拉奉联合法舒地尔应用于急性脑梗死患者的治疗效果观察

目的:观察依达拉奉联合法舒地尔应用于急性脑梗死(acute cerebral infarction,ACI)患者的治疗效果及其安全性。方法:选取我院2011年1月-2014年1月收治的急性脑梗死患者96例,随机分为观察组和对照组,每组48例。观察组患者应用盐酸法舒地尔联合依达拉奉静脉滴注,对照组患者单独应用盐酸法舒地尔静脉滴注射。观察并比较两组患者的治疗效果、神经功能缺损的变化情况及不良反应的发生情况等。结果:治疗前,两组患者NIHSS、BI评分及NSE水平比较无明显差异(P0.05);治疗后,两组患者NIHSS、BI评分及NSE水平均较治疗前明显改善,且观察组改善更明显,差异具有统计学意义(P0.05);观察组治疗总有效率高于对照组,差异具有统计学意义(P0.05);两组不良反应发生率无明显差异(P0.05)。结论:依达拉奉联合法舒地尔对急性脑梗死患者的临床效果显著,不仅可以改善患者的神经功能缺损情况,而且能够改善NSE水平,值得临床推广应用。     

急性脑梗死患者血清心肌酶学变化的临床意义及相关危险因素分析

目的:探讨急性脑梗死患者血清心肌酶学变化与预后的关系及导致急性脑梗死患者心肌酶学变化的相关危险因素。方法:回顾性分析临床及影像资料齐全且确诊的140例急性脑梗死患者(发病14天内),根据有无血清心肌酶学升高分为血清心肌酶学升高的急性脑梗死组A组(43例),血清心肌酶学正常的急性脑梗死组B组(97例),应用美国国立卫生研究院卒中量表评分(NIHSS)比较两组神经功能缺损情况,并对两组病人血清心肌酶学(包括天冬氨酸氨基转移酶(AST)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、血糖、血脂、纤维蛋白原和血压等结果进行分析。结果:A组(31%)患者血清心肌酶学均增高,与B组比较均有显著性差异(P<0.01);发病后1天A、B两组患者临床神经功能缺损程度评分无显著性差异,发病后4、8、10天A、B两组患者临床神经功能缺损程度评分有显著性差异(P<0.01);A组高血压、糖尿病与B组比较有显著性差异(P<0.05);而血脂及纤维蛋白原两组比较无显著性差异。结论:急性脑梗死患者血清心肌酶学升高者预后不良;高血压、糖尿病是急性脑梗死患者血清心肌酶学升高的相关危险因素。     

Visfatin、IL-6、TNF-α与2型糖尿病的相关研究

目的:探讨血浆visfatin、IL-6、TNF-α与2型糖尿病的关系。方法:2型糖尿病患者60例,正常对照组30例。根据体重指数分为肥胖组和非肥胖组。检测空腹血浆胰岛素、糖化血红蛋白、血糖、血脂、血压、visfatin、TNF-α、白介素-6等。计算体重指数、腰臀比值及稳态模型胰岛素抵抗指数(HOMA-IR)。结果:2型糖尿病组血浆visfatin、IL-6、TNF-α水平显著高于正常对照组(P<0.05);2型糖尿病组与正常肥胖组比较,糖尿病非肥胖组visfatin(301.60±58.07)明显升高,糖尿病肥胖组visfatin(336.68±37.61)、TNF-α(3.58±1.10)明显升高(P<0.05)。多元线性相关分析表明,在肥胖的2型糖尿病患者中血浆TNF-α与糖化血红蛋白显著正相关,血浆IL-6与血糖(FPG)显著正相关,血浆visfatin与腰臀比值(WHR)显著正相关(P<0.05)。结论:visfatin、IL-6、TNF-α的变化可能对2型糖尿病的发生、发展具有一定的作用。     

纳洛酮联合依达拉奉治疗重症脑梗死的临床疗效及对血浆TNF-α及IL-6水平的影响

目的:探讨纳洛酮联合依达拉奉治疗重症脑梗死的临床疗效及对血浆肿瘤坏死因子(TNF)-α、白介素(IL-6)水平的影响。方法:选择2014年10月至2016年10月我院接诊的92例重症脑梗死患者,通过随机数表法分为观察组(n=46)和对照组(n=46)。两组均给予降脂、控制血糖、血压、降颅压、维持水电解质、营养脑细胞等常规治疗。对照组在此基础上给予依达拉奉的静脉滴注,剂量30 mg,2次/d;观察组在对照组的基础上给予纳洛酮的静脉滴注,剂量2 mg,1次/d,均连续治疗14 d。比较两组临床疗效及治疗前后血浆TNF-α、IL-6、NIHSS评分、Barthel指数的变化以及不良反应的发生情况。结果:治疗14d后,观察组临床疗效总有效率明显高于对照组(P0.05)。与治疗前比较,两组治疗后血浆TNF-α、IL-6水平、NIHSS评分均显著下降(P0.05),Barthel指数明显上升(P0.05),且观察组血浆TNF-α、IL-6水平、NIHSS评分均明显低于对照组(P0.05),Barthel指数显著高于对照组(P0.05)。两组治疗过程中均未有严重不良反应发生。结论:纳洛酮联合依达拉奉治疗重症脑梗死患者的临床效果显著,可促进神经功能恢复,且安全性高,可能与其有效降低血浆血浆TNF-α、IL-6水平有关。     

Role for dopamine in malonate-induced damage in vivo in striatum and in vitro in mesencephalic cultures

Defects in mitochondrial energy metabolism have been implicated in the pathology of several neurodegenerative disorders. In addition, the reactive metabolites generated from the metabolism and oxidation of the neurotransmitter dopamine (DA) are thought to contribute to the damage to neurons of the basal ganglia. We have previously demonstrated that infusions of the metabolic inhibitor malonate into the striata of mice or rats produce degeneration of DA nerve terminals. In the present studies, we demonstrate that an intrastriatal infusion of malonate induces a substantial increase in DA efflux in awake, behaving mice as measured by in vivo microdialysis. Furthermore, pretreatment of mice with tetrabenazine (TBZ) or the TBZ analogue Ro 4-1284 (Ro-4), compounds that reversibly inhibit the vesicular storage of DA, attenuates the malonate-induced DA efflux as well as the damage to DA nerve terminals. Consistent with these findings, the damage to both DA and GABA neurons in mesencephalic cultures by malonate exposure was attenuated by pretreatment with TBZ or Ro-4. Treatment with these compounds did not affect the formation of free radicals or the inhibition of oxidative phosphorylation resulting from malonate exposure alone. Our data suggest that DA plays an important role in the neurotoxicity produced by malonate. These findings provide direct evidence that inhibition of succinate dehydrogenase causes an increase in extracellular DA levels and indicate that bioenergetic defects may contribute to the pathogenesis of chronic neurodegenerative diseases through a mechanism involving DA.     

2018年中国植物科学若干领域重要研究进展

2018年中国植物科学继续呈现快速发展的态势, 我国科学家在国际植物科学主流学术刊物发表论文数量大幅增加, 取得了多项具有重要影响的成果。调控植物生长-代谢平衡实现可持续农业发展入选2018年度中国科学十大进展; 中国被子植物区系进化历史研究入选2018年度中国生命科学十大进展。以水稻为代表的农作物和果蔬等经济作物研究在国际上已呈现出明显的优势, 若干领域已从“追赶”状态跨越到“领跑”地位。该文对2018年中国科学家在植物科学若干领域取得的重要研究成果进行了概括性评述, 旨在全面追踪和报道当前中国植物科学领域的发展前沿和热点, 展示中国科学家所取得的杰出成就。     

2017年中国植物科学若干领域重要研究进展

2017年中国植物科学继续保持高速发展态势, 重大成果频出, 具体表现在中国植物学家在国际顶级学术期刊发表的文章数量平稳上升。中国植物科学领域的研究工作者成果精彩纷呈, 如新型广谱抗病机制的发现、水稻广谱抗病遗传基础及机制和疫霉菌诱发病害成灾机制研究等。2017年中国生命科学领域十大进展评选中, 有两项植物科学领域的研究成果入选。水稻生物学、进化与基因组学和激素生物学等领域学科发展突出。另外, 值得一提的是, 长期从事高等植物与代谢途径调控分子网络研究和水稻品种设计育种的李家洋院士的研究成果“水稻高产优质性状形成的分子机理及品种设计”荣获2017年国家自然科学一等奖。这一具有重大国际影响的开创性贡献标志着中国植物科学在该领域的国际科学前沿居于引领和卓越地位。该文对2017年中国本土科学家在植物科学若干领域取得的重要研究成果进行了系统梳理, 旨在全面追踪和报道当前中国植物科学领域发展的最新前沿动态, 与广大读者共同分享我国科学家所取得的辉煌成就。     

我国葫芦科植物离体培养研究进展

葫芦科植物包括多种瓜类蔬菜,对其进行离体培养研究具有重要的理论和实践意义。综述了国内在葫芦科植物器官培养、体细胞胚胎发生、花药培养、原生质体培养和体细胞杂交及离体遗传转化等方面取得的研究进展,并对葫芦科植物离体培养、遗传转化与育种的前景作了展望。     

SSTR5 ablation in islet results in alterations in glucose homeostasis in mice

Somatostatin (SST) peptide is a potent inhibitor of insulin secretion and its effect is mediated via somatostatin receptor 5 (SSTR5) in the endocrine pancreas. To investigate the consequences of gene ablation of SSTR5 in the mouse pancreas, we have generated a mouse model in which the SSTR5 gene was specifically knocked down in the pancreatic beta cells (betaSSTR5Kd) using the Cre-lox system. Immunohistochemistry analysis showed that SSTR5 gene expression was absent in beta cells at three months of age. At the time of gene ablation, betaSSTR5Kd mice demonstrated glucose intolerance with lack of insulin response and significantly reduced serum insulin levels. Insulin tolerance test demonstrated a significant increase of insulin clearance in vivo at the same age. In vitro studies demonstrated an absence of response to SST-28 stimulation in the betaSSTR5Kd mouse islet, which was associated with a significantly reduced SST expression level in betaSSTR5Kd mice pancreata. In addition, betaSSTR5Kd mice had significantly reduced serum glucose levels and increased serum insulin levels at 12 months of age. Glucose tolerance test at an older age also indicated a persistently higher insulin level in betaSSTR5Kd mice. Further studies of betaSSTR5Kd mice had revealed elevated serum C-peptide levels at both 3 and 12 months of age, suggesting that these mice are capable of producing and releasing insulin to the periphery. These results support the hypothesis that SSTR5 plays a pivotal role in the regulation of insulin secretion in the mouse pancreas.     

2018年中国植物科学若干领域重要研究进展

2018年中国植物科学继续呈现快速发展的态势, 我国科学家在国际植物科学主流学术刊物发表论文数量大幅增加, 取得了多项具有重要影响的成果。调控植物生长-代谢平衡实现可持续农业发展入选2018年度中国科学十大进展; 中国被子植物区系进化历史研究入选2018年度中国生命科学十大进展。以水稻为代表的农作物和果蔬等经济作物研究在国际上已呈现出明显的优势, 若干领域已从“追赶”状态跨越到“领跑”地位。该文对2018年中国科学家在植物科学若干领域取得的重要研究成果进行了概括性评述, 旨在全面追踪和报道当前中国植物科学领域的发展前沿和热点, 展示中国科学家所取得的杰出成就。     

我国葫芦科植物离体培养研究进展

葫芦科植物包括多种瓜类蔬菜,对其进行离体培养研究具有重要的理论和实践意义.综述了国内在葫芦科植物器官培养、体细胞胚胎发生、花药培养、原生质体培养和体细胞杂交及离体遗传转化等方面取得的研究进展,并对葫芦科植物离体培养、遗传转化与育种的前景作了展望.     

Apoptosis in experimental myocardial infarction in situ and in the perfused heart in vitro

We report the appearance of apoptotic cells in experimental myocardial infarction (rabbit heart) in in situ and in vitro preparations. Apoptosis was recognized by intravital staining with Hoechst 33342 (Ho342), by nick-end labeling (TUNEL) and by DNA laddering. A steady rise in the relative number of apoptotic cardiomyocytes (apoptotic index) was noted in in situ preparations. Apoptosis was first noted 6 h after the onset of ischemia with its highest value occurring after 72 h. Apoptotic nuclei were absent in remote areas of the left and right ventricles. Apoptotic nuclei within the infarcted area showed diminished intensity of Ho342 fluorescence. Three days after ischemia, a border zone adjacent to the infarcted area consisting of apoptotic macrophages was recognized. A novel finding was the appearance of apoptotic cardiomyocytes in the isolated perfused ischemic heart. Occurring as early as 50 min after the onset of ischemia, a high apoptotic index was present adjacent to the ligature placed around the coronary artery. This observation provides the opportunity to selectively examine factors leading to apoptosis in the ischemic heart under controlled experimental conditions.     

Changes in aquatic vegetation in Rhine floodplain streams in Alsace in relation to disturbance

Abstract. Changes are described in aquatic vegetation in oligotrophic, groundwater-fed Rhine floodplain streams in Alsace (eastern France), resulting from disturbance. Disturbance factors include changes in nutrients, either permanent ones - effluent from a waste water treatment plant or trout hatcheries - or periodic ones: flooding. Regular inputs of high levels of phosphate and ammonia modified the macrophyte vegetation in these streams. The floristic composition, which was characteristic of oligotrophic waters upstream of the eutrophicated sector, changed to that of a eutrophic situation as originally found downstream. Periodic disturbance by floods which normally occur once a year, irregularly eutrophicates the small streams, causing the development of a mixture of eutrophic and oligotrophic species. Six macrophyte communities are distinguished, indicating different trophic levels. The aquatic vegetation is adapted to the variations of phosphate and ammonia levels. Hence, aquatic macrophytes can be used as bio-indicators of fluctuations in water nutrient levels in relation to the type of disturbance.     

Morphine-potentiated platelet aggregation in in vitro and platelet plug formation in in vivo experiments

The detailed mechanisms underlying morphine-signaling pathways in platelets remain obscure. Therefore, we systematically examined the influence of morphine on washed human platelets. In this study, washed human platelet suspensions were used for in vitro studies. Furthermore, platelet thrombus formation induced by irradiation of mesenteric venules with filtered light in mice pretreated with fluorescein sodium was used for an in vivo thrombotic study. Morphine concentration dependently (0.6, 1, and 5 microM) potentiated platelet aggregation and the ATP release reaction stimulated by agonists (i.e., collagen and U46619) in washed human platelets. Yohimbine (0.1 microM), a specific alpha(2)-adrenoceptor antagonist, markedly abolished the potentiation of morphine in platelet aggregation stimulated by agonists. Morphine also potentiated phosphoinositide breakdown and intracellular Ca(2+) mobilization in human platelets stimulated by collagen (1 microg/ml). Moreover, morphine (0.6-5 microM) markedly inhibited prostaglandin E(1) (10 microM)-induced cyclic AMP formation in human platelets, while yohimbine (0.1 microM) significantly reversed the inhibition of cyclic AMP by morphine (0.6 and 1 microM) in this study. The thrombin-evoked increase in pH(i) was markedly potentiated in the presence of morphine (1 and 5 microM). Morphine (2 and 5 mg/g) significantly shortened the time require to induce platelet plug formation in mesenteric venules. We concluded that morphine may exert its potentiation in platelet aggregation by binding to alpha(2)-adrenoceptors in human platelets, with a resulting inhibition of adenylate cyclase, thereby reducing intracellular cyclic AMP formation followed by increased activation of phospholipase C and the Na(+)/H(+) exchanger. This leads to increased intracellular Ca(2+) mobilization, and finally potentiation of platelet aggregation and of the ATP release reaction.