社区精神分裂症患者代谢综合征影响因素

背景 精神分裂症患者是罹患代谢综合征的高风险人群。既往关于代谢综合征影响因素的研究主要集中于住院精神分裂症患者,对社区精神分裂症患者的研究较少。目的 探索广州市社区精神分裂症患者不同代谢综合征风险层级的影响因素,为社区精神分裂症患者代谢综合征干预提供参考。方法 于2021年11月,选取广州市精神卫生信息系统在册在管且完成2020年度健康体检的精神分裂症患者3 339例。从信息系统导出患者健康体检资料,采用《中国2型糖尿病防治指南（2020年版）》评估患者是否罹患代谢综合征。根据《精神分裂症患者代谢综合征管理的中国专家共识》,将患者分为高风险组（n=423）、临界组（n=1 524）和代谢综合征组（n=1 392）。采用多元Logistic回归分析社区精神分裂症患者罹患代谢综合征的危险因素。结果 社区精神分裂症患者代谢综合征患病率为41.69%。单因素分析显示,三组在性别（χ²=44.610）、年龄（χ²=55.992）、婚姻状况（χ²=30.755）、病程（χ²=25.913）和体质量指数（χ²=829.265）方面差异均有统计学意义（P均<0.01）。Kruskal-Wallis H检验显示,三组患者腰围（H=920.331）、收缩压（H=436.673）、舒张压（H=393.337）、空腹血糖（H=807.304）、甘油三酯（H=1 134.125）、高密度脂蛋白胆固醇（H=593.615）水平差异均有统计学意义（P均<0.01）。Logistic回归分析显示,年龄≥50岁（OR=1.761,95% CI：1.087~2.853）、超重（OR=2.418,95% CI：1.862~3.140）和肥胖（OR=57.903,95% CI：14.340~233.802）是社区精神分裂症患者成为代谢综合征临界人群的危险因素（P<0.05或0.01）;女性（OR=1.295,95% CI：1.034~1.622）、年龄40~49岁（OR=2.597,95% CI：1.582~4.263）、年龄≥50岁（OR=4.392,95% CI：2.609~7.395）、超重（OR=7.844,95% CI：6.018~10.223）和肥胖（OR=426.785,95% CI：105.724~1 722.839）是社区精神分裂症患者成为代谢综合征人群的危险因素（P<0.05或0.01）。结论 社区精神分裂症患者代谢综合征患病率较高,女性、年长、超重和肥胖是精神分裂症患者罹患代谢综合征的高风险因素。     

老年急性缺血性脑卒中患者颈动脉斑块检出率及其与脑卒中复发的相关性

目的 应用多普勒彩色超声诊断仪评估老年急性缺血性脑卒中（AIS）患者颈动脉斑块检出情况,总结斑块发生的高危因素,并分析其与AIS复发的相关性。方法 以2020年1月至2020年6月于常州市第一人民医院神经内科和老年医学科住院的首次发生AIS,并且72 h内入院的老年患者236例为研究对象。依据颈动脉超声检查结果分为颈动脉斑块组（199例）和无颈动脉斑块组（37例）。收集并分析2组患者的临床资料及随访1.5年后脑卒中复发情况。结果 老年AIS患者颈动脉斑块检出率为84.3%。60~69岁、70~79岁及≥80岁患者颈动脉斑块检出率分别为74.7%、86.9%、96.0%,随着年龄增长颈动脉斑块检出率逐渐增加。颈动脉斑块组女性、高血压史和糖尿病史的比例明显高于无斑块组（均P<0.05）。颈动脉斑块组与无颈动脉斑块组脑卒中复发事件发生率比较,差异有统计学意义（P<0.05）。多因素Logistic回归分析结果显示,年龄（OR=1.070,95%CI：1.02~1.122,P=0.005）、糖尿病史（OR=2.262,95%CI：1.055~4.850,P=0.036）、颈动脉斑块（OR=8.128,95%CI：1.077~61.348,P=0.042）是AIS复发的独立影响因素。结论 老年AIS患者颈动脉斑块检出率高。年龄、性别、高血压史、糖尿病史是颈动脉粥样硬化的危险因素。年龄、糖尿病史、颈动脉斑块与脑卒中复发事件发生相关。     

淀粉样脑血管病相关脑出血患者血肿增大的影响因素

目的 分析淀粉样脑血管病（CAA）相关脑出血患者住院期间血肿增大的影响因素。方法 分析2016年7月—2023年7月江南大学附属医院收治于神经外科、神经内科、急诊科符合CAA纳入标准的患者242例，将其分为血肿增大组48例和血肿无增大组194例，对影响血肿增大的因素进行Logistic分析。结果 Logistic分析显示高龄（OR：1.064，95%CI：1.018-1.113，P=0.006）、高收缩压（OR：1.063，95%CI：1.015-1.113，P=0.009）、使用三七类药物（OR：5.078，95%CI：2.191-11.766，P＜0.001）、高血钙水平（OR：0.033，95%CI：0.005-0.202，P=0.033）是CAA相关脑出血患者住院期间血肿增大的影响因素。结论 CAA相关脑出血患者血肿增大的影响因素中高龄、高收缩压、使用三七类药物为危险因素，高血钙水平为保护因素。     

产前抑郁风险预测简易模型的构建与验证

背景 近年来,孕妇心理问题已成为我国重要的公共卫生问题,抑郁是孕期最常见心理问题,目前研究多集中在产前抑郁的治疗方面,缺少产前抑郁风险预测模型的构建。目的 建立产前抑郁风险预测简易模型,为预防孕妇抑郁提供参考。方法 于2021年5月-2022年2月,连续选取在南充市三所医院就诊的803名孕妇为研究对象。采用自制问卷收集孕妇的社会人口学信息、产科与医学信息、心理信息,采用抑郁自评量表（SDS）评定其抑郁症状。按照8∶2有放回地、随机将研究对象分为模型组（n=635）和检验组（n=168）,采用二元Logistic回归分析孕妇抑郁的危险因素,构建预测模型,采用ROC曲线对预测模型的价值进行验证。结果 ①产前无伴侣陪伴（β=-0.692,OR=0.501,95% CI：0.289~0.868）、末次月经期情绪低落（β=-1.510,OR=0.221,95% CI：0.074~0.656）、末次月经期情绪紧张（β=-1.082,OR=0.339,95% CI：0.135~0.853）、婆媳关系不满意（β=-1.228,OR=0.293,95% CI：0.141~0.609）以及婆媳关系一般（β=-0.831,OR=0.436,95% CI：0.260~0.730）是孕妇产前抑郁的危险因素（P<0.05或0.01）。②模型组ROC曲线下面积（AUC）为0.698,95% CI：0.646~0.749,约登指数最大为0.357,灵敏度为0.606,特异度为0.751;检验组AUC=0.672,95% CI：0.576~0.767,约登指数最大值为0.263,灵敏度为0.556,特异度为0.707。结论 本研究构建的产前抑郁风险预测简易模型具有较好的判别效度。     

烟雾病围手术期卒中危险因素分析

目的 脑血运重建术是目前烟雾病外科治疗的有效方式,但围手术期卒中发生率可达15.6%,且这部分患者预后不佳。该研究拟分析烟雾病围手术期卒中发生的危险因素,进而指导临床加强围手术期管理,以降低围手术期卒中发生率并改善患者预后。方法 纳入中南大学湘雅医院神经外科2011年1月—2021年4月手术治疗102例烟雾病患者的基本信息和影像学资料,采用多因素Logistic回归分析筛选该类患者围手术期卒中发生的危险因素。结果 102例烟雾病患者的平均发病年龄为28.22岁,共行118侧脑血运重建术,包括51次联合血运重建术和67次间接血运重建术。烟雾病围手术期卒中发生率为6.78%,其中缺血性卒中5例,出血性卒中3例,无死亡病例发生。多因素Logistic回归分析显示,高铃木分期(OR: 9.814;95%CI: 1.655~58.204, P=0.012)、低脑梗死评分(OR: 0.646;95%CI: 0.440~0.948, P=0.026)及脑白质高信号（WMHs）(OR: 7.302;95%CI: 1.203~44.310, P=0.031)是烟雾病围手术期卒中发生的危险因素。结论 具有高铃木分期、低脑梗死评分及WMHs特征的烟雾病患者围手术期卒中发生风险高,需对这些患者严格管理。     

症状性颈动脉狭窄患者CEA术后的预后改善及影响因素

目的 评估症状性颈动脉狭窄（SCS）患者颈动脉内膜剥脱术（CEA）后长、短期预后情况及影响因素。方法 分析首都医科大学三博脑科医院2014年1月—2019年12月经影像学检查确诊的79例SCS患者的临床资料,包括患者的既往病史、临床表现、实验室指标、影像学表现、治疗,以及术前、术后的改良Rankin量表（mRS）分级。分析术后3和24个月的预后改善情况。多因素Logistic回归分析影响因素,建立临床预测模型并对其进行准确性及预测效能评价。结果 SCS患者CEA术前、术后3个月、术后24个月的mRS分级分别为（1.78±1.10）、（1.32±1.37）和（0.89±1.25）。与术前相比,术后3和24个月均明显改善（P＜0.01）。多因素Logistic回归分析显示,CEA术后3个月,心肌梗死（OR=0.06,95%CI=0.01-0.32）和高脂血症（OR=0.13,95%CI=0.03-0.47）是影响因素。CEA术后24个月,心肌梗死（OR=0.09,95%CI=0.00-0.66）、高脂血症（OR=0.05,95%CI=0.00-0.29）和中性粒细胞/淋巴细胞比值（NLR）（OR=0.11,95%CI=0.02-0.50）是影响因素。通过构建的列线图来进行预测有较高的准确性及预测效能。结论 SCS患者CEA术后长、短期神经功能均较术前均有显著改善。心肌梗死、高脂血症是影响CEA术后短期预后的危险因素,心肌梗死、高脂血症、NLR是影响CEA术后长期预后的危险因素。NLR可预测SCS患者CEA术后的长期预后,术前低NLR（＜2.62）的患者预后更好。     

酒精使用障碍严重程度的影响因素及风险预测模型构建

背景 酒精使用障碍（AUD）是常见的慢性复发性精神疾病,对于重度AUD,需早期快速识别并及时妥善处理,以避免不可逆的伤害发生。目前,对AUD严重程度的评估主要基于临床医师对患者的精神检查,关于AUD严重程度影响因素及预测模型的研究有限。目的 分析AUD患者疾病严重程度的影响因素,构建风险预测模型,为评估AUD患者的疾病严重程度提供参考。方法 回顾性选取2017年1月1日—2022年12月31日南宁市第五人民医院收治的、符合《精神障碍诊断与统计手册（第5版）》（DSM-5）AUD诊断标准的1 358例首次住院患者为研究对象,收集其基本资料,根据疾病严重程度分为轻中度组（n=330）和重度组（n=1 028）。按7∶3将患者分为训练集和测试集,在训练集样本中构建Logistic回归模型,在测试集样本中采用受试者工作特征（ROC）曲线分析该模型对AUD严重程度的预测价值。结果 与轻中度组相比,重度组居住地在城市（χ²=7.804）、农民（χ²=17.991）、饮酒频率高于1~2次/天（χ²=35.267）的比例更高,初次饮酒年龄更大（t=-3.858）,合并躯体疾病数量更多（Z=-22.782）,γ-谷氨酰胺转移酶（χ²=259.940）和总胆红素异常（χ²=148.552）的比例更高（P均<0.01）。在训练集中进行的Logistic分析结果表明,农民（OR=2.024,95% CI：1.352~3.029）、初次饮酒年龄较大（OR=1.075,95% CI：1.025~1.129）、用餐时间外也饮酒（OR=3.988,95% CI：2.408~6.606）、总胆红素水平异常（OR=1.034,95% CI：1.000~1.069）、合并更多的躯体疾病（OR=4.386,95% CI：2.636~7.298）是AUD更严重的危险因素。该模型在测试集中的ROC曲线下面积（AUC）为0.906。结论 在精神专科医院中,农民、初次饮酒年龄较大、用餐时间外也饮酒、总胆红素水平异常、合并更多的躯体疾病可能是重度AUD的危险因素。     

网络认知行为治疗对癌症患者心理痛苦、抑郁、焦虑和生活质量影响的Meta分析

背景 网络认知行为治疗（ICBT）越来越多地应用于缓解癌症患者的焦虑抑郁情绪,但目前尚无ICBT对癌症患者焦虑、抑郁、心理痛苦以及生活质量影响的荟萃分析。目的 运用系统评价的方法,探讨ICBT对缓解癌症患者心理痛苦、抑郁、焦虑症状以及提高生活质量的效果。方法 于2022年3月28日,以PubMed、PsycINFO、Embase、Cochrane Library、Web of Science、中国知网、维普、万方、中国生物医学文献数据库为数据源,系统收集关于癌症患者心理痛苦、抑郁、焦虑、生活质量、且以ICBT为治疗手段的随机对照试验（RCT）。评价纳入文献的偏倚风险后,采用Stata 17.0进行Meta分析。结果 共纳入12项RCT,包括1 686例患者。Meta分析结果显示,与对照组接受的干预措施相比,ICBT有助于缓解癌症患者的心理痛苦（SMD=-0.547,95% CI：-1.090~-0.145,P<0.01）,但对抑郁（SMD=-0.652,95% CI：-1.734~0.002,P=0.051）、焦虑（SMD=-1.045,95% CI：-3.656~0.101,P=0.088）以及生活质量（SMD=0.234,95% CI：-0.064~0.449,P=0.112）的改善效果不明显。ICBT组脱落率高于对照组（OR=1.795,95% CI：1.358~2.374,P<0.01）。结论 ICBT对癌症患者的心理痛苦有一定的缓解作用,但对抑郁和焦虑症状以及生活质量的改善不明显。     

短程认知行为治疗改善精神分裂症患者生活质量的效果及影响因素

背景 精神分裂症病程迁延,患者社会功能受损、生活质量明显降低,药物治疗联合心理治疗对患者生活质量的改善尤为重要。短程认知行为治疗（BCBT）已广泛应用于临床,但目前有关BCBT的研究更多关注患者症状的改善,缺少对生活质量改善的相关报道。目的 评价BCBT联合常规治疗对改善精神分裂症患者生活质量的效果及影响因素。方法 选取2011年8月—2016年12月在首都医科大学附属北京安定医院门诊随诊、符合《国际疾病分类（第10版）》（ICD-10）精神分裂症诊断标准的患者210例。采用随机数字表法分为研究组和对照组各105例。两组均接受常规治疗,研究组在此基础上接受为期12周、共8次BCBT。在基线期和治疗12周末、随访26周末、随访52周末,采用阳性和阴性症状量表（PANSS）、个体和社会功能量表（PSP）以及世界卫生组织生存质量测定量表简表（WHOQOL-BREF）进行评定。结果 重复测量方差分析结果显示,PANSS总评分的时间效应、时间与组间的交互效应均有统计学意义（F=118.783、8.083,P均<0.01）;PSP总评分的时间效应、组间效应以及时间与组间的交互效应均有统计学意义（F=94.358、4.048、5.490,P<0.05或0.01）;WHOQOL-BREF总评分的时间效应、组间效应以及时间与组间的交互效应均有统计学意义（F=12.330、4.168、4.142,P<0.05或0.01）。二元Logistic回归分析显示,BCBT联合常规治疗（OR=1.861,95% CI：1.004~3.448）、年龄小（OR=1.044,95% CI：1.001~1.088）是精神分裂症患者生活质量改善的保护因素,基线期PANSS评分高（OR=0.972,95% CI：0.945~0.999）是患者生活质量改善的危险因素。结论 与常规治疗相比,BCBT联合常规治疗对改善精神分裂症患者生活质量的效果显现更早,且长期效果更好。     

血小板相关参数对胶质瘤患者预后的影响

目的 探讨术前血小板相关参数对胶质瘤患者肿瘤复发的预测作用。方法 分析联勤保障部队第九〇九医院2015—2017年收治的93例胶质瘤患者临床病理资料,根据随访期间肿瘤是否复发分为无复发组（n=52）和复发组（n=41）,分析血小板相关参数与胶质瘤分级的相关性,采用ROC曲线分析血小板计数（PLT）、血小板体积分布宽度（PDW）、血小板压积(PCT)、平均血小板体积（MPV）、平均血小板体积/血小板计数（MPV/PLT）对肿瘤复发的预测作用,多因素Cox分析肿瘤复发的影响因素,采用Kaplan-Meier曲线分析这些因素对肿瘤复发的影响。结果 胶质瘤Ⅲ、Ⅳ级患者PLT、PCT、高于胶质瘤Ⅰ、Ⅱ级患者（t=-2.388、-2.335,均P<0.05）;胶质瘤Ⅲ、Ⅳ级患者中MPV、MPV/PLT低于胶质瘤Ⅰ、Ⅱ级患者（均P<0.05）;无复发组患者PLT和PCT低于复发组（均P<0.05）;无复发组患者MPV和MPV/PLT高于复发组（均P<0.05）;PLT的ROC曲线下面积（UAC）为0.630（95%CI=0.517~0.743,P=0.032）,阈值为216×10⁹/L;MPV的UAC为0.633（95%CI=0.518~0.747,P=0.029）,阈值为8.65 fL;MPV/PLT的UAC为0.731（95%CI=0.626~0.835,P<0.001）,阈值为0.040;多因素分析结果发现,肿瘤分级（Ⅲ、Ⅳ）、MPV≤8.65 fL、MPV/PLT≤0.040是术后肿瘤复发的危险因素（95%CI分别为1.778~3.530、1.730~4.450、1.811~6.067,均P<0.05）;肿瘤分级（Ⅲ、Ⅳ）预测术后肿瘤复发曲线下面积为0.679（95%CI=0.569~0.789,P=0.003）。Kaplan-Meier曲线分析显示,MPV≤8.65 fL患者术后3年复发率高于MPV>8.65 fL患者（Long Rank=10.990,P=0.001）;MPV/PLT≤0.040患者术后3年复发率高于MPV/PLT>0.040患者（Long Rank=6.289,P=0.012）。结论 胶质瘤患者术前MPV和MPV/PLT与术后肿瘤复发有关,可以用于肿瘤预后预测,具有一定临床意义。 [国际神经病学神经外科学杂志, 2023, 50(4): 29-33]     

Neuroimaging in epilepsy in tropics

Epilepsy is a major public health problem in many tropical countries. Also, some of the tropical diseases are major contributors to the higher prevalence of epilepsy in these countries. The etiologic factors responsible for epilepsy in these countries are quite different from those in the developed world. This article discusses the etiologic factors and neuroimaging of epilepsy in light of the conditions in these tropical countries.     

癫痫与抑郁关系的研究进展

抑郁是癫痫患者中常见的精神障碍,严重地影响了患者的生活质量。传统的观点认为癫痫患者因为存在着诸多社会学问题易出现抑郁倾向,癫痫和抑郁是单向的联系,但大量的研究已经证明癫痫和抑郁之间存在双向的联系,一种异常状态的存在可能易转化为另一种异常状态的发展。癫痫和抑郁存在着共同的发病机制。本文主要就癫痫和抑郁的双向联系以及抗抑郁药物在癫痫患者中的应用进行阐述。     

Sudanophilic lipid accumulation in astrocytes in periventricular leukomalacia in monkeys

Summary Sudanophilic lipid accumulation is a characteristic feature of periventricular leukomalacia (PVL) of infants. At least two types of lipid-containing cells have been identified, one being the macrophage, the other the pre-myelin glial cell. A third type of lipid-containing cell has been seen in two monkeys with spontaneous PVL. Electron microscopically this cell appears to be an astrocyte. This probably represents a reaction of the astrocyte to hypoxia and may be the equivalent of the hypertrophic astrocytes found in human infants.Supported in part by NIH grant HDO 8633 and the Regional Primate Research Center Grant RR-00166     

Increase in cathepsin D activity in rat brain in aging

Cathepsin D-like activity in homogenates of five brain areas of 3-month-old and 24-month-old Fischer 344 rats was measured. With hemoglobin as substrate at pH 3.2, more than 90% of the activity was inhibited by pepstatin. In each area studied, activity was more than twice as high in the old rat brain: 140-160% higher in the cortex, cerebellum, pons-medulla, and striatum and 90-100% higher in the hippocampus and spinal cord. The greatly increased metabolic capacity in the absence of an increase in protein turnover may have a role in age-related pathological degeneration in the brain.     

Characteristics of nociceptors in the periodontium--an in vitro study in rats

Recent studies have indicated that nociceptors can be classified into various types according to their physiological properties. These studies have clarified that the frequency distribution of various nociceptor types is different among body sites and animal species. In the present study, we investigated the physiological properties of rat's periodontal nociceptors in an in vitro jaw-nerve preparation. Responses were recorded from functional single filaments in the inferior alveolar nerve. To determine the nociceptor type, calibrated von Frey filaments, heat, and bradykinin (BK) stimuli were used. We found five subtypes of nociceptors in the periodontal ligaments of the lower incisor: Adelta-high threshold mechanonociceptors (Adelta-HTM, n=28), Adelta-mechanoheat nociceptors (Adelta-MH, n=6), Adelta-polymodal nociceptors (Adelta-POLY, n=26), C-high threshold mechanonociceptors (C-HTM, n=3) and C-polymodal nociceptors (C-POLY, n=4). Most nociceptors were Adelta-innervated, while only a small number of C-innervated nociceptors were found. The present results suggest that periodontal nociceptors transmit mainly fast pain, and may thus play a role in rapid detection of injure-related stimuli during mastication.     

Gender in Voice Perception in Autism

Deficits in the perception of social stimuli may contribute to the characteristic impairments in social interaction in high functioning autism (HFA). Although the cortical processing of voice is abnormal in HFA, it is unclear whether this gives rise to impairments in the perception of voice gender. About 20 children with HFA and 20 matched controls were presented with voice fragments that were parametrically morphed in gender. No differences were found in the perception of gender between the two groups of participants, but response times differed significantly. The results suggest that the perception of voice gender is not impaired in HFA, which is consistent with behavioral findings of an unimpaired voice-based identification of age and identity by individuals with autism. The differences in response times suggest that individuals with HFA use different perceptual approaches from those used by typically developing individuals.     

Defects in Bioenergetic Coupling in Schizophrenia

Synaptic neurotransmission relies on maintenance of the synapse and meeting the energy demands of neurons. Defects in excitatory and inhibitory synapses have been implicated in schizophrenia, likely contributing to positive and negative symptoms as well as impaired cognition. Recently, accumulating evidence has suggested that bioenergetic systems, important in both synaptic function and cognition, are abnormal in psychiatric illnesses such as schizophrenia. Animal models of synaptic dysfunction demonstrated endophenotypes of schizophrenia as well as bioenergetic abnormalities. We report findings on the bioenergetic interplay of astrocytes and neurons and discuss how dysregulation of these pathways may contribute to the pathogenesis of schizophrenia, highlighting metabolic systems as important therapeutic targets.     

Ethnic disparities in problem behaviour in adolescence contribute to ethnic disparities in social class in adulthood

BACKGROUND: It is important for prevention of social class disparities to know how ethnic disparities in social class arise among migrant children. We contribute to this understanding by examining the role of problem behaviour in adolescence. METHODS: Prospective observational study with 753 Dutch native and 217 Turkish migrant adolescents (11-18 year) followed for 10 years. Internalising and externalising problems were assessed in adolescence and employment status and occupational level were assessed in adulthood. The difference in odds ratios (OR) before and after adjustment for internalising and externalising problems was an indication of the predictive value of disparities in internalising and externalising problems for the development of social class disparities. RESULTS: A total of 135 (62%) of the Turkish and 602 (80%) of the Dutch adults were employed. Internalising and externalising problems were not associated with employment status. Of the employed, 65 (48%) Turkish and 179 (30%) Dutch adults worked in low-level occupations (p < 0.0001). Internalising and externalising problems were associated with both ethnicity and occupation. The OR for low-level occupation for Turkish adults was 1.78 (1.19-2.65), indicating ethnic disparities. Adjustment for internalising problems lowered the OR with 36% to 1.50 (0.97-2.31), and adjustment for externalising problems lowered it with 8% to 1.72 (1.15-2.57). Findings were similar for men and women and did not vary by age. CONCLUSIONS: Ethnic disparities in occupational level in adulthood could partly be attributed to disparities in mental health between Turkish migrants and Dutch natives in adolescence. Prevention of ethnic disparities in mental health at young age may therefore also contribute to the prevention of occupational differences in adulthood.     

Progress in neuroprotection in Parkinson's disease

Slowing or aborting the progress of neurodegeneration in Parkinson's disease (PD) remains the most important unmet need of this disorder. There are several recent developments in trial design and also in drugs under investigation for possible neuroprotective effect. Emphasis has been placed on clinical as opposed to imaging end-points and these include change in a clinical rating scale, e.g. United Parkinson's disease Rating Scale (UPDRS), or time to additional therapy. The introduction of the delayed-start, or wash-in, trial design adds an additional dimension to drug evaluation for neuroprotection. Compounds that have been recently tested in clinical trial include the monoamine oxidase-B inhibitor rasagiline, the anti-apoptotic agents TCH346 and CEP1347, and the promitochondrial agent creatine. The dopamine agonists have been evaluated for a neuroprotective effect using imaging end-points. Perhaps the most important and simplest concept for neuroprotection has been the theory that early dopaminergic support for the degenerating dopaminergic system per se provides significant long-term clinical benefit for PD patients.     

Changes in parasympathetic system in medulla oblongata in male pigs in the course of tachycardia-induced cardiomyopathy

Background

Autonomic imbalance constituting a fundamental feature of heart failure (HF) has been assessed mainly at the periphery. Changes in the functioning of autonomic centers in the brain remain unclear. We investigated the molecular elements of parasympathetic system, i.e. α7 nicotinic acetylcholine receptor (α7nAChR) and enzymes metabolizing acetylcholine (acetylcholinesterase, AChE, choline acetyltransferase, ChAT) in medulla oblongata (MO) of male pigs with chronic tachycardia-induced cardiomyopathy.

Methods

The mRNA levels of AChE, ChAT, α7nAChR and X-box binding protein 1 (spliced form, XBP1s) in MO were analyzed using qPCR, AChE and ChAT activities using spectrophotometry, proteasome activity using fluorometry, and the protein level of α7nAChR using Western blotting.

Results

The development of systolic HF was accompanied by an increase in circulating catecholamines, a decrease in the AChE and α7nAChR mRNA in MO, an increase in AChE activity (all p < 0.05), and no change in either the mRNA or activity of ChAT. Both circulating catecholamine levels and AChE activity were inversely related to systolic function of left myocardial ventricle (p < 0.05). The level of α7nAChR protein in MO and its cytoplasmatic fraction were higher in pigs with moderate and severe HF as compared to the other animals (p < 0.01). There was no difference in proteasome activity in MO between diseased and healthy animals, whereas the XBP1s mRNA decreased during HF progression (p < 0.05).

Conclusions

Molecular elements of parasympathetic system are changed within the medulla oblongata during the progression of systolic non-ischemic heart failure in male pigs, indicating a functional link between MO and heart in HF.