N-乙酰半胱氨酸对大鼠肺炎链球菌肺炎的保护性研究

目的探讨N-乙酰半胱氨酸(NAC)对肺炎链球菌感染大鼠所致肺炎是否有保护作用。方法本实验采用国际通用方法制造肺炎链球菌肺部感染模型。用清洁级Wistar大鼠24只,随机分为3组,每组8只,A组(未灌NAC注菌组)、B组(灌NAC注菌组)、C组(未灌药未注菌组)。从实验第1天开始A组给予NAC药物灌胃,B组以等量无菌注射用水灌胃。第4天A、B组通过气管注入0.4ml肺炎链球菌稀释液,对照组通过气管注入0.4ml无菌生理盐水,每组仅注入1次;第7天后处死取材,测定中性粒细胞表面CD11b/c、中性粒细胞活性氧浓度(ROS),白介素-10(IL-10)、白介素-6(IL-6)含量。病理切片,观察肺组织结构变化。结果 A组显微镜下明显可见肺泡大小不一致,肺泡间隔增宽增厚,间质内大量中性粒细胞、淋巴细胞浸润。B组也可见上述病理变化,但较A组减轻,C组肺泡大小较一致,肺泡间隔无明显增宽增厚,间质内极少量中性粒细胞及淋巴细胞浸润。AB两组间中性粒细胞CD11b/c比较差异具有统计学意义(F=53.65,P0.01);两组间中性粒细胞活性氧(ROS)比较差异具有统计学意义(F=63.97,P0.01);两组间IL-10比较差异具有统计学意义(F=74.66,P0.01);两组间IL-6比较差异具有统计学意义(F=238.59,P0.01),以上指标均B组较A组值低。结论 N-乙酰半胱氨酸能够减轻大鼠肺炎链球菌肺炎的炎症反应和肺组织破坏,其抗氧化作用对肺炎链球菌所致肺炎可能有一定保护作用。     

小茴香精油对肝纤维化大鼠抗氧化应激损伤作用的研究

目的 评价小茴香精油在肝纤维化大鼠模型中抗氧化应激损伤及抗肝纤维化的作用.方法 肝纤维化模型的构建.SD大鼠皮下注射4ml/kg四氯化碳橄榄油溶液,同时给予高脂低蛋白饲料共5周.设空白对照组(A组)8只,正常饲养;预防阶段模型对照组(B组)10只,造模同时给予等渗盐水灌胃;小茴香预防组(C组)10只,造模同时给予小茴香精油灌胃,剂量为3 ml/kg ;治疗阶段模型对照组(D组)22只,造模后给予等渗盐水灌胃;小茴香治疗组(E组)22只,造模后给予小茴香精油灌胃,剂量为3 ml/kg;扶正化瘀对照组(F组)22只,造模后给予扶正化瘀胶囊与等渗盐水悬混液灌胃,剂量为0.4 g/kg.分别于第5周末处死A、B、C组大鼠,第6、7、8、9周末处死D、E、F组各4～6只大鼠.检测血清ALT、AST、透明质酸、层黏蛋白、8-羟基-2-脱氧鸟嘌呤含量,肝组织匀浆超氧化物歧化酶、谷胱甘肽过氧化物酶、丙二醛.肝组织行HE染色、马松染色和α平滑肌肌动蛋白免疫组织化学染色.计量资料先进行正态性检验和方差齐性检验,满足方差分析条件时采用两因素析因设计的方差分析,差异有统计学意义后两两比较采用LDL检验.不满足方差分析条件和等级资料采用秩和检验.结果A、B、C3组超氧化物歧化酶活力差异有统计学意义(286.33±37.90) U/mg、(242.22±33.21) U/mg、(323.78±53.16) U/mg, F=8.649,P=0.002);谷胱甘肽过氧化物酶分别为(297.25±54.29) U/mg、(148.62±15.57) U/mg、(221.65±53.39)U/mg(F=26.468,P=0.000);丙二醛分别为(1.01±0.37) nmol/mg、(4.29±1.85) nmol/mg、(2.00±0.42) nmol/mg (F=18.13,P=0.000);8-羟基-2-脱氧鸟嘌呤含量含量为(35.44±2.19) ng/L、(50.25±8.29) ng/L、(39.20±4.00) ng/L(F=16.332,P=0.000).炎症活动度在C组明显低于B组(Z=-2.29,P=0.022);E组轻于D组(Z=-2.51P=0.012),F组轻于D组(Z=-2.30,P=0.021);纤维化分期E组与D组差异有统计学意义(Z=-2.81,P=0.005),F组与D组比较差异有统计学意义(Z=-2.59P=0.015).结论 小茴香精油具有减轻肝脏炎症反应、防治肝纤维化进展的作用,其机制可能与抗氧化应激损伤有关.     

阿苯达唑微球肝动脉灌注对大鼠肝泡状棘球蚴病的治疗作用

目的观察阿苯达唑-PEG6000固体分散体壳聚糖微球经肝动脉灌注治疗大鼠肝泡状棘球蚴病的效果。方法将肝泡状棘球蚴病模型大鼠30只,随机均分为3组,即生理盐水对照组(A)、空白微球组(B)和阿苯达唑微球组(C),A、B和C组分别经肝动脉灌注0.3 ml生理盐水、空白微球2.7 mg/kg(溶于0.3 ml生理盐水)、阿苯达唑-PEG6000固体分散体壳聚糖微球2.7 mg/kg(溶于0.3 ml生理盐水)。于灌注后第1、3、7、14和42天采集大鼠外周静脉血,检测白细胞(WBC)、门冬氨酸氨基转移酶(AST)和丙氨酸氨基转移酶(ALT)的值。第42天处死全部大鼠,取肝泡状棘球蚴组织,观察各组病理变化。结果各组大鼠白细胞第1天出现暂时性升高[A组(86.11±19.14)×109/L、B组(117.11±21.76)×109/L和C组(118.11±24.52)×109/L],第7天恢复正常[A组(7.85±6.57)×109/L、B组(11.73±4.85)×109/L和C组(8.49±1.36)×109/L]。B、C组在第3天AST、ALT达到最高值[B组AST(193.15±21.57)U/L、ALT(78...     

黄芪注射液对慢性阻塞性肺疾病患者外周血Th17/Treg细胞平衡的影响及意义

目的探讨黄芪注射液干预前后慢性阻塞性肺疾病(COPD)患者外周血Th17细胞、Treg细胞占CD4+T细胞的比例及白介素-10(IL-10)的表达水平,及黄芪注射液对其的作用。方法收集COPD急性加重期(A组)、稳定期(B组)、肺功能正常吸烟者(C组)及肺功能正常非吸烟者(D组)各20例,分别抽取患者空腹静脉血制备单个核细胞悬液(PBMC),分为空白组和黄芪组,应用流式细胞术检测各组黄芪注射液干预前后Th17细胞、Treg细胞占CD4+T细胞的比例及IL-10的表达水平。结果CD4+Th17细胞的比例:空白组均高于黄芪组(P0.05),空白组:A组(2.87±0.90)%高于B组(2.07±0.76)%、C组(1.20±0.42)%、D组(1.02±0.30)%,B组高于C、D组,C组和D组相比差异无统计学意义(P0.05);黄芪组:A组(1.51±0.93)%高于B组(0.94±0.65)%、C组(0.75±0.45)%、D组(0.68±0.37)%(P0.05),B、C、D组组间两两比较差异无统计学意义(P0.05);CD4+Treg细胞的比例:黄芪组均高于空白组(P0.05),在黄芪组,D组(8.04±2.65)%高于A组(4.76±1.43)%、B组(5.89±1.93)%、C组(6.50±2.2)%(P0.05),B组和C组相比差异无统计学意义,C组高于A组(P0.05);在空白组,D组(6.29±3.24)%高于A组(2.42±1.45)%、B组(4.13±1.83)%、C组(4.41±2.67)%(P0.05),B组和C组相比差异无统计学意义,C组高于A组(P0.05);外周血IL-10水平:黄芪组均高于空白组(P0.05),黄芪组:D组(7.25±1.32)%高于A组(4.76±1.31)%、B组(6.32±1.75)%、C组(6.02±1.39)%(P0.05),B组和C组相比差异无统计学意义,C组高于A组(P0.05);空白组:D组(5.21±1.07)%高于A组(2.96±1.25)%、B组(4.00±0.81)%、C组(4.31±0.90)%(P0.05),B组和C组相比差异无统计学意义,C组高于A组(P0.05);Th17/Treg细胞的比值:空白组均高于黄芪组(P0.05),黄芪组:A组(0.34±0.21)%均高于B组(0.17±0.13)%、C组(0.14±0.10)%、D组(0.11±0.07)%(P0.05);空白组,A组(4.27±7.77)%均高于B(0.60±0.33)%、C(0.31±0.19)%、D组(0.21±0.13)%(P0.05)。结论 Th17/Treg比值升高,平衡失调,可能是COPD发病的免疫机制;黄芪注射液在一定程度上能调节Th17/Treg比例失衡,对COPD的治疗可能有一定的疗效。     

单酰甘油脂肪酶对人肝细胞癌裸鼠移植瘤的影响及其机制

目的探讨单酰甘油脂肪酶(MAGL)在人肝细胞癌(HCC)裸鼠移植瘤生长中的作用和机制。方法移植的SMMC-7721细胞株分为SMMC-7721~(WT)组(未处理)、SMMC-7721~(MAGL-KD)组(MAGL沉默)、SMMC-7721~(MAGL-OE)组(MAGL过表达)和SMMC-7721~(Vector)组(空载体转染) 4组。将27只雄性BALB/c裸鼠分为4组建立裸鼠皮下移植瘤模型,即A组(注射SMMC-7721~(WT)组细胞株,n=12)、B组(注射SMMC-7721~(MAGL-KD)组细胞株,n=5)、C组(注射SMMC-7721~(MAGL-OE)组细胞株,n=5)及D组(注射SMMC-7721~(Vector)组细胞株,n=5),其中A组又分为A1(正常饲喂,n=4)、A2[(高脂饲喂(HFD)+JZL184(MAGL的特异性抑制剂,n=4)和A3 (HFD饲喂,n=4) 3个亚组。观察并比较4组肿瘤体积变化,瘤体内增殖细胞核抗原(PCNA)、金属基质蛋白酶(MMP) 2、血浆溶血性磷脂酸(LPA)和前列腺素E2(PGE2)的表达水平。计量资料多组间比较采用单因素方差分析,进一步两两比较采用SNK-q检验。结果 MMC-7721~(WT)组、SMMC-7721~(MAGL-KD)组、SMMC-7721~(MAGL-OE)组3组间MAGL蛋白相对表达水平比较差异有统计学意义(0. 377±0. 026 vs 0. 182±0. 055 vs 0. 689±0. 019,F=33. 382,P 0. 001),SMMC-7721~(MAGL-KD)组MAGL蛋白表达水平显著低于SMMC-7721~(WT)组(P 0. 05),SMMC-7721~(MAGL-OE)组显著高于SMMC-7721~(WT)组(P 0. 05); A、B、C、D 4组间裸鼠皮下移植瘤大小比较差异有统计学意义[(4236. 125±1284. 283) mm~3vs (1883. 375±552. 977) mm~3vs (10 146. 061±1842.264) mm~3vs (4307. 452±2070. 708) mm~3,F=6. 804,P=0. 023],C组的裸鼠皮下移植瘤的生长速度比A组更快(P 0. 05),而B组比A组慢(P 0. 05); A、B、C 3组间PCNA和MMP2水平比较差异均有统计学意义(PCNA:25 843. 821±4201. 310 vs 17 426. 95±5139. 202 vs 39 753. 103±5721. 444,F=21. 482,P 0. 001; MMP2:52 841. 621±4339. 253 vs 35 511. 451±8251. 423 vs 68 274. 731±6418. 594,F=11. 526,P 0. 001),B组PCNA和MMP2水平均明显低于A组(P值均0. 05),而C组均高于A组(P值均0.05); A1、A2、A3 3组间肿瘤体积比较差异有统计学意义[(23 476. 289±483. 872) mm~3vs (18 593. 851±1385. 805) mm~3vs (37 703.198±2925. 254) mm~3,F=47. 371,P=0. 004],与A1组相比,A3组的裸鼠皮下移植瘤体积增长速度更快(P 0. 05),A2组明显受到抑制(P 0. 05); A1、A2、A3 3组间PGE2水平比较差异有统计学意义[(0. 109±0. 023)μmol/L vs (0. 056±0. 010)μmol/L vs(0. 168±0. 024)μmol/L,F=16. 492,P 0. 001],A3组PGE2水平明显高于A1组(P 0. 05),A2组明显低于A1组(P 0. 05);B、C、D 3组间PGE2水平比较差异有统计学意义[(0. 069±0. 025)μmol/L vs (0. 175±0. 023)μmol/L vs (0. 096±0. 019)μmol/L,F=31. 550,P 0. 001],B组PGE2水平明显低于D组(P 0. 05),C组明显高于D组(P 0. 05)。结论 MAGL可能通过调控PGE2促进裸鼠HCC皮下移植瘤的生长,提示MAGL可能成为未来治疗HCC的潜在靶点。     

正加速度适应性训练对大鼠胃黏膜PGI_2、TXA_2含量及TXA_2/PGI_2比值的影响

目的:研究正加速度(+Gz)适应性训练对大鼠胃黏膜前列环素(prostacyclin,PGI2)、血栓素A2(thromboxane A2,TXA2)含量及TXA2/PGI2比值变化的影响.方法:40只♂SD大鼠随机分为5组,每组8只,分别标记为为A、B、C、D、E组.A组大鼠为空白对照,不做处理,B组大鼠+5 Gz值暴露5 min,1次/d,连续暴露5 d,C组大鼠+10 Gz值暴露5 min,1次/d,连续暴露5 d,D组大鼠适应性训练(即+4 Gz值暴露3 min,1次/d,连续暴露5 d)后+5 Gz值暴露5 min,1次/d,连续暴露5 d,E组大鼠适应性训练(即+4 Gz值暴露3 min,1次/d,连续暴露5 d)后+10 Gz值暴露5 min,1次/d,连续暴露5 d.试验结束后肉眼和光学显微镜下观察胃黏膜损伤情况,计算损伤指数,ELISA法检测胃黏膜内TXB2、6-酮-前列腺素F1?(6-keto-prostaglandin F1?,6-K-PGF1?)的含量,并计算TXB2/6-K-PGF1?的比值.结果:肉眼和光学显微镜下观察,除A组外,其余各组胃黏膜均有损伤,D组损伤轻于B组,E组损伤轻于C组.适应性训练后,D组损伤指数小于B组(0.875±0.641 vs 1.750±0.707,P0.05),E组损伤指数小于C组(2.250±1.035 vs 5.625±1.767,P0.05);D组TXB2低于B组(159.588 pg/m L±36.216 pg/m L vs251.018 pg/m L±50.845 pg/m L,P0.01),E组TXB2低于C组(150.476 pg/m L±48.589p g/m L v s 331.538 p g/m L±79.102 p g/m L,P0.01);D组6-K-P G F1?高于B组(72.242p g/m L±12.413 p g/m L vs 52.015 p g/m L±11.827 pg/m L,P0.01),E组6-K-PGF1?高于C组(87.426 pg/m L±15.833 pg/m L vs 44.726pg/m L±18.867 pg/m L,P0.01);D组TXB2/6-K-PGF1?比值小于B组(2.283±0.705 vs 5.128±1.788,P0.01),E组TXB2/6-K-P G F1?比值小于C组(2.250±1.035 vs 8.599±4.157,P0.01).结论:适应性训练可明显减轻持续+Gz暴露带来的胃黏膜损伤,其机制与PGI2含量升高、TXA2含量降低以及TXA2/P G I2比值降低有关.     

扶正逐瘀中药联合内镜介入治疗急性梗阻性化脓性胆管炎继发全身炎症反应的疗效分析

[目的]观察扶正逐瘀中药联合内镜介入治疗急性梗阻性化脓性胆管炎(AOSC)继发全身炎症反应(SIRS)的疗效。[方法]随机选取AOSC继发SIRS的患者45例,随机分为清热解毒中药组(A组,在西医常规治疗基础上加服清热解毒中药)、扶正逐瘀中药组(B组,在A组的基础上加服扶正逐瘀中药)、及对照组(C组,仅应用西医常规治疗),每组15人,于治疗前、口服中药第3天、第7天检验血清白细胞计数(WBC)、降钙素原(PCT)、白介素6(IL-6)。[结果]A组、B组、C组中分别有1、1和2例被剔除,其余患者完成试验。口服中药第7天,检测41例患者白细胞计数:A组:(8.42±1.88)×109/L(与C组比较,差异无统计学意义);B组:(7.55±1.11)×109/L(与C组比较,差异有统计学意义);C组:(8.85±1.60)×109/L。降钙素原计数:A组:(0.83±0.39)ng/ml(与C组比较,差异无统计学意义);B组:(0.73±0.28)ng/ml(与C组比较,差异有统计学意义);C组:(1.08±0.39)ng/ml。白介素6:A组:(22.89±11.05)ng/L(与C组比较,差异无统计学意义);B组:(13.99±4.85)ng/L(与C组比较,差异有统计学意义);C组:(28.72±13.63)ng/L。[结论]清热解毒中药联合扶正逐瘀中药对AOSC继发SIRS的治疗有辅助治疗效果,可加快感染指标的恢复。     

妊娠期肺炎的临床分析

目的 了解妊娠期肺炎患者的临床特点和预后.方法 回顾性分析2005年2月至2011年2月住院的妊娠期肺炎51例,其中妊娠期甲型H1N1流感肺炎组16例,妊娠期社区获得性肺炎组35例.结果 妊娠期甲型H1N1流感肺炎组白细胞(6.49±2.54)×109/L低于妊娠期社区获得性肺炎组白细胞(12.14±4.93)×109/L,(P＜0.000 1＜0.05);妊娠期甲型H1N1流感肺炎组C反应蛋白(85.07±61.02) mg/L高于妊娠期社区获得性肺炎组C反应蛋白(46.13±35.46) mg/L(P=0.030 2＜0.05).在胸部CT上,妊娠期甲型H1N1流感肺炎组12例(75％)比妊娠期社区获得性肺炎组17例(40％)更多出现双肺病变(P =0.020 3).妊娠期甲型H1N1流感肺炎组死胎4例(25％),妊娠期社区获得性肺炎组死胎0例(0％)(P=0.011 7).结论 妊娠期甲型H1N1流感肺炎组白细胞一般正常或不升高,低于妊娠期社区获得性肺炎组.前者C反应蛋白比后者升高的更明显,炎症反应更重.妊娠期甲型H1N1流感肺炎组肺部多出现双肺受累,死胎多.     

支气管哮喘大鼠CD4+CD25+T细胞的变化及地塞米松干预作用的研究

目的 研究支气管哮喘(简称哮喘)大鼠模型支气管肺泡灌洗液(BALF)、血液、脾脏CD4+CD25+T细胞的变化,及地塞米松对CD4+CD25+T细胞的影响.方法 50只SD大鼠随机分为5组,空白对照(A)组,哮喘(B)组,地塞米松1(C)组、地塞米松2(D)组,地塞米松3(E)组.A组第l天给予腹腔注射生理盐水l ml,第15～21天每天给予生理盐水雾化.B、C、D、E组用卵蛋白建立哮喘大鼠模型,第1天,每只大鼠腹腔注射抗原l ml(卵蛋白1 mg+灭活百日咳杆菌9×106个+氢氧化铝干粉100 mg)混悬液,第15～21天给予1%的卵蛋白雾化30 min,C、D、E组于雾化后分别给予腹腔注射地塞米松0.2 mg/kg、1 mg/kg、2 mg/kg.采用流式细胞仪检测的方法 ,观察大鼠体内BALF、外周血、脾脏CD4+CD25+T细胞的变化及使用不同剂量地塞米松后对其的影响.结果 B组BALF、外周血、脾脏CD4+CD25+T细胞表达占CD4+T细胞的百分比分别是(42.21±5.62)%、(12.69±2.70)%、(11.15±1.05)%,A组结果 分别是(18.76±5.85)%、(6.21±1.73)%、(7.85±2.13)%.B组与A组比较,差异均具有统计学意义(P＜0.01,P＜0.01,P＜0.05);C组、D组、E组BALF中CD4+CD25+T细胞占CD4+T细胞的百分比表达分别是(10.49±4.03)%、(13.28±5.12)%、(7.51±5.39)%,显著低于A组和B组,(P＜0.05,P＜0.01);外周血中,C组(6.03±1.43)%、D组(4.88±0.95)%与A组(6.21±1.73)%比较,差异无统计学意义,E组(3.49±0.62)%与C组、A组比较,差异有统计学意义(P＜0.05).脾脏中,C组(7.25±1.82)%、D组(8.63±3.18)%与A组(7.85±2.13)%比较,差异无统计学意义,E组(3.38±1.37)%与C组、D组、A组比较,差异有统计学意义(P＜0.05).结论 CD4+CD25+T细胞在哮喘大鼠体内有明显的优势表达,可能是哮喘发病的机制之一.地塞米松可以抑制CD4+CD25+T细胞的表达.BALF内CD4+CD25+T细胞的变化与外周血和脾脏的变化具有一致性,监测外周血或脾脏CD4+CD25+T细胞变化可了解肺部情况.     

不同尿酸水平老年冠心病患者血管内超声检查结果比较研究

目的探讨不同尿酸水平的老年冠心病患者血管内超声检查结果的差异.方法选取本院2017年12月至2020年5月收治的老年冠心病确诊患者145例为观察对象,所有患者均接受尿酸和血管内超声检查,根据患者的尿酸水平将其分为A组(尿酸≤199μmol/L)、B组(尿酸200~399μmol/L)和C组(尿酸≥400μmol/L),对三组患者的血管内超声检查指标进行对比分析.结果A组与B组患者左主干狭窄程度均低于C组(F=5.625,P=0.039);B组与C组患者斑块纤维帽厚度并无明显差异,均小于观察A组(F=7.825,P=0.020);A、B和C三组患者的斑块面积分别是[(8.29±3.14)mm²,(11.12±1.73)mm²和(14.67±0.91)mm²,F=6.384,P=0.028]、斑块最大厚度分别是[(1.38±0.09)mm,(1.76±0.24)mm和(2.19±0.18)mm,F=6.827,P=0.015]均存在明显差异,由低到高依次为A组、B组、C组.结论老年冠心病患者机体尿酸水平升高可导致斑块面积、斑块厚度增加,并引起斑块纤维帽厚度减小,导致不稳定斑块形成风险增加,严重威胁患者的生命安全,应加强此类患者机体尿酸的监控与调节.     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.