褪黑素对支气管哮喘小鼠胶原沉积及基质金属蛋白酶9和基质金属蛋白酶组织抑制剂1 mRNA与蛋白表达的动态调节

目的应用小鼠慢性支气管哮喘（简称哮喘）模型，观察褪黑素对慢性哮喘小鼠肺组织中胶原沉积的影响及其机制。方法96只SPF级雄性BALB／c小鼠按随机数字表法分为5组。对照组（21只）腹腔注射生理盐水；哮喘组（22只）腹腔注射生理盐水；褪黑素组（23只）腹腔注射褪黑素；地塞米松组（23只）腹腔注射地塞米松；褪黑素拮抗组（7只）腹腔注射褪黑素拮抗剂2-苯基-N-乙酰色胺。根据实验要求每组采用卵白蛋白致敏并反复雾化吸入2、4、8周时再分为2、4、8周亚组。对照组（每组均为7只）；哮喘组（分别为7、7、8只）；褪黑素组（分别为7、8、8只）；地塞米松组（分别为7、8、8只）；而褪黑素拮抗组只做2周组（7只）。实验造成慢性哮喘模型。用Masson三原色法染胶原纤维；用免疫组化方法标记蛋白；用MetaMorph软件测量单位长度基底膜周径上的胶原面积（Wcol／Pbm）和单位面积上基质金属蛋白酶9（MMP-9）及基质金属蛋白酶组织抑制剂1（TIMP-1）免疫组化阳性面积（PA／UA）；用半定量逆转录-聚合酶链反应（RT-PCR）法测定肺组织相应蛋白mRNA水平。结果褪黑素组2、4、8周WcoL／Pbm分别为（11．8±1．3）、（12．3±1．1）、（12．7±1．4）μm^2／μm，哮喘2、4、8周组分别为（14．5±1．5）、（15．8±1．8）、（16．2±1．4）μm^2／μm，两组比较差异有统计学意义（td值分别为3．89、5．96、5．50，P均〈0．01）；褪黑素组2、4、8周MMP-9的PA／UA像素分别为（9．7±4．9）、（14．8±4．9）、（11．0±6．8）万，哮喘2、4、8周组分别为（15．7±6．1）、（26．2±6．9）、（24．6±6．0）万，两组比较差异有统计学意义（td值分别为3．00、4．83、5．50，P均〈0．01）；褪黑素组2、4、8周MMP-9mRNA水平表达分别为0．80±0．40、0．68±0．15、0．67±0．24，哮喘2、4、8周组分别为1．48±0.29、1．40±0.50、1.20±0．40，两组比较差异有统计学意义（td值分别为3．92、4．50、3．29，P均〈0．01）；地塞米松组2、4、8周Wcol／Pbm（11．6±1．3、12．3±1．0、13．0±1．7）μm^2／μm、MMP-9蛋白[（12．5±5．6）、（14．0±4．7、13．6±4．8）万]和mRNA水平（0．69±0．11、0．61±0．16、1．10±0．40）均较哮喘2、4、8周组降低。褪黑素拮抗2周组与哮喘2周组以上各指标比较差异均无统计学意义（td值=0．96，P〉0．05）。结论早期使用褪黑素可抑制胶原沉积，其作用与地塞米松相当。褪黑素可能通过MMP-9介导的途径抑制哮喘气道重塑。     

菜菔硫烷对低硒病毒性心肌损伤小鼠Ⅱ相酶和一氧化氮的影响

目的 研究Ⅱ相酶和一氧化氮（NO）在低硒病毒性心肌损伤中的变化以及十字花科蔬菜成分菜菔硫烷（SF）的影响。方法 采用低硒和常硒病毒性心肌损伤小鼠模型，观察心肌组织Ⅱ相酶和NO的变化及SF对其的影响。结果 病毒感染使低硒条件下谷胱甘肽硫转移酶（GST）水平增高[（22．46±2．08）×10^3、（19．36±2．03）×10^3U／g，P〈0．05]，而常硒条件下使醌还原酶（QR）水平增高[（24．40±1．18）×10^3、（22．04±1．25）×10^3U／g，P〈0．01]，各SF保护组Ⅱ相酶活性均明显高于相应未保护组（P〈0．05）；病毒感染使小鼠血清NO水平升高（P〈0．01）。常硒SF保护组NO水平显著低于未保护组[（45．98±3．16）、（61．33±8．54）μmol／L，P〈0．01]。结论 SF可通过诱导心肌组织Ⅱ相酶活性．提高抗氧化能力以及降低血清NO水平减轻炎症反应来保护损伤的心肌。     

异莲心碱防止高血压大鼠左室肥厚的可能机制

背景既往报告异莲心碱是从莲子心中分离的一种双苄基喹啉生物碱单体，具有抗心律失常、Ca^2＋拮抗及阻断α受体作用，对高血压左室肥厚有不同程度的改善。高血压左室肥厚心肌肌浆网钙泵（SERCA）活力较正常心肌降低。目的探讨异莲心碱对高血压大鼠左室肥厚及SERCA活力的影响。方法将二肾一夹肾血管性高血压大鼠（RHR）模型，随机分为3组：正常对照组、肾血管性高血压大鼠对照组（未治疗RHR组）和异莲心碱治疗组。在异莲心碱治疗组持续给药10周后，分别测定各组大鼠的血压、左室质量／体质量，以及左室心肌SERCA活力。结果治疗后，异莲心碱治疗组血压（136．4±14．6）mmHg较未治疗RHR组（189．8±4．4）mmHg显著降低（P〈0．01）；异莲心碱治疗组左室质量／体质量（2．23±0．43）也较未治疗RHR组（2．93±0．52）显著降低（P〈0．05）；异莲心碱治疗组左室心肌SERCA活力[（0．91±0．18）μmol／（gprotein·min）]较未治疗RHR组[（0．61±0．23）μmol／（gprotein·min）]显著升高（P〈0．05），但仍较正常对照组[（1．32±0．18）μmol／（gprotein·min）]低（P〈0．01）。结论异莲心碱能降低RHR的血压，减低RHR的左室质量／体质量，对高血压左室肥厚具有一定的防治作用；其机制可能与异莲心碱能升高RHR肥厚心肌肌浆网SERCA活力，改善心肌细胞内钙超载有关。     

硫化氢在大鼠急性支气管哮喘模型中的变化及意义

目的观察卵白蛋白（OVA）诱导的大鼠急性支气管哮喘（简称哮喘）模型，内源性硫化氢（H2S）生成的变化以及应用外源性硫氢化钠（NaHS，H2S供体）处理对哮喘大鼠的影响，探讨气体信号分子H2S在哮喘发病中的作用。方法24只健康SD大鼠按随机数字表法分为正常对照组、哮喘组和NaHS干预组，每组8只。致敏后28d测定所有大鼠肺功能并观察大鼠支气管周围炎性细胞浸润程度并进行评分；采用敏感硫电极测定血浆及肺组织H2S的生成量；采用酶促反应法测定大鼠肺组织匀浆中胱硫醚-γ-裂解酶（CSE）活性；用Western blot法测定大鼠肺组织中CSE蛋白含量（每组3只）。结果哮喘组大鼠呼气峰流量（PEF）、血浆及肺组织中H2S分别为（2．90±0．70）L／s、（10±3）、（4．9±1．3）μmoL／L，对照组分别为（6．50±0．10）L／s、（54±10）、（24．1±8．0）μmoL／L，NaHS干预组大鼠分别为（5．70±0．50）L／s、（17±4）、（15．3±4．0）μmol／L，3组间比较差异有统计学意义（F值分别为112．13、110．10、27．34，P均〈0．01）；哮喘组大鼠肺组织匀浆每毫克蛋白中CSE活性和肺组织匀浆中CSE蛋白含量[用相对吸光度（A）值表示]分别为（1．00±0．10）nmol·min^-1·mg^-1、0．20±0．10，正常对照组分别为（1．80±0．10）nmo]·min^-1·mg^-1、0．90±0．30，NaHS干预组大鼠分别为（1．60±0．20）nmo]·min^-1·mg^-1、1．10±0．20，3组间比较差异有统计学意义（F值分别为79．39、12．28，P均〈0．05）；光镜下支气管周围炎性细胞浸润程度评分[用中位数（四分位数）]表示，正常对照组为1（0～1）分，哮喘组为3（2～4）分，NaHS干预组为1（1～2）分，3组间比较差异有统计学意义（H=16．93，P〈0．01）；哮喘组肺组织H2S含量与PEF呈正相关（r=0．74，P〈0．01）；与光镜下支气管周围炎性细胞浸润程度评分呈负相关（r=-0．64，P〈0．01）。结论内源性H2S参与了大鼠急性哮喘发病过程，外源性NaHS可以减轻哮喘气道炎症，对哮喘急性发病起到保护作用。     

氯通道CIC-1、CIC-2在人心房肌的表达及与心房颤动的关系

目的研究氯通道CIC-1和CIC-2基因在人心房组织的表达及与心房颤动（AF）的关系。方法将71例风湿性心瓣膜病接受换瓣手术患者分为三组，窦性心律（SR）组31例，阵发性房颤（PAF）组7例，慢性房颤（CAF）组33例，于术中获取右心耳组织，应用半定量逆转录-聚合酶链反应（RT—PCR）检测心房组织CIC-1和CIC-2的mR—NA相对含量。结果（1）CIC—1、CIC-2基因在人心房组织有表达。②与SR组比较，PAF组CIC-1的mRNA表达增加但无统计学意义（1．05±0．22vs1．01±0．13，P〉0．05），CAF组的表达明显增加（1．25±0．18vs1．01±0．13，P〈0．001），CAF组较PAF组亦明显增加（P〈0．01）。CIC-1的mRNA表达水平与左房内径、AF持续时间呈正相关[（r=0．344，P=0．003）（r=0．405，P〈0．001）]。③与SR组比较，PAF组CIC-2的mRNA表达无增加（1．03±0．14vs1．04±0．15，P〉0．05），CAF组的表达明显增加（1．26±0．13vs1．04±0．15，P〈0．001），CAF组较PAF组亦明显增加（P〈0．01）。CIC-2的mRNA表达与左房内径、AF持续时间呈正相关[（r=0．441，P〈0．001）（r=0．331，P=0．0C15）]。结论AF患者CIC-1、CIC-2的mRNA表达水平的增加可能是心房肌电重构的分子基础。     

非小细胞肺癌组织中核因子κB的活性及其与肿瘤细胞增殖的关系

目的研究非小细胞肺癌组织中核因子κB（nuclear Factor-κB，NF—κB）的活性及其与细胞增殖、自发性细胞凋亡的关系。方法2006年5至10月收集30例非小细胞肺癌组织标本及15例肺癌患者癌旁5cm肺组织标本。NF—κB活性通过凝胶电泳迁移率改变试验（EMSA）检测，用RT—PCR和Western blot方法检测CyclinD1含量，免疫组织化学染色法检测增殖细胞核抗原（PCNA）蛋白含量，TUNEL法检测细胞凋亡。结果癌旁肺组织、鳞癌组织、腺癌组织中NF—κB活性（吸光度，A值）分别为24826±3724、28028±4204、35425±5317，三组比较差异有统计学意义（F=78．96，P〈0．01）。鳞癌组织、腺癌组织中NF—κB活性高于癌旁肺组织中NF—κB活性，腺癌组织中NF—κB活性高于鳞癌组织中NF—κB活性。健康肺组织、鳞癌组织、腺癌组织中CyclinD1 mRNA表达量分别为2．04±0．24、2．91±0．37、4．13±0．36，三组比较差异有统计学意义（F=62．43，P〈0．01）。癌旁肺组织、鳞癌组织、腺癌组织中Cyclin D1蛋白表达量分别为0．31±0．06、0．43±0．07、0．58±0．08，三组比较差异有统计学意义（F=89．24，P〈0．01）。癌旁肺组织、鳞癌组织、腺癌组织中PCNA蛋白表达量分别为0．32±0．09、0．42±0．10、0．54±0．16，三组比较差异明显。癌旁肺组织、鳞癌组织、腺癌组织中凋亡指数分别为（2．58±0．39）％、（2．27±0．34）％、（2．92±0．59）％，三组比较无明显差异。鳞癌组织中NF—κB活性与CyclinD1 mRNA、CyclinD1蛋白、PCNA蛋白均呈正相关（r值分别为0．51、0．54和0．60，P均〈0．05）；腺癌组织中NF—κB活性与CyclinD1mRNA、CyclinD1蛋白、PCNA蛋白均呈正相关（r值分别为0．60、0．64和0．68，P均〈0．05）；鳞癌、腺癌组织中NF—κB活性与细胞凋亡指数无相关关系。结论在非小细胞肺癌组织中NF—κB活性增高。非小细胞肺癌组织中NF—κB的异常活化可能与细胞增殖有关，但不影响自发性细胞凋亡。     

肿瘤坏死因子α对暴发性肝衰竭小鼠肠上皮细胞紧密连接蛋白表达的影响

目的 研究TNFα对暴发性肝衰竭（FHF）小鼠大肠上皮细胞紧密连接蛋白occludin表达的影响。方法 采用D-氨基半乳糖（GaIN）和内毒素（LPS）联合腹腔注射（ip）制备FHF小鼠动物模型,并设立TNFα组（TNFα10μs／kg,ip）,TNFα抗体组（注射LPS和GaIN前30min尾静脉注射TNFd抗体100μg/只）。在不同的时间点（6h,9h）处死动物,应用免疫组织化学技术、Westernblot及实时定量PCR检测各组小鼠大肠上皮细胞紧密连接蛋白occludin表达的变化。结果 在生理盐水（NS）对照组,几乎整张切片上均可见到沿大肠黏膜上皮细胞膜顶端呈线性分布的occludin阳性染色,但FHF组及TNFα组小鼠的阳性染色较之明显减弱,TNFα抗体组occludin的阳性反应与Ns对照组比较无明显减弱。Westernblot结果与免疫组织化学结果相一致,FHF组及TNFα组小鼠9h时occludin蛋白含量明显下降,与NS对照组相比差异有统计学意义（0．36±0．05,0．48±0．02比0．71±0．09,P〈0．05）,TNFα抗体组与NS对照组相比差异无统计学意义（0．74±0．03比0．71±0．09,P〉0．05）。实时定量PCR结果显示,FHF组与TNFα组小鼠6h时occludinmRNA水平最低,与NS对照组相比差异有统计学意义（0．72±0．04,0．81±0．03比1．00±0．05,P〈0．05）,TNFα抗体组与Ns对照组相比差异无统计学意义（1．01±0．10比1．00±0．05,P〉0．05）。结论 在小鼠暴发性肝衰竭过程中,TNFα介导大肠上皮细胞间紧密连接蛋白occludin表达的下降。     

甲状腺功能减退对成年小鼠空间学习记忆及海马神经颗粒素表达的影响

目的观察甲状腺功能减退对成年雄性昆明小鼠空间学习记忆功能及海马内神经颗粒素（Ng）表达的影响。方法将成年雄性昆明小鼠随机分为对照组、丙硫氧嘧啶（PTU）组、PTU＋T4（甲状腺素）组。对照组饮用自来水，PTU和PTU＋T4组饮用含0．1％PTU水。6周后，PTU＋T4组腹腔注射T4（20μg·kg^-1·d^-1），连续2周。Morris水迷宫观察小鼠的空间学习记忆能力，免疫组化分析海马各亚区Ng蛋白的表达。结果PTU组小鼠体质量、血清B、T4显著低于对照组（P〈0．05）；水下平台的潜伏期明显长于对照组（P〈0．05）；Ng蛋白表达水平海马CA1区（6．61±1．25）和齿状回DG区（6．40±0．94）低于对照组（8．91±1．08、8．82±1．23，P〈0．05）。T4替代治疗后，上述各项检查与对照组比较，差异无统计学意义（P〉0．05）。结论甲状腺功能减退可逆性损害成年雄性小鼠空间学习记忆功能，其机制可能与CA1和DG区Ng蛋白表达减少有关。     

多房棘球绦虫重组BCG-EmⅡ/3疫苗诱导小鼠脾细胞亚群变化的研究

目的 探讨多房棘球绦虫重组BCG—EmⅡ／3疫苗免疫和多房棘球绦虫（Em）原头节攻击后小鼠脾CD4^＋和CD8^＋T淋巴细胞亚群的变化。方法 Balb／c小鼠随机分为疫苗皮下注射组、鼻腔接种组、空载体对照组、卡介苗（BCG）对照组和磷酸缓冲液（PBS）对照组。疫苗免疫8周时用Em原头节进行攻击，感染后18周杀鼠取脾，分离脾细胞，流式细胞仪检测脾CD4^＋和CD8^＋T淋巴细胞亚群的百分比。结果 疫苗皮下注射组和鼻腔接种组的脾CD4^＋T细胞亚群比值分别为0．345±0．018、0．314±0．014，与PBS对照组（0．216±0．027）比较明显增高（q值分别为3．93、3．76，P〈0．01）；CD8^＋T细胞亚群比值分别为0．091±0．005、0．083±0．007，与PBS对照组（0．085±0．018）比较无明显变化（q值分别为0．92、0．89，P〉0．05）；CD4^＋／CD8^＋亚群比值分别为3．81±0．30、3．80±0．44，与PBS对照组（2．75±1．08）比较明显增高（q值分别为3.25、3．06，P〈0．01）。皮下注射组的CD4^＋和CD8^＋T细胞亚群数目显著高于鼻腔内接种组（q值分别为3．52、2．63，P〈0．01或〈0．05）。结论 CD4^＋T细胞亚群在多房棘球绦虫重组BCG-EmⅡ／3疫苗诱导的小鼠抗Em原头节攻击感染的保护性免疫机制中起关键作用。     

特发性局灶节段性肾小球硬化患者SYNPO基因变异和多态性分析

目的：探讨特发性局灶节段性肾小球硬化（idiopathicFSGS）中SYNPO基因变异和多态（SNP）特点。方法：以82例特发性FSGS和70例健康人为研究对象。盐析法提取外周血基因组DNA、引物设计、PCR扩增后测序。基因数据库匹配筛选，结合患者肾组织Synaptopodin和患者父母头发DNA检测验证其致病意义。SNP位点H—W平衡检验后行基因频率、基因型和临床表型关联分析。结果：1例5’UTR变异1—24G〉A，其父母未发现相同变异，。肾组织Synaptopodin较正常和非变异NSFSGS组下降（321．33±18．01比514．00±31．21，P〈0．01）；1例单核苷酸变异437C〉T（Pro146Leu），肾组织Synaptopodin较正常和非变异非NSFSGS组下降（385．67±15．95比635．50±23．95，P〈0．01）；1例单核苷酸变异1903A〉c（Thr635Pro），其父母未发现相同变异，肾组织Synaptopodin较正常和非变异NSFSGS组明显下降（160．67±27．68比514．00±31．21，P〈0．01）；另外发现1例新同义变异1488C〉T（Thr496Thr）和5例同义变异1578C〉T（Pr0526Pro）。未发现疾病易感SNP位点。结论：散发性FSGS患者中可能存在SYNPO基因致病变异位点，其可能在散发性FSGS发病中起作用。     

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.     

MUTATION FREQUENCY IN NURSES AND PHARMACISTS WORKING WITH CYTOTOXIC DRUGS

Individuals occupationally exposed to cytotoxic drugs may be at risk owing to the effects of these agents on DNA. As an index of DNA damage, in vivo mutations were measured in lymphocytes from 24 oncology nurses or pharmacists and 24 matched controls. Mutation frequency was significantly increased in exposed individuals and appeared to be related to duration of exposure. However, the overall magnitude of the increase was small and its biological significance remains to be determined.     

A single injection of adrenergic agonists enhances pineal melatonin production in Turkish hamsters

Abstract: The purpose of this study was to determine whether the pineal gland of Turkish hamsters (Mesocricetus brandti) responds to adrenergic agonists with an increase in melatonin production, and, if it does, whether the sensitivity of the pineal gland to agonists would differ throughout the dark phase. Adult Turkish hamsters weighing 110–210 g received a subcutaneous injection of isoproterenol (ISO, 1 mg/kg B.W.) or norepinephrine (NE, 1 mg/kg B.W.) at different times of night. Animals exposed to LD 16:8 responded to ISO or NE with increased pineal melatonin content only when injected at dawn, when endogenous melatonin is at basal or near-basal levels. When the 8 hr scotophase was entirely replaced with light, the responsiveness to ISO injections at dawn disappeared. In animals exposed to light from 30 min prior to injection to the time of sacrifice, ISO injections increased pineal melatonin content (P < 0.005, three-way ANOVA), which varied, depending on the specific time of injection (effect of time of night, P < 0.05, three-way ANOVA). These results demonstrate that (1) adrenergic agonists enhance the production of pineal melatonin in Turkish hamsters, (2) this stimulatory effect takes place late, but not early in the 8 hr scotophase, and (3) the adrenergic induction of pineal melatonin production in Turkish hamsters requires priming by darkness during the appropriate circadian phase.     

Immune effector mechanisms in malaria: An update focusing on human immunity

The past decade has witnessed dramatic decreases in malaria‐associated mortality and morbidity around the world. This progress has largely been due to intensified malaria control measures, implementation of rapid diagnostics and establishing a network to anticipate and mitigate antimalarial drug resistance. However, the ultimate tool for malaria prevention is the development and implementation of an effective vaccine. To date, malaria vaccine efforts have focused on determining which of the thousands of antigens expressed by Plasmodium falciparum are instrumental targets of protective immunity. The antigenic variation and antigenic polymorphisms arising in parasite genes under immune selection present a daunting challenge for target antigen selection and prioritization, and is a given caveat when interpreting immune recall responses or results from monovalent vaccine trials. Other immune evasion strategies executed by the parasite highlight the myriad of ways in which it can become a recurrent infection. This review provides an update on immune effector mechanisms in malaria and focuses on our improved ability to interrogate the complexity of human immune system, accelerated by recent methodological advances. Appreciating how the human immune landscape influences the effectiveness and longevity of antimalarial immunity will help explain which conditions are necessary for immune effector mechanisms to prevail.     

Secondary aortoduodenal fistula

Aorto-duodenal fistulae （ADF） are the most frequent aorto-enteric fistulae （80%）, presenting with upper gastrointestinal bleeding. We report the first case of a man with a secondary aorto-duodenal fistula presenting with a history of persistent occlusive syndrome. A 59-year old man who underwent an aortic-bi-femoral bypass 5 years ago, presented with dyspepsia and biliary vomiting. Computed tomography scan showed in the third duodenal segment the presence of inflammatory tissue with air bubbles between the duodenum and prosthesis, adherent to the duodenum. The patient was submitted to surgery, during which the prosthesis was detached from the duodenum, the intestine failed to close and a gastro-jejunal anastomosis was performed. The post-operative course was simple, secondary ADF was a complication （0.3%-2%） of aortic surgery. Mechanical erosion of the prosthetic material into the bowel was due to the lack of interposed retroperitoneal tissue or the excessive pulsation of redundantly placed grafts or septic procedures. The third or fourth duodenal segment was most frequently involved. Diagnosis of ADF was difficult. Surgical treatment is always recommended by explorative laparotomy. ADF must be suspected whenever a patient with aortic prosthesis has digestive bleeding or unexplained obstructive syndrome. Rarely the clinical picture of ADF is subtle presenting as an obstructive syndrome and in these cases the principal goal is to effectively relieve the mechanical bowel obstruction.     

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.     

Married to M. tuberculosis: risk of infection and disease in spouses of smear-positive tuberculosis patients

Objectives To quantify the risk of infection and disease in spouses of tuberculosis patients and the extent to which intervention could reduce the risk in this highly exposed group. Methods We compared HIV prevalence, TB prevalence and incidence and tuberculin skin test (TST) results in spouses of TB patients and community controls. HIV‐positive spouses were offered isoniazid preventive therapy (IPT), and TST was repeated at 6, 12 and 24 months. Results We recruited 148 spouses of smear‐positive patients ascertained prospectively and 3% had active TB. We identified 203 spouses of previously diagnosed smear‐positive patients, 11 had already had TB, and the rate of TB was 2.4 per 100 person years(py) over 2 years (95% CI 1.15–5.09). 116 were found alive and recruited. HIV prevalence was 37% and 39% in the prospective and retrospective spouse groups and 17% in controls. TST was ≥10 mm in 80% of HIV negative and in 57% of HIV‐positive spouses ascertained retrospectively; 74% HIV negative and 62% HIV‐positive spouses ascertained prospectively, and 48% HIV negative and 26% HIV‐positive community controls. Of 54 HIV‐positive spouses, 18 completed 6‐month IPT. At 2 year follow‐up, 87% of surviving spouses had TST ≥10 mm and the rate of TB was 1.1 per 100 py (95% CI 0.34–3.29). Conclusions Spouses are a high‐risk group who should be screened for HIV and active TB. TST prevalence was already high by the time the spouses were approached but further infections were seen to occur. Uptake and adherence to IPT was disappointing, lessening the impact of short‐duration therapy.