Functional meaning of tryptophan-induced increase of 5-HT metabolism as clarified by in vivo voltammetry

Differential pulse voltammetry with carbon fiber electrodes was used to study serotonin (5-HT) metabolism in freely moving rats. The electrodes implanted in the striatum recorded the extracellular 5-hydroxyindoleacetic acid (5-HIAA) oxidation peak after oral tryptophan (150 mg/kg). This 5-HT precursor did not modify the 5-HIAA peak in any rat tested, but it raised 5-HIAA levels determined in total tissue by a classical biochemical method (HPLC). The administration of 5-hydroxytryptophan (5-HTP) (25 mg/kg i.p.) induced an increase of 5-HIAA detectable both in the extracellular medium by voltammetry and in tissue samples. As previously shown, dorsal raphe electrical stimulation raises extracellular 5-HIAA in the striatum and this effect is enhanced by pretreatment with tryptophan. The results suggest that tryptophan in 'normal' conditions enhances 5-HT metabolism without affecting 5-HT release unless such release is stimulated. 5-HTP increases 5-HT metabolism and release.     

Mechanism of action of lithium on acetylcholine receptor metabolism in skeletal muscle

Changes in the levels of cations within skeletal muscle are thought to mediate the neural regulation of turnover of extrajunctional acetylcholine receptors (AChRs). We have used lithium as a probe of these cation influences because of its resemblance to calcium and other ions. In the present experiments we studied the mechanism of action of lithium on AChR metabolism in cultured mammalian skeletal muscle. We measured the effects of lithium on AChR turnover (using [125I]alpha-bungarotoxin binding), and evaluated the resemblance of lithium and calcium in producing their effects on AChR metabolism. Our results provide insight into the mechanisms of action of lithium and the cellular processes controlling AChR metabolism in muscle. Lithium reduces the number of AChRs in skeletal muscle in vitro to a degree similar to that which we previously reported in vivo. Lithium appears to enter cells via both sodium and calcium channels. It then produces its effect on levels of AChRs primarily by selectively reducing AChR synthesis and insertion into the surface membrane. Lithium induces this change in AChR metabolism in a manner resembling neural and calcium-mediated effects on AChRs. Phosphoinositide pathways may be involved in the lithium-induced effects. Further analysis of the effects of lithium on AChR turnover should provide new information about the mechanisms underlying the cellular control of receptor metabolism.     

大鼠肝缺血再灌注损伤时脑组织损伤机制的探讨

缺血再灌注损伤是一种全身性反应，某个器官的缺血再灌注损伤可引起其他器官不同程度的损害，即远隔器官的次级损伤。研究表明，肝缺血再灌注（I／R）损伤不仅导致肝功能衰竭，也可引起心、肺、肾等脏器的损伤，且损伤主要发生在再灌注阶段。脑组织是最易受影响的器官之一，肝I／R可引起脑组织损伤。本实验旨在观察肝I／R损伤时c-fos基因、诱导型一氧化氮合酶（iNOS）在脑组织中表达和髓过氧化物酶（MPO）、丙二醛（MDA）水平变化及相互关系，并以琥珀酸脱氢酶（SDH）、三磷酸腺苷（ATP）酶、乳酸脱氢酶（LDH）、乳酸（LD）等指标的变化，探讨肝I／R损伤时脑组织能量代谢的变化及其可能的机制。     

不同糖耐量个体血浆内脂素水平的变化

目的探讨不同糖耐量人群血浆内脂素(visfatin)水平变化及其与体重指数(BMI)、腰臀比(WHR)、血糖、血浆胰岛素水平等的关系。方法采用酶联免疫法测定了2型糖尿病(DM)、糖耐量受损(IGT)患者和正常健康人空腹和糖负荷后2h血浆内脂素水平,并分析血浆内脂素与BMI、WHR、胰岛素抵抗指数(HOMA-IR)、血脂、血糖、血浆胰岛素和游离脂肪酸(FFA)水平等的关系。结果(1)2型DM患者空腹和糖负荷后2h血浆内脂素水平明显低于正常对照组[(11.63±7.48)μg/L vs(16.82±6.06)μg/L和(12.02±6.86)μg/L vs(16.26±7.78)μg/L,均P＜0.05],IGT组内脂素水平介于2型DM和对照组之间；肥胖组血浆内脂素水平较非肥胖组有升高趋势；(2)相关性研究显示,血浆内脂素水平与WHR呈正相关(r=0.42,P＜0.01),与糖负荷后2h血糖(2hPG)和HbA_(IC)呈明显负相关(r=-0.33,P＜0.01和r=～0.25,JP＜0.05)；(3)多元线性逐步回归分析表明WHR、HbA_(IC)空腹血糖、2hPG、高密度脂蛋白胆固醇分别是影响血浆内脂素水平的独立相关因素。结论血浆内脂素水平与糖代谢状态有关,并可能在肥胖和2型糖尿病的发生和发展中具有一定的作用。     

Covalent adducts of proteins with acetaldehyde in the liver as a result of acetaldehyde administration in drinking water

BACKGROUND/AIMS: Acetaldehyde, the first metabolic product of ethanol, has been suggested to be responsible for several adverse effects of ethanol through its ability to form covalent adducts with proteins and cellular constituents. It has recently been suggested that acetaldehyde derived from microbial ethanol oxidation in the gut could also contribute to the effects of ethanol in the liver. The present work aimed to examine whether modification of proteins by acetaldehyde occurs in rat liver as a result of acetaldehyde administration in drinking water. METHODS: Rats were fed with either 0.7% acetaldehyde (n=10) or water (n=10) for 11 weeks. At the end of the feeding period, liver specimens were processed for immunohistochemistry for protein adducts with acetaldehyde and for hepatic cell type-specific protein markers. RESULTS: Mild fatty change was found in the liver of the acetaldehyde-treated animals but not in the control animals. Immunohistochemical stainings for acetaldehyde adducts revealed intensive positive staining for acetaldehyde adducts in eight (80%) of the animals fed with acetaldehyde. The adducts were predominantly perivenular, although positive staining also occurred along the sinusoids and in the periportal area. Double immunofluorescence staining experiments revealed that hepatocytes were the primary targets of acetaldehyde adduct deposition, although stellate cells and Kupffer cells also showed weak positive reactions. CONCLUSIONS: The present data indicate that acetaldehyde-protein adducts are formed in the liver of animals following acetaldehyde administration in drinking water, which may contribute to the hepatotoxicity of extrahepatic acetaldehyde. These findings should be implicated in studies on the extrahepatic pathways of ethanol oxidation.     

Identification of differentially expressed genes in normal mucosa, adenoma and adenocarcinoma of colon by SSH

Abbreviation CRC colorectal cancer.SSHsuppression subtrsctive hybridization.LD PCR longdistance polymerase chain reaction.HLA human leukocyteantigen.IGRBP insulin-like growth factor binding protein.GN guanylin,EF1 elongation factor 1AIM To construct subtracted cDNA libraries and furtheridentify differentially expressed genes that are related tothe development of colorectal carcinoma(CRC).METHODS Suppression subtractive hybridization(SSH)was done on cDNAs of normal mucosa,adenoma andadenocarcinoma tissues from the same patient.Threesubtracted cDNA libraries were constructed and thenhybridized with forward and backward subtracted probesfor differential screening.Positive clones from eachsubtracted cDNA library were selected for sequencing andBLAST analysis.Finally,virtual Northern Blot confirmedsuch differential expression.RESULTS By this way,there were about 3-4×10~2clones identified in each subtracted cDNA library,inwhich about 85% positive clones were differentiallyscreened.Sequencing and BLAST homology searchrevealed some clones containing sequences of knowngene fragments and several possibly novel genes showingfew or no sequence homologies with any knownsequences in the database.CONCLUSION All results confirmed the effectiveness andsensitivity of SSH.The differentially expressed genesduring the development of CRC can be used to shed lighton the pathogenesis of CRC and be useful genetic markersfor early diagnosis and therapy.     

鲑鱼降钙素对老年骨科手术后患者骨代谢的影响

目的：观察老年患者骨科围术期骨代谢变化特点及术后应用鲑鱼降钙素对骨代谢的影响。方法年龄＞60岁老年患者90例纳入本研究,男性21例,女性69例。其中行髋关节手术37例,膝关节手术38例,腰椎手术15例。将研究对象随机分为2组,治疗组45例,术后应用鲑鱼降钙素＋碳酸钙片＋活性维生素D抗骨质疏松治疗;对照组45例,术后应用碳酸钙片＋活性维生素D治疗。分别于术前、术后1周、术后3个月测定静脉血骨钙素（OC）及Ⅰ型胶原交联C端肽（β-CTX）水平;于术前、术后3个月采用DEXA双能X线骨密度仪测定患者腰椎及髋部骨密度。结果共78例患者完成随访,对照组（n＝37）术后1周β-CTX均值较术前明显升高（P＜0.001）,术后3个月较术前变化无统计学意义（P＞0.05）;治疗组（n＝41）术后1周β-CTX均值较术前明显升高（P＜0.001）,术后3个月较术前明显降低（P＜0.05）;对照组术后1周OC均值较术前明显降低（P＜0.05）,术后3个月较术前无明显变化（P＞0.05）;治疗组术后1周OC均值较术前明显降低（P＜0.001）,术后3个月较术前无明显变化（P＞0.05）;治疗组与对照组腰椎、髋部BMD术前与术后3个月差异均无统计学意义（均P＞0.05）。结论老年患者接受骨科手术前后骨代谢发生改变,手术后1周骨吸收过程活跃,骨形成过程受抑制;术后应用鲑鱼降钙素3个月抗骨质疏松治疗能有效抑制骨吸收,但对促进骨形成无明显影响。     

不同Child?Pugh分级血吸虫性肝硬化并发糖代谢异常的临床观察

目的 目的 分析不同Child?Pugh分级血吸虫性肝硬化患者并发糖代谢异常情况。方法 方法 观察90例不同Child?Pugh分 级血吸虫性肝硬化患者空腹血糖 （FBG）、 餐后2 h血糖 （2hBG）、 餐后3 h血糖 （3hBG）、 血清口服胰岛素 （FINS）、 胰岛素释放 指数 （IRI）、 胰岛素抵抗指数 （IRS） 变化。结果 结果 90例血吸虫性肝硬化患者随着Child?Pugh分级增加, 糖代谢异常逐渐加 重, 但大多患者 （83.1%） FBG正常或轻度升高。7例肝源性糖尿病患者中, 仅1例为女性。结论 结论 血吸虫性肝硬化并发糖代 谢异常的比例较低, 且以男性发病为主。