Melatonin reduces nitric oxide synthase activity in rat hypothalamus

Abstract: In this report, rat hypothalamic nitric oxide synthase (NOS) activity is shown to be partially inhibited by physiological concentrations of the pineal hormone melatonin. In vitro studies demonstrate that 1 nM melatonin, which approximates the physiological concentration of the hormone at night, significantly inhibited NOS activity. In vivo studies show that administering melatonin or collecting the hypothalamus from animals at night, when endogenous melatonin levels are elevated, results in a significant decrease of NOS activity. Results also show that calmodulin may be involved in this process since its presence in the incubation medium prevents the inhibitory effect of melatonin on NOS activity.     

Immunology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.     

Serotonin 5- HT (2C) receptor knockout mice: autoradiographic analysis of multiple serotonin receptors.

Quantitative receptor autoradiography was used to study possible alterations of the densities of multiple serotonin (5-HT) receptor subtypes and of serotonin transporter in the brain of 5-HT(2C) receptor knockout mice. The radioligands employed were [(3)H]citalopram, [(3)H]WAY100,635, [(3)H]8-OH-DPAT, [(3)H]GR125743, [(3)H]sumatriptan, [(3)H]MDL100,907, [(125)I](+/-)DOI, [(3)H]mesulergine, [(3)H]5-HT, [(3)H]GR113808, and [(3)H]5-CT. As expected, radioligands that label 5-HT(2C) receptors showed a complete absence of labeling in mutant mice choroid plexus and significantly reduced densities in other brain regions expressing 5-HT(2C) receptors. With the rest of the radioligands, no significant alterations in the densities of labeled sites were found in any brain region. In situ hybridization showed no changes in 5-HT(2A) receptor and serotonin transporter mRNA levels, whereas 5-HT(2C) receptor mRNA levels were reduced in certain brain regions. The present results indicate that the mouse serotonergic system does not exhibit compensatory up- or down-regulation of the majority of its components (serotonin transporter and most 5-HT receptor subtypes) in response to the absence of 5-HT(2C) receptors.     

巢式聚合酶链反应检测脑脊液中单纯疱疹病毒DNA

应用巢式聚合酶链反应(PCR)检测患者脑脊液(CSF)中单纯疱疹病毒1型(HSV-1)DNA。23例经鞘内HSV-1特异性IgG抗体检测阳性的“HSV-1型性脑炎(HSE)”中19例PCR阳性,4例阴性患者病程均超过1个月。22例IgG阴性的“散发性脑炎”中7例PCR阳性,此7例皆于发病1周内检查CSF,其中2例取材于发病当日。1周后复查7例患者,CSF PCR仍为阳性,IgG皆阴性,提示PCR适用于HSE的早期诊断。     

CD15 (LeuM1) immunoreactivity: Prognostic factor for sporadic and hereditary medullary thyroid cancer?

Patients treated for sporadic and hereditary medullary thyroid carcinoma (MTC) have varying rates of persistent disease, recurrence, and survival. The aim of this study was to correlate the immunoreactivity of the monoclonal antibody CD15 (LeuM1) to initial clinical findings and the outcome of treatment. The primary tumors of 75 patients with sporadic MTC, 7 with hereditary disease, and 3 members of MEN 2A families were studied. Of these subjects 74 (87%) showed no or little immunoreactivity (<15% positive cells; score 0) in most tumors. The remaining 13% had surgery for tumors with more than 15% cells with positive staining (score I). There was no correlation between LeuM1 immunoreactivity and sex, age, and type of MTC. There was, however, a significant correlation with the pTNM classification and UICC staging. The prognosis for patients with score 0 was significantly better than score 1 patients. CD15 immunoreactivity appears to be a predictive factor in sporadic and hereditary MTC. Lymph node dissection seems to be more successful in patients with score 0 tumors than in those with score 1 tumors. The question of reoperation in patients with recurrence of disease (especially with biochemical recurrence or persistence) should be discussed on the basis of CD15 immunoreactivity.

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Resumen Los pacientes tratados para carcinoma medular, esporádico y hereditario, de la glándula tiroides (CMT) exhiben grandes variaciones en las tasas de enfermedad persistente, recidiva y sobrevida. El propósito del presente estudio fue establecer la correlación entre la inmunorreactividad del anticuerpo CD15 (LeuM1) y los hallazgos clínicos iniciales, así como con el resultado final del tratamiento.Se estudiaron los tumores primarios de 75 pacientes con CMT esporádico, de siete con enfermedad hereditaria y de 3 miembros de familias con síndrome NEM2A.Setenta y cuatro pacientes (87%) exhibieron ninguna o muy baja inmunorreactividad (menos de 15% de células positivas; puntaje 0) en la mayoría de los tumores. El 13% restante fue sometido a cirugía por tumores con más de 15% de las células con coloración positiva (puntaje 1). No se evidenció correlación entre la inmunorreactividad LeuM1 y el sexo, edad o tipo del CMT. Sin embargo, sí apareció una correlación significativa con la clasificiación pTNM y la estadificación de la UICC. El pronóstico de los pacientes con puntaje 0 resultó significativamento mejor que el de los pacientes con puntaje 1.La inmunorreactividad CD15 parece ser un factor de predicción de pronóstico en el CMT esporádico y familiar. La disección ganglionar parece ser más exitosa en pacientes con tumores de puntaje 0 que en los que portan tumores con puntaje 1.El interrogante en cuanto a reoperación en pacientes con recidiva de la enfermedad (especialmente cuando hay recidiva o persistencia bioquímica) debe ser considerada con base en la inmunorreactividad CD15.

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Résumé Les taux de maladie persistante, de récidive et de survie chez des patients traités pour cancer médullaire sporadique et héréditaire de la thyroïde (CMT) sont très variables. Le but de cette étude a été de corréler l'immunoréactivité des anticorps monoclonaux CD15 (LeuM1) à des données cliniques initiales et l'évolution finale du traitement des CMT. On a étudié 75 patients ayant un CMT primitif, sept ayant une maladie héréditaire, et trois membres d'une famille MEN 2A. Soixante quatre patients (87%) avaient peu ou pas d'immunoréactivité (moins de 15% de cellules positive: score = 0). Les 13% restants ont eu une chirurgie pour les tumeurs ayant un pourcentage > 15 (score = 1). Il n'y avait aucune corrélation entre l'immunoréactivité LeuM1 et le sexe, l'âge et le type de CMT. Il y avait, en revanche, une corrélation significative entre la classification pTMN et le stage UICC. Le pronostic des patients ayant un score = 0 était significativement meilleur que celui des patients ayant un score = 1. L'immunoréactivité CD15 apparaît comme étant un facteur pronostique des CMT. Le curage lymphatique

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Members and institutions are listed in Table 1.     

Pharmacology of the AC AT Inhibitor Avasimibe (CI‐1011)

Avasimibe is a novel orally bioavailable ACAT inhibitor, currently under clinical development (phase III trials). It was safe when administered to rats, dogs, and humans. In vitro studies in human macrophages demonstrated that avasimibe reduces foam cell formation not only by enhancing free cholesterol efflux, but also by inhibiting the uptake of modified LDL. The concentration‐dependent reduction in cellular cholesteryl ester content in these cells was not accompanied by an increase in intracellular free cholesterol, which is in agreement with a good safety profile for avasimibe. In the liver, avasimibe caused a significant reduction in the secretion of apo B and apo B‐containing lipoproteins into plasma. Avasimibe induced cholesterol 7α‐hydroxylase and increased bile acid synthesis in cultured rat hepatocytes, and its administration to rats did not produce an increase in lithogenicity index of the bile. The hypolipidemic efficacy of the compound was demonstrated in cholesterol‐fed as well as in non‐cholesterol‐fed animals. In these models, plasma cholesterol levels were reduced, mainly due to the decrease in the non‐HDL cholesterol fraction. Clinical data are scarce, but in a study performed in 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia, avasimibe, 50–500 mg/day, significantly reduced plasma total triglyceride and VLDL‐cholesterol. Although total cholesterol, LDL‐cholesterol, and HDL‐cholesterol were unchanged, it must be stressed that animal data suggest that avasimibe may have direct antiatherosclerotic activity in addition to its cholesterol‐lowering effect. Avasimibe treatment can also contribute to increase plaque stability, as it reduces the accumulation of lipids in the arterial wall, inhibits macrophage infiltration into the media and reduces matrix metalloproteinase expression and activity. Moreover, avasimibe and statins have been shown to have synergistic effects, and the combination therapy may not only inhibit atherosclerotic lesion progression but also induce lesion regression, independently of changes in plasma cholesterol.     

错畸形患者的Howes值测量分析

目的:本研究采用Howes法评估牙弓骨量与牙量的协调性,探讨其在正畸临床诊断与矫治设计确定拔牙与非拔牙中的应用价值。方法:选取第四军医大学口腔医学院正畸门诊患者80人,男、女拔牙与非拔牙各20例。测量牙量(TM)、双尖牙弓宽径(PMD)、双尖牙根尖基骨宽径(PMBAW)、基骨弓长度(BAL),并计算PMD/TM、PMBAW/TM、BAL/TM值,对其进行统计学处理与分析。结果:男女两组比较TM、PMD、PMBAW、BAL值有显著性差异,男性大于女性;但PMD/TM、PMBAW/TM、BAL/TM值无统计学意义;拔牙组与非拔牙组比较,PMD/TM、PMBAW/TM、BAL/TM值有显著性差异。结论:采用Howes法评估牙弓骨量与牙量对正畸临床的诊断和拔牙与非拔牙矫治设计有一定的指导意义。     

阻塞性睡眠呼吸暂停综合征患者手术治疗的麻醉研究

目的：探讨阻塞性睡眠呼吸暂停综合征(obstructive sleep apnea syndrome，OSAS)患者手术治疗的麻醉处理。方法：72例OSAS患者手术前先正压通气治疗(continue positive airway pressure，CPAP)和评价上气道，55例患者经鼻或经口气管插管全身麻醉；在手术完毕患者完全清醒后拔除插管。结果：72例患者中，轻度16例、中度24例、重度32例。合并晨起高血压28例，心电图均有不同程度心肌缺血的表现；红细胞增多症12例；腭咽平面Ⅰ级9例、Ⅱ级24例、Ⅲ级的27例、Ⅳ级12例。术前3．5d行自动调压正压通气治疗(Auto—CPAP)，经口气管内插管48例，经鼻气管内插管6例，均无术中插管困难和术后高血压危象，呼吸道梗阻发生。结论：充分认识OSAHS患者全身麻醉的手术风险，术前CPAP治疗和上气道评估，术中正确处理、严格掌握气管内插管、术后拔管的时机，是保证OSAHS患者手术成功、麻醉安全的关键。     

胃镜取上消化道异物112例体会

我院从2000年至2005年,共用电子胃镜取上消化道异物112例,经急诊胃镜取出104例,失败2例,效果良好。胃镜取异物具有方便快捷、价廉、创伤小等优点,值得推广,现将取得的经验操作体会报告如下。1资料与方法1.1一般资料本组中男74例,女38例,年龄2岁~65岁,平均年龄42岁,10岁以下儿童为17例,112例中咽部异物17例,均为鱼刺,食道异物35例,胃内异物56例,十二指肠球部异物2例,降部异物2例,除外咽部17例鱼刺,所剩95例中难取异物44例,其中带钩义齿11例,刀片8例,玻璃片6例,铁片3例,铁钉2例,铁勺2例,戒指2例,枣核1例,牙刷4例,方便筷2例,围棋3例。1.2器械OLYMPUS电子胃镜、活检钳、鼠齿钳、网篮、胃镜套管、自制的内镜前端保护套(制作方法:将避孕套前端剪开尾端固定在镜头前方1cm并反折,用一皮圈固定外接一拉线,使用石蜡油润滑)。1.3操作方法1.3.1术前准备详细询问病史,了解异物的大小、形状、材质,并行拍片进一步了解有无气腹症及异物所处位置及性状。对锐利者准备好保护装置,胃内食物较多者嘱其平卧,禁食水,保持平静,必要时用X线透视动态了解异物是否移动。1.3.2麻醉采用利多卡因...