Morphologic evaluation of the liver in hereditary angioedema patients on long-term treatment with androgen derivatives

17 alpha-Alkylated androgens are highly effective in preventing attacks in HAE patients. These drugs, however, seem to be implicated in the development of cholestatic jaundice, peliosis hepatis, and liver tumors. In order to assess the risk-benefit balance of the long-term therapy with androgen derivatives, a follow-up investigation was performed in 13 HAE patients. The results of this study indicate that long-term treatment (15 to 47 mo) with low doses of danazol or stanozolol does not induce significant hepatic damage detectable by laboratory tests or liver biopsy. However, the limited number of patients, although in a rather long period of observation, still suggests a careful control and the use of minimal effective doses.     

Selective uptake of [3H]glutamine and [3H]glutamate into neurons and satellite cells of dorsal root ganglia in vitro

The uptake of [³H]glutamate and [³H]glutamine into rat dorsal root ganglia has been examined by autoradiography and thin-layer chromatography. [³H]glutamate was selectively accumulated by satellite glial cells and after 10 min, 53% of this had been converted to [³H]glutamine. [³H]glutamine, on the other hand, entered neuronal perikarya and 40% was converted to [³H]glutamate. It is suggested that these selective uptake processes provide supporting evidence for the existence of a neuronal-glial glutamine cycle in dorsal root ganglia. Small dark (B) cells accumulated 6 times as much [³H]glutamine as did large light (A) cells. The reasons for this marked difference in the metabolism of the two main types of dorsal root ganglion neurone are discussed.     

Effects of nigral application of muscimol on release of [3H]γ-aminobutyrate and on multi-unit activity in various cat thalamic nuclei

The release of [³H]γ-aminobutyrate (GABA) neosynthesized from [³H]glutamine was estimated in one substantia nigra and in the ipsilateral thalamus of halothane-anesthetized cats by perfusing a [³H]glutamine-enriched physiological medium through a push-pull cannula implanted in the two structures under investigation. After two hours of superfusion, muscimol (10^?6 M) was delivered through the nigral push-pull cannula for 50–60 min and local- and distal-evoked changes of [³H]GABA release were analyzed. In some experiments, changes of global neuronal activity induced by muscimol application were recorded in different thalamic nuclei, using a bipolar electrode. In a few of the above experiments, biochemical and electrophysiological determinations were simultaneously performed in the substantia nigra and the thalamus. The nigral application of muscimol (10^?6 M) induced locally an activation of the substantia nigra reticulata cells, as well as an increase in release of [³H]GABA.Distally, in the thalamus, two types of biochemical and electrophysiological responses were observed according to the localization of the tip of the push-pull cannula or the electrode. (1) An increased release of [³H]GABA and a depression of the global multi-unit cellular activity were obtained in the ventralis medialis-ventralis lateralis, the centralis lateralis and the paracentralis nuclei. These effects could reflect an activation of the GABAergic nigrothalamic neurons projecting to these different thalamic nuclei. (2) In contrast, in the medialis dorsalis paralamellar zone adjacent to the intralaminar nuclei of the thalamus, a decrease of [³H]GABA release and an activation of the multi-unit activity were obtained. These latter results may suggest either a polysynaptic response or the non-GABAergic nature of the nigrothalamic neurons afferent to the medialis dorsalis paralamellar zone.     

Cellular localization of the uptake of [3H]taurine and [3H]β-alanine in cultures of the rat central nervous system

The cellular localization of the uptake of [³H]taurine and [³H]β-alanine was studied in cultures of rat central nervous system using autoradiography. In brain stem and spinal cord cultures, both amino acids were taken up by neurones and glial cells. In cerebellar cultures, [³H]taurine was accumulated by all glial cells and by a small number of neurones, whereas [³H]β-alanine was only taken up by glial elements. The uptake of both amino acids was sodium and temperature dependent, indicating an active transport mechanism.The results provide further support for the hypothesis that taurine and β-alanine are neurotransmitters in the mammalian central nervous system.     

Reflections on experimental and human pathology of aggression

On the basis of the already proposed distinction between "normal" and "pathological" aggression in laboratory animals, it is essayed an integration of the experimental findings derived from a specific animal model of aggression with the available clinical information on human violent behavior. The too disregarded importance of the role played by the inhibitory control of brain functions, appears instead reportedly essential in the regulation of emotions and behavior, and is of great relevance in explaining the behavioral changes that follow induced or spontaneous impairment of the serotonergic system of the brain. As a matter of fact, the numerous evidences indicate that genetic predisposition and induced or acquired defects of serotonergic inhibitory control greatly concur to precipitate anomalous strong aggression. Interestingly, the cluster of symptoms presented by laboratory rats in consequence of the serotonergic discontrol, has many unexpected similarities with several pathological conditions of man. This fact confers to laboratory experiments the value of a tool aimed at a better understanding of the biological mechanisms which underlie corresponding alterations of human conduct, with special reference to pathological aggression and violence. In this line, some specific nutrient defects and/or malabsorption conditions can be important in the facilitation or elicitation of mental illness including human aggression. In addition, the efficacy and neurochemical action of those substances capable to partially or completely block or prevent experimental aggression, will likely assume equal relevance in the management or prevention of human violent behavior.     

Gadd45β和Gadd45γ在亚砷酸钠所致的MIHA细胞周期改变中的作用

目的 探索Gadd45β和Gadd45γ在亚砷酸钠所致的MIHA细胞周期改变中的作用,为砷中毒的人群防治提供依据。方法 收集贵州省兴仁县雨樟镇交乐病区砷中毒人群以及格沙屯正常人群分别作为砷中毒组和对照组,实时荧光定量PCR检测各组人群Gadd45β和Gadd45γ基因mRNA表达水平。同时,分别以不同剂量亚砷酸钠、不同时间处理MIHA细胞,流式细胞术测定细胞周期改变情况,实时荧光定量PCR和免疫印迹法分别检测Gadd45β和Gadd45γ基因mRNA表达水平和蛋白表达情况。在上述实验基础上,针对Gadd45β和Gadd45γ基因分别设计的siRNA作用于染砷的MIHA细胞,反向验证Gadd45β和Gadd45γ基因在砷致细胞周期改变过程中的影响。统计学分析采用独立样本t检验比较两组间差异,采用单因素方差比较多组间差异。结果 人群实验研究发现,与对照组相比,砷中毒患者Gadd45β和Gadd45γ基因mRNA表达水平升高（t = 2.576,P = 0.011;t = 2.312,P = 0.022）;MIHA细胞中,随亚砷酸钠染毒剂量、染毒时间增加,细胞G2/M期比例明显升高（F剂量 = 340.136,P＜0.001;F时间 = 49.194,P＜0.001）;在相对较低亚砷酸钠浓度（低于20 μmol/L）、一定时间内（低于48 h）Gadd45β和Gadd45γ基因mRNA和蛋白表达水平随染砷剂量、染砷时间升高而升高,超过该浓度范围和作用时间后,出现表达下降的现象（Gadd45β:F剂量-蛋白 = 37.568,P＜0.001;F剂量- mRNA = 9.771,P＜0.001;F时间-蛋白 = 61.144,P＜0.001;F时间- mRNA = 46.366,P = 0.001;Gadd45γ:F剂量-蛋白 = 12.989,P = 0.001;F剂量- mRNA = 23.613,P＜0.001;F时间-蛋白 = 27.425,P＜0.001;F时间- mRNA = 37.969,P＜0.001）。转染siRNA分别下调Gadd45β和Gadd45γ的表达后,细胞周期都出现G2/M期比例下调（t = 3.053,P = 0.038;t = 14.47,P＜0.001）。结论 砷致Gadd45β和Gadd45γ基因表达水平升高在其诱导MIHA细胞出现G2/M期阻滞过程中发挥重要作用。     

Human Peripheral Eosinophils with Receptors for IgM: Demonstration and Ultrastructural Morphology

Receptors for IgM were detected on peripheral blood human eosinophils by a rosette technique with ox red blood cells coated with the IgM fraction of the specific immunserum. Between 14 % and 43 % (mean 27 %) FcµR positive cells were found after an overnight incubation period at 37°C by using this technique. The specificity of the receptors for IgM was assessed by studying the inhibitory capacity of purified human IgM in the rosette assay. From an ultrastructural point of view, the EA^M rosette-forming cells are mature eosinophlic granulocytes characterized by a nucleus with a variable number of lobes and a certain number of «first type» granules partially or totally devoid of their content.     

丙种球蛋白治疗内眼术后顽固性角膜水肿的临床分析

目的：探讨丙种球蛋白治疗内眼术后顽固性角膜水肿的临床价值。方法：对内眼术后顽固性角膜水肿的18例18只眼均采用人丙种球蛋白治疗。结果：17例17只眼经治疗后,于裂隙灯显微镜下观察,角膜内皮及基质水肿均在3d内完全吸收,视力提高3～5行。1只眼经治疗后,症状有所改善,但病情有反复,属治疗无效。结论：丙种球蛋白治疗内眼术后角膜内皮及基质顽固性水肿有显著疗效。     

肿瘤坏死因子、更生霉素和干扰素-γ联合应用对人卵巢癌裸鼠模型的协同作用

目的：研究联合应用肿瘤坏死因子（TNF）、干扰素－γ（IFN－γ）和更生霉素（KSM）对人卵巢癌裸鼠模型的协同作用。方法：将荷瘤裸鼠随机分成4组，分别用生理盐水、KSM、TNF＋IFN－γ、KSM＋TNF＋IFN－γ处理，观察肿瘤生长情况。结果：各组肿瘤相对体积比较，KSM组和KSM＋TNF＋IFN－γ组与对照组比较，差异有显著性（P＜0．05和P＜0．01）；TNF＋IFN－γ组与对照组比较，差异无显著性（P＞0．05），而KSM＋TNF＋IFN－γ组与KSM组比较，差异有显著性（P＜0．05）。结论：KSM与TNF、IFN－γ联合应用有协同抗卵巢癌细胞系3AO的作用，为临床应用提供了理论依据。     

乙型肝炎肝硬化患者血清IL-18、IFN-γ水平变化的研究

目的探讨乙型肝炎肝硬化患者血清白细胞介素-18(IL-18)、γ-干扰素(interferonγ,IFN-γ)水平与肝功能状态的关系。方法采用ELISA法检测42例肝硬化患者及25例正常人血清IL-18、IFN-γ水平,并同时检测肝功能指标。结果肝硬化患者血清IL-18、IFN-γ水平显著高于对照组(P<0.01),且随着肝损害的加重而升高,Child-pugh肝功能分级C级增高最著,其升高水平依次为C级>B级>A级。IL-18和IFN-γ与血清TBil及ALT正相关,两细胞因子间呈正相关。结论IL-18、IFN-γ参与乙型肝炎肝硬化的病理过程,与肝硬化炎症活动情况、肝功能损害及预后密切相关,检测血清IL-18、IFN-γ水平有助于判断肝硬化的病情和预后。