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。     

The Nutraceutical N-Palmitoylethanolamide (PEA) Reveals Widespread Molecular Effects Unmasking New Therapeutic Targets in Murine Varicocele

Varicocele is an age-related disease with no current medical treatments positively impacting infertility. Toll-like receptor 4 (TLR4) expression is present in normal testis with an involvement in the immunological reactions. The role of peroxisome proliferator-activated receptor-α (PPAR-α), a nuclear receptor, in fertility is still unclear. N-Palmitoylethanolamide (PEA), an emerging nutraceutical compound present in plants and animal foods, is an endogenous PPAR-α agonist with well-demonstrated anti-inflammatory and analgesics characteristics. In this model of mice varicocele, PPAR-α and TLR4 receptors’ roles were investigated through the administration of ultra-micronized PEA (PEA-um). Male wild-type (WT), PPAR-α knockout (KO), and TLR4 KO mice were used. A group underwent sham operation and administration of vehicle or PEA-um (10 mg/kg i.p.) for 21 days. Another group (WT, PPAR-α KO, and TLR4 KO) underwent surgical varicocele and was treated with vehicle or PEA-um (10 mg/kg i.p.) for 21 days. At the end of treatments, all animals were euthanized. Both operated and contralateral testes were processed for histological and morphometric assessment, for PPAR-α, TLR4, occludin, and claudin-11 immunohistochemistry and for PPAR-α, TLR4, transforming growth factor-beta3 (TGF-β3), phospho-extracellular signal-Regulated-Kinase (p-ERK) 1/2, and nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) Western blot analysis. Collectively, our data showed that administration of PEA-um revealed a key role of PPAR-α and TLR4 in varicocele pathophysiology, unmasking new nutraceutical therapeutic targets for future varicocele research and supporting surgical management of male infertility.     

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。     

Effects of di-(2-ethylhexyl)-phthalate (DEHP) and its metabolites on fatty acid homeostasis regulating proteins in rat placental HRP-1 trophoblast cells.

Di-(2-ethylhexyl)-phthalate (DEHP) is a widely used plasticizer and ubiquitous environmental contaminant. The potential health hazards, including teratogenicity, from exposure to DEHP may be related to the role of DEHP or its metabolites in the trans-activation of peroxisome proliferator-activated receptors (PPARs). Fetal essential fatty acid (EFA) homeostasis is controlled by directional transfer across the placenta through a highly regulated process, including PPAR activation. Using HRP-1 rat trophoblastic cells, the effects of DEHP and two of its metabolites, mono-(2-ethylhexyl)-phthalate (MEHP) and 2-ethylhexanoic acid (EHA), on the mRNA and protein expression of the three known PPAR isoforms (alpha, beta, and gamma), fatty acid transport protein 1 (FATP1), plasma membrane fatty acid binding protein (FABPpm), and the heart cytoplasmic fatty acid binding protein (HFABP) were investigated. This study also investigated the functional effects of exposure on the uptake and transport of six long chain fatty acids (LCFAs): arachidonic acid (AA), docosahexaenoic acid (DHA), linoleic acid (LA), alpha-linolenic acid (ALA), oleic acid (OA), and stearic acid (SA). In the presence of DEHP, MEHP, and EHA, the expression of PPARalpha, PPARgamma, FATP1, and HFABP were up-regulated in a dose- and time- dependent manner, while PPARbeta and FABPpm demonstrated variable expression. The uptake rates of EFAs (AA, DHA, LA, ALA) increased significantly upon exposure, and the transport of AA (omega-6) and DHA (omega-3) were directionally induced. These results suggest that DEHP, MEHP, and EHA can influence EFA transfer across HRP-1 cells, implying that these compounds may alter placental EFA homeostasis and potentially result in abnormal fetal development.     

共轭亚油酸对肥胖大鼠PPARγ基因表达及血清瘦素水平的影响

目的　研究不同剂量共轭亚油酸 (CLA)对饮食诱导肥胖大鼠PPARγ基因、瘦素、血糖、血脂的影响。方法　选用雄性Wistar大鼠 ,随机分为对照组、高脂组、高脂 +CLA组 (每 10 0g饲料含CLA分别为 0 75g、1 5 0g、3 0 0g) ,于第 12周末处死动物 ,计算脂 体比 ,测定大鼠血糖、血脂及瘦素水平 ,并应用RT PCR的方法检测大鼠白色脂肪组织过氧化物酶体增殖物激活受体γ(PPARγ)的表达水平。结果　CLA可降低肥胖大鼠血糖、甘油三酯 (TG)、总胆固醇 (TC)及瘦素水平 ,增加脂肪组织PPARγmRNA的表达水平。结论　CLA可降低肥胖大鼠血糖、血脂 ,并可通过激活PPARγ下调瘦素水平 ,有改善肥胖大鼠的瘦素抵抗作用。