Narp regulates long-term aversive effects of morphine withdrawal.

Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. Because Narp is an immediate early gene product that is secreted at synaptic sites and binds to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, the authors found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, the authors evaluate whether long-term aversive effects of morphine withdrawal are altered in Narp knockout (KO) mice. The authors found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than do wild type (WT) controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of oxidative damage due to excessive protein ingestion on pancreas function in mice

The present study was undertaken to evaluate the effect of oxidative damage due to excessive protein diet on pancreas function in mice. For this purpose, thirty male (C57BL/6J) mice were randomly divided into three groups and fed on different diets as follows: group 1 was fed on a normal diet, group 2 was fed on an excessive protein diet and group 3 was fed on an excessive protein diet supplemented with 0.06 g/kg cysteamine. Each group was fed for 2 weeks, and then pancreas samples were collected to examine oxidative and antioxidant parameters and pancreas function. The results showed that ingestion of an excessive protein diet markedly increased contents of malondialdehyde (MDA) and decreased T-AOC and activities of antioxidants SOD and GSH-Px, compared with a normal diet (P < 0.05). Pancreas weight and concentration of protein, DNA and RNA were significantly higher (P < 0.05), digestive enzyme activities were significantly lower and levels of somatostatin and insulin were higher in mice fed with an excessive protein diet than those fed with a normal protein diet. In the group fed with excessive protein diet supplemented with cysteamine, oxidative stress was mitigated and pancreas function was improved. These data demonstrate that excessive protein ingestion could increase oxidative damage of free radicals on pancreas function through destroying the balance of oxidants and antioxidants.     

胶原多肽钙的制备及小鼠应用试验

以制革厂准备工段的边角废料为原料,经酶两步法水解制备出高纯度的胶原多肽,选择合适的钙源使之和胶原多肽复合,制备出易于人体吸收、胶原与钙双补的新型补钙制剂,经小鼠应用试验证明效果良好。     

发酵小麦制酒精残渣中寡肽的抗氧化及免疫活性

研究从发酵小麦制酒精残渣中提取分离出的寡肽抗氧化和免疫活性。将112 只4 周龄雌性健康昆明小鼠随机分成14 组,基础对照组和实验1～6组饲喂正常基础料的同时分别灌胃生理盐水、低、中、高3 个剂量的寡肽（五肽和七肽）,高脂对照组和实验7～12组饲喂高脂料的同时分别灌胃生理盐水、低、中、高3 个剂量的寡肽（五肽和七肽）,连续灌胃28 d后,测定基础对照组和实验1～6组血清中丙二醛（malondialdehyde,MDA）含量,肝匀浆中MDA含量、超氧化物歧化酶（superoxide dismutase,SOD）、过氧化氢酶（catalase,CAT）和谷胱甘肽过氧化物酶（glutathione peroxidase,GSH-Px）活性,脾脏中淋巴T细胞CD3＋、CD4＋和CD8＋数量,测定基础对照组、高脂对照组和实验7～12组十二指肠、空肠和回肠中MDA含量、SOD、CAT、GSH-Px活性。结果显示,与高脂对照组相比,灌胃寡肽后,血清、肝脏和肠道中MDA含量显著下降（P＜0.05）,SOD、CAT、GSH-Px活性显著升高（P＜0.05）,CD4＋/CD8＋显著升高（P＜0.05）。结果表明寡肽均具有体内抗氧化能力和免疫活性,而且能够清除高脂饮食带来的氧化损伤。     

仿刺参卵和体壁多肽的制备及免疫活性

以仿刺参卵和体壁为原料制备多肽,测定其基本营养成分和分子质量分布,并研究其对淋巴细胞增殖作用和小鼠免疫功能的影响。采用生物酶解技术和切向流超滤技术分离和制备仿刺参卵和体壁多肽,磺酰罗丹明B比色分析法测定了多肽质量浓度（10、50、100、500 μg/mL）对小鼠淋巴细胞增殖（spleen lymphocyte proliferation,SLP）能力的影响,设定水对照组和多肽低、中、高（日剂量83.3、166.7、500.0 mg/kg）剂量组进行30 d小鼠灌胃实验,检测了小鼠脏器/体质量、迟发型变态反应能力、伴刀豆球蛋白A诱导的小鼠脾淋巴细胞转化能力、抗体生成细胞数、小鼠血清溶血素水平、小鼠碳廓清能力、小鼠腹腔巨噬细胞吞噬鸡红细胞能力及自然杀伤细胞活力等指标。结果表明,仿刺参卵和体壁1～10 kDa多肽（EP1和BWP1）在500 μg/mL时均对SLP具有显著的促进作用,其粗蛋白含量分别为64.74、70.25 g/100 g,氨基酸总量分别为45.69、63.26 g/100 g,分子质量分别分布在130～1 600 Da及130～2 500 Da之间。经口服灌胃给予小鼠不同剂量的多肽30 d,EP1可提高小鼠的细胞免疫功能和单核-巨噬细胞吞噬功能,BWP1可提高小鼠的体液免疫功能和单核-巨噬细胞吞噬功能。结果提示EP1和BWP1均具有增强免疫力的功能,可开发为新的免疫调节产品。     

复方芦荟口服液的毒理学安全性与通便功效研究

评价一种以低聚果糖、水苏糖、芦荟、黑木耳为原料的复方口服液的通便功效和毒理学安全性。依据《保健食品检验与评价技术规范(2003年版)》,进行小鼠小肠运动试验、首次排便时间和粪便粒数、粪便重量的测定试验、小鼠急性经口毒性试验、鼠伤寒沙门氏菌/哺乳动物微粒体酶试验(Salmonella Typhimurium/Mammals Microsomal Enzyme Test,Ames试验)、小鼠骨髓细胞微核试验、小鼠精子畸形试验、大鼠30 d灌胃毒性试验。试验各观测点及终末期大、小鼠体质量均无组间差异(P>0.05);与便秘模型对照组相比,样品各剂量组5 h内排便粒数均无显著性差异(P>0.05),首便时间均提前(P<0.05,P<0.01),1.0和3.0 ml/kg?BW剂量组墨汁推进率均提高(P<0.01),3.0 ml/kg?BW剂量组5 h内粪便重量增加(P<0.05);小鼠急性经口毒性最大耐受剂量(maximum tolerable dose,MTD)大于15.00 g/kg?BW;不论加S9与否,在最高剂量达5 μl/皿的条件下,样品各剂量组标准测试菌株TA97a、TA98、TA100和TA102回复突变数均未超过相应溶剂对照值的两倍;与溶剂对照相比,样品各剂量组小鼠微核细胞率、精子畸变率未见显著变化(P>0.05);样品各剂量组雌、雄大鼠均活动、生长正常,进食量、食物利用率以及肝、肾、脾、睾丸等脏器湿重与脏体比均无显著性差异(P>0.05);血液学及血生化指标检测值均在本实验室历史参考值范围内;10.0 ml/kg?BW剂量组雌、雄大鼠未发现与口服液明显有关的组织病理学改变。该口服液具有通便功效,未见其急性毒性、遗传毒性或亚急性经口毒性。     

Induction of adaptive response <i>in utero </i>by ionizing radiation: A radiation quality dependent phenomenon

Investigation on possible induction of adaptive response (AR) by high-liner energy transfer (LET) particleradiation for protection against low-LET photon radiation-induced detrimental effects has not yet been performed inutero. This study verified if an AR could be induced by high-LET particle radiation from accelerated heavy ionsagainst low-LET X-ray radiation-induced detrimental effects on fetal mice. Total body irradiation of pregnantC57BL/6J mice were performed by delivering a priming dose ranging from 10 mGy to 320 mGy of particle radiationon gestation day 11 followed one day later by a challenge dose at 3500 mGy from X-ray radiation. The monoenergeticbeams of carbon, silicon and iron with the LET values of about 15, 55, and 200 KeV/μm, respectively, were examined.Significant suppression by the priming radiation of the detrimental effects (fetal death, malformation, or low bodyweight) was used as the endpoints for judgment of a successful AR induction on gestation day 18. Existence of ARwas not observed. On the other hand, the priming dose of high-LET particle radiation, in some cases, even increasedthe detrimental effects induced by the challenge dose from low-LET X-ray radiation. Although existence of ARinduced by high-LET radiation in cultured mammalian cells in vitro and in certain tissues of laboratory mice in vivowas demonstrated, the present study did not suggest that low dose of high-LET particle radiation could induce an ARin fetal mice inutero under the setup of our experimental system.     

Activity of Oritavancin and Its Synergy with Other Antibiotics against Mycobacterium abscessus Infection In Vitro and In Vivo

Background: Pulmonary disease caused by Mycobacterium abscessus (M. abscessus) spreads around the world, and this disease is extremely difficult to treat due to intrinsic and acquired resistance of the pathogen to many approved antibiotics. M. abscessus is regarded as one of the most drug-resistant mycobacteria, with very limited therapeutic options. Methods: Whole-cell growth inhibition assays was performed to screen and identify novel inhibitors. The IC₅₀ of the target compounds were tested against THP-1 cells was determined to calculate the selectivity index, and then time–kill kinetics assay was performed against M. abscessus. Subsequently, the synergy of oritavancin with other antibiotics was evaluated by using checkerboard method. Finally, in vivo efficacy was determined in an immunosuppressive murine model simulating M. abscessus infection. Results: We have identified oritavancin as a potential agent against M. abscessus. Oritavancin exhibited time-concentration dependent bactericidal activity against M. abscessus and it also displayed synergy with clarithromycin, tigecycline, cefoxitin, moxifloxacin, and meropenem in vitro. Additionally, oritavancin had bactericidal effect on intracellular M. abscessus. Oritavancin significantly reduced bacterial load in lung when it was used alone or in combination with cefoxitin and meropenem. Conclusions: Our in vitro and in vivo assay results indicated that oritavancin may be a viable treatment option against M. abscessus infection.     

What Can We Learn from FGF-2 Isoform-Specific Mouse Mutants? Differential Insights into FGF-2 Physiology In Vivo

Fibroblast growth factor 2 (FGF-2), ubiquitously expressed in humans and mice, is functionally involved in cell growth, migration and maturation in vitro and in vivo. Based on the same mRNA, an 18-kilo Dalton (kDa) FGF-2 isoform named FGF-2 low molecular weight (FGF-2LMW) isoform is translated in humans and rodents. Additionally, two larger isoforms weighing 21 and 22 kDa also exist, summarized as the FGF-2 high molecular weight (FGF-2HMW) isoform. Meanwhile, the human FGF-2HMW comprises a 22, 23, 24 and 34 kDa protein. Independent studies verified a specific intracellular localization, mode of action and tissue-specific spatiotemporal expression of the FGF-2 isoforms, increasing the complexity of their physiological and pathophysiological roles. In order to analyze their spectrum of effects, FGF-2LMW knock out (ko) and FGF-2HMWko mice have been generated, as well as mice specifically overexpressing either FGF-2LMW or FGF-2HMW. So far, the development and functionality of the cardiovascular system, bone formation and regeneration as well as their impact on the central nervous system including disease models of neurodegeneration, have been examined. This review provides a summary of the studies characterizing the in vivo effects modulated by the FGF-2 isoforms and, thus, offers a comprehensive overview of its actions in the aforementioned organ systems.     

The Effect of Functional Fiber on Microbiota Composition in Different Intestinal Segments of Obese Mice

The gastrointestinal tract is a heterogeneous ecosystem with distinct, stratified environments, which leads to different microbial composition in different intestinal segments. The regional heterogeneity of intestinal microbiota complicates the relationship between diet and microbiota. Few studies have focused on the effects of different diets on microbiota in different intestinal segments. This study aimed to investigate the effects of functional fiber on the microbial composition in multiple intestinal segments from a high-fat diet compared with a normal chow diet. We found that the response of microbiota from different intestinal segments to diet was related to the intestinal physiologic function and the physicochemical properties of dietary nutrients. A high-fat diet drove changes in the microbial composition in the hindgut, possibly by affecting the digestive environment of the foregut, and increased the regional heterogeneity of the whole intestinal microbiota. The supplementation of functional fiber promoted the microbial transfer and colonization from the anterior to the posterior intestinal segments, and increased the regional similarity of intestinal microbiota accordingly, particularly within the hindgut. The gut fermentation of the functional fiber, which mainly occurred in the hindgut, resulted in a significant change in the microbial composition and metabolism in the cecum and colon, with richer carbohydrate metabolism-related bacteria, including Mucispirillum, Prevotella, Anaerostipes, Oscillospira, Ruminococcus, Bacteroides, Coprococcus, Ruminococcus (Lachnospiraceae), and Allobaculum, and higher production of acetate and butyrate. We concluded that multiple regulatory mechanisms of diets which affect microbiota composition exist, including microbial metabolism, microbial migration, and the regulation of the intestinal environment.