Expression of manganese superoxide dismutase is not altered in transgenic mice with elevated level of copper-zinc superoxide dismutase

In evaluating the relative expression of copper-zinc and manganese superoxide dismutase (CuZnSOD and MnSOD) in vivo in states like Down syndrome in which one dismutase is present at increased levels, we measured activities of both enzymes, in tissues of control and transgenic mice constitutively expressing increased levels of CuZnSOD, during exposure to normal and elevated oxygen tensions. Using SOD gel electrophoresis assay, CuZnSOD and MnSOD activities of brain, lung, heart, kidney, and liver from mice exposed to either normal (21%) or elevated (>99% oxygen, 630 torr) oxygen tensions for 120 h were compared. Whereas CuZnSOD activity was elevated in tissues of transgenic relative to control mice under both normoxic or hyperoxic conditions, MnSOD activities in organs of transgenic mice were remarkably similar to those of controls under both conditions. To confirm the accuracy of this method in quantitating MnSOD relative to CuZnSOD expression, two other methods were utilized. In lung, which is the organ exposed to the highest oxygen tension during ambient hyperoxia, a sensitive, specific ELISA for MnSOD was used. Again, MnSOD protein was not different in transgenic relative to control mice during exposure to air or hyperoxia. In addition, lung MnSOD protein was not changed significantly by exposure to hyperoxia in either group. In kidney, a mitochondrion-rich organ, SOD assay, before and after inactivation of CuZnSOD with diethyldithiocarbamate, was used. MnSOD activity was not different in organs from air-exposed transgenic relative to control mice. The data indicated that expression of MnSOD in vivo was not affected by overexpression of the CuZnSOD and, therefore, the two enzymes are probably regulated independently.     

Oral administration of a tri-therapy for central pattern generator activation in paraplegic mice: Proof-of-concept of efficacy

Spinal cord injury (SCI) is a neurological condition, for which no cure exists, typically leading to an immediate and irreversible loss of sensory and voluntary motor functions accompanied by significant health problems. We conducted proof-of-concept experiments aimed at assessing efficacy upon oral administration of a novel combination therapy for central pattern generator (CPG) activation and corresponding locomotor movement generation in completely paraplegic animals. Co-administration orally (by gavage) of buspirone, levodopa and carbidopa was found to dose-dependently induce episodes of steady weight-bearing stepping in low-thoracic (Th9/10) spinal cord-transected (Tx) mice (with no other form of assistance or training). Robust hindlimb stepping with weight-bearing capabilities was induced with the tri-therapy but not with clinically relevant doses of these compounds administered separately. These results provide evidence suggesting that this drug combination may be ideally suited to constitute a first-in-class therapy (CPG activator) for locomotor activity induction in chronic SCI individuals, given that efficacy was shown using commercially available brain-permeable small molecules, already known as safe for the treatment of various neurological indications.     

雄性Fmr1基因敲除小鼠血液生理生化指标及性激素水平的比较研究

目的比较雄性Fmr1基因敲除小鼠和FVB小鼠血液生理生化值和血清性激素水平，探讨Fmr1基因对动物生长发育和生殖生理等方面的影响。方法分别测定血液生理指标、血清生化指标、血清电解质和血清E2、LH、FSH、T和PRL的含量，并进行统计学处理和分析。结果雄性Fmr1基因敲除小鼠与FVB小鼠比较，血液生理指标中MCV和PCT有显著差异（P〈0．05），而RBC、HCT、HGB、MCH和WBC等无显著差异（P〉0．05）；血清生化指标中除TBIL、[IP^3＋]、[Mg^2＋]（P〈0．05）和AIP、BUN（P〈0．01）外，TPROT、GLB、A／G、BUN、CREAT、[K^＋]、[Na^＋]等项均无显著差异（P〉0．05）。性激素水平E2、LH值差异无显著性（P〉0．05），FSH、T、PRL差异极显著（P〈0．01）。结论Fmr1基因可影响动物的某些生理生化及激素水平。     

The dendritic cell niche in chronic obstructive pulmonary disease

The pulmonary innate immune system is heavily implicated in the perpetual airway inflammation and impaired host defense characterizing Chronic Obstructive Pulmonary Disease (COPD). The airways of patients suffering from COPD are infiltrated by various immune and inflammatory cells including macrophages, neutrophils, T lymphocytes, and dendritic cells. While the role of macrophages, neutrophils and T lymphocytes is well characterized, the contribution of dendritic cells to COPD pathogenesis is still the subject of emerging research. A paper by Botelho and colleagues in the current issue of Respiratory Research investigates the importance of dendritic cell recruitment in cigarette-smoke induced acute and chronic inflammation in mice. Dendritic cells of the healthy lung parenchyma and airways perform an important sentinel function and regulate immune homeostasis. During inflammatory responses the function and migration pattern of these cells is dramatically altered but the underlying mechanisms are incompletely understood. Botelho and colleagues demonstrate here the importance of IL-1R1/IL-1α related mechanisms including CCL20 production in cigarette-smoke induced recruitment of dendritic cells and T cell activation in the mouse lung.     

Gut-associated immune effector responses in immunocompetent and immunocomprimised mice with Giardia lamblia

Abstract Significantly higher Giardia lamblia trophozoites load in the intestine of infected mice accompanied pronounced influx of suppressor/cytotoxic T cells (Lyt 2.2⁺), T cells (Thy 1.2⁺) and significant reduction in IgA-containing cells in the gut during the establishment and peak phases of infection. The induction of helper/inducer T cells (Lyt 1.1⁺) and significant enhancement of IgA-containing cells in gut resulted in the decline of the trophozoite loads. However, the prior treatment of animals with dexamethasone alone resulted in significant reduction in helper/inducer T cells (Lyt 1.1⁺) and the IgA-containing cells in the gut; the percents of suppressor/cytotoxic T cells (Lyt 2.2⁺) and IgM-containing cells remained unaltered. Although the G. lamblia infection in such animals further significantly increased the influx of suppressor/cytotoxic T cells, the late response of helper/inducer T cells and IgA-containing cells was abrogated during the decline phase of infection. The significant reduction in the trophozoite load — despite immuno-suppressive therapy — appeared to be due to unaltered IgM response in such animals which probably took over the function of IgA in defense against G. lamblia . The data of the investigation thus suggested a role of helper/inducer T cells and antibodies producing cells in gut as important effector cells resulting in the termination of primary G. lamblia infection.     

Berberine improves the intestinal antioxidant status of laboratory mice,Mus musculus

Oral administration of berberine chloride to mice induced an obvious enhancement in jejunal health status as expressed by the significant reduction of apoptotic cells within the intestinal villi from 15.5 to 8.3 apoptotic cell/10 VCU. In addition, jejunal antioxidant biomarkers were significantly improved as revealed by the increase in the activities of catalase and glutathione peroxidase enzymes with a concurrent increase in reduced glutathione levels and total antioxidant capacity. Also, it was associated with a significant decrease in oxidative damage biomarkers of hydrogen peroxides, malondialdehyde, nitrite/nitrate, inducible nitric oxide synthase and protein carbonyl content. Moreover, BBR treatment induced a reduction in the pro-inflammatory cytokine, TNF-α by about 40%. It is highly recommended to use berberine as food supplements or as natural drug therapy to enhance the antioxidant status within the intestinal tissue.     

Effect of gold nanoparticles on mice splenomegaly induced by schistosomiasis mansoni

Schistosomiasis is still one of the main parasitic diseases that affect human health in tropical regions. Whilst praziquantel (PZQ) is the main classic antischistosomal drug, the need for new drugs is still a must due to the low effectiveness of the drug on the schistosome young worms, and the evolving of PZQ resistant strains. Nanotechnology is one of the most important recent and current methods used to treat human diseases including parasitic ones. Therefore, the present study aimed to examine the curative role of gold nanoparticles (GNPs) on splenic tissue of mice infected with Schistosoma mansoni Sambon, 1907. High-resolution transmission electron microscopy was used for characterization of nanoparticles (NP). GNPs of 1 mg/kg mice body weight were inoculated into mice infected with S. mansoni. The parasite caused deteriorations in histological architecture of the spleen tissue, and splenomegaly. Additionally, the parasite induced a significant reduction in splenic tissue glutathione levels; however, the concentrations of nitric oxide and malondialdehyde were significantly increased. Treatment of mice with GNPs reduced the extent of histological impairment and oxidative stress in spleen tissue. Therefore, our results demonstrate the protective role of GNPs against splenic damage in mice infected with S. mansoni.     

小鼠乳腺细胞凋亡及瘦素对凋亡的影响

目的系统的研究小鼠乳腺发育周期中乳腺细胞凋亡情况，并阐明瘦素对乳腺细胞凋亡的影响。方法以小鼠乳腺为实验材料，采用TUNEL法系统地研究小鼠乳腺在青春期、妊娠期、泌乳期和退化期的整个发育周期中的细胞凋亡情况，并通过培养基中添加瘦素的方法研究瘦素对乳腺细胞凋亡的影响。结果在青春期50～60d、妊娠期10～16d、退化期1～10d检测到较多的细胞凋亡，其中退化期细胞凋亡最为显著。添加瘦素培养的乳腺细胞凋亡信号明显增多。结论小鼠乳腺发育不同时期细胞凋亡同结构和功能发育之间相互联系。同时通过小鼠乳腺组织体外培养的方法，证明瘦素在退化期乳腺组织中可明显诱导组织凋亡。     

实验小鼠种群管理（英文）

2009年11月份在西安举行由中国实验动物学会发起的实验动物医药技术培训研讨会上,本人做了关于实验小鼠种群管理的演讲。其主题涵盖了小鼠繁殖性能的维护和基因工程种群的管理。本篇文章的目的在于强调其所涵盖的材料并为进一步研究提供参考。如若对本文所讨论的内容希望有更深刻的理解,这篇文章所引用的参考资料值得进一步的阅读。另外本文未涉及远交系小鼠的繁殖培育和基因管理,但如有需要可以联系本文作者,可推荐需阅读的材料清单。     

Characterization of Brucella abortus S19 as a challenge strain for use in a mouse model of brucellosis

The objective of this project was to conduct a feasibility study to determine whether the Brucella abortus S19 vaccine infects and persists in mice and determine whether S19 can be used as a challenge strain for vaccine trial studies. Groups of BALB/c mice were inoculated (intraperitoneally, subcutaneously, intranasally) and euthanized to determine colonization titers in the spleens and lungs. This study showed that S19 does infect and persist in the tissues of mice for 8 weeks and demonstrates that S19 can be used, safely and economically under BSL2 containment, as the challenge strain for future trials to evaluate vaccine efficacy.