Lithium suppresses excitotoxicity-induced striatal lesions in a rat model of Huntington's disease

Huntington's disease is a progressive, inherited neurodegenerative disorder characterized by the loss of subsets of neurons primarily in the striatum. In this study, we assessed the neuroprotective effect of lithium against striatal lesion formation in a rat model of Huntington's disease in which quinolinic acid was unilaterally infused into the striatum. For this purpose, we used a dopamine receptor autoradiography and glutamic acid decarboxylase mRNA in situ hybridization analysis, methods previously shown to be adequate for quantitative analysis of the excitotoxin-induced striatal lesion size.Here we demonstrated that subcutaneous injections of LiCl for 16 days prior to quinolinic acid infusion considerably reduced the size of quinolinic acid-induced striatal lesion. Furthermore, these lithium pre-treatments also decreased the number of striatal neurons labeled with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. Immunohistochemistry and western blotting demonstrated that lithium-elicited neuroprotection was associated with an increase in Bcl-2 protein levels.Our results raise the possibility that lithium may be considered as a neuroprotective agent in treatment of neurodegenerative diseases such as Huntington's disease.     

Immune regulation in self tolerance: functional elimination of a self-reactive, counterregulatory CD8+ T lymphocyte circuit by neonatal transfer of encephalitogenic CD4+ T cells lines.

Transfer of encephalitogenic, CD4+ T lymphocyte lines into syngeneic adult Lewis rats not only leads to the development of experimental autoimmune encephalomyelitis (EAE), but, in addition, to the expansion of counterregulatory, CD8+ T lymphocyte clones which are able to lyse specifically the encephalitogenic T cells in vitro and to neutralize their encephalitogenic capacity in vivo. In striking contrast, in neonatal rats, which still lack myelin (autoantigens), injection of the same encephalitogenic lines neither mediates EAE, nor confers protection in later life against the myelin-specific T cells. In fact, this treatment results in the life-long functional elimination of counterregulatory, clonotypic CD8+ T lymphocytes, which cannot even be reinduced by repeated injections of the relevant CD4+ T line. These data seem to point to a self-protective T cell control mechanism which is developed within the immune system prior to, and thus independent of the appearance of the appropriate self antigen.     

CD4 monoclonal antibody pairs for immunosuppression and tolerance induction

A pair of rat anti-mouse CD4 monoclonal antibodies (mAb) have been selected which bind to different epitopes of the molecule. Both the mAb are rat IgG2b and show clear synergistic activity in complement lysis in vitro. When injected together in vivo, they exhibit an improved immunosuppressive effect, compared to each antibody alone, on allogeneic graft rejection, humoral responses and on tolerance induction. Limiting dilution analysis indicates that the in vivo depletion of interleukin 2-producing cells is improved using both mAb by 2-3-fold over that obtained with the individual antibodies. As little as 60 ng per mouse of the CD4 antibody pair was sufficient to allow the induction of tolerance to human gamma-globulin, even without elimination of the CD4+ cells. The results suggest that appropriate antibody pairs may be good candidates for effective immunosuppressive serotherapy in man.     

Novel micro-crosslinked poly(organophosphazenes) with improved mechanical properties and controllable degradation rate as potential biodegradable matrix

As biodegradable materials, linear polyphosphazenes undergo rapid hydrolysis degradation but exhibit poor mechanical properties. Blending with biodegradable polyesters or inorganic particles strengthen their mechanical properties but give rise to slower degradation rate. To balance the mechanical properties and the degradation rate, micro-crosslinked polyphosphazenes were synthesized in this study. Their glass transition temperatures, mechanical properties, and in vitro degradation behavior were investigated. 2-hydroxyethyl methacrylate (HEMA) was firstly attached to the side chain along with glycine ethyl ester to prepare co-substituted poly(organophosphazene) with pendant ethenyl substituents. The co-substituted poly(organophosphazene) was blended with HEMA or acrylic acid (AA) followed by a free radical polymerization to prepare micro-crosslinked poly(organophosphazenes). The resulting crosslinked polymers showed two separate glass transition temperatures depending on the HEMA or AA feed. Incorporation of crosslinking affected the mechanical properties positively. Crosslinked poly(organophosphazenes) showed an approximately 11-17 fold increase in terms of modulus of elasticity when compared to the linear counterpart. In vitro degradation tests indicated that HEMA-crosslinked polymers hydrolyzed at a retarded rate while AA-crosslinked polymers hydrolyzed at a moderate rate compared to linear polymers.     

大鼠膈神经传出和传入神经成分在脊髓内的分布

采用HRP追踪法,对成年大鼠膈神经运动纤维的起源和初级传入神经元胞体的位置及在其中枢突脊髓的投射进行了观察。结果表明,膈神经运动纤维在脊髓标记(膈核)主要分布在注射侧C_3-C_5脊髓节段的前角。隔神经感觉纤维初级传入标记的神经元见于注射侧C_3-C_6后根节,其中C_4标记的细胞数最多。     

A micro-mechanics model of dentin mechanical properties

Application of a micro-mechanics cell model to dentin composites for determination of their effective mechanical properties is discussed in this paper. The dilute micro-mechanics model for fibre-reinforced composites is utilized and the corresponding cell model is chosen to consist of a circular hollow cylinder filled with liquid or gas phase, which is surrounded by two circular cylindrical shells, a thin shell and a matrix phase. Each layer of cylindrical shell is here considered as a composite consisting of collagen fibrils, with mineralized hydroxyapatite, loosely connected to their neighbours, and water (or gas in the case of dry dentin composite). Determination of the effective material properties of such a three phase composite is discussed. Using the cell model the effect of porosity, thickness of each cylindrical shell, and mineral content on material properties is analysed. Results obtained from nano-indentation observations are compared with numerical predictions of the analytical model.     

Modeling the development of acquired clinical immunity to Plasmodium falciparum malaria

Individuals living in regions where malaria is endemic develop an acquired immunity to malaria which enables them to remain asymptomatic while still carrying parasites. Field studies indicate that cumulative exposure to a variety of diverse Plasmodium parasites is required for the transition from symptomatic to asymptomatic malaria. This study used a simulation model of the within-host dynamics of P. falciparum to investigate the development of acquired clinical immunity under different transmission conditions and levels of parasite diversity. Antibodies developed to P. falciparum erythrocyte membrane protein 1 (PfEMP1), a clonally variant molecule, were assumed to be a key human immunological response to P. falciparum infection, along with responses to clonally conserved but polymorphic antigens. The time to the development of clinical immunity was found to be proportional to parasite diversity and inversely proportional to transmission intensity. The effect of early termination of symptomatic infections by chemotherapy was investigated and found not to inhibit the host's ability to develop acquired immunity. However, the time required to achieve this state was approximately double that compared to when no treatment was administered. This study demonstrates that an immune response primarily targeted against PfEMP1 has the ability to reduce clinical symptoms of infections irrespective of whether treatment is administered, supporting its role in the development of acquired clinical immunity. The results also illustrate a novel use for simulation models of P. falciparum infections, investigation of the influence of intervention strategies on the development of naturally acquired clinical immunity.     

我国正常生育力男子精浆的微量元素研究

本文报告测试了68例正常生育力成年男子精浆中的锌、铜,铁等微量元素和镁,测试结果如下:锌130±5.64μg/ml,铜1.84±0.158μg/ml,铁0.801±0.104μg/ml,镁103.86±10.01μg/ml。所测得的数值均在正常范围内。在正常范围内的精液,精浆中的锌、镁含量与精液质量(精子密度和活动力)之间无显著差异。但铜的含量与精子活动度关系密切,含量高则活动度差,反之则活动度好。铁的含量与精子密度关系也十分密切,含量高时精子密度也高。     

Dietary Aspects to Incorporate in the Creation of a Mobile Image-Based Dietary Assessment Tool to Manage and Improve Diabetes

Diabetes is the seventh leading cause of death in United States. Dietary intake and behaviors are essential components of diabetes management. Growing evidence suggests dietary components beyond carbohydrates may critically impact glycemic control. Assessment tools on mobile platforms have the ability to capture multiple aspects of dietary behavior in real-time throughout the day to inform and improve diabetes management and insulin dosing. The objective of this narrative review was to summarize evidence related to dietary behaviors and composition to inform a mobile image-based dietary assessment tool for managing glycemic control of both diabetes types (type 1 and type 2 diabetes). This review investigated the following topics amongst those with diabetes: (1) the role of time of eating occasion on indicators of glycemic control; and (2) the role of macronutrient composition of meals on indicators of glycemic control. A search for articles published after 2000 was completed in PubMed with the following sets of keywords “diabetes/diabetes management/diabetes prevention/diabetes risk”, “dietary behavior/eating patterns/temporal/meal timing/meal frequency”, and “macronutrient composition/glycemic index”. Results showed eating behaviors and meal macronutrient composition may affect glycemic control. Specifically, breakfast skipping, late eating and frequent meal consumption might be associated with poor glycemic control while macronutrient composition and order of the meal could also affect glycemic control. These factors should be considered in designing a dietary assessment tool, which may optimize diabetes management to reduce the burden of this disease.