Human CD4+CD25+ Regulatory T Cells Suppress Anti-Porcine Xenogeneic Responses

Due to the shortage of human organs, xenotransplantation is being explored as an alternative to allotransplantation, but immune rejection remains a major hurdle to its implementation. We tested the ability of human CD4+CD25+ T cells (Treg cells) to suppress CD4+ T cell-mediated anti-porcine xenoresponses usingin vitroassays. Human Treg cells were hyporesponsive to porcine cell stimulation and suppressed the proliferative response of CD4+CD25- T cells in a dose-dependent manner, and comparison of the allo- and xenoresponses indicated that more Treg cells might be required to suppress the xenogeneic response than the allogeneic response. Stimulation of CD4+CD25- T cells with porcine cells resulted in secretion of IFN-gamma, TNF-alpha, IL-10, IL-6 and IL-2, and Treg cells suppressed the secretion of these cytokines, as well as the CD4+CD25- T-cell cytolytic response against porcine cells. These results suggest a potential role for Treg cells in promoting xenograft survival.     

A prospective study of the association of cerebrospinal fluid monoamine metabolite levels with lethality of suicide attempts in patients with bipolar disorder

Objectives:  Bipolar disorder is a severe illness that is associated with suicidal behavior. A biological predictor of highly lethal suicide attempts in patients with bipolar disorder would be valuable. We hypothesized that cerebrospinal fluid (CSF) monoamine metabolite levels are related to lethality of suicide attempts in bipolar patients and examined the relation between CSF 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and maximum lethality of suicide attempts at baseline and during a 2-year follow up.
Methods:  Twenty-seven bipolar depressed patients participated in the study. Demographic and clinical parameters were examined and recorded. Lumbar punctures were performed and CSF 5-HIAA, HVA, and MHPG were assayed by high-performance liquid chromatography with electrochemical detection. Following discharge, patients were evaluated after 3 months, 1 year, and 2 years. Each follow-up interview included an in-depth assessment of suicidal behavior during the intervening time period.
Results:  Six subjects made suicide attempts during the 2-year follow-up. Bipolar patients who attempted suicide during the follow-up period had higher aggression and hostility scale scores compared to bipolar subjects who did not make a suicide attempt during the follow-up period. CSF 5-HIAA, HVA, and MHPG levels were negatively correlated with the maximum lethality of suicide attempts during the 2-year follow-up period.
Conclusions:  Our finding is the first observation that CSF monoamine metabolite levels may be predictors of lethality of suicide attempts in patients with bipolar disorder. Further studies are necessary to answer the question whether CSF monoamine metabolite levels are clinically useful biochemical predictors of highly lethal suicide attempts or completed suicides.     

The effect of anti-IL-4 monoclonal antibody, rapamycin and interferon-γ on airway hyperreactivity to acetylcholine in mice

Background The role of IgE in airway hyperreaetivity is obscure. Objective In order to clarify the role of IgE in airway hyperreactivity, we investigated the effect of anti-IL-4 monoclonal antibody, rapamycin and interferon-γ on the antigen-induced IgE response, airway eosinophilia and hyperreactivity in mice. Methods Mice were immunized with an antigen (ovalbumin; OA) at intervals of 12 days. OA was inhaled 10 days after the secondary immunization. Twenty-four hours after the last inhalation, airway reactivity to acetylcholine was measured and bronchoalveolar lavage fluid (BALF) was obtained. Results Three inhalations of antigen caused an increase in the number of eosinophils in bronchoalveolar lavage fluid (BALF) and in airway hyperreactivity to acetylcholine with a significant elevation of serum IgE level. Anti-IL-4 at a dose of 1000 μg/animal and rapamycin at doses between 0.1 and 1 mg/kg inhibited the IgE production, but did not affect the airway eosinophilia or hyperreactivity to acetylcholine. In contrast, IFN-γ clearly inhibited the antigen-induced airway eosinophilia and hyperreactivity, but did not affect the IgE antibody production. Conclusion These results suggest that the inhibition of IgE production does not suppress the onset of airway hyperreactivity and eosinophilia in mice, and that IFN-γ inhibits the antigen-induced airway hyperreactivity, probably due to the inhibition of airway eosinophilia.     

Antioxidant and glutathione-related enzymatic activities in rat sciatic nerve

The present work tries to establish the antioxidant capacity of the peripheral nervous tissue of the rat, in terms of the enzymatic activities present in this tissue that either prevent the formation of activated species as the semiquinone radical (DT-diaphorase), protect against activated oxygen species (superoxide dismutase, glutathione peroxidase), conjugate natural toxic products or xenobiotics (glutathione S-transferases, especially the activity conjugating 4-hydroxy-nonenal), or complete the glutathione system metabolism (glutathione disulfide reductase, γ-glutamyl transpeptidase). All the activities studied are lower in this tissue than they are in liver, except for γ-glutamyl transpeptidase. The relevance of the results obtained and its possible relationship with different neuropathies is discussed. It is concluded that the peripheral nervous tissue is by far less protected than the liver against oxidative damage.     

Endotoxin-induced uveitis (EIU) in the rat: A study of inflammatory and immunological mechanisms

Endotoxin-induced uveitis (EIU) can be produced by systemic injection of endotoxin (ET). It is not clear yet why exclusive ocular involvement occurs in this model. To clarify this question and to establish the sequence of inflammatory events, EIU was induced in Lewis rats by footpad injection of Salmonella ET. Ocular inflammatory response (anterior chamber cells and proteins), aqueous inflammation mediators (thromboxane B₂, prostaglandin E₂, leukotriene B₄ and substance P) and MHC class 2 (Ia) antigen expression in the ciliary body were monitored for 72 hours. Thromboxane B₂ was detected early in the aqueous humor, peaking already 1 hour after ET injection. Prostaglandin E₂ & leukotriene B₄ peaks and a second peak of thromboxane B₂ were recorded 18 hours after ET-injection, at the time of maximal ocular inflammation. MHC-class 2 expression was first detected in the ciliary body stroma at the vascular level 6 hours after ET injection and was massively expressed in the ciliary body epithelium at 18 and 72 hours. It is hypothetized that ciliary body endothelium is particularly sensitive to the effect of ET and is the site of thrombocyte adherence. Vascular damage leads in succession to cellular infiltration, release of inflammation mediators and disruption of blood-ocular barrier. MHC-class 2 expression is a secondary phenomenon and is probably at the origin of additional tissue damage from immune effector mechanisms.     

薄层扫描法测定复脉定冲剂中远志有效成分的含量

采用薄层扫描法对复脉定冲剂中远志有效成分３，４，５－三甲氧基反式肉桂酸乙酯的含量进行测定。方法简单、快速，结果可靠，可作为该制剂的质控标准。     

抗棘球蚴药物研究:3-取代苯基-5-取代-1,2,4-噁二唑的合成

合成了3-取代苯基-5-取代-1,2,4-(口恶)二唑类化合物50个,经感染棘球蚴的小鼠初筛,部分化合物对棘球蚴有不同程度的作用,化合物13、28和30对棘球蚴的囊重抑制率分别为70、75.6和71.6%,其中化合物13对棘球蚴的生发层有损害作用。     

超抗原TSST-1之靶TCRVβHV4序列的特征分析

首先对人和小鼠的TCRVβ的氨基酸序列进行多序列对准,就Vβ之HV4片段进行比较,分析与超抗原TSST-1结合的四种Vβ（小鼠Vβ3、Vβ15、Vβ17和人Vβ2）之HV4序列内是否存在特定的氨基酸残基排列主型。结果发现:小鼠Vβ3和Vβ17的HV4具有特异的RFSAXCXSNS主型,而小鼠Vβ15和人β2的HV4则含独特的KFXIXH主型。提示:与TSST-1结合的四种Vβ所对应的T细胞识别表位可能不止一个。     

精氨酸加压素（AVP）的衍生物AVP4—8不能作用于AVPV1a受体而诱发电流反应

在微量注射大量肝脏ｍＲＮＡ之后，通过电压箝方法进行功能鉴定，两栖类卵母细胞成功地表达了ＡＶＰＶ１ａ受体。但在灌流ＡＶ４－８溶液时，却不能诱导卵母细胞产生内向振荡电流反应。提示ＡＶＰ４－８不能通过ＡＶＰＶ１ａ受体而介导生理学效应。     

Demonstration of synergistic effects of hyperthermia and photodynamic therapy using the chick chorioallantoic membrane model.

The chick chorioallantoic membrane (CAM) model was used to study vascular effects of photodynamic therapy (PDT) and hyperthermia (HPT) and the synergism of these modalities. The CAM is a convenient medium for monitoring the modifications of the vasculature. It is possible to view the CAM and to examine structural changes of individual blood vessels in real time. Moreover, the CAM is a closed system which lends itself to mathematical modeling of the temporal and spatial temperature profile and in which HPT can be performed quantitatively and to a selected depth, using different lasers. A porphyrin-type photosensitizer solution was applied to areas of the CAM, defined by teflon O-rings placed on the surface. Uptake dynamics of the sensitizer into the CAM was determined by analyzing its fluorescence in vivo. The CAM area was irradiated with a dual-wavelength laser system composed of a dye laser at 644 nm (to induce PDT) and a CO2 laser at 10.6 microns (to bring about HPT). Damage to the CAM vasculature, due to combined PDT+HPT, was compared to the outcome of the separate modalities, and a synergistic effect of about 40% was observed.