Angiotensin II increases neuronal delayed rectifier K(+) current: role of 12-lipoxygenase metabolites of arachidonic acid

Angiotensin II (Ang II) elicits an Ang II type 2 (AT(2)) receptor-mediated increase in voltage-dependent delayed rectifier K(+) current (I(KV)) in neurons cultured from newborn rat hypothalamus and brain stem. In previous studies, we have determined that this effect of Ang II is mediated via a Gi protein, activation of phospholipase A(2) (PLA(2)), and generation of arachidonic acid (AA). AA is rapidly metabolized within cells via lipoxygenases (LO), cyclooxygenase (COX) or p450 monooxygenase enzymes, and the metabolic products are known regulators of K(+) currents and channels. Thus in the present study, we have investigated whether the AT(2) receptor-mediated effects of Ang II on neuronal I(KV) require AA metabolism and if so, which metabolic pathways are involved. The data presented here indicate that the stimulatory actions of Ang II and AA on neuronal I(KV) are attenuated by selective blockade of 12-LO enzymes. However, the effects of Ang II are not altered by blockade of 5-LO or p450 monooxygenase enzymes. Furthermore, the actions of Ang II are mimicked by a 12-LO metabolite of AA, but 5-LO metabolites such as leukotriene B(4) and C(4) do not alter neuronal I(KV). These data indicate that the AT(2) receptor-mediated stimulation of neuronal I(KV) is partially mediated through 12-LO metabolites of AA.     

125I-白细胞介素-8在小鼠体内的分布研究

为了解白细胞介素 - 8的体内行为 ,用 Bolton- Hunter法对 IL- 8进行 1 2 5I标记 ,并测定它在小鼠体内的分布 ;得到了 1 2 5I- IL- 8在小鼠血、心、肝、肺、肾、骨、脾等脏器中的分布以及它在血液中的快相半排期 T1 /2α为 0 .3 2 h和慢相半排期 T1 /2β为 8.0 1h。1 2 5I- IL- 8主要通过肾排除     

近红外信息辐照对免疫抑制大鼠体液免疫功能的影响

本实验观察了近红外信息辐照(辐照)对免疫抑制大鼠体液免疫功能的调整作用。取大鼠54只随机分为三组:甲组各鼠腹腔注射环磷酰胺(CY,75mg/kg)和伤寒沙门氏菌鞭毛抗原(HAg,7×10~8菌体/只),同时各鼠每天全身辐照1h,共4周;乙组腹腔注射CY和HAg丙组仅腹腔注射HAg。结果甲、乙、丙三组于第四周末的存活率分别为83.3％、38.1％和66.7％(甲与乙组比较P<0.05);第四周末血清总IgG含量分别为141.4±17.6U/ml,120.3±16.6U/ml和117.0±22.9U/ml(甲组与其它两组比较P<0.01);第二周末抗H抗体效价分别为1:91.9、1:46.6和1:149.3(甲与乙组比较P<0.05;乙与丙组比较P<0.01)。结果表明,辐照对免疫功能低下的机体有增强免疫功能的作用。     

Clonal analysis of palmar fibromatosis: a study whether palmar fibromatosis is a real tumor

Background  

Palmar fibromatosis that arises in the palmar soft tissue is characterized by infiltrative growth with a tendency toward local recurrence but does not metastasize. This study investigated the clonality of this process in twelve female patients, each with a single lesion, by examining the pattern of X-chromosome inactivation.     

Activation of invariant NK T cells protects against experimental rheumatoid arthritis by an IL-10-dependent pathway

Invariant natural killer T (iNKT) cells are a unique lymphocyte subtype implicated in the regulation of autoimmunity and a good source of protective Th2 cytokines. Agonist alpha-galactosylceramide (alpha-GalCer) of iNKT cells exert a therapeutical effect in type 1 diabetes. We investigated whether iNKT activation with alpha-GalCer was protective in collagen-induced arthritis (CIA) in DBA/1 mice, a standard model of rheumatoid arthritis. Here, we have shown that in vivo iNKT cell function was altered in DBA/1 mice since stimulation with alpha-GalCer led to decreased IL-4 and IFN-gamma levels in sera, as compared with C57BL/6 mice. alpha-GalCer induced a clear-cut diminution of clinical and histological arthritides. An anti-IL-10 receptor antibody abrogated the protective effect of alpha-GalCer, suggesting a key role for IL-10 in the protection against CIA by activated iNKT cells. Confirming these data, disease protection conferred by alpha-GalCer correlated with the ability of LN CD4+ cells to secrete larger amounts of IL-10. These findings suggest that in CIA susceptibility to autoimmunity is associated with dysfunctions of iNKT cells. Our demonstration that iNKT cell activation by alpha-GalCer remains efficient in CIA-prone DBA/1 mice to provide protective IL-10 suggests that this could be used therapeutically to treat autoimmune arthritis.     

Protection by a taurine supplemented diet from lead-induced deficits of long-term potentiation/depotentiation in dentate gyrus of rats in vivo

Previous studies have demonstrated that synaptic plasticity, which includes long-term potentiation (LTP) and depotentiation (DP) in hippocampus, is important for learning and memory. The purpose of this study is to evaluate the effect of taurine via drinking water on the lead-induced impairments of LTP and DP in rat dentate gyrus (DG) in vivo. The experiments were carried out in four groups of rats (control, lead-exposed, control and lead-exposed with a taurine-supplement diet, respectively). The input-output (I/O) function, excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude were measured in the DG area of adult rats (60-90 days) in response to stimulation applied to the lateral perforant path. The results show that: 1. chronic lead exposure impaired LTP/DP measured on both EPSP slope and PS amplitude in DG area of the hippocampus; 2. in control rats, taurine had no effect on LTP/DP; 3. the amplitudes of LTP/DP of lead-exposed group were significantly increased by applying taurine. These results suggest that dietary taurine supplement could protect rats from the lead-induced impairments of synaptic plasticity and might be a preventive medicine to cure the cognitive deficits induced by lead.     

Haplotypes produced from rare variants in the promoter and coding regions of angiotensinogen contribute to variation in angiotensinogen levels

The most efficient study design to map genes underlying complex traits will be determined by assumptions about whether the genetic effects are likely to be due to relatively few common variants or multiple rare variants. To examine the possibility that rare variants may influence blood pressure, we sequenced a 6.8 kb region of the angiotensinogen (AGT) gene in 29 male Nigerians with high plasma AGT levels and 28 with low levels. The frequency of haplotypes produced from rare variants in the promoter and coding regions was significantly different between the two groups, and it is unlikely that this difference was due to the manner in which the rare variants were selected. Further analysis suggested that most of the haplotypes produced by these rare variants are found on a haplotype background created by three common SNPs. Our study confirms in an additional trait that rare variants can influence the distribution of complex traits; whether these variants can be captured by common SNPs or haplotypes requires further investigation.     

Functional organization of enhancer (ENII) of hepatitis B virus.

A new enhancer ENII, located in the X open reading frame and immediately upstream of the core gene promoter, has recently been identified in the genome of hepatitis B virus. We have studied the functional constituents of this new enhancer in different cell lines. ENII can be divided into two functional elements, A and B, corresponding to two major binding sequences for nuclear protein factors. Element A alone gave very low activity; however, it was a modulatory element important for cell-type specificity. Element B was shown to be the basic functional element of ENII, which retained about 70% of the enhancer activity of the complete ENII in HepG2 cells. Element B can be further dissected into three subunits, B1, B2, and B3, which act synergistically. A 52-bp sequence is identified as the core sequences of element B. A model for the mechanism of ENII function is proposed.     

Diagnosis and taxonomy of periodical psychosis

The concept and taxonomy of periodic psychosis still remains in controversy for the past 100 years. In China, it was first reported by Ji, and thereafter various rinds of terminology and views were given by different authors. In the presentation, clinical investigation and follow up were carried out in 62 cases. In many of these cases, the so-called "periodic psychosis" or "phasophrenia" was early clinical features of schizophrenia or manic-depression. In those cases with apparent symptoms and signs of diencephalic function, differential diagnosis should be carried out from organic brain syndrome. In a small number of cases, their clinical manifestations, conforming to previous diagnostic criteria, might be an uncommon syndrome. It was concluded by the authors that until now periodic could be considered only as a clinical syndrome rather than a disease entity.     

催经止孕药Ru-486的临床药代动力学

应用高效液相色谱法(HPLC)研究了抗孕激素药,Ru-486的临床药代动力学。六名志愿受试者,一次口服Ru-486 50毫克后测得该药的药代动力学各项参数,血药半寿期t 1/2 33.0小时,一级消除速率常数Kel 0.021 hr~(-1),血药表观容积Vd 120.1 Liter,体内血药总廓清率Cl2.5 Liter/hr,药-时曲线下面积Auc 19825.1 ng/ml/hr。实验表明,服药后一小时血药浓度迅即达高峰,随后转入消除期,血浆药物浓度在消除相的头4～8小时消除较快,而后逐渐减慢,持续24小时,到48小时血药浓度已较低(0.15±0.07μg/ml)。