Altered enzyme activities of xenobiotic biotransformation in kidneys after subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) to rats

Activities of the xenobiotic metabolizing enzymes were measured in the liver, kidney, duodenum and lung microsomes and cytosol fractions of Wistar rats after subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a potent bacterial mutagen in chlorinated drinking water. MX was administered by gavage at the dose level of 30 mg/kg for 18 weeks (low dose), or at the dose level which was raised gradually from 45 mg/kg for 7 weeks via 60 mg/kg for 2 weeks to a clearly toxic dose of 75 mg/kg for 5 weeks (high dose). Microsomal and cytosolic preparations were made and the activities of 7-ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-dealkylase (PROD), NADPH-cytochrome-c-reductase, UDP-glucuronosyltransferase (UDPGT) and glutathione-S-transferase (GST) were measured. Kidneys were affected most. A dose-dependent decrease was observed in EROD (90% in males, 80% in females at the high dose) and in PROD (58% in females, at the high dose) in kidneys. An increase was, however, detected in kidney NADPH-cytochrome-c-reductase (66% in females at high dose), UDPGT (89% in males and 97% in females at high dose) and GST activities (56% in males and 50% in females at high dose). MX caused only a few changes in the enzyme activities of the liver. The EROD activity was decreased 25% to 37%, both in the livers of males and females, but the total content of P450s was not altered. Hepatic GST activity was elevated in females in a dose-dependent manner (31% and 44%). GST activity was elevated in duodenum in females (59%) at the high dose. There were no marked changes in the enzyme activities in the lungs. MX was a weak inhibitor of EROD activity both in the liver and kidney microsomes in vitro, decreasing the EROD activity by 53% and 43%, respectively at the concentration of 0.9 mM. The results indicate that MX decreases the activity of phase I metabolism enzymes, but induces phase II conjugation enzyme activities, particularly in kidneys in vivo. It is possible that these changes contribute to metabolism of MX in kidneys and renders them susceptible to MX in the course of repeated exposure.     

口溃液治疗复发性口腔溃疡208例疗效观察

口溃液主要成分为三氯化铁。本品经对２０８例复发性口腔溃疡患者的临床疗效观察，总有效率为９７．１％，并具有显效迅速，作用持久、涂抹方便等优点。     

β2-glycoprotein I, anti-β2-glycoprotein I, and fibrinolysis

β₂-glycoprotein-I (β₂GPI) is a phospholipid-binding plasma protein that consists of five homologous domains. Domain V is distinguished from others by bearing a positively charged lysine cluster and hydrophobic extra C-terminal loop. β₂GPI has been known as a natural anticoagulant regulator. β₂GPI exerts anticoagulant activity by inhibition of phospholipid-dependent coagulation reactions such as prothrombinase, tenase, and factor XII activation. It also binds factor XI and inhibits its activation. On the other hand, β₂GPI inhibits anticoagulant activity of activated protein C. According to the data from knockout mice, β₂GPI may contribute to thrombin generation in vivo. Phospholipid-bound β₂GPI is one of the major target antigens for antiphospholipid antibodies present in patients with antiphospholipid syndrome (APS). Binding of pathogenic anti-β₂GPI antibodies increases the affinity of β₂GPI to the cell surface and disrupts the coagulation/fibrinolysis balance on the cell surface. These pathogenic antibodies activate endothelial cells via signal transduction events in the presence of β₂GPI. Impaired fibrinolysis has been reported in patients with APS. Using a newly developed chromogenic assay, we demonstrated lower activity of intrinsic fibrinolysis in euglobulin fractions from APS patients. Addition of monoclonal anti-β₂GPI antibodies with β₂GPI also decreased fibrinolytic activity in this assay system. β₂GPI is proteolytically cleaved by plasmin in domain V (nicked β₂GPI) and becomes unable to bind to phospholipids, reducing antigenicity against antiphospholipid antibodies. This cleavage occurs in patients with increased fibrinolysis turnover. Nicked β₂GPI binds to plasminogen and suppresses plasmin generation in the presence of fibrin, plasminogen, and tissue plasminogen activator (tPA). Thus, nicked β₂GPI plays a role in the extrinsic fibrinolysis via a negative feedback pathway loop.     

异丙酚对MPTP损伤的小鼠黑质多巴胺神经元的保护作用

目的　观察异丙酚对 1 甲基 4 苯基 1,2 ,3 ,6 四氢吡啶 (1 methyl 4 phenyl 1,2 ,3 ,6 tetrahydropyridineMPTP)损伤的小鼠纹状体多巴胺神经元的影响以及可能的作用机制。方法　给予Propofol 10 0mg/ (kg·d)后注射MPTP 2 0mg/ (kg·d) ,用药 6d。 12d后分离纹状体应用高效液相 -电化学方法检测纹状体多巴胺、二羟基苯乙酸及高香草酸的含量水平 ,应用12 5I- β-CIT放射性配基和免疫组化的方法检测多巴胺转运蛋白的活性和黑质神经元的损伤情况。结果　异丙酚可增加MPTP模型鼠多巴胺及其代谢产物的含量 ,异丙酚处理组DA ,DOPAC ,HVA的含量分别为 (8.2 417± 1.692 ) μg/ g、(1.3 81± 0 .486) μg/g和 (1.63 3 9± 0 .5 73 ) μg/ g ,与MPTP损伤组比较 ,明显增加。异丙酚亦可抑制黑质酪氨酸羟化酶 (TH)阳性神经元的减少。MPTP组注射MPTP 6d后 ,纹状体DAT为 (5 .3 13± 0 .64 2 )与正常组 (6.992± 0 .5 48) μg/ g比较显著下降 (P <0 .0 1) ,P +M组纹状体DAT为 (6.5 65± 0 .40 5 ) ,明显高于MPTP组 (P <0 .0 1) ,即减轻纹状体内多巴胺转运蛋白密度下降。结论　异丙酚对MPTP损伤的DA神经元具有一定的保护作用 ,其保护作用可能与抑制多巴胺转运蛋白活性有关     

精神分裂症服用氯氮平能降低其甲状腺素水平的对照分析

目的探索氯氮平治疗是否影响T3、T4和TSH水平.方法对17例精神分裂症患者,给予氯氮平治疗第4天和第4周末分别测定T3、T4和TSH水平.结果治疗第4周末的T3(3.309±0.689)、T4(9.449±1.941)水平比第4天的T3(3.915±0.850)、T4(11.178±2.180)水平明显降低(P均＜0.05).结论氯氮平治疗能降低甲状腺素水平.     

Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma

BACKGROUND: Microbial intestinal colonization in early in life is regarded to play a major role for the maturation of the immune system. Application of non-pathogenic probiotic bacteria during early infancy might protect from allergic disorders but underlying mechanisms have not been analysed so far. OBJECTIVE: The aim of the current study was to investigate the immune effects of oral application of probiotic bacteria on allergen-induced sensitization and development of airway inflammation and airway hyper-reactivity, cardinal features of bronchial asthma. METHODS: Newborn Balb/c mice received orally 10(9) CFU every second day either Lactobacillus rhamnosus GG or Bifidobacterium lactis (Bb-12) starting from birth for consecutive 8 weeks, during systemic sensitization (six intraperitoneal injections, days 29-40) and airway challenge (days 54-56) with ovalbumin. RESULTS: The administration of either Bb-12 or LGG suppressed all aspects of the asthmatic phenotype: airway reactivity, antigen-specific immunoglobulin E production and pulmonary eosinophilia (mean: 137 vs. 17 and 13 cellsx10(3)/mL, respectively). Antigen-specific recall proliferation by spleen cells and T-helper type 2 cytokine production (IL-4, IL-5 and IL-10) by mesenteric lymph node cells also showed significant reduction, while TGF production remained unchanged. Oral LGG administration particularly suppressed allergen-induced proliferative responses and was associated with an increase in numbers of TGF-beta-secreting CD4+/CD3+ T cells in mesenteric lymph nodes (6.5, 16.7%) as well as nearly 2-fold up-regulation of Foxp3-expressing cells in peribronchial lymph nodes. CONCLUSIONS: Neonatal application of probiotic bacteria inhibits subsequent allergic sensitization and airway disease in a murine model of asthma by induction of T regulatory cells associated with increased TGF-beta production.     

可逆性胆碱酯酶抑制剂的研究:2-氧化-1,3,2-二氧磷杂环己烷类化合物的合成

本文报道2-氧化-1,3,2-二氧磷杂环己烷类衍生物的合成,希望寻找效果较好的可逆性胆碱酯酶抑制剂。初步药理实验证明,所合成的大部分化合物具有一定的抑制乙酰胆碱酯酶的作用,且毒性较低。通过对中间体Ⅱ进行质谱分析,发现该类化合物中大部分存在M-57碎片离子峰,利用高分辨质谱和亚稳离子测定,确定了该碎片离子的生成过程。     

东芝DFP-2000A数字减影系统故障检修

介绍东芝DFP-2000A数字减影系统维修实例,并论述该机图像存储系统采用的RAID3等级的磁盘阵列。