硝苯啶、硫氮(艹卓)酮对兔实验性动脉粥样硬化症的影响

硝苯啶和硫氮(艹桌)酮不明显影响血清脂蛋白组分水平,但均显著抑制家兔主动脉动脉粥样硬化形成,降低血浆过氧化脂质、血栓烷和主动脉内中膜胆固醇、磷脂及钙含量,升高血浆6-酮-PGF_(1α),使,TXB_2/6-酮-PGF_(1α)趋于平衡。说明钙在血栓烷-前列环素代谢中起重要作用。     

Skinfold thickness versus isotope dilution for body fat assessment during simulated microgravity: results from three bed-rest campaigns in men and women with and without countermeasures

Because body composition is altered during head-down bed rest (HDBR), body mass can not be used as an index of energy balance. Consequently diet allowances should not be based on body mass evolution but on fat mass changes. Though criticized, skinfold thickness (ST) is the costless, easiest and fastest method to use for such an objective. The aim of this study was to compare the percentage of body fat (%BF) estimated by ST with the isotope dilution of H₂¹⁸O. We compiled data from three HDBR campaigns, one on women (n=8) in November 1998 and two on the same men (n=8) in December 1997 (without countermeasure) and January 1998 (with thigh-cuffs countermeasure), according to a crossover design. Body composition was assessed before and after 6 days of HDBR. %BF was derived from the biceps, triceps, sub-scapular and sup-iliac ST according to Durnin and Wormersly (1974). Fat-free mass was measured on the same day by H₂¹⁸O dilution and fat mass was calculated by the difference with body mass and expressed as a percentage. Based on precision tests, the minimum measurable change by ST was 1.1%BF for single measurement point. Both intercepts (F _4,30=0.89, P=0.45) and slopes (F _4,30=0.74; P=0.57) of the ST versus dilution relationships were not affected by the periods (December vs January), experimental conditions (control vs HDBR vs HDBR + thigh cuffs) or sex allowing the derivation of a common relationship %BF_st=0.94 × %BF_dil (F _1,47=97.9, P<0.0001; non-significant intercept excluded) with a bias between methods of −1.7±2.0 %BF (95% CI: −5.8, 2.4 %BF). ST can be used to measure %BF during HDBR provided great care is placed on training and changes are higher than 1.1 %BF. If the method can be applied for in-flight energy balance monitoring given the high observed energy deficit, a tight monitoring of the individual nutritional status as needed during simulation appears, however, dubious based on this solely method.     

Relationship of human adenoviruses 12, 18, and 31 as determined by hemagglutination inhibition.

Adenoviruses 12 and 31, but not Ad18, agglutinate rat blood cells at high titer, providing suitable blood cells be available and a prolonged contact period of virus with the erythrocytes is allowed. Purified virus particles show direct, and virus-free supernatants show direct and indirect, hemagglutination, ie, enhancement of HA by heterologous antiserum. Hemagglutination inhibition with rabbit antisera shows cross-reactions between Ad12 and Ad31 with titers 4--32 times lower than with homologous antigens; Ad18 antisera react with antigens from both of the other serotypes. No cross-reactions were seen with antisera from other adenoviruses. This suggests an antigenic relationship of the three viruses of subgroup IV in their fiber antigen gamma, in addition to the known relation in the hexon (epsilon), which is apparent in cross-neutralization.     

Suppression of autoimmune disease in NZB/W F1 mice by treatment with the novel immunomodulator BTS 63155.

Autoimmune disease in NZB/W F1 mice was treated from 23 weeks of age with the novel immunomodulator BTS 63155 and, for comparative purposes, the established immunosuppressive agent cyclosporin A. Both drugs significantly improved survival compared with untreated controls. Lupus nephritis was also significantly reduced in the drug-treated groups, and this was related to reduced glomerular deposition of IgG. Autoantibody (ANA) levels were lowered by treatment with cyclosporin A, but not by BTS 63155. This latter finding may indicate a different mode of action for the two drugs. In a long term study, neither drug effected a complete cure, as autoimmune disease recurred on withdrawal of drug treatment.     

Natural antibodies against the immunoglobulin F(ab′)2 fragment cause elimination of antigens recognized by the F(ab′)2 from the circulation

A humanized monoclonal IgG1 antibody, designated hC4G1, recognizes the fibrinogen receptor glycoprotein (GP)IIb/IIIa on platelets and inhibits platelet aggregation. When the F(ab′)₂ fragment of hC4G1 (F(ab′)₂ hC4G1) was administered to cynomolgus monkeys, all the monkeys showed inhibition of platelet aggregation ex vivo. Unexpectedly, a significant decrease in platelet count was observed in 5 of 18 monkeys. Antibodies against F(ab′)₂ hC4G1 were detected in the plasma of these monkeys by ELISA. Antibody activity in the plasma of these monkeys was significantly correlated with the intensity of platelet decrease (r = 0.84). The natural monkey antibodies to F(ab′)₂ hC4G1 were directed against the C-terminal region of F(ab′)₂ fragment common to all human and humanized IgG antibodies. Natural homo-reactive antibodies were also detected in human plasma from 15 of 40 healthy volunteers. Specificity was closely similar to that of the monkey antibodies. Affinity-purified human homo-reactive antibodies enhanced phagocytosis of platelets treated with the F(ab′)₂ hC4G1. Monkey plasma with high homo-reactive antibody activity was confirmed to decrease platelet count when administered together with F(ab′)₂ hC4G1 to a monkey with low antibody activity. These results suggest that F(ab′)₂ of humanized and human antibodies causes elimination of the corresponding antigens from the circulation by homo-reactive antibodies.     

Fluoropyrimidine chemotherapy in a rat model: comparison of fluorouracil metabolite profiles determined by high-field 19F-NMR spectroscopy of tissues ex vivo with therapy response and toxicity for locoregional vs systemic infusion protocols

A Sprague-Dawley rat model with DS sarcoma transplanted in the thigh was used to compare transcatheter locoregional i.a. and systemic i.v. administration of 5-fluorouracil (FU) at 12 dose-rate schedules: 25, 50 and 100 mg/kg; bolus, 1, 5 and 24 h infusions. In experiment A tumor (62/67 animals) as well as liver and kidney (56/67 animals) were excised 1 h after a single bolus or 1 h infusion or at the end of 5 and 24 h infusions. (19)F-NMR spectroscopy at 11.7 T was used to quantitate FU and its metabolites in ca. 1 g of tissue at 4 degrees C. In experiment B analogous FU treatments were repeated for 5 days (rats 80+11 controls). Tumor volumes vs time, various blood parameters and survival times were recorded, and a log growth rate parameter log GR, a response index RI, and a toxicity index TI were calculated. The i.a. vs i.v. ratios for tumor concentrations of FU and total anabolites (F-Nucl) were >1 for nearly all treatments and increased with infusion time at the higher doses. F-Nucl in tumor correlated linearly with total fluorine concentration (Tot. F range 30-1100 nmol/g) over all treatments (r=0.92, slope=0.45, p<0.0001). For non-bolus i.v. treatments [FU+F-Nucl] decreased linearly with decreasing FU dose rate (r(2)=0.74, zero intercept), while i.a. treatments showed non-linear behavior. For non-bolus treatments the mean log GR per treatment group showed a negative correlation (r=-0.87) with log[F-Nucl]. The most effective non-toxic treatments were 25 mg/kg over 5 or 24 h; the i.a. route was superior to i.v. on the basis of [FU+F-Nucl], RI, the reduction in log GR, and Kaplan-Meier survival statistics. For liver and kidney Tot. F (>83% FU catabolites) reached ca. 3-4 and 6-7 micromol/g, respectively, at the highest dose rates for either route; F-Nucl were detected only for Tot. F>500 nmol/g and increased exponentially as Tot. F increased (toxic treatments). The concentrations of the main catabolite (alpha-fluoro-beta-alanine, FBAL) in tumor did not correlate with Tot. F but rather with FBAL levels in kidney (r=0.90, all treatments), indicating that uptake of liver-derived FBAL from the circulation is the major source of FBAL in tumor.     

Endogenous brain angiotensin II disrupts passive avoidance behavior in rats

The presence of angiotensinogen, the precursor of angiotensin II (ANG II), in brain tissue and in cerebrospinal fluid (CSF) allows stimulation of endogenous brain ANG II by renin. Passive avoidance tests were performed in female Wistar rats. The animals received an electrical shock after entering a black box on the first experimental day. Avoidance was tested every 24 h for 5 consecutive days. Renin in doses of 0.01 and 0.1 units was injected once into the lateral brain ventricles 2 min before the first test. CSF ANG II increased from 40 to 4547 and 5152 fmol per ml (means), respectively. A dose-dependent disruption of avoidance learning was observed, the frequency to enter the black box increasing from 11% (control) to 29% and 46%, and the latency decreasing from 165 (control) to 143 and 116 sec, respectively. These effects were statistically significant (P less than 0.001) for more than 24 h and returned to control levels after 48 to 120 h. Administration of the converting-enzyme inhibitor SQ 14225 i.v.t. prior to renin injections abolished the renin effects. Injections of renin given 22 h after learning were without effect.     

The prognostic role of the extent of Y microdeletion on spermatogenesis and maturity of Sertoli cells

Substantial involvement of the Y chromosome in sexual development and spermatogenesis has been demonstrated. Over the last decade, varying extent of Y chromosome microdeletions have been identified among infertile patients with azoospermia or oligozoospermia. These microdeletions were clustered in three main regions named AZFa, AZFb, and AZFc. Analysis of the Y chromosome microdeletion was found to be of prognostic value in cases of infertility, both in terms of clinical management as well as for understanding the aetiology of the spermatogenesis impairment. However, the accumulated data are difficult to analyse, due to the variable extent of these deletions, the different sequence-tagged sites (STS) used to detect the microdeletions, and the non-uniformity of the histological terminology used by different investigators. This debate discusses the chances of finding testicular spermatozoa in men with a varying extent of Y chromosome microdeletions. The genotype and germ cell findings in men with AZFa microdeletions as well as those that include more than a single AZF region are reviewed, as is the effect of Y chromosome AZF microdeletions on the maturity of the Sertoli cells.     

IL-18在体外培养系统中诱导肿瘤快速杀伤效应及肿瘤特异性CTL

目的应用rhlL-18在体外培养系统(Coculture system in vitro，CCs)中诱导快速肿瘤杀伤效应及诱导肿瘤特异性细胞毒性T淋巴细胞(Cytotoxic T Lymphocyte，CTL)。方法 采用StemSep^TM免疫磁性细胞分离法分离人外周血NK细胞、T细胞及树突细胞(DCs)，流式细胞仪分析细胞表型，125I-UdR标记的细胞毒实验检测杀伤活性，ELISA方法检测IFN-7的产生量。结果 在CCs中，rhIL-18诱导出快速肿瘤杀伤效应，这种杀伤效应无抗原特异性、不受MHC限制，DCs和T细胞的存在与否对其无明显影响。在同一培养系统中，肿瘤抗原存在的条件下，96h后，rhIL-18能够诱导并促进CTL介导的肿瘤特异性杀伤效应。结论 rhIL-18能够在体外培养系统中相继诱导肿瘤快速杀伤效应及肿瘤特异性CTL。