持续压力超负荷对兔左心室细胞凋亡的影响

OBJECTIVE: To study the effect of chronic pressure overload on the apoptosis of the left ventricle myocytes in rabbits. METHODS: Rabbit models of chronic pressure overload-induced heart failure were prepared in which dynamic changes of apoptotic myocytes in the left ventricle were observed by way of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. RESULTS: Only a few apoptotic cells was observed in the sham-operated group, while in the experimental group, the apoptotic left ventricle myocytes significantly increased after operation, presenting a peak level between day 3 and day 7. Seven days after the operation, the apoptotic myocytes began to decrease and till day 14, the apoptotic cell number had been smaller than that measured on day 1. When signs of heart failure set in, the apoptotic myocytes were again increased (P<0.001). CONCLUSION: During chronic pressure overload, myocyte apoptosis in the left ventricle is elevated at the early stages and undulates subsequently, with the peak occurring before hypertrophy is obvious.     

高效液相色谱法测定右旋儿茶素血浆浓度及药代动力学参数

本文建立了体液中右旋儿茶素的RP-HPLC测定方法。采用C_(18)键合相硅胶为填料的固相提取柱进行样品预处理,右旋儿茶素的提取回收率为79.8%.应用二极管阵列检测器对色谱峰纯度进行鉴定。该法精密度好,方法回收率近100%,日内、日间的变异系数为2.4～5.6%,血浓69.6～1160 ng/ml范围内呈线性关系,r=0.9993。家兔静注右旋儿茶素18mg/kg,其药代动力学过程符合二室模型,分布相半衰期为0.129 h,消除相半衰期为1.19h。     

Early life experiences linked to diabetes mellitus: a study of African-American migration.

African Americans experienced massive internal migrations that shifted more than 6 million Southern-born blacks to other sections of the United States over the past century, a trend that only recently has been reversed. Whenever mass migration takes place, there is an opportunity to examine the role of the native and relocated environments in the development of disease. This article examines those relationships for diabetes mellitus, a group of diseases that disproportionately affect African-Americans relative to other racial and ethnic groups in the United States. Age-specific and age-adjusted rates with 95% confidence intervals were calculated for males and females for combinations of five regions of birth and four regions of residence at time of death. Southern-born males had statistically significantly higher death rates from diabetes than did their counterparts who died in the same regions in 9 of 16 comparisons. For females, those born in the South had statistically significantly higher rates in 15 of 16 comparisons. The results of this study indicate that place of birth and early life experiences are statistically associated with diabetes mortality among African Americans regardless of place of residence at time of death.     

The plasminogen-activation system in ovarian tumors

We studied the plasminogen activation system in tumor tissue by measuring the antigen level of the 2 plasminogen activators, tissue-type (t-PA) and urokinase-type (U-PA) and their inhibitors, plasminogen-activator inhibitors type-1 (PAI-1) and type-2 (PAI-2) in the tissue extracts of 43 human benign and malignant ovarian tumors. U-PA levels were significantly higher in malignant than in benign tumors. In addition, U-PA antigen levels were higher in the metastatic tissue of advanced disease (FIGO stage III) than in the primary localized tumor (FIGO stage I/II). Also PAI-1 concentrations tended to be higher in malignant than in benign tumors, but this difference was not statistically significant. In contrast, t-PA levels were lower in metastatic than in non-metastatic tumors, whereas PAI-2 levels were unrelated to the stage of ovarian malignancy. These results were integrated in a plasminogen-activation-dependent malignancy index (U-PA × PAI-1/t-PA). This index distinguished the different groups of benign ovarian tumors, localized and metastatic ovarian carcinomas better than U-PA levels. It could be useful as a prognostic indicator in ovarian cancer © 1993 Wiley-Liss, Inc.     

Fictive oesophageal peristalsis evoked by activation of muscarinic acetylcholine receptors in rat nucleus tractus solitarii

The aim of the present study was to determine if muscarinic acetylcholine receptor-mediated peristaltic rhythmogenesis in the rat oesophagus is a central motor program that can be generated without peripheral sensory support. In anaesthetized male Sprague-Dawley rats, pressure-ejection of glutamate (10–20 pmol) and muscarine (5–10 pmol) in the subnucleus centralis of the nucleus tractus solitarii (NTS_C) evoked monophasic pressure waves and rhythmic oesophageal peristalsis, respectively, but did not change mean arterial blood pressure or respiration. Application of muscarine (50–100 pmol) to the NTS extraventricular surface evoked rhythmic multi-unit burst discharges in the compact formation of the nucleus ambiguus (AMB_C) that led to oesophageal peristalsis in a phase-locked manner. Evoked rhythmic AMB_C activity persisted during neuromuscular blockade with curare, although the peak frequency of individual bursts was decreased. In a brainstem slice preparation, intracellular and whole cell patch recordings from AMB_C neurones during focal stimulation of the NTS_C region with muscarine revealed rhythmic depolarizing waves that showed a pattern similar to that of rhythmic oesophageal peristalsis. The present findings support the concept that medullary circuits comprising premotor neurones of the NTS_C are intrinsically capable of generating rhythmic oesophagomotor output, but are subject to a powerful modulation by peripheral sensory feedback.     

Validation of the Taiwan Birth Registry using obstetric records.

BACKGROUND AND PURPOSE: Birth certificates are a major source of population-based data often used in maternal and child health research, but their value depends upon the level of accuracy of the data. The purpose of this study was to assess the validity of the birth registry data in Taiwan. METHODS: Obstetric records of a total of 2779 infants born at a municipal hospital in Taipei between 1995 and 1997 were abstracted and linked to the Taiwan Birth Registry (TBR). Concordance was presented by agreement percentages for various birth characteristics including gender, birth order, birth weight, and gestational age. Concordance was further assessed using Cohen's k and sensitivity/specificity for both birth weight and gestational age, with both variables categorized according to their customary definitions. RESULTS: Missing data for specific items in the TBR ranged from 0% (gender) to 1.6% (birth order). The birth registry accurately reported all 4 selected items, with the highest and lowest concordance percentage noted for gender (99.0%) and gestational age (88.3%), respectively. The level of agreement indicated by the Cohen's k statistic ranged from 0.92 to 0.96 for birth weight and gestational age when both variables were treated as categorical variables. CONCLUSIONS: The TBR showed a low rate of missing information and high levels of validity for the elements frequently used in maternal and child health research in Taiwan.     

Carvedilol protects ischemic cardiac mitochondria by preventing oxidative stress.

Ischemia negatively affects mitochondrial function by inducing the mitochondrial permeability transition (MPT). The MPT is triggered by oxidative stress, which occurs in mitochondria during ischemia as a result of diminished antioxidant defenses and increased reactive oxygen species production. It causes mitochondrial dysfunction and can ultimately lead to cell death. Therefore, drugs able to minimize mitochondrial damage induced by ischemia may prove to be clinically effective. We analyzed the effect of carvedilol, a beta-blocker with antioxidant properties, on mitochondrial dysfunction. Carvedilol decreased levels of TBARS (thiobarbituric acid reactive substances), an indicator of oxidative stress, which is consistent with its antioxidant properties. Regarding cell death by apoptosis, although ischemia did increase caspase-8-like activity, there were no changes in caspase-3-like activity, which is activated downstream of caspase-8; this may indicate that the apoptotic cascade is not activated by 60 minutes of ischemia. We conclude that carvedilol protects ischemic mitochondria by preventing oxidative mitochondrial damage, and, by so doing, it may also inhibit the formation of the MPT pore.     

An oral selective M3 cholinergic receptor antagonist in COPD.

Cholinergic antagonists have been used since the early 1900s as bronchodilators for chronic obstructive pulmonary disease (COPD). The present study investigated whether an oral muscarinic M3-selective anticholinergic agent (OrM3) would provide an improved therapeutic advantage compared with an inhaled anticholinergic agent in patients with COPD. A 6-week, multicentre, randomised, placebo- and active-controlled, parallel-group study was performed at 56 sites in the USA. In total, 412 male and female patients (aged 35-86 yrs) with a clinical history consistent with COPD were randomised to receive OrM3 0.5, 2, 3 or 4 mg orally once daily, ipratropium bromide 36 mug by inhalation four times daily or placebo. OrM3 demonstrated a significant dose-related improvement in serial forced expiratory volume in one second and a trend for dose-related improvement in patient-reported symptoms compared with placebo. However, at a dose that provided efficacy less than that of ipratropium, the incidence of dose-related, mechanism-based side-effects for OrM3 exceeded those observed for ipratropium. In patients with chronic obstructive pulmonary disease, the oral M3-selective agent did not offer a therapeutic advantage over inhaled ipratropium. These results do not support the hypothesis that high selectivity for muscarinic M3 receptors over airway neuronal M2 receptors will represent a more effective therapy than current inhaled anticholinergics in obstructive airway disease.