Degenerative cerebral alterations in Chinese aged 65 years or older

The brains of 57 consecutive Chinese patients, aged 65 years or above, dying in a regional general hospital, the causes of death of whom were not primarily intracranial, were examined for parameters of degenerative brain disease--reduction in brain weight, ventricular enlargement, neurofibrillary tangles, senile plaques, granulovacuolar degenerations, and ischemic lesions. Semi-quantitative analysis of these morphological changes suggests that, though generally similar to those observed among Caucasians, they occurred much less frequently, and, as regards senile plaques, in smaller numbers. These observations suggest a lower prevalence of "senile" cerebral alterations in Chinese than in Caucasians.     

Flavonoids ofElscholtzia cristata

Apigenin, apigenin-7-O-glucoside, luteolin-7-O-glucoside and linarin were isolated fromElscholtzia cristata (Labiatae).     

A sensitive and simplified HPLC analysis for the determination of fluconazol in human plasma

A sensitive and simplified HPLC assay of fluconazol is described. The calibration curve of fluconazol in plasma ranging 0–10 μ g/ml was linear with the correlation coefficients of 0.9900. The limit of detection was 0.3 μ g/ml. The average recovery of the drug was 89.1±9.05%. After oral administration of single dose(150mg) of fluconazol in man, C_max and T_max were 3 μg/ml and 4hr., respectively.     

Quantitation of protein adducts as a marker of genotoxic exposure: immunologic detection of benzo(a)pyrene -- globin adducts in mice

Immunologic methods have been developed for the determinationof benzo(a)pyrene (BP)-protein adducts and validated in animalstreated with (³H)BP. A previously developed antibody, 8E11,which recongnizes 7ß, 8-dihydroxy-9, 10-epoxy-7, 8,9, 10tetrahydrobenzo(a)pyrene (BPDE-I)-modified DNA or proteinas well as BPDE-I- tetraols, was used. The sensitivity of theassay was increased by enzymatic digestion of the modified proteinwith insoluble protease into peptides and amino acids beforeanalysis. In a competitive enzymelinked immunosorbent assay(ELISA) with digested BPDE-I-modified bovine serum albumin,50% inhibition occured at 400 fmol of adduct compared to 1450fmol for the nondigested albumin. Analysis of globin (Gb) isolatedfrom animals treated in vivo with 0.3–3 mg (³H)BP indicatedthat the ELISA could detect 90–100% of the adducts determinedby radioactivity. Levels of adducts in lung and liver DNA andserum albumin were correlated with the levels of Gb adducts.Of the total radioactivity associated with hemoglobin, only10% was from Gb while {small tilde}80% was from the heme fractionand the remainder from free BP metabolites. Significant cross-reactivityof antibody 8E11 was found with several BP-diols and phenols,suggesting that the immunoassay will not only be specific forBPDE-I adducts but will also detect adducts of other BP metabolitesas well as other aromatic hydrocarbon diol epoxides. An immunoaffinitycolumn of antibody 8E11 coupled to Sepharose 4B was used toisolate modified peptides from the digested Gb. About 65% ofthe applied radioactivity was retained on the column. Between1 and 2 mg of non-modified digested Gb could be added to thesample without interfering with binding of adducts. Proteindigestion and immunoaffinity chromatography should be usefulfor the measurement of protein adducts in biomonitoring studies.     

Buthionine sulfoximine-mediated depletion of glutathione in intracranial human glioma-derived xenografts

D-54 MG, a human glioma-derived continuous cell line growing as subcutaneous or intracranial xenografts in athymic mice, was found to be sensitive to the effects of D,L-buthionine-(SR)-sulfoximine, a selective inhibitor of gamma-glutamylcysteine synthetase. Intraperitoneal administration of one dose of buthionine sulfoximine (BSO, 5 mmol/kg) resulted in depletion of total intracellular glutathione to 57 and 47% of control 12 hr, and 73 and 23% of control 24 hr, after BSO in subcutaneous and intracranial xenografts respectively. Concurrent measurement of total glutathione in the contralateral (non-tumor-containing) cerebral hemisphere in mice bearing intracranial D-54 xenografts demonstrated insignificant depletion of glutathione. Multiple doses of BSO, at 12-hr intervals, resulted in further depletion to 27% (s.c.) and 16.5% (i.c.) of control 12 hr following the final dose of BSO. Quantitative analysis of BSO delivery to xenograft and contralateral brain tissue revealed transfer constants, K1, of 15.8-24.1 x 10(-3) and 2.4 x 10(-3) ml.g-1.min-1 for xenograft and "normal" brain respectively. This highly selective depletion of glutathione in neoplastic tissue versus surrounding non-neoplastic host tissue may have therapeutic implications for the rational use of chemotherapeutic and radiotherapeutic intervention.     

Rapid characterization of mutagenic aromatic amines in energy-related materials by short column liquid chromatography with electrochemical detection

A liquid Chromatograph equipped with a short (3 cm) reverse phase column and electrochemical detector was used to characterize aromatic amines in shale oil, synthetic oil, and coal gasification streams. Five major peaks were produced from each sample mixture. The composition of the peaks was determined by high performance liquid chromatography with a long (25 cm) reverse phase column and by gas chromatography/mass spectrometry. Amines in the various peaks included aminonaphthalenes, aminobiphenyls, aminofluorenes, and aminophenanthrenes plus aminoanthracenes. The concentration of aminofluorenes, and aminophenanthrenes plus aminoanthracenes correlated with relative mutagenicity of the base fraction from the oils or tars. The levels of 2- and 3-ringed aromatic amines from shale oil and oil from the Great Plains commercial coal gasification plan were 24 and 184 g/g tar, respectively, while the respective mutagenicities were 8 and 214 revertants/g base fraction. This technique has the advantages of high sensitivity and rapid analysis, and could be used to screen for the presence of mutagens in synthetic fuel samples.     

Dose-response curves of homovanillic acid in pre-frontal cortex and caudate following antipsychotic drugs: relation to clinical potencies

Dose-response curves for the elevation of homovanillic acid (HVA) levels, determined by high performance liquid chromatography using electrochemical detection, in the pre-frontal cortex and caudate of rats after acute treatment with 12 antipsychotic drugs are presented. The order of potency in both brain regions was: haloperidol fluphenazine > loxapine > trifluoperazine > thiothixene > molindone > clopenthixol > chlorpromazine > metoclopramide > thioridazine > clozapine > sulpiride. This ranking is roughly correlated with that based on clinical potencies. The relative elevation of the content of HVA was weaker in the pre-frontal cortex than in the caudate for all drugs tested, except clozapine at a high dose.     

全科医学基层实践基地师资综合评价指标体系的构建

目的 构建一套科学、系统的全科医学基层实践基地师资综合评价指标体系,为全科基层实践基地的师资遴选、评价和考核提供参考。方法 在文献研究、专家咨询和小组讨论的基础上,初步构建全科基层实践基地师资原始指标体系。选择具有中级及以上职称,并长期从事医学教育管理、全科医疗与教学、基层医疗卫生服务与管理工作的32名专家,进行两轮德尔菲专家函询,并对函询结果进行统计分析,确定全科基层实践师资综合评价指标。运用层次分析法计算各指标权重并进行一致性检验。运用Yaahp统计学软件进行数据录入和处理。结果 构建出包含3个一级指标、12个二级指标和61个三级指标的全科医学基层实践基地师资综合评价指标体系。3个一级指标分别为师资遴选纳入标准、教学能力评价标准、师资考核标准;权重系数分别为0.334、0.525、0.142。结论 本研究构建的指标体系具有较好的科学性和系统性,为进一步加强全科基层实践基地师资队伍的建设和管理、提升全科住院医师培养质量,提供了理论依据。     

Antiarrhythmic actions of tedisamil: Studies in rats and primates

Tedisamil is a new bradycardic agent, previously shown to block transient outward and delayed rectifier potassium currents in cardiac tissue [1,2]. In the present study tedisamil caused bradycardia and Q-Tc widening in rats and primates. Q-Tc widening is indicative of class III antiarrhythmic actions. In keeping with this, tedisamil had antiarrhythmic activity against electrical and ischemia-induced arrhythmias in rats. In rats, 0.5–4 mg/kg IV tedisamil caused parallel and dose-related increases in action-potential duration, Q-Tc interval, and refractory period; and decreases in maximum ventricular following frequency. In primates after 0.5–2.0 mg/kg IV, findings were similar for indices of Q-T widening and decreases in maximum ventricular following frequency. Tedisamil did not change QRS width, nor did it increase threshold currents for capture of ventricles, nor for fibrillo-flutter at doses below 4 mg/kg in rats. These findings were consistent with the lack of significant sodium-channel blockade. However, upon increasing the dose to 4 mg/kg, ventricular fibrillo-flutter could not be induced in rats by electrical stimulation; instead, only ventricular tachycardias with slow rates occurred. Ischemia-induced ventricular fibrillation was reduced in a dose-related manner by tedisamil in rats. The overall incidence of ischemia-induced ventricular tachycardia was not markedly reduced, but rates during tachycardic episodes were lower. When pacing was used to overcome tedisamil-induced bradycardia, antiarrhythmic actions during ischemia were more pronounced. These findings are consistent with the hypothesis that tedisamil increased refractoriness, which resulted in extended path lengths for reentry circuits and slower rates during episodes of ventricular tachycardia. High doses of tedisamil increased path lengths so much that the multiple reentry circuits of fibrillation could no longer occur. The limited study in primates suggests similar mechanisms could occur in humans.