MODULATION OF ALCOHOL PREFERENCE BY NMDA ANTAGONISTS IN MALE RATS

Chronic alcoholization by alcohol inhalation was used to studythe properties of magnesium, a non-competitive NMDA receptorantagonist, and CGP 39551, a competitive NMDA receptor antagonist,on behavioural dependence as estimated by the free-choice paradigm[alcohol 10% (v/v) vs. water], on the hypermotility after alcoholwithdrawal, and finally on the cortical vascularization. Thefirst experimental group received the drugs per os during thewhole alcoholization period. Magnesium (20 mg/kg/day) decreasedthe alcohol dependence while CGP 39551 (5 and 10 mg/kg/day)increased, in a dose-dependent manner, the dependence to alcohol.A second group of animals received the same drugs at the samedosages, not simultaneously during chronic alcoholization, butimmediately after alcoholization in one shot i.p. injection.In this case, rats receiving 5 mg/kg CGP 39551 never showedany dependence towards alcohol, while 10 mg/kg CGP 39551 or20 mg/kg magnesium prolonged the number of days of alcohol dependence.These results thus indicate the close interaction between NMDAreceptor function and dependence for alcohol. Magnesium hadno effects on hypermotility, while CGP 39551-treated animalspresented a decrease in the hypermotility observed after alcoholwithdrawal. Neither drug affected the hypervasculanzation accompanyingthe chronic alcoholization.     

水八角的生药学研究

目的：通过对四川民间药掌裂叶秋海棠、一点血、美丽秋海棠根茎的生药学研究,为该类药的临床应用、质量标准的制定和进一步开发利用提供资料。方法：性状鉴别、显微鉴别和薄层色谱鉴定相结合。结果：木栓组织、纤维、石细胞、腺毛的存在与否和形态特征存在种间差异,三者均含芦丁和槲皮素。结论：首次对三种秋海棠进行了生药学研究     

LYME PERICARDITIS LEADING TO TAMPONADE

We report the case of a 62-yr-old man who presented with Lymepericarditis leading to cardiac tamponade shortly followed byan arthritis. IgM and IgG antibodies to Borrelia burgdorferiwere demonstrated in serum by indirect immunofluorescence. Borreliaburgdorferi was demonstrated and identified in pericardial fluidby indirect immunofluorescence using serum from a patient withproven Lyme disease and by a monoclonal antibody immuno-goldsilver stain. Spirochetes were also found in synovial biopsiesusing a silver stain. The tamponade was treated with pericardiocentesis;the arthritis was treated with intravenous ceftriaxone (2 gonce daily) for 14 days. The patient recovered completely withindays of commencing treatment. This case report demonstratesthat borrelial infection may lead to pericarditis and cardiactamponade. KEY WORDS: Borrelia burgdorferi infection, Arthritis, Pericarditis, Tamponade     

Determination of left ventricular volume by two-dimensional echocardiography: comparison with magnetic resonance imaging

Left ventricular volume was determined in 12 healthy volunteersusing a newly developed two-dimensional echocardio-graphic delineationmethod. The results were compared with those of magnetic resonanceimaging, which served as the method of reference. Left ventricularend-diastolic volume was 123 ± 12 ml, echocardiographicallydefined, and 121 ± 12 ml calculated with magnetic resonanceimaging. End-systolic volume was 41 ± 7 ml on echocardiographyand 37±6 ml on magnetic resonance imaging. Left ventricularejection fraction was 67 ± 4%, echocardiographicallydefined, and 70 ± 5%, calculated with magnetic resonanceimaging. There was no statistical difference for any of themeasured parameters. Interstudy and inter-observer variabilitywas minimal. In conclusion, in healthy volunteers left ventricularvolume was accurately defined, using this newly developed two-dimensionalechocardiographic delineation method. During endocardial delineationa dynamic display is continuously available on a second window,allowing precise visual edge-detection. Moreover, correctionscan be made easily and quickly. These two advantages enhancethe accuracy of the method, even in cases of poor echogenicity.     

Vital exhaustion, extent of atherosclerosis, and the clinical course after successful percutaneous transluminal coronary angioplasty

It has been observed that vital exhaustion, a state characterizedby unusual tiredness, increased irritability and feelings ofdemoralization not uncommonly precedes myocardial infarctionin apparently healthy individuals. This observation raised thequestion as to whether vital exhaustion is a marker of subclinicalcoronary disease. To answer that question the condition wasassessed in 105 male patients (mean age 54·8 year) beforeand 2 weeks after successful percutaneous transluminal coronaryangioplasty (PTCA) by the Maastricht questionnaire. Vital exhaustionwas found to be significantly correlated with the number ofdiseased vessels before PTCA and to decrease significantly afterPTCA. However, the association was rather modest (R²=0·08)and most patients remained exhausted after PTCA. During a follow-upperiod of 1·5 years, 32 patients (30%) experienced anew cardiac event (cardiac death, myocardial infarction, coronaryartery bypass grafting, repeat PTCA, a new coronary lesion orrecurrent angina with documented ischaemia). Univariate andmultivariate analyses showed that the number of diseased vessels,hypercholesterolaemia, and vital exhaustion were independentlyassociated with future events. The odds ratios were 3·74(P=0·02), 3·08 (P=0·08) and 3·07(P=0·04), respectively. It is concluded that the tirednesspreceding a cardiac event is only modestly associated with theextent of coronary artery disease and that a state of exhaustionafter PTCA increases the risk for a new cardiac event.     

Occupational transmission of HIV in health care workers: A review

Health care workers have a small but real risk of acquiringHIV infection as a result of occupational exposure. In thispaper, we review all reports in the scientific literature from1984 through to December 1993 of confirmed and probable casesof HIV seroconversion after a specific occupational exposure.A total of 64 confirmed cases have been reported, 24 in Europe,36 in the USA and 4 in other countries. Most seroconversionshave resulted from percutaneous exposure (91%) to AIDS patients(62%), usually caused by hollow bore needlestick injuries inflictedduring blood drawing procedures. Almost all seroconversionshave been detected within 6 months of exposure (94%) and haveusually been preceded by an episode of acute illness (73%).Ten seroconversions have occurred in spite of partial or completecourses of zidovudine prophylaxis. An additional 113 probablecases have been reported, 75 in the USA, 35 in Europe and 3in other countries. Aggregating the results of the prospectivestudies carried out, it is calculated that the risk of seroconversionfollowing percutaneous exposure is 0.33% or 3 in 1000 exposures(95% Cl: 0.21–0.52%), while the risk following mucocutaneousexposure is much lower (0.04%, 95% Cl: 0.006–0.31%). Thedocumented failure of zidovudine prophylaxis following occupationalexposure in a number of instances indicate its effect is, atbest, only partial; furthermore, exposure to source patientswho have been receiving the drug may lead to transmission ofzidovudine-resistant strains of HIV. Risk factors for occupationalexposure to HIV and for transmission, given that an exposurehas occurred, are discussed.     

Induction of Cytochrome P450 Isoenzymes after Toxicokinetic Interactions between 2,3,7,8-Tetrachlorodibenzo-p-dioxin and 2,2',4,4',5,5'-Hexachlorobiphenyl in the Liver of the Mouse

One group of male C57BL/6J mice received a single oral doseof 1 nmol 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg. Sixother groups received single oral doses of 100, 300, or 1000µmol2,2',4,4',5,5'-hexachlorobiphenyl (HxCB)/kg, alone or in combinationwith 1 nmol/kg TCDD. Liver deposition of both compounds wasstudied at Day 3 after dosage. Hepatic CYP1A1 and CYP1A2 proteinlevels and related 7-ethoxyres-orufin-O-deethylation (EROD)and acetanilide 4-hydroxylation (ACOH) activities were alsostudied. A significant increase in the hepatic deposition ofTCDD was observed in all three mixed dose groups but TCDD didnot influence hepatic HxCB deposition. TCDD did increase bothCYP1A1 and CYP1A2 protein levels. In the HxCB-treated groups,CYP1A2 levels were also increased in a dose-dependent way butCYP1A1 levels were not increased. CYP1A2 activities (ACOH),but not protein levels, in the TCDD groups cotreated with HxCBwere higher than those in the group treated with TCDD alone.CYP1A1-dependent EROD activity and CYPlA2-dependent ACOH activitywere induced in all treated dose groups. It is concluded thatthe present results do not confirm a direct role of CYP1A2 inductionin the increase of hepatic TCDD levels by HxCB cotreatment inthe mixed HxCB/TCDD dose groups. However, in this aspect, thediscrepancy between CYP1A2 activities and protein levels remainsto be explained.     

Potentiation of the mitogenic effect of estrogen on the pituitary-gland by alcohol-consumption

The effect of alcohol on estrogen-regulated lactotropic cell proliferation was examined in Fisher 344 rats. Alcohol was administered for 2 weeks using liquid diet containing 8.7% ethanol (v/v) and 37% ethanol-derived calories. The control group was pair-fed with an isocaloric diet minus the ethanol or adlib-fed with normal diet. Ethanol-treated rats showed mean blood ethanol concentrations between 60-90 mg/dl. Alcohol treatment did not effect the body growth rate, but increased the DNA synthesis in lactotropes and reduced the levels of lactotropic growth inhibitory transforming growth factor-beta 1 (TGF-beta 1) protein and mRNA in the pituitary. These results suggest that alcohol promotes estrogen-induced lactotropic proliferation, possibly by down regulating the inhibitory TGF-beta 1 control of lactotropic function.     

Job stress, absenteeism and coronary heart disease European cooperative study (the JACE study): Design of a multicentre prospective study

Background: The motives, objectives and design of a multicentreprospective study on job stress, absenteeism and coronary heartdisease in Europe (the JACE study) is presented in this paper.Some specific gaps in the reviewed literature are explicitlytapped into by the JACE study. Its objectives are i) to comparethe distributions of the Karasek job stress scales for the samebroad categories of occupations in different European countries(in males and females), ii) to study the predictive power ofthe job stress scales and the job strain model for one yearof sickness absence (in males and females) and iii) to studythe predictive power of the job stress scales and the job strainmodel for a three year incidence of coronary heart disease (Inmales only). Methods: In answering these questions, relationsare studied controlling for gender, age, level of education,company size, physical work risks and shift work, as well astraditional risk factors for CHD (i.e serum cholesterol, serumHDL cholesterol, smoking habits and blood pressure). The JACEstudy is a Biomed 1 concerted action. The JACE group consistsof eight participating centres from six countries, i.e. fromBelgium and Sweden (two centres), France, Italy, Spain, Swedenand The Netherlands (each one centre). The coordination of thegroup is in Brussels. The participating centres brought in over15, 000 European workers to test the hypotheses.     

Combination of methotrexate and sulphasalazine in patients with rheumatoid arthritis: pharmacokinetic analysis and relationship to clinical response

1. The influence of sulphasalazine (SASP) on the pharmacokinetics of low dose methotrexate (MTX) and the relation between pharmacokinetic variables and clinical response was studied in 15 patients with active rheumatoid arthritis despite >6 months of SASP treatment.
2. SASP was stopped for 2 weeks. Thereafter a single oral dose of 7.5 mg MTX was administered after a standard breakfast. Blood was sampled initially every 30 min, thereafter hourly during 8 h. Urine was sampled every hour. Then 2000 mg SASP daily + 7.5 mg MTX weekly was given. After 4 weeks the same procedure was repeated supplemented with concomitant administration of 1000 mg SASP. Clinical measurements included Ritchie articular index, number of swollen joints, ESR and the disease activity score. Pharmacokinetic analysis was performed using a two- compartment model with first order absorption and lag time. Results are given as mean (s.d.). Paired t-test or signed rank test were applied in the statistical analysis.
3. Pharmacokinetics of MTX without vs with SASP, means±s.d. were as follows: AUC: 673±179 vs 628±210 (95% confidence interval [CI] of the difference was −71 to 159) ng ml⁻¹ h, MRT: 5.2±1.3 vs 5.2±1.1 (95% CI −0.4 to 0.4) h, t½,z: 4.3±1.1 vs 4.2±1.1 (95% CI −0.3 to 0.5) h, V /F: 59.3 ±29.3 vs 65.5±25.3 (95% -23.8 to 11.4) l, CL/F: 12.3±5.0 vs 13.5±4.8 (95% CI −4.5 to 2.3) l h⁻¹. CL_R/F: 6.2±1.3 vs 6.3±2.1 (95% CI −1.3 to 1.1) l h⁻¹. All P values were ≥0.3.
4. A weak correlation existed between the change of ESR and the MRT, the t½,z and the V /F (Spearman correlation coefficients of 0.43, 0.50 and 0.50 respectively, 0.05<P<0.1).
5. There is no significant influence of chronic SASP administration on the pharmacokinetics of MTX or vice versa. Of the clinical variables, only the ESR correlated consistently with some pharmacokinetic variables of MTX.