Acetylcholinesterase activity and menstrual remissions in myasthenia gravis.

Menstrually related temporary remissions of myasthenic symptoms are reported to occur in 25 to 50% of female patients. Even though this has been attributed to hormonal changes associated with the menstrual cycle the underlying mechanism of this hormonal influence has remained elusive. The present study demonstrated a cyclical variation in the activity of red cell acetylcholinesterase (EC 3.1.1.7) enzyme (AChE) with a marked reduction at the time of menstrual remission of symptoms of myasthenia. These cyclical changes were abolished by thymectomy. It appears, therefore, that menstrual remission in myasthenia is at least partly due to hormone-induced changes in AChE activity. This process seems to be under the control of the thymus gland.     

Resveratrol,a natural aryl hydrocarbon receptor antagonist,protects lung from DNA damage and apoptosis caused by benzo[a]pyrene

Benzo[a]pyrene (BaP) is an agonistic ligand for the aryl hydrocarbon receptor (AhR) and a major environmental carcinogen implicated in the aetiology of lung cancer through the induction of benzo[a]pyrene diol epoxidation (BPDE) and BPDE-DNA adducts. Because BaP metabolization requires cytochrome P-450 1A1 (CYP1A1) induction through activation of the AhR, we hypothesized that resveratrol, a natural competitive inhibitor of AhR, could prevent these adverse effects of BaP on the lung. Balb-C mice were injected for 5 weeks with corn oil, BaP (5 mg kg(-1) week(-1)), resveratrol (50 mg kg(-1) week(-1)) or BaP + resveratrol. Immunohistochemistry was performed on lung sections for the determination of CYP1A1 protein, BPDE-DNA adducts and apoptosis. A semi-quantitative immunohistochemistry score (H score) was used for data analysis. Mice exposed to BaP had a significant induction of lung BPDE-DNA adducts when compared with controls (H scores: control, 26, interquartile range 18-33; BaP, 276, interquartile range 269-288; P < 0.01). The BPDE-DNA adduct induction by BaP was abrogated significantly by resveratrol (H score: BaP + resveratrol, 103, interquartile range 96-113). A similar pattern was found by immunohistochemistry for apoptosis (H scores: control, 121, interquartile range 102-137; BaP, 288, interquartile range 282-292, P < 0.05; BaP + resveratrol, 132, interquartile range 121-141, P = NS) and CYP1A1 (H scores: control, 170.3, interquartile range 164-175; BaP, 302.3, interquartile range 291-315, P < 0.05; BaP + resveratrol, 200.7, interquartile range 174-215, P = NS). Western blotting confirmed that resveratrol prevented BaP-induced CYP1A1 expression. This increase in CYP1A1 expression in response to BaP administration most likely causes BaP metabolism, BPDE-DNA adduct formation and subsequent apoptosis. All BaP-induced effects could be prevented by resveratrol, suggesting a possible chemopreventive role for this natural phytoalexin against the development of lung cancer.     

Coagulation abnormalities after total hip prosthesis (THP), a rare cause: antibiotic prophylaxis

A 87-year-old patient developed coagulation abnormality following hip surgery related to the prophylactic use of cefamandole. Cefamandole as others cephalosporins with a methyl-tetrazol-thiol lateral chain interferes with the vitamin K regeneration cycle as do oral anticoagulants. Therefore, the use of others antibiotics or systematic vitamin K1 supplementation or single dose of cefamandole is recommended for patients with renal failure or with malnutrition. Vitamin K1 supplementation is a simple method resulting in complete resolution of the coagulation disorder.     

c-crbB2 gene amplification and protein expression in ovarian epithelial tumors: Evaluation of their respective prognostic significance by multivariate analysis

c-erbB2 gene amplification or over-expression has been reported in ovarian cancer, but their prognostic value remains conflicting. To investigate the respective prognostic significance of c-erbB2 gene amplification and protein over-expression, tumor samples were obtained from 65 patients with ovarian adenocarcinoma (9 FIGO stage I, 7 stage ll, 38 stage III and 11 stage IV) followed up for a median period of 71 months. c-erbB2 gene amplification (>2.5 a.u.) was detected in 9/65 (14%) adenocarcinomas and in none of 5 benign and 8 borderline ovarian epithelial tumors also analyzed. Specimens from 52 of the 65 adenocarcinomas were available for immunohistochemi-cal analysis. c-erbB2 protein expression was observed in 23/52 (44%) adenocarcinomas. No correlation was found between c-erbB2 gene copy number and protein expression. There was no correlation of c-erbB2 gene copy number or protein expression with any of the clinico-pathological factors analyzed (i.e., GIGO stage, histological type, histological grade and residual tumor). On univariate analysis, c-erbB2 gene amplification was associated with poorer survival (p = 0.04). However, in the multivariate analysis of clinico-pathological factors and c-erbB2 gene copy number, c-erbB2 gene amplification did not retain any independent prognostic significance (p = 0.19). No significant survival difference was found between patients with and without c-erbB2 protein over-expression in univariate or multivariate analyses. Therefore, neither c-erbB2 gene amplification nor c-erbB2 protein over-expression appears to be a significant prognostic marker in patients with ovarian carcinoma. © 1995 Wiley-Liss, Inc.