Contribution of increased minimal coronary resistance and attenuated vascular adaptive remodeling to myocardial ischemia in patients with systemic hypertension and ventricular hypertrophy

This study assessed the impact of coronary vascular adaptive remodeling and coronary vascular reactivity on myocardial ischemia in patients with hypertension and left ventricular hypertrophy. Myocardial ischemia is associated with impaired endothelium-independent vasodilation of resistance coronary arteries and increased minimal coronary resistance. These changes may occur in association with lumen reduction caused by attenuated adaptive remodeling in response to plaque accumulation.     

Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid

BACKGROUND & AIMS: Aberrant crypt foci, precursors of colonic adenoma, are frequently positive for glutathione-S-transferase P1-1. Because deoxycholic acid is an apoptosis-inducing xenobiotic in the colon, we examined the possibility that aberrant crypt foci, through the cytoprotecting function of glutathione-S-transferase P1-1, resist deoxycholic acid-induced apoptosis, thereby surviving to become adenomas and subsequently cancer. METHODS: Glutathione-S-transferase P1-1 or cyclooxygenase-2 expression and the percentage of apoptotic cells in aberrant crypt foci were examined by immunohistochemistry and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, respectively. Glutathione-S-transferase P1-1 was transfected into colon cancer cells (M7609) and human lung fibroblasts, and deoxycholic acid-induced apoptosis was evaluated by a dye-uptake assay and flow cytometry. Binding of deoxycholic acid to glutathione-S-transferase P1-1 was analyzed by circular dichroism and immunoprecipitation. Caspase activities were determined by colorimetric protease assay, and sulindac binding to glutathione-S-transferase P1-1 was determined by inhibition assay of glutathione-S-transferase P1-1 activity. RESULTS: Aberrant crypt foci showed positive immunostaining for glutathione-S-transferase P1-1 but negative staining for cyclooxygenase-2. The percentage of apoptotic cells in aberrant crypt foci was significantly lower than in healthy epithelium, and the difference became more apparent with deoxycholic acid treatment. The impaired sensitivity of aberrant crypt foci to deoxycholic acid was restored by the glutathione-S-transferase P1-1-specific inhibitor gamma-glutamyl-S-(benzyl)cysteinyl-R-phenylglycine diethylester. By transfection of glutathione-S-transferase P1-1, M7609 cells became more resistant to deoxycholic acid-induced apoptosis than mock transfectants. Direct binding of glutathione-S-transferase P1-1 to deoxycholic acid was proven by circular dichroism and by immunoprecipitation. The aberrant crypt foci in adenoma patients treated with sulindac, which was shown to bind to glutathione-S-transferase P1-1, underwent apoptosis in 4 days and mostly regressed in 2-3 months. CONCLUSIONS: Glutathione-S-transferase P1-1 protects aberrant crypt foci from deoxycholic acid-induced apoptosis and may play a pivotal role in early colon carcinogenesis.     

Antibiotic susceptibility of glutaraldehyde-tolerant Mycobacterium chelonae from bronchoscope washing machines

BACKGROUND: Contamination of bronchoalveolar lavage fluid is a major problem in the world. Although 2% glutaraldehyde (GA) is widely used as a disinfectant for bronchoscope cleaning, recently, GA-tolerant mycobacteria have been isolated, which makes this problem more complicated. METHODS: We studied the susceptibility to GA and antibiotics of mycobacteria isolated from bronchoscope washing machines in our hospital. We also studied the minimum inhibitory concentrations of GA and antibiotics with pump inhibitors. RESULTS: Twenty-nine mycobacteria were isolated, of which 26 were Mycobacterium chelonae. Among 18 isolates of M chelonae, excluding 8 isolates in which some results were not reproducible, 50% (9 of 18) were 2% GA-tolerant. One hundred percent (9 of 9) of the GA-tolerant isolates and 11% (1 of 9) of the GA-sensitive isolates were either resistant or intermediately resistant to 2 or 3 classes of antibiotics. Efflux pump inhibitors did not influence the susceptibility to GA and antibiotics. CONCLUSIONS: It was suggested that there might be an association of GA tolerance with antibiotic resistance in M chelonae. There may a different mechanism(s) other than that involving efflux pumps with regard to GA tolerance and antibiotic resistance in M chelonae. When bronchoscopy-related mycobacterial infections are suspected, physicians and clinical microbiologists should exercise care in handling GA-tolerant mycobacteria, which may be resistant to multiple antibiotics.