Mitochondrial adenine nucleotide translocase is modified oxidatively during aging

The purpose of this study was to test the hypothesis that elevation in protein oxidative damage during the aging process is a targeted rather than a stochastic phenomenon. Oxidative damage to proteins in mitochondrial membranes in the flight muscles of the housefly, manifested as carbonyl modifications, was detected immunochemically with anti-dinitrophenyl antibodies. Adenine nucleotide translocase (ANT) was found to be the only protein in the mitochondrial membranes exhibiting a detectable age-associated increase in carbonyls. The age-related elevation in ANT carbonyl content was correlated with a corresponding loss in its functional activity. Senescent flies that had lost the ability to fly exhibited a relatively higher degree of ANT oxidation and a greater loss of functional activity than their cohorts of the same age that were still able to fly. Exposure of flies to 100% oxygen resulted in an increase in the level of ANT carbonyl content and a loss in its activity. In vitro treatment of mitochondria with a system that generated hydroxyl free radicals caused an increase in ANT carbonyl level and a decrease in ANT exchange activity. ANT was also the only mitochondrial membrane protein exhibiting adducts of the lipid peroxidation product 4-hydroxynonenal. Results of this study indicate that proteins in mitochondrial membranes are modified selectively during aging.     

Traumatic rupture of duodenal diverticulum. Report of a case and literature review

Duodenal diverticulum is a common anatomic abnormality. Its inflammatory perforation is a rare complication, with less than 100 cases reported in the available literature. Traumatic perforation is exceedingly rare (only 3 cases reported). In this report one more case of traumatic perforation is presented, and the literature is reviewed focusing on the pathogenic, diagnostic and therapeutic aspects of this severe disease.     

National trends in the use of antibiotics by primary care physicians for adult patients with cough

BACKGROUND: Increased antibiotic use for outpatient illnesses has been identified as an important determinant of the recent rise in antibiotic resistance among common respiratory pathogens. Efforts to reduce the inappropriate use will need to be evaluated against current trends in the outpatient use of antibiotics. OBJECTIVES: To examine national trends in the use of antibiotics by primary care physicians in the care of adult patients with cough and identify patient factors that may influence antibiotic use for these patients. METHODS: This study was based on a serial analysis of results from all National Ambulatory Medical Care Surveys beginning in 1980 (when therapeutic drug use was first recorded) to 1994 (the most recent survey year available). These surveys are a random sampling of visits to US office-based physicians in 1980, 1981, 1985, and annually from 1989-1994. Eligible visits included those by adults presenting to general internists, family practitioners, or general practitioners with a chief complaint of cough. A total of 3416 visits for cough were identified over the survey years. Survey results were extrapolated, based on sampling weights in each year, to project national rates of antibiotic use for patients with cough. Additional analyses examined the rates of antibiotic use stratified by patient age, race, and clinical diagnosis. RESULTS: Overall, an antibiotic was prescribed 66% of the time during office visits for patients with cough: 59% of patient visits in 1980 rising to 70% of visits in 1994 (P = .002 for trend). In every study year, white, non-Hispanic patients and patients younger than 65 years were more likely to receive antibiotics compared with nonwhite patients and patients 65 years or older, respectively. CONCLUSIONS: The rate of antibiotic use by primary care physicians for patients with cough remained high from 1980 to 1994, and was influenced by nonclinical characteristics of patients.     

Oxidized LDL promotes vascular endothelial cell pinocytosis via a prooxidation mechanism

Human low density lipoprotein (LDL) is prepared in the presence of antioxidants and is oxidized to different levels (measured by thiobarbituric acid reactive substance) with copper ion. The effects of unoxidized LDL and oxidized LDL (ox-LDL) on stress fiber formation, cell membrane ruffling, and pinocytosis (measured by [14C]sucrose uptake) in cultured human umbilical cord vein endothelial cells (EC) are compared. We show that at a concentration range of 100 to 200 microg cholesterol/ml, both unoxidized LDL and ox-LDL promote EC elongation and stress fiber formation, but the effect by the latter is more prominent when compared at the same dose range. In addition, ox-LDL also induces EC membrane ruffling and promotes pinocytosis. These effects are positively correlated with the extent of LDL oxidation and depend on the dose of ox-LDL. Ox-LDL-promoted membrane ruffling and pinocytosis are effectively blocked by brief preexposure of the cells to antioxidants. In contrast, stress fiber formation is not affected by antioxidant pretreatment. Although unoxidized LDL also promotes [14C]sucrose uptake, it is less potent than ox-LDL and significantly higher concentrations are required to produce a detectable effect. Unlike ox-LDL, unoxidized LDL-enhanced pinocytosis is not accompanied by the appearance of membrane ruffling; therefore, they may act via different mechanisms. Elevated pinocytosis may increase transcytotic activity of the endothelium, leading to an increased influx of plasma components such as LDL into the subendothelial space.