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Biomedical subjects

M Traber

Publications and source records attributed to M Traber.

8 recordsLinked to original sources

Acrolein-induced cytotoxicity in cultured human bronchial epithelial cells. Modulation by alpha-tocopherol and ascorbic acid.

Acrolein is a highly reactive unsaturated hazardous air pollutant of human health concern, particularly as a component of cigarette smoke. In this study, the mechanisms of acrolein-induced cytotoxicity in human bronchial epithelial cells (HBE1) and the modulating effects of antioxidants were examined. Our results show that acrolein induces a cell death pathway in human bronchial epithelial cells, which retain key features of apoptosis, as indicated by phosphatidylserine (PS) externalization and DNA fragmentation. Acrolein-induced apoptosis was associated with depletion of cellular GSH and intracellular generation of oxidants. Supplementation of cells with either alpha-tocopherol or ascorbic acid was found to strongly inhibit acrolein-induced apoptosis and to prevent the increase in the generation of intracellular oxidants, although GSH depletion was unaffected. Moreover, recovery of cellular GSH levels after acrolein exposure was enhanced following either alpha-tocopherol or ascorbic acid supplementation. The intracellular generation of oxidants following acrolein exposure seems to be an important event triggering the apoptotic response in this model system.

Acrolein↗

[Ultrasound endometrium follow-up during tamoxifen treatment: Really not reliable or useful after all?].

AIM: To investigate whether an examination of the endometrium of women treated with tamoxifen (TAM) is useful or not. METHOD: 40 breast cancer patients who displayed a thickened endometrium of > 8 mm and/or vaginal bleeding were included in the study. They received daily TAM adjuvantly. Histologic clarification by hysteroscopy and D&C was recommended for patients with an endometrium of > 8 mm or vaginal bleeding. RESULTS: In our collective, the mean endometrial thickness was 13.7 +/- 5.6 mm (SD). 32 patients underwent a histological examination. Most had a benign lesion; in 2 cases we merely found a cystic atrophy (11 mm, 18 mm), 2 displayed atypical tissue (13 mm, 25 mm) and 2 an endometrial cancer (19 mm, 33 mm). All patients with atypical tissue or cancer had an endometrial thickness markedly above the norm, but 3 of them were not bleeding. No linear correlation between thickness of the endometrium and duration of TAM intake was found. CONCLUSION: To detect early premalignant or malignant changes of the endometrium, we recommend histological examination by hysteroscopy and dilatation and curettage when the endometrium is > 8 mm thick, even in the absence of symptoms. Therefore, these patients should have regular examinations by transvaginal ultrasound once or twice a year. Moreover, continuing regular screening of the endometrium for years after termination of tamoxifen-therapy is also to be recommended.

Adult↗

Is there a vitamin E paradox?

In addition to epidemiologic studies that suggest a benefit for high intakes of alpha-tocopherol, studies of supplementation in humans have clearly shown that alpha-tocopherol decreases lipid peroxidation, platelet aggregation, and functions as a potent anti-inflammatory agent. In the five large prospective clinical trials with alpha-tocopherol therapy, four have shown a beneficial effect on cardiovascular end-points (two studies on a primary end-point and two studies on other cardiovascular end-points). Thus, the totality of evidence based on the epidemiologic data, in-vitro studies and animal models, and the clinical trials appears to support a benefit for alpha-tocopherol supplementation in patients with pre-existing cardiovascular disease. However, definitive recommendations must await ongoing clinical trials.

Adult↗

Micronutrient antioxidants and smoking.

Cigarette smoking is a major risk factor in such human diseases as cardiovascular disease (especially atherosclerosis), lung cancer (the leading world-wide cancer killer), and chronic obstructive pulmonary disease (COPD). An avalanche of studies has suggested that a diet rich in fruit and vegetables is associated with decreased risk for atherosclerosis and cancer. However, the dietary intake of fruits and vegetables, as well as antioxidant micronutrients, is decreased in smokers. This, along with evidence of increased utilization of ascorbic acid and alpha-tocopherol, possibly on the basis of increased oxidative stress, contributes to the low plasma antioxidant concentrations seen in many smokers. This review addresses selected mechanistic considerations of this relationship.

Antioxidants↗

Phenotypic analysis of mice expressing exclusively apolipoprotein B48 or apolipoprotein B100.

Apolipoprotein (apo)-B is found in two forms in mammals: apo-B100, which is made in the liver and the yolk sac, and apo-B48, a truncated protein made in the intestine. To provide models for understanding the physiologic purpose for the two forms of apo-B, we used targeted mutagenesis of the apo-B gene to generate mice that synthesize exclusively apo-B48 (apo-B48-only mice) and mice that synthesize exclusively apo-B100 (apo-B100-only mice). Both the apo-B48-only mice and apo-B100-only mice developed normally, were healthy, and were fertile. Thus, apo-B48 synthesis was sufficient for normal embryonic development, and the synthesis of apo-B100 in the intestines of adult mice caused no readily apparent adverse effects on intestinal function or nutrition. Compared with wild-type mice fed a chow diet, the levels of low density lipoprotein (LDL)-cholesterol and very low density lipoprotein- and LDL-triacylglycerols were lower in apo-B48-only mice and higher in the apo-B100-only mice. In the setting of apo-E-deficiency, the apo-B100-only mutation lowered cholesterol levels, consistent with the fact that apo-B100-lipoproteins can be cleared from the plasma via the LDL receptor, whereas apo-B48-lipoproteins lacking apo-E cannot. The apo-B48-only and apo-B100-only mice should prove to be valuable models for experiments designed to understand the purpose for the two forms of apo-B in mammalian metabolism.

Animals↗

Cholesterol turnover and tissue distribution in the guinea pig in response to dietary cholesterol.

Cholesterol turnover and tissue cholesterol distribution were studied in guinea pigs fed either a control diet or one containing 0.1% cholesterol. Dietary cholesterol caused a significant increase in the cholesterol concentration in liver, red blood cells and small intestine, but not in plasma. Most of the increase in total body cholesterol could be accounted for as an increase in liver esterified cholesterol content. Feeding the 0.1% cholesterol-containing diet did not significantly change either the absorption of an oral dose of tracer cholesterol or the endogenous cholesterol synthesis rate. Steady state cholesterol input-output rate and total traced mass of cholesterol were significantly greater, and mean transit time was significantly longer in the animals fed the cholesterol containing diet. These data suggest that the maintenance of cholesterol homeostasis in the nonhypercholesterolemic cholesterol-fed guinea pig depends on liver accumulation of esterified cholesterol as well as on increased output of cholesterol.

Animals↗