Association between cigarette smoking and lipid peroxidation in a controlled feeding study

BACKGROUND: Cigarette smoke may promote atherogenesis by producing oxygen-derived free radicals that damage lipids. However, evidence in support of this hypothesis is inconsistent because most studies did not control for aspects of diet (antioxidants and lipid substrate) that may confound the association between smoking and measures of lipid peroxidation. METHODS AND RESULTS: The relationships between cigarette smoking and two measures of lipid peroxidation, breath ethane (an in vivo assay) and thiobarbituric acid-reactive substances (TBARS, an in vitro assay), were examined in 123 adults (11% of whom were smokers) participating in a controlled feeding study. After 3 weeks of controlled feeding on a common diet (36% total fat, 14% saturated fats, 6% polyunsaturated fats, and 12% monounsaturated fats), breath and fasting serum samples were collected for measurement of ethane and TBARS, respectively. Baseline characteristics of smokers and nonsmokers were similar, including several indices related to diet and nutritional status (albumin, cholesterol, body mass index, and oxygen radical-absorbing capacity). Cigarette smokers had significantly higher breath ethane (8.88 versus 1.71 pmol/L; P<.0001) and TBARS (24.0 versus 20.7 micromol/mL; P=.008) than nonsmokers. The interval between breath collection and the time the last cigarette was smoked was significantly and inversely correlated with breath ethane. Neither measure of lipid peroxidation was associated with measures of serum cholesterol or albumin, body mass index, or serum oxygen radical-absorbing capacity. CONCLUSIONS: Cigarette smokers have higher rates of in vivo and in vitro lipid peroxidation. These results support the hypothesis that the atherogenic effects of smoking are mediated in part by free radical damage to lipids.     

Effect of calmodulin on the activity of NAD-kinase from rabbit liver

It has been shown that rabbit liver NAD-kinase is a Ca(2+)-dependent, calmodulin-regulated enzyme. Differences were found between the sensitivity of the alpha- and beta-forms of the enzyme to calmodulin. The maximal activation of the NAD-kinase alpha-form was observed at a calmodulin/NAD-kinase ratio equal to 2, that of the beta-form--at 4. Further increases in the above parameter (up to 10) had no effect on the activity of the alpha-form, whereas that of the beta-form dropped down to the initial (basal) level.     

Perfluorocarbons are effective oxygen carriers in cardiopulmonary bypass

Intravascular perfluorochemical (PFC) emulsions together with a high oxygen (O2) tension may increase the delivery of dissolved O2 to useful levels. A severely anemic model of cardiopulmonary bypass (CPB) was used to test the hypothesis that a novel PFC emulsion (PFCE; Oxygent [Alliance Pharmaceutical Corp., San Diego, CA] 90% w/v perflubron) used at a high PO2 during bypass delivers sufficient O2 to ameliorate hypoxic myocardial contractile dysfunction. Acutely anemic dogs (N = 42; hematocrit = 15.8 +/- 0.6% [mean +/- SEM] before CPB and 10.9 +/- 0.1% during CPB) were divided into four groups. Group 1 was a control (n = 12). As CPB was initiated, groups 2 (n = 10), 3 (n = 10), and 4 (n = 10) had 1.35 g PFC.kg-1, 2.7 g PFC.kg-1, or 5.4 g PFC.kg-1 added via the venous return cannula. Pre-CPB and post-CPB cardiac function was measured by the first derivative of left ventricular pressure (dP/dtmax). The dP/dtmax on separation from CPB was: group 1, 619 +/- 96; group 2, 738 +/- 56; group 3, 782 +/- 101; and group 4, 828 +/- 100 (p < 0.05 groups 3 and 4 versus group 1). Mortality during the first hour after separation from CPB was higher in group 1 than in PFCE treated dogs; however, this trend did not attain statistical significance (p < 0.065). The PFC dose was higher in survivors than in nonsurvivors (2.6 +/- 0.4 g PFC.kg-1 versus 1.2 +/- 0.5 g PFC.kg-1; p < 0.05). A PFCE used at a high PO2 provides sufficient physically dissolved O2 to relieve myocardial hypoxic injury in a severely anemic model of CPB. Current PFCEs are effective O2 carriers. This finding suggests that they can be used as a temporary erythrocyte substitute to diminish the need for allogeneic transfusions during cardiac operations.     

Ahch, the mouse homologue of DAX1: cloning, characterization and synteny with GyK, the glycerol kinase locus

We cloned the murine full-length cDNA encoding Ahch, the mouse homologue of DAX1 (DSS-AHC Region on Human X Chromosome, Gene1) which is the gene responsible for human X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH). Sequence analysis revealed that the murine and human cDNAs have 65% aa identity and 75% aa similarity overall. The cysteine residues in the putative DNA binding domain, which may interact with Zn2+ ions to form zinc fingers, are 100% conserved between the two species, indicating that the novel zinc-finger structures in DAX1 may be functional. In addition, mouse interspecific backcrosses show that the Ahch gene is closely linked to the glycerol kinase locus, GyK, on the mouse X chromosome, indicating that the order of the loci is conserved in this syntenic region between mouse and human.     

Fat and female fecundity: prospective study of effect of body fat distribution on conception rates

OBJECTIVES: To study the effect of body fat distribution in women of reproductive age on fecundity. DESIGN: Prospective cohort study of all women who had entered a donor insemination programme. SETTING: One fertility clinic serving a large part of the midwest of the Netherlands. SUBJECTS: Of 542 women attending the clinic for artificial insemination for the first time, 500 women were eligible for study. MAIN OUTCOME MEASURES: Probability of conception per cycle and number of insemination cycles before pregnancy or stopping treatment. RESULTS: A 0.1 unit increase in waist-hip ratio led to a 30% decrease in probability of conception per cycle (hazard ratio 0.706; 95% confidence interval 0.562 to 0.887) after adjustment for age, fatness, reasons for artificial insemination, cycle length and regularity, smoking, and parity. Increasing age was significantly related to lower fecundity (p < 0.05); very lean and obese women were less likely to conceive (p < 0.10) as were women with subfertile partners (p < 0.10). All other exposure variables were not significantly related to fecundity. CONCLUSIONS: Increasing waist-hip ratio is negatively associated with the probability of conception per cycle, before and after adjustment for confounding factors. Body fat distribution in women of reproductive age seems to have more impact on fertility than age or obesity.     

Influence of short-term dietary measures on dioxin concentrations in human milk

Breast-feeding may expose infants to high levels of toxic chlorinated dioxins. To diminish intake of these lipophilic compounds by the baby, two diets were tested for their ability to reduce concentrations of dioxins in human milk. The diets were a low-fat/high- carbohydrate/low-dioxin diet. (about 20% of energy intake derived from fat) and a high fat /low-carbohydrate/low-dioxin diet. These diets were tested in 16 and 18 breast-feeding women, respectively. The test diets were followed for 5 consecutive days in the fourth week after delivery. Milk was sampled before and at the end of the dietary regimen, and dioxin concentrations and fatty acid concentrations were determined. Despite significant influences of these diets on the fatty acid profiles, no significant influence on the dioxin concentrations in breast milk could be found. We conclude that short-term dietary measures will not reduce dioxin concentration in human milk.     

Biotin determination by three different methods: specificity and application to urine and plasma ultrafiltrates of patients with and without disorders in biotin metabolism

A microbiological, an avidin-binding and a streptavidin-binding method for biotin determination were compared. All three methods detected biotin equally well but they exhibit different specificities for derivatives of biotin. The microbiological assay has the highest specificity and is the method of choice for biotin determination in biotinidase-deficient patients. The specificity of streptavidin-binding has not been investigated so far. Application of the three methods to urine samples of patients with and without biotin therapy indicated that only 50% of biotin equivalents measured with the avidin method correspond to authentic biotin as previously shown. The other 50% comprise mainly bisnorbiotin and biotin-d-sulfoxide. HPLC-separation of urine samples prior to assay confirmed this finding and revealed a bisnorbiotin oxidation product and an unknown compound as further biotin metabolites. The latter was measurable by all three methods and not detectable in plasma ultrafiltrate. This was the only metabolite which was able to restore deficient 3-methylcrotonyl-CoA carboxylase activity in biotin-deficient fibroblasts. The combination of the three methods together with HPLC-separation proved to be a valuable analytical tool for the identification of the main biotin metabolites in biological fluids.