Oral contraceptive use and ovarian cancer risk among carriers of BRCA1 or BRCA2 mutations

Women with mutations of the genes BRCA1 or BRCA2 are at increased risk of ovarian cancer. Oral contraceptives protect against ovarian cancer in general, but it is not known whether they protect against the disease in carriers of these mutations. We obtained self-reported lifetime histories of oral contraceptive use from 451 women who carried mutations of BRCA1 or BRCA2. We used conditional logistic regression to estimate the odds ratios associated with oral contraceptive use, comparing the histories of 147 women with ovarian cancer (cases) to those of 304 women without ovarian cancer (controls) who were matched to cases on year of birth, country of residence and gene (BRCA1 vs BRCA2). Reference ages for controls had to exceed the ages at diagnosis of their matched cases. After adjusting for parity, the odds-ratio for ovarian cancer associated with use of oral contraceptives for at least 1 year was 0.85 (95 percent confidence interval, 0.53-1.36). The risk decreased by 5% (1-9%) with each year of use (P for trend=0.01). Use for 6 or more years was associated with an odds-ratio of 0.62 (0.35-1.09). These data support the hypothesis that long-term oral contraceptive use reduces the risk of ovarian cancer among women who carry mutations of BRCA1 or BRCA2

Overfeeding, Autonomic Regulation and Metabolic Consequences

The autonomic nervous system plays an important role in the regulation of body processes in health and disease. Overfeeding and obesity (a disproportional increase of the fat mass of the body) are often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The overfeeding-induced changes in autonomic outflow occur with typical symptoms such as adiposity and hyperinsulinemia. There might be a causal relationship between autonomic disturbances and the consequences of overfeeding and obesity. Therefore studies were designed to investigate autonomic functioning in experimentally and genetically hyperphagic rats. Special emphasis was given to the processes that are involved in the regulation of peripheral energy substrate homeostasis. The data revealed that overfeeding is accompanied by increased parasympathetic outflow. Typical indices of vagal activity (such as the cephalic insulin release during food ingestion) were increased in all our rat models for hyperphagia. Overfeeding was also accompanied by increased sympathetic tone, reflected by enhanced baseline plasma norepinephrine (NE) levels in both VMH-lesioned animals and rats rendered obese by hyperalimentation. Plasma levels of NE during exercise were, however, reduced in these two groups of animals. This diminished increase in the exercise-induced NE outflow could be normalized by prior food deprivation. It was concluded from these experiments that overfeeding is associated with increased parasympathetic and sympathetic tone. In models for hyperphagia that display a continuously elevated nutrient intake such as the VMH-lesioned and the overfed rat, this increased sympathetic tone was accompanied by a diminished NE response to exercise. This attenuated outflow of NE was directly related to the size of the fat reserves, indicating that the feedback mechanism from the periphery to the central nervous system is altered in the overfed state.

A disposable electrochemical immunosensor for the determination of leptin in serum and breast milk

The preparation of a disposable electrochemical immunosensor for the quantification of the hormone leptin is described in this work. The preparation approach involved immobilization of a specific biotinylated anti-leptin antibody on the surface of streptavidin-functionalized magnetic beads (StreptMBs) and a sandwich-type immunoassay involving the target analyte, monoclonal anti-leptin, and IgG labeled with alkaline phosphatase (AP-IgG). The electrochemical transduction step was accomplished by trapping the MBs bearing the immunoconjugates onto screen-printed carbon electrodes (SPCEs) by means of an Nd magnet and measuring the electrochemical oxidation of the 1-naphthol generated in the AP enzyme reaction upon 1-naphthyl phosphate (1-NPP) additions by differential pulse voltammetry (DPV). A calibration plot with a linear range between 5 and 100 pg mL 1 as well as a detection limit of 0.5 pg mL 1 (3sb/m) were achieved. This value is more than 27 times lower than that reported in the only voltammetric immunosensor for leptin described in the literature until now. The usefulness of the immunosensor was demonstrated by analyzing different types of real samples: human serum, infant powdered milk, and breast milk from a nursing mother with two months of breastfeeding

A1C Level and Future Risk of Diabetes: A Systematic Review

The use of A1C for the identification of persons with undiagnosed diabetes has been investigated for a number of years (1–3). A1C better reflects long-term glycemic exposure than current diagnostic tests based on point-in-time measures of fasting and postload blood glucose (4,5) and has improved test-retest reliability (6). In addition, A1C includes no requirement for fasting or for the oral glucose tolerance test's 2-h wait. These advantages should lead to increased identification and more timely treatment of persons with diabetes. Recently, an American Diabetes Association (ADA)-organized international expert committee recommended the adoption of the A1C assay for the diagnosis of diabetes at a cut point of 6.5% (7). This cut point was primarily derived from a review of studies that examined the association of A1C values with incident retinopathy, and some of the most influential data were obtained from recently published prospective studies. Retinopathy was chosen as the ultimate criterion because it is among the main complications of diabetes. Identification of the point on the A1C distribution most closely related to future retinopathy will identify persons in the greatest need of interventions for the prevention of diabetes complications. In addition to utility and convenience, A1C could help identify persons at increased risk of developing diabetes. This is an important public health priority since a structured lifestyle program or the drug metformin can reduce the incidence of diabetes by at least 50 and 30%, respectively (8). Ideally, selection of diagnostic cut points for pre-diabetes would be based on evidence that intervention, when applied to the high-risk group of interest, results not only in the prevention of diabetes but also later complications. However, currently there are no trials that can provide data to determine the ideal method for defining cut points. In the absence of such data, expert committees had to rely on information about the shape of risk curves for complications such as retinopathy. Previous expert committees assembled to address this issue have noted that there is no clear difference in retinopathy risk between different levels of impaired glucose tolerance (7). We are unaware of published prospective studies of adequate sample size or duration that have followed people in various pre-diabetic categories across the full span of time until complications developed. In the absence of informative trials (as well as prospective studies), the studies that measure A1C at baseline and incident diabetes may provide the definitions of high-risk states. To better define A1C ranges that might identify persons who would benefit from interventions to prevent or delay type 2 diabetes, we carried out a systematic review of published prospective studies that have examined the relationship of A1C to future diabetes incidence