Determinants of serum levels of vitamin D: a study of life-style, menopausal status, dietary intake, serum calcium, and PTH

Background: Low blood levels of vitamin D (25-hydroxy D3, 25OHD3) in women have been associated with an increased risk of several diseases. A large part of the population may have suboptimal 25OHD3 levels but high-risk groups are not well known. The aim of the present study was to identify determinants for serum levels of 25OHD3 in women, i.e. factors such as lifestyle, menopausal status, diet and selected biochemical variables. Methods: The study was based on women from the Malmo Diet and Cancer Study (MDCS), a prospective, population-based cohort study in Malmo, Sweden. In a previous case-control study on breast cancer, 25OHD3 concentrations had been measured in 727 women. In these, quartiles of serum 25OHD3 were compared with regard to age at baseline, BMI (Body Max Index), menopausal status, use of oral contraceptives or menopausal hormone therapy (MHT), life-style (e. g. smoking and alcohol consumption), socio-demographic factors, season, biochemical variables (i.e. calcium, PTH, albumin, creatinine, and phosphate), and dietary intake of vitamin D and calcium. In order to test differences in mean vitamin D concentrations between different categories of the studied factors, an ANOVA test was used followed by a t-test. The relation between different factors and 25OHD3 was further investigated using multiple linear regression analysis and a logistic regression analysis. Results: We found a positive association between serum levels of 25OHD3 and age, oral contraceptive use, moderate alcohol consumption, blood collection during summer/autumn, creatinine, phosphate, calcium, and a high intake of vitamin D. Low vitamin D levels were associated with obesity, being born outside Sweden and high PTH levels. Conclusions: The present population-based study found a positive association between serum levels of 25OHD3 and to several socio-demographic, life-style and biochemical factors. The study may have implications e. g. for dietary recommendations. However, the analysis is a cross-sectional and it is difficult to suggest Lifestyle changes as cause-effect relationships are difficult to assess

Structure-activity relationship studies of novel benzophenones leading to the discovery of a potent, next generation HIV nonnucleoside reverse transcriptase inhibitor.

Despite the progress of the past two decades, there is still considerable need for safe, efficacious drugs that target human immunodeficiency virus (HIV). This is particularly true for the growing number of patients infected with virus resistant to currently approved HIV drugs. Our high throughput screening effort identified a benzophenone template as a potential nonnucleoside reverse transcriptase inhibitor (NNRTI). This manuscript describes our extensive exploration of the benzophenone structure-activity relationships, which culminated in the identification of several compounds with very potent inhibition of both wild type and clinically relevant NNRTI-resistant mutant strains of HIV. These potent inhibitors include 70h (GW678248), which has in vitro antiviral assay IC(50) values of 0.5 nM against wild-type HIV, 1 nM against the K103N mutant associated with clinical resistance to efavirenz, and 0.7 nM against the Y181C mutant associated with clinical resistance to nevirapine. Compound 70h has also demonstrated relatively low clearance in intravenous pharmacokinetic studies in three species, and it is the active component of a drug candidate which has progressed to phase 2 clinical studies

Vitamin D in women of reproductive age and during pregnancy - Focus on intake, status and adiposity

Vitamin D is attained either through synthesis in the skin by sun exposure or through diet. Vitamin D status is important for skeletal health but optimal vitamin D status may also be important in the development of other diseases such as type 2 diabetes, gestational diabetes, preeclampsia, and cancer. Circulating vitamin D is known to be decreased in obese compared to non-obese individuals. There is a lack of documented knowledge on vitamin D status and intake in Swedish women of reproductive age and during pregnancy. The aim of this thesis was to compare vitamin D status and intake between obese and normal-weight women. In a cross-sectional study in women of reproductive age and in a longitudinal study during pregnancy, blood samples, adipose tissue biopsies, and information on dietary intake were collected. Data on lifestyle including physical activity and sun exposure were also collected. Vitamin D status, measured as serum 25-hydroxyvitamin D [25(OH)D], was lower in obese women of reproductive age compared with normal-weight women. In contrast, circulating vitamin D-binding protein was higher in the obese women. Despite reporting a higher vitamin D intake, the obese pregnant women had lower serum 25(OH)D compared with normal-weight women in early pregnancy. A higher proportion of the obese compared with normal-weight women had 25(OH)D concentrations that might be defined as insufficient. Circulating 25(OH)D concentrations below 25 nmol/L were uncommon in both pregnant and non-pregnant women. Dietary vitamin D intake was between 7.2 and 8.8 µg/day during pregnancy and in non-pregnant obese and normal-weight women, and a major part did not reach national dietary recommendations. There were no major differences in vitamin D intake between obese and normal-weight women. Vitamin D and its metabolites were detected in adipose tissue and were localized in the lipid droplet in the adipocyte. The present studies show that Swedish obese women of reproductive age and during pregnancy have lower circulating 25(OH)D compared with normal-weight women but few had very low concentrations. However, what effects an increased circulating 25(OH)D would have on long-term health in obese individuals is yet to be studied. The fact that obese women had higher circulating vitamin D-binding protein is interesting and should be further examined to clarify why, and what impact that may have on the action of vitamin D. We found no evidence of a lower vitamin D intake in obese women, thus, the intake was not contributing to the lower circulating 25(OH)D. Many women do not reach the recommendations for vitamin D intake. Actions should be taken to improve dietary intake of vitamin D in women of reproductive age and during pregnancy, this might have future implications not only for women’s health but for generations to come. Intervention studies are urgently needed to explore the effect of vitamin D status and intake during pregnancy and in obese subjects

A Novel Biosensing System Using Biological Receptor for Analysis of Vascular Endothelial Growth Factor

An immunosensor with rapid and ultrasensitive response for vascular endothelial growth factor (VEGF) has been built up with 4-aminothiophenol (4-ATP) onto the gold surfaces. Quantitative analysis of VEGF was performed by recording the impedance changing of the gold electrode surface by binding of VEGF. The human vascular endothelial growth factor receptor 1 (VEGF-R1, Flt-1) was used as a biorecognition element for the first time in the literature. VEGF-R1 was covalently immobilized via 4-ATP self-assembled monolayer formed on gold thin film covered surface. Construction of the biosensor was carefully characterised by the techniques such as electrochemistry and electrochemical impedance spectroscopy. In order to characterize impedance data, Kramers-Kronig transform was performed on the experimental impedance data. The limit of detection of the immunosensor for qualitative detection was 100 pg/mL while the LOD for quantitative detection could down to 100 pg/mL by using the VEGF-R1 based biosensor. Finally, artificial serum samples spiked with VEGF was analyzed by the proposed immunosensor to investigate useful of the biosensor for early biomarker diagnosis.TUBITAK (The Scientific and Technological Research Council of Turkey)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109 T 172]The authors greatly appreciate the support of the TUBITAK (The Scientific and Technological Research Council of Turkey, Project number: 109 T 172)

Calcium co-ingestion augments postprandial glucose-dependent insulinotropic peptide1–42, glucagon-like peptide-1 and insulin concentrations in humans

Purpose - This study determined whether calcium co-ingestion potentiates postprandial GIP1–42 and GLP-1 concentrations in humans and the concomitant impact on insulin, appetite sensations and substrate metabolism. Methods - Ten healthy males consumed two energy- and macronutrient-matched meals in a double-blind, randomized, crossover design. The calcium content of the control meal was 3 mg/kg body mass, which was increased to 15 mg/kg body mass with calcium co-ingestion. Circulating concentrations of GIP1–42, GLP-1 and insulin were determined over a 180-min postprandial period, followed by 60 min of exercise. Visual analogue scales were used to determine subjective appetite sensations. Rates of energy expenditure and substrate (lipid and carbohydrate) oxidation were estimated using indirect calorimetry. Results - Calcium co-ingestion resulted in a 47 % increase in GIP1–42, a 22 % increase in GLP-1 and a 19 % increase in insulin areas under the curve for the 120 min following consumption (all P 0.05). Conclusion - Ingestion of a high-calcium meal potentiates postprandial GIP1–42, GLP-1 and insulin concentrations in humans. Subjective appetite is also temporarily suppressed, although substrate metabolism is unaffected