Fatty acid reesterification but not oxidation is increased by oral contraceptive use in women.

We evaluated the hypothesis that fatty acid reesterification would be increased during rest and exercise in the midluteal menstrual cycle phase and during oral contraceptive use, when ovarian hormone concentrations are high, compared with the early follicular phase. Subjects were eight moderately active, weight-stable, eumenorrheic women (24.8 +/- 1.2 yr, peak oxygen consumption = 42.0 +/- 2.3 ml.kg(-1).min(-1)) who had not taken oral contraceptives for at least 6 mo. Plasma free fatty acid (FFA) kinetics were assessed in the 3-h postprandial state by continuous infusion of [1-(13)C]palmitate and [1,1,2,3,3-(2)H]glycerol during 90 min of rest and 60 min of exercise at 45% and 65% peak oxygen consumption in the early follicular and midluteal menstrual cycle phases and during the inactive- and high-dose phases following 4 mo of oral contraceptive use. Plasma FFA rates of appearance, disappearance, and oxidation increased significantly from rest to exercise with no differences noted between menstrual cycle or oral contraceptive phases or exercise intensities. Compared with either menstrual cycle phase, oral contraceptive use resulted in an increase in plasma-derived fatty acid reesterification and a decrease in the proportion of plasma FFA rate of disappearance that was oxidized at rest and during exercise. Endogenous and exogenous synthetic ovarian hormones do not exert a measurable influence on plasma FFA turnover or oxidation at rest or during moderate-intensity exercise in the 3-h postprandial state when carbohydrate use predominates. The increase in whole body lipolytic rate during exercise noted previously with oral contraceptive use is not matched by an increase in fatty acid oxidation and results in an increase in reesterification. Synthetic ovarian hormones contained in oral contraceptives increase lipolytic rate, but fatty acid oxidation during exercise is determined by exercise intensity and its metabolic and endocrine consequences.     

Membrane changes associated with lysis of red blood cells by hypochlorous acid

This study was carried out to investigate HOCl-induced lysis of human erythrocytes. Using reagent HOCl with isolated red cells, we showed that the rate of lysis was dependent on the dose of HOCl per red cell rather than on the concentration of oxidant. The process was inhibited by scavengers such as methionine and taurine, but only if they were present at the time of addition of HOCl. Lysis was preceded by a decrease in cell density, a change in the deformability of the membrane as evidence by ektacytometry, and an increase in K⁺-leak. Electron microscopy showed extensive disruption of the membrane. Increasing doses of HOCl caused progressive loss of membrane thiols, bu complete thiol oxidation by N-ethylmaleimide did not result in an equivalent rate of lysis. Restoration of oxidised thiols by incubation with glucose did not significantly alter the pattern of lysis. Taken together, these results suggest that thiol oxidation was not responsible for HOCl-mediated lysis. There was evidence of increasing crosslinking of membrane proteins on electrophoresis, only some of which was due to the formation of disulfides. TLC of the membrane lipids indicated that there may be formation of chlorohydrins by reaction of HOCl with the fatty acid double bonds. This reaction results in the formation of a more polar species which, if formed, would be extremely disrupting to the lipid bilayer. The results indicate that HOCl-mediated damage to the membrane proteins or to the lipid bilayer comprises an initial damaging event that sets the cells on a path toward eventual lysis.     

Decreased Ca pump ATPase activity associated with increased density in human red blood cells

Red blood cells (rbcs) from five different normal humans were separated according to density using a simple procedure. The procedure involved centrifugation for 30 minutes in small glass tubes in the absence of any density gradient medium. This produced a column of rbcs arranged according to their density. Samples of the top 8% of the columns and bottom 8% of the columns were removed from the tubes with a micropipet. From each donor, samples of the least and most dense cells, respectively, were pooled from multiple tubes for each donor and designated "top" and "bottom" cells. These top and bottom cells were compared with unselected (total) cells from the same subjects, respectively. Top cells were larger and bottom cells were smaller than total cells. ATPase activities were operationally defined and measured in saponin lysates of these rbcs. The Ca pump ATPase (both in the calmodulin-activated and calmodulin-independent states [achieved by addition of compound 48/80]) of the top cells exhibited greater activity, and the Ca pump ATPase of bottom cells exhibited lower activity than total cells. It was suggested that loss of Ca pump ATPase activity is associated with rbc aging and may be a determinant of rbc life span. A mechanism for the loss of Ca pump ATPase activity was suggested. This speculative mechanism is based upon selective proteolysis of the Ca pump ATPase by the Ca-activated protease, calpain.     

Weekly iron-folic acid supplementation with regular deworming is cost-effective in preventing anaemia in women of reproductive age in Vietnam

Background

To estimate the cost and cost-effectiveness of a project administering de-worming and weekly iron-folic acid supplementation to control anaemia in women of reproductive age in Yen Bai province, Vietnam.

Methods and Findings

Cost effectiveness was evaluated using data on programmatic costs based on two surveys in 2006 and 2009 and impact on anaemia and iron status collected in 2006, 2007, and 2008. Data on initial costs for training and educational materials were obtained from the records of the National Institute of Malariology, Parasitology and Entomology and the Yen Bai Malaria Control Program. Structured questionnaires for health workers at district, commune and village level were used to collect ongoing distribution and monitoring costs, and for participants to collect transport and loss of earnings costs. The cost per woman treated (defined as consuming at least 75% of the recommended intake) was USD0.76 per annum. This estimate includes financial costs (for supplies, training), and costs of health care workers'' time. Prevalence of anaemia fell from 38% at baseline, to 20% after 12 months. Thus, the cost-effectiveness of the project is assessed at USD 4.24 per anaemia case prevented per year. Based on estimated productivity gains for adult women, the benefit:cost ratio is 6.7∶1. Cost of the supplements and anthelminthics was 47% of the total, while costs of training, monitoring, and health workers'' time accounted for 53%.

Conclusion

The study shows that weekly iron-folic acid supplementation and regular de-worming is a low-cost and cost-effective intervention and would be appropriate for population-based introduction in settings with a high prevalence of anaemia and iron deficiency and low malaria infection rates.     

Catechol-o-methyltransferase gene polymorphism is associated with skeletal muscle properties in older women alone and together with physical activity

Background

Muscle strength declines on average by one percent annually from midlife on. In postmenopausal women this decrement coincides with a rapid decline in estrogen production. The genetics underlying the effects of estrogen on skeletal muscle remains unclear. In the present study, we examined whether polymorphisms within COMT and ESR1 are associated with muscle properties and assessed their interaction and their combined effects with physical activity.

Methodology/Principal Findings

A cross-sectional data analysis was conducted with 434 63-76-year-old women from the population-based Finnish Twin Study on Aging. Body anthropometry, muscle cross-sectional area (mCSA), isometric hand grip and knee extension strengths, and leg extension power were measured. COMT Val158Met and ESR1 PvuII genotypes were determined by the RFLP method. mCSA differed by COMT genotypes (p = 0.014) being significantly larger in LL than HL individuals in unadjusted (p = 0.001) and age- and height-adjusted model (p = 0.004). When physical activity and age were entered into GEE model, COMT genotype had a significant main effect (p = 0.038) on mCSA. Furthermore, sedentary individuals with the HH genotype had lower muscle mass, strength and power, but they also appeared to benefit the most from physical activity. No association of ESR1 PvuII polymorphism with any of the muscle outcomes was observed.

Conclusions/Significance

The present study suggests that the COMT polymorphism, affecting the activity of the enzyme, is associated with muscle mass. Furthermore, sedentary individuals with potential high enzyme activity were the weakest group, but they may potentially benefit the most from physical activity. This observation elucidates the importance of both environmental and genetic factors in muscle properties.     

Influence of oral contraceptive use on endothelial t-PA release in healthy premenopausal women

We determined the influence of oral contraceptives (OC) on the capacity of the endothelium to release tissue-type plasminogen activator (t-PA). Twenty-three healthy premenopausal women were studied: 12 nonusers and 11 users of OC. Net endothelial release rates of t-PA were calculated as the product of the arteriovenous concentration gradient and forearm plasma flow in response to intra-arterial bradykinin (BK: 12.5-50 ng. 100 ml tissue(-1) x min(-1)) and sodium nitroprusside (SNP: 1.0-4.0 microg x 100 ml tissue(-1) x min(-1)). Net release of t-PA antigen and increment in t-PA activity across the forearm to BK increased (P < 0.01) in a dose-dependent fashion and to similar extents in the nonusers and users of OC. At the highest BK dose, net release of t-PA antigen was 64.5 +/- 8.2 and 66.2 +/- 15.4 ng x 100 ml tissue(-1) x min(-1) in the nonusers and users of OC, whereas the net increment in t-PA activity was 18.6 +/- 3.0 and 16.0 +/- 2.0 IU. 100 ml tissue(-1) x min(-1), respectively. There was no effect of SNP on t-PA release in either group. These results indicate that endothelial t-PA release is not altered in premenopausal women who use oral contraception.     

Leisure-time physical activity is associated with reduced risks of breast cancer and triple negative breast cancer in Nigerian women

BackgroundLeisure-time physical activity(LTPA) is associated with a reduced risk of breast cancer, but this has less been investigated by cancer subtypes in Africans living in Sub-Saharan Africa(SSA). We examined the associations between LTPA and breast cancer including its subtypes in Nigerian women and explored the effect modification of body size on such associations.MethodsThe sample included 508 newly diagnosed primary invasive breast cancer cases and 892 controls from the Nigerian Integrative Epidemiology of Breast Cancer(NIBBLE) Study. Immunohistochemical(IHC) analysis was available for 294 cases. Total metabolic equivalents(METs) per hour/week of LTPA were calculated and divided by quartiles(Q1 <3.75, Q2:3.75–6.69, Q3:6.70–14.74, Q4:14.75 ≤). We applied logistic regressions to estimate the adjusted Odds Ratios(ORs) between LTPA and breast cancer and by its molecular subtypes and whether age-adjusted associations are modified by BMI.ResultsThe mean age(Mean±SD) of cases vs. controls(45.5 ± 11.1vs.40.1 ± 9.0) was higher, and the mean total METs hour/week was higher in controls vs. cases(11.9 ± 14.9vs.8.3 ± 11.1,p-value<0.001). Overall, 43.2%(N = 127/294) were classified as HRP, and 41.8%(N = 123/294) as TNBC. Women in the higher LTPA quartiles(Q3-Q4) vs. Q1 had lower odds of having breast cancer(OR_Q4vs.Q1=0.51,95%CI:0.35–0.74) and TNBC(OR_Q4vs.Q1=0.51, 95%CI:0.27–0.96), but not HRP(OR_Q4vs.Q1=0.61,95%CI:0.34–1.09) after adjusting for age, age at first menarche, body size, breastfeeding, menopausal, parity, contraceptives, demographics, alcohol, smoking, and physical activity at home and work. Lastly, LTPA and its age-adjusted association with breast cancer was more pronounced in women with BMI< 30 vs. BMI 30 + .ConclusionsLTPA may reduce the risk of breast cancer, especially TNBC, which is the more aggressive and prevalent molecular subtype of breast cancer in SSA.     

Risks,benefits size and clinical implications of combined oral contraceptive use in women with polycystic ovary syndrome

Background

Polycystic ovary syndrome (PCOS) is a complex condition with high risk for dyslipidemia, dysglycemia, venous thromboembolism, cardiovascular disease and metabolic syndrome. Because the combined oral contraceptive (COC) use has also been associated with impaired fasting glucose, insulin resistance and increased risk of thromboembolism disease, it is rationale to think that the combination of oral contraceptive and PCOS could make it worse or increase the risks.

Objective

To examine the current data regarding potential additional risks and benefits of contraceptive use, highlights the major gap in knowledge for designing future studies and, when possible, suggests an adequate COC formulation for a determined PCOS phenotype.

Methods

English-language publications reporting on the influence of COCS in the development of venous thromboembolism in PCOS patients published until 2017 were searched using PubMed, Cochrane database, and hand search of references found in consulted articles. Ranges of collected data are given; the pooled data are presented as median and first and third quartiles. Wilcoxon signed-ranks test for paired samples was used to compare before-after original data. P value was set at 0.05.

Results

Most of COCs preparations significantly decrease androgens, and increase sex-hormone binding globulin. Therefore, the benefits of COCs are clear in patients with proved hyperandrogenemia. Regarding the impact of COCs on carbohydrate metabolism of PCOS subjects, the data were inconsistent but they tended to show no additional risk. Regarding lipids, most COCs consistently increased high-density lipoprotein cholesterol, triglycerides and total cholesterol concentrations but the clinical implications of these changes need additional studies.

Conclusion

The review showed consistent beneficial effect of COCs, particularly for hyperandrogenemic PCOS patients. The benefit size of COC’s use by normoandrogenemic PCOS patients is uncertain and need more investigation. The effects of COC use on carbohydrate metabolism of women with PCOS are still unresolved since most studies are observational but the current results demonstrated that COCs do not make their levels worse and may improve insulin sensitivity. The impact of COCs on lipids of PCOS patients seems to be clearer and most preparations increase total cholesterol, high-density lipoprotein cholesterol and triglycerides. In summary, it is important to balance the potential benefits and risks of the COCs individually before prescribing them for PCOS women.

     

Mitochondrial DNA copy number in peripheral blood cells declines with age and is associated with general health among elderly

The role of the mitochondria in disease, general health and aging has drawn much attention over the years. Several attempts have been made to describe how the numbers of mitochondria correlate with age, although with inconclusive results. In this study, the relative quantity of mitochondrial DNA compared to nuclear DNA, i.e. the mitochondrial DNA copy number, was measured by PCR technology and used as a proxy for the content of mitochondria copies. In 1,067 Danish twins and singletons (18–93 years of age), with the majority being elderly individuals, the estimated mean mitochondrial DNA copy number in peripheral blood cells was similar for those 18–48 years of age [mean relative mtDNA content: 61.0; 95 % CI (52.1; 69.9)], but declined by ?0.54 mtDNA 95 % CI (?0.63; ?0.45) every year for those older than approximately 50 years of age. However, the longitudinal, yearly decline within an individual was more than twice as steep as observed in the cross-sectional analysis [decline of mtDNA content: ?1.27; 95 % CI (?1.71; ?0.82)]. Subjects with low mitochondrial DNA copy number had poorer outcomes in terms of cognitive performance, physical strength, self-rated health, and higher all-cause mortality than subjects with high mitochondrial DNA copy number, also when age was controlled for. The copy number mortality association can contribute to the smaller decline in a cross-sectional sample of the population compared to the individual, longitudinal decline. This study suggests that high mitochondrial DNA copy number in blood is associated with better health and survival among elderly.     

Paraoxonase 1 activity in the sperm-rich portion of boar ejaculates is positively associated with sperm quality

Associations of the activity of the paraoxonase 1 (PON1) enzyme with boar sperm quality still needs to be characterized, since boar ejaculates present distinct portions with differences in sperm concentration and quality. This study evaluated PON1 activity in the serum, in the distinct portions of boar ejaculates and estimated correlations with sperm quality parameters. Ejaculates and blood samples were collected from six boars for three weeks (two per week per boar; n = 36). Serum and post-spermatic portion PON1 activities were positively correlated (P = 0.01) but were both uncorrelated with the PON1 activity in the sperm-rich portion and in the whole ejaculate (P > 0.05). Differences in PON1 activity among boars were only observed in the sperm-rich portion of the ejaculate (P < 0.05). The PON1 activity in the serum and in the post-spermatic portion was generally negatively correlated with parameters of spermatozoa kinetics (P < 0.05). In the sperm-rich portion, PON1 activity was positively correlated with sperm concentration (P < 0.0001), curvilinear distance and velocity (both P < 0.05) and DNA integrity (P < 0.05), but negatively correlated with straightness and linearity (P < 0.05). Thus, boar ejaculates with increased PON1 activity in the sperm-rich portion may present increased concentration and spermatozoa with acceptable curvilinear velocity and distance and DNA integrity, which suggests that PON1 activity may be a biomarker for potential fertility.     

Early life expenditure in sexual competition is associated with increased reproductive senescence in male red deer

The evolutionary theories of senescence predict that investment in reproduction in early life should come at the cost of reduced somatic maintenance, and thus earlier or more rapid senescence. There is now growing support for such trade-offs in wild vertebrates, but these exclusively come from females. Here, we test this prediction in male red deer (Cervus elaphus) using detailed longitudinal data collected over a 40-year field study. We show that males which had larger harems and thereby allocated more resources to reproduction during early adulthood experienced higher rates of senescence in both harem size and rut duration. Males that carried antlers with more points during early life did not show more pronounced declines in reproductive traits in later life. Overall, we demonstrate that sexual competition shapes male reproductive senescence in wild red deer populations and provide rare empirical support for the disposable soma theory of ageing in males of polygynous vertebrate species.     

Docosahexaenoic acid is a potent inducer of apoptosis in HT-29 colon cancer cells

Some studies have shown that dietary intake of polyunsaturated fatty acids of the n-3 series may have inhibitory effect on the growth of tumor cells both in vivo and in vitro. However, the cellular and molecular mechanisms by which n-3 fatty acids reduce the growth of tumor cells remain poorly understood. In the present studies, we compared the potency of a variety of n-3 and n-6 fatty acids in modulating the apoptotic cell death in HT-29 colon cancer cells. Of all fatty acids examined, we found that docosahexaenoic acid (22:6n-3; DHA) is a potent inducer of apoptosis in a time- and dose-dependent manner. Indomethacin, a cyclooxygenase inhibitor, is ineffective in blocking the apoptosis induced by DHA, suggesting that DHA-induced apoptosis in HT-29 cells is not mediated through the cyclooxygenase pathway. In contrast, the DHA-induced apoptosis is partially reversed by a synthetic antioxidant, butylated hydroxytoluene, indicating that lipid peroxidation may be involved in apoptotic signaling pathway induced by DHA. DHA treatment decreased bcl-2 levels in association with apoptosis, whereas bax levels remained unchanged. These results suggest that decreased expression of bcl-2 by DHA might increase the sensitivity of cells to lipid peroxidation and to programmed cell death.