The Influence of Hormonal Contraception on Vitamin D Supplementation on Serum 25(OH)D3 Status in Premenopausal Women: A Prospective Double-Blind Placebo Random Controlled Trial

Background: A number of cross-sectional studies have highlighted a potential benefit of estrogen-containing contraception on serum 25-hydroxyvitamin D (25(OH)D) levels. The purpose of the present prospective study was to determine whether oral vitamin D3 supplementation significantly increases serum 25(OH)D more for women taking the estrogen-containing oral contraception than those not taking this medication. Methods: Thirty-eight premenopausal adult females aged 18 - 45 years old were recruited from a university campus; exclusion criteria included those presently taking vitamin D supplementation, those who stopped or started taking oral contraception in last 6 months and those taking any other form of contraception. A prospective doubleblind placebo design was implemented; the dependent variable was serum 25(OH)D and the independent variables were using or not using oral estrogen-containing contraception, and vitamin D3 or placebo supplementation. Participants were tested 4 weeks apart, and blood samples were collected using a capillary blood spot sample method and analyzed by liquid chromatography-tandem mass spectrometry. An independent technician prepared the identical supplement bottles with either 100 placebo pills or 100 active vitamin D3 pills (1,000 IU per pill) and participants randomly selected a supplement bottle. Results: Baseline measurements of 25(OH)D were non-significantly 11% higher in those taking estrogen. ANOVA results revealed a significant two-way interaction between supplementation group (treatment vs. placebo) and treatment period (before vs. after) (P < 0.001), demonstrating a substantial rise in serum 25(OH)D for the treatment group compared with the placebo group. The results also identified a three-way interaction (P = 0.014) on serum 25(OH)D between the three independent variables, with the vitamin D oral contraception group having significantly greater serum 25(OH)D increases (from 45.9 to 98.3 nmol/L) compared with those not taking oral contraception (44.2 - 69.6 nmol/L) (P = 0.019). Conclusions: The estrogen-containing oral contraception increases serum 25(OH)D in premenopausal women with a magnified effect in those taking vitamin D supplementation. Future studies need to examine the relationship between estrogen, vitamin D supplementation, serum 25(OH)D, 1,25(OH)D, parathyroid hormone and other markers of bone metabolisms

Mechanisms of cell uptake and toxicity of the anticancer drug cisplatin

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.Two major issues which hamper the use of the anticancer drug cisplatin are the development of cancer cell resistance and its nephrotoxicity. One possible mechanism by which resistance is reported to develop is a reduction in drug uptake across the cell membrane. While the passive uptake of cisplatin has long been cited as an important contribution, far greater attention has been given to active modes of uptake, particularly in recent research. Using unilamellar lipid vesicles together with the stopped-flow kinetic method we show here that the permeability coefficient of cisplatin increases significantly with the chloride concentration of the medium. This supports the hypothesis that cisplatin can enter cells via passive permeation through the lipid phase of the membrane, but becomes trapped within the cytoplasm because dissociation of chloride ligands yields a membrane-impermeant positively-charged aqua derivative. This is important evidence for a major role of passive membrane diffusion in the uptake of cisplatin, and suggests that reduced cell uptake is unlikely to be a significant mechanism leading to the development of drug resistance. Studies of rubidium ion uptake into the cytoplasm of Xenopus oocytes via the Na+,K+-ATPase show significant inhibition of this ion pump when cisplatin is present in the cytoplasm. Because Na+,K+-ATPase activity is essential to the survival of all animal cells, e.g. via maintenance of cell volume, and the Na+,K+-ATPase is expressed at particularly high levels within the membranes of kidney tubules where it plays a crucial role in nutrient reabsorption, these results suggest that cisplatin-induced inhibition of the Na+,K+-ATPase is a likely contributing cause for the nephrotoxicity of cisplatin.DFG, EXC 314, Unifying Concepts in Catalysi

Cardiorespiratory profile and performance demands of elite hip-hop dancers: Breaking and new style

Dancers need to constantly maintain and develop their physiological capabilities to support their performances. Previously these physiological demands have been investigated only in traditional dance styles such as ballet and modern. The aim of this study was to examine the physiological demands of two types of hip-hop: new style and break dance. Nine female new style dancers (age 20±6 yrs, height 163.5±1.4 cm, mass 55.8±22 kg) and 9 male break dancers (age 23±4.2 yrs, height 178.2±5.7 cm, mass 62.1±7.7 kg) volunteered for the study. Each subject completed a maximal graded treadmill test and a dance performance routine, either new style (approx 1:45-2:30 min) or breaking (2 min). Breathe-by-breathe gas analysis and heart rate (HR) were collected by a portable gas analyser, and blood lactate (BLa) was measured at the end of the treadmill test and each routine. The male breaker dancers had significantly higher VO2 peak than other equivalent dancers in other genres, whilst the female new style dancers were similar to that previously reported for female dancers. Performance data showed significant differences between the two styles for VO2, HR, and BLa (p<0.001) and for VO2 and HR relative to individual maximal treadmill data (p<0.05). New style is more comparable to other theatrical dance genres, with a lower relative mean VO2 demand, whilst break dance is shorter in duration, allowing a higher cardiorespiratory demand and generating significant levels of blood lactate. This difference is also reflected in the dancers' cardiorespiratory profiles

The Role of the Entorhinal Cortex in Extinction: Influences of Aging

The entorhinal cortex is perhaps the area of the brain in which neurofibrillary tangles and amyloid plaques are first detectable in old age with or without mild cognitive impairment, and very particularly in Alzheimer's disease. It plays a key role in memory formation, retrieval, and extinction, as part of circuits that include the hippocampus, the amygdaloid nucleus, and several regions of the neocortex, in particular of the prefrontal cortex. Lesions or biochemical impairments of the entorhinal cortex hinder extinction. Microinfusion experiments have shown that glutamate NMDA receptors, calcium and calmodulin-dependent protein kinase II, and protein synthesis in the entorhinal cortex are involved in and required for extinction. Aging also hinders extinction; it is possible that its effect may be in part mediated by the entorhinal cortex

A atividade das SRC quinases é necessária para a formação e a evocação da memória para a tarefa de esquiva inibitória

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Bolaamphiphile Analogues of 12-bis-THA Cl2 Are Potent Antimicrobial Therapeutics with Distinct Mechanisms of Action against Bacterial, Mycobacterial, and Fungal Pathogens

12-Bis-THA Cl2 [12,12'-(dodecane-1,12-diyl)-bis-(9-amino-1,2,3,4-tetrahydroacridinium) chloride] is a cationic bolalipid adapted from dequalinium chloride (DQC), a bactericidal anti-infective indicated for bacterial vaginosis (BV). Here, we used a structure-activity-relationship study to show that the factors that determine effective killing of bacterial, fungal, and mycobacterial pathogens differ, to generate new analogues with a broader spectrum of activity, and to identify synergistic relationships, most notably with aminoglycosides against Acinetobacter baumannii and Pseudomonas aeruginosa, where the bactericidal killing rate was substantially increased. Like DQC, 12-bis-THA Cl2 and its analogues accumulate within bacteria and fungi. More hydrophobic analogues with larger headgroups show reduced potential for DNA binding but increased and broader spectrum antibacterial activity. In contrast, analogues with less bulky headgroups and stronger DNA binding affinity were more active against Candida spp. Shortening the interconnecting chain, from the most lipophilic twelve-carbon chain to six, improved the selectivity index against Mycobacterium tuberculosis in vitro, but only the longer chain analogue was therapeutic in a Galleria mellonella infection model, with the shorter chain analogue exacerbating the infection. In vivo therapy of Escherichia coli ATCC 25922 and epidemic methicillin-resistant Staphylococcus aureus 15 (EMRSA-15) infections in Galleria mellonella was also achieved with longer-chain analogues, as was therapy for an A. baumannii 17978 burn wound infection with a synergistic combination of bolaamphiphile and gentamicin. The present study shows how this class of bolalipids may be adapted further to enable a wider range of potential applications. IMPORTANCE While we face an acute threat from antibiotic resistant bacteria and a lack of new classes of antibiotic, there are many effective antimicrobials which have limited application due to concerns regarding their toxicity and which could be more useful if such risks are reduced or eliminated. We modified a bolalipid antiseptic used in throat lozenges to see if it could be made more effective against some of the highest-priority bacteria and less toxic. We found that structural modifications that rendered the lipid more toxic against human cells made it less toxic in infection models and we could effectively treat caterpillars infected with either Mycobacterium tuberculosis, methicillin resistant Staphylococcus aureus, or Acinetobacter baumannii. The study provides a rationale for further adaptation toward diversifying the range of indications in which this class of antimicrobial may be used

Do Cochrane summaries help student midwives understand the findings of Cochrane systematic reviews: the BRIEF randomised trial.

BackgroundAbstracts and plain language summaries (PLS) are often the first, and sometimes the only, point of contact between readers and systematic reviews. It is important to identify how these summaries are used and to know the impact of different elements, including the authors’ conclusions. The trial aims to assess whether (a) the abstract or the PLS of a Cochrane Review is a better aid for midwifery students in assessing the evidence, (b) inclusion of authors’ conclusions helps them and (c) there is an interaction between the type of summary and the presence or absence of the conclusions.MethodsEight hundred thirteen midwifery students from nine universities in the UK and Ireland were recruited to this 2 × 2 factorial trial (abstract versus PLS, conclusions versus no conclusions). They were randomly allocated to one of four groups and asked to recall knowledge after reading one of four summary formats of two Cochrane Reviews, one with clear findings and one with uncertain findings. The primary outcome was the proportion of students who identified the appropriate statement to describe the main findings of the two reviews as assessed by an expert panel.ResultsThere was no statistically significant difference in correct response between the abstract and PLS groups in the clear finding example (abstract, 59.6 %; PLS, 64.2 %; risk difference 4.6 %; CI −0.2 to 11.3) or the uncertain finding example (42.7 %, 39.3 %, −3.4 %, −10.1 to 3.4). There was no significant difference between the conclusion and no conclusion groups in the example with clear findings (conclusions, 63.3 %; no conclusions, 60.5 %; 2.8 %; −3.9 to 9.5), but there was a significant difference in the example with uncertain findings (44.7 %; 37.3 %; 7.3 %; 0.6 to 14.1, p = 0.03). PLS without conclusions in the uncertain finding review had the lowest proportion of correct responses (32.5 %). Prior knowledge and belief predicted student response to the clear finding review, while years of midwifery education predicted response to the uncertain finding review.ConclusionsAbstracts with and without conclusions generated similar student responses. PLS with conclusions gave similar results to abstracts with and without conclusions. Removing the conclusions from a PLS with uncertain findings led to more problems with interpretatio

Comparing United States and Canadian population exposures from National Biomonitoring Surveys: Bisphenol A intake as a case study

The Centers for Disease Control and Prevention provides biomonitoring data in the United States as part of the National Health and Nutrition Examination Survey (NHANES). Recently, Statistics Canada initiated a similar survey — the Canadian Health Measures Survey (CHMS). Comparison of US and Canadian biomonitoring data can generate hypotheses regarding human exposures from environmental media and consumer products. To ensure that such comparisons are scientifically meaningful, it is essential to first evaluate aspects of the surveys' methods that can impact comparability of data. We examined CHMS and NHANES methodologies, using bisphenol A (BPA) as a case study, to evaluate whether survey differences exist that would hinder our ability to compare chemical concentrations between countries. We explored methods associated with participant selection, urine sampling, and analytical methods. BPA intakes were also estimated to address body weight differences between countries. Differences in survey methods were identified but are unlikely to have substantial impacts on inter-survey comparisons of BPA intakes. BPA intakes for both countries are below health-based guidance values set by the US, Canada and the European Food Safety Authority. We recommend that before comparing biomonitoring data between surveys, a thorough review of methodologic aspects that might impact biomonitoring results be conducted