Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

BACKGROUND: Paradoxical sleep deprivation (PSD) associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ) in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR) compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. METHODS: The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group). To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg) or testosterone (0.5 mg/kg or 1.0 mg/kg) administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain. RESULTS: A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role of progesterone in the occurrence of genital reflexes, SHR were treated daily during the sleep deprivation period with progesterone; after the administration of this hormone and challenge with cocaine, we observed a significant increase in erectile events compared with the vehicle PSD SHR+cocaine group. CONCLUSION: Our data showed that the low frequency of genital reflexes found in SHR sleep deprived rats may be attributed to the lower concentrations of progesterone in these rats, based on the observation that progesterone replacement increased genital reflexes in this strain

Are proton pump inhibitors the first choice for acute treatment of gastric ulcers? A meta analysis of randomized clinical trials

BACKGROUND: Gastric ulcers are a frequent problem in the United States. Proton pump inhibitors have been shown to increase healing rates and improve clinical symptoms. The objective of this study is to compare gastric ulcer healing rates for patients treated with a proton pump inhibitor (PPI) (omeprazole, rabeprazole, pantoprazole, or lansoprazole), an histamine 2- receptor antagonist (ranitidine) or placebo. METHODS: A literature search was conducted to identify randomized, controlled clinical trials that included a PPI in at least one treatment arm and assessed the gastric ulcer healing rates endoscopically. The healing rates were estimated for each treatment at specific time points, and Rate Ratios (RR) and 95% confidence intervals (CI) were estimated for each trial. RESULTS: Sixteen trials met the inclusion criteria: four compared a PPI versus placebo, nine compared a PPI versus ranitidine (no trials of rabeprazole versus ranitidine met the inclusion criteria), and three compared a newer PPI (lansoprazole, pantoprazole or rabeprazole) versus omeprazole. In relation to ranitidine, the pooled RR of PPIs (lansoprazole, omeprazole and pantoprazole) was 1.33 (95% CI 1.24 to 1.42) at four weeks. In each trial, greater improvement in the studied clinical symptoms was found with the newer PPIs (rabeprazole, pantoprazole and lansoprazole) when compared to omeprazole. CONCLUSION: In this study treatment with PPIs resulted in higher healing rates than ranitidine or placebo. This evidence suggests that the first choice for gastric ulcer treatment for the greater relief of symptoms is one of the newer PPIs

Global Development and Climate Change: A Game Theory Approach

The increasing concern with climate change is one of the main issues of our time, and thus we aim to theoretically and mathematically analyse its causes. However our approach follows a different stream of thought, presenting the reasoning and decision-making processes between technical and moral solutions. We have resorted to game theory models in order to demonstrate cooperative and non-cooperative scenarios, ranging from the traditional to the evolutionary within game theory. In doing so we are able to glimpse the development of modern society and a paradigm shift regarding human control over nature and to what extent it is harmful to the sustainability of our environment and the survival of future generations. Merging different fields of knowledge, we present a theoretical-philosophical approach, combined with empirical-mathematical solutions taking into account the agent-based behaviour guided blindly by instrumental rationality

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Effect of treating Schistosoma haematobium infection on Plasmodium falciparum-specific antibody responses

<p>Abstract</p> <p>Background</p> <p>The overlapping geographical and socio-economic distribution of malaria and helminth infection has led to several studies investigating the immunological and pathological interactions of these parasites. This study focuses on the effect of treating schistosome infections on natural human immune responses directed against plasmodia merozoite surface proteins MSP-1 (DPKMWR, MSP1₁₉), and MSP-2 (CH150 and Dd2) which are potential vaccine candidates as well as crude malaria (schizont) and schistosome (whole worm homogenate) proteins.</p> <p>Methods</p> <p>IgG1 and IgG3 antibody responses directed against <it>Schistosoma haematobium </it>crude adult worm antigen (WWH) and <it>Plasmodium falciparum </it>antigens (merozoite surface proteins 1/2 and schizont extract), were measured by enzyme linked immunosorbent assay (ELISA) in 117 Zimbabweans (6–18 years old) exposed to <it>S. haematobium </it>and <it>P. falciparum </it>infection. These responses were measured before and after anti-helminth treatment with praziquantel to determine the effects of treatment on anti-plasmodial/schistosome responses.</p> <p>Results</p> <p>There were no significant associations between antibody responses (IgG1/IgG3) directed against <it>P. falciparum </it>and schistosomes before treatment. Six weeks after schistosome treatment there were significant changes in levels of IgG1 directed against schistosome crude antigens, plasmodia crude antigens, MSP-1₁₉, MSP-2 (Dd2), and in IgG3 directed against MSP-1₁₉. However, only changes in anti-schistosome IgG1 were attributable to the anti-helminth treatment.</p> <p>Conclusion</p> <p>There was no association between anti-<it>P. falciparum </it>and <it>S. haematobium antibody </it>responses in this population and <it>a</it>nti-helminth treatment affected only anti-schistosome responses and not responses against plasmodia crude antigens or MSP-1 and -2 vaccine candidates.</p

Strategies of a parasite of the ant–Acacia mutualism

Mutualisms can be exploited by parasites—species that obtain resources from a partner but provide no services. Though the stability of mutualisms in the presence of such parasites is under intensive investigation, we have little information on life history traits that allow a species to be a successful mutualist or rather a parasite, particularly in cases where both are closely related. We studied the exploitation of Acacia myrmecophytes by the ant, Pseudomyrmex gracilis, contrasting with the mutualistic ant Pseudomyrmex ferrugineus. P. gracilis showed no host-defending behavior and had a negative effect on plant growth. By preventing the mutualist from colonization, P. gracilis imposes opportunity costs on the host plant. P. gracilis produced smaller colonies with a higher proportion of alates than did the mutualist and thus showed an “r-like” strategy. This appears to be possible because P. gracilis relies less on host-derived food resources than does the mutualist, as shown by behavioral and stable isotope studies. We discuss how this system allows the identification of strategies that characterize parasites of mutualisms

RegNetB: Predicting Relevant Regulator-Gene Relationships in Localized Prostate Tumor Samples

<p>Abstract</p> <p>Background</p> <p>A central question in cancer biology is what changes cause a healthy cell to form a tumor. Gene expression data could provide insight into this question, but it is difficult to distinguish between a gene that causes a change in gene expression from a gene that is affected by this change. Furthermore, the proteins that regulate gene expression are often themselves not regulated at the transcriptional level. Here we propose a Bayesian modeling framework we term RegNetB that uses mechanistic information about the gene regulatory network to distinguish between factors that cause a change in expression and genes that are affected by the change. We test this framework using human gene expression data describing localized prostate cancer progression.</p> <p>Results</p> <p>The top regulatory relationships identified by RegNetB include the regulation of RLN1, RLN2, by PAX4, the regulation of ACPP (PAP) by JUN, BACH1 and BACH2, and the co-regulation of PGC and GDF15 by MAZ and TAF8. These target genes are known to participate in tumor progression, but the suggested regulatory roles of PAX4, BACH1, BACH2, MAZ and TAF8 in the process is new.</p> <p>Conclusion</p> <p>Integrating gene expression data and regulatory topologies can aid in identifying potentially causal mechanisms for observed changes in gene expression.</p