Sex steroid concentrations and localization of steroidogenic enzyme expression in free-ranging female northern fur seals (Callorhinus ursinus)

Recent precipitous population declines in northern fur seal (Callorhinus ursinus) and other Alaskan pinniped populations are due in part to reduced fecundity and have emphasized deficits in basic reproductive knowledge of these species. Following estrus and mating, fertilized female pinnipeds experience an obligatory delayed implantation lasting several months and non-pregnant (pseudopregnant) females are indistinguishable by sex steroid levels during this time. The current study examined circulating steroid concentrations and ovarian expression of key steroid-synthesizing enzymes in northern fur seals to identify changes associated with embryonic implantation, data necessary for estimating early pregnancy rates of the population. Blood samples were collected from 84 female fur seals captured on an Alaskan rookery from October 15 to November 30, a period spanning the end of the delay and subsequent uterine implantation of the fertilized blastocyst in this species. Concentrations of progesterone, estradiol, and estrone measured in blood collected during boreal fall were contrasted with samples collected during late summer from post-ovulatory females and males. Serum sex steroids were also related to ovarian expression of key enzymes responsible for androgen (17alpha-hydroxylase/17,20-lyase, cytochrome b5, and 3beta-hydroxysteroid dehydrogenase) and estrogen (aromatase cytochrome P450) synthesis. Enzymes necessary for androgen synthesis were highly expressed in ovaries, and accordingly, endocrine profiles were expanded to include DHEA, androstenediol, androstenedione, and testosterone. Estradiol concentrations were universally low and free and conjugated estrone were the primary circulating estrogens in fur seal sera. No implantation-associated peak was identified for estrogens or progesterone and mean values of progesterone and estrone were actually greater in female serum samples collected during summer than fall. However, there was a significant positive relationship between fall sampling date and testosterone concentration. Additionally, DHEA concentrations in females were lower in samples collected during the implantation period than during the summer embryonic delay. These data suggest androgens may play a substantial regulatory role in the embryonic delay of northern fur seals.     

Antitubercular Activity of Compounds Isolated from Pelargonium sidoides.

Abstract

The recent increase in the incidence of tuberculosis with the emergence of multidrug-resistant (MDR) cases has lead to the search for new drugs that are effective against MDR strains of Mycobacterium tuberculosis. and can augment the potential of existing drugs against tuberculosis. Pelargonium sidoides. DC (Geraniaceae) is highly valued by traditional healers for its curative properties and is well-known to treat coughs, diarrhea, and tuberculosis. The butanol root extract was found have bioactive inhibitory activity against M. tuberculosis. at a concentration of 2.5 × 10³ µg/mL. Phytochemical analysis of the active fraction from the root of P. sidoides. led to the isolation and identification of six compounds: coumarins (umckalin, scopoletin, 6,8-dihydroxy-5.7-dimethoxy-2H.-benzopyran-2-one, and 6,8-dihydroxy-7-methoxy-2H.-benzopyran-2-one) and flavonoids (catechin and epigallocatechin, which is reported for the first time from P. sidoides.). The isolated compounds were evaluated for antitubercular activity with M. smegmatis. and M. tuberculosis.. Intracellular activity of these compounds was also investigated using THP-1 human macrophages infected with M. tuberculosis.. The isolated compounds did not show activity inhibitory against M. tuberculosis., intracellularly and extracellularly, at the highest concentration tested in the current study. Epigallocatechin and scopoletin showed good inhibitory activity against M. smegmatis., exhibiting a minimum inhibitory concentration (MIC) of 7.8 µg/mL. Catechin and umckalin exhibited MIC values of 31.25 and 62.5 µg/mL, respectively.     

Cytotoxic T lymphocytes to Plasmodium falciparum epitopes in an area of intense and perennial transmission in Tanzania

Studies in The Gambia have provided indirect evidence that cytotoxic T lymphocytes (CTL) play a protective role against malaria in humans and recently, using allele-specific HLA class I peptide motifs, several peptide epitopes for CTL in four pre-erythrocytic Plasmodium falciparum antigens have been identified in naturally exposed Gambians. However, CTL levels were low, suggesting that boosting these low levels by immunization might provide substantial protection. In the Kilombero valley of Tanzania, malaria transmission is holoendemic and 300 times more intense than in The Gambia. We report here that several of the epitopes identified in The Gambia are also recognized in naturally exposed, partially immune Tanzanian adults and that levels of CTL are similar to or slightly higher than in Gambian subjects, despite the much higher inoculation rate. We report a new HLA-A2.1-restricted epitope from the thrombospondin-related anonymous protein (TRAP) and we demonstrate that peptide epitopes in TRAP are naturally processed for recognition by CTL from naturally exposed humans. The common allele of a variable HLA-B7-restricted epitope in the circumsporozoite protein behaved as an altered peptide ligand (APL) with respect to CTL cognate for a rarer allelic variant of this epitope, suggesting that APL antagonism may occur in natural CTL responses to P. falciparum. The moderate levels of CTL observed, even in this area of intense malaria transmission, points to the need to assess candidate vaccines aimed at increasing CTL levels.     

A magnetic tape database for a real-time medical information system.

The activity profile of a file of General Practitioners' Medical Records is such that the cost of storage medium must be carefully balanced against the worst possible access time in the case of emergencies. The acceptable use of a magnetic tape data base in a Real-Time Medical Information System is analyzed, and the practical experience of operating such a system is summarised. Possible extensions to the scheme for use with larger data bases are outlined.     

Level of utilization and provider-related barriers to the use of hydroxyurea in the treatment of sickle cell disease patients in Jos,North-Central Nigeria

BackgroundHydroxyurea is underutilized by sickle cell health-care providers in Nigeria despite available evidence of its effectiveness in reducing the manifestations and complications of sickle cell disease (SCD).ObjectivesTo assess the level of utilization and provider-related barriers to the use of hydroxyurea in SCD therapy in Jos, Nigeria.MethodsA cross-sectional study conducted among 132 medical doctors providing care for SCD patients. Data on sociodemographics, utilization and barriers to hydroxyurea use were obtained. The barriers were fed cumulatively into the logistic regression model as predictors of utilization.ResultsOf the 132 care providers, 88 (67%) had been in medical practice for ≥6years. The level of utilization of hydroxyurea was 24.2%. The significant barriers that predicted the non-utilization of hydroxyurea included lack of expertise (OR=5.1; 95% CI=2.65–9.05), lack of clinical guidelines (OR=3.84; 95% CI=2.37–14.33), fear of side-effects (OR=0.50; 95% CI=0.22–0.68) and doubt about its effectiveness (OR=0.30; 95% CI=0.20–0.90).ConclusionThe level of utilization of hydroxyurea in the treatment of SCD among the care providers is sub-optimal with the lack of expertise in its use identified as the most prominent barrier. There is an urgent need for the training of sickle cell care-providers and the development of clinical guidelines on hydroxyurea use.     

Person-centred sexual and reproductive health: A call for standardized measurement

Person-centred sexual and reproductive health (PCSRH) care refers to care that is respectful of and responsive to people's preferences, needs, and values, and which empowers them to take charge of their own sexual and reproductive health (SRH). It is an important indicator of SRH rights and quality of care. Despite the recognition of the importance of PCSRH, there is a gap in standardized measurement in some SRH services, as well as a lack of guidance on how similar person-centred care measures could be applied across the SRH continuum. Drawing on validated scales for measuring person-centred family planning, abortion, prenatal and intrapartum care, we propose a set of items that could be validated in future studies to measure PCSRH in a standardized way. A standardized approach to measurement will help highlight gaps across services and facilitate efforts to improve person-centred care across the SRH continuum.

Patient or Public Contribution

This viewpoint is based on a review of validated scales that were developed through expert reviews and cognitive interviews with services users and providers across the different SRH services. They provided feedback on the relevance, clarity, and comprehensiveness of the items in each scale.