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The article offers tips for general practitioner (GP) tutors on how to support medical students in times of trouble in Great Britain. It notes that one of a good proxy markers of poor student performance is the student's poor attendance. A researcher on the aspect is claimed to have found that the attitudes of students to course attendance rely deeply on college discipline, wherefore, having their absence ignored is inferred to likely heighten such behaviour.

The focus on the refinement, reduction and replacement of animal use in toxicity testing requires the development of cell-based systems that mimic the effects of xenobiotics in human tissues. The human adrenocortical carcinoma cell line, H295R, has been proposed as a model for studies on adrenal steroidogenesis and its disruption. In this study, expression profiles for nine adrenal steroidogenic genes were characterized in H295R cells using real-time RT-PCR. Treatment with forskolin increased cortisol secretion and stimulated transcription of all the steroidogenic genes except SULT2A1. The transcript profile from H295R cells in the presence and absence of forskolin was compared with the transcript profile from human adrenal glands. The gene expression pattern observed in the forskolin-treated H295R cells was more similar to that in the human adrenal gland, than the expression pattern in untreated cells. To examine H295R cells as a possible in vitro system for the assessment of adrenal disruption using molecular endpoints, the insecticide lindane ( γ-hexachlorocyclohexane) was used. In vivo, lindane has been shown to inhibit testicular, ovarian and adrenal steroidogenesis. It was demonstrated that lindane reduced cortisol secretion, downregulated the expression of a subset of the genes encoding steroidogenic enzymes and repressed transcriptional activation of the steroidogenic acute regulatory protein (StAR) gene promoter. Thus the H295R cell line provides a good in vitro system for the analysis of the human adrenal steroidogenic pathway at the level of hormone production and gene expression. This in vitro test can be used for the rapid detection of adrenal endocrine disruption and as a tool for mechanistic studies. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Dehydroepiandrosterone sulphate(DHEAS) is a steroid product of the adrenal gland, which circulates in high concentrations, but whose functions are largely unknown. There is evidence for antiproliferative effects of DHEAS in neoplastic tissue. The present study was designed to investigate the effects of DHEAS on vascular endothelial cell proliferation. It was found that DHEAS at physiological concentrations(10µM) caused inhibition of cellular growth, which was reversible following removal of the steroid. This effect was not mimicked by other steroids, suggesting that it is not mediated by androgen or estrogen receptors. Uptake of 3H-thymidine was not altered by DHEAS, suggesting that this steroid may induce apoptosis in vascular endothelial cells. [ABSTRACT FROM AUTHOR]

Dehydroepiandrosterone (DHEA) is the major steroid product of the adrenal cortex yet it still remains controversial as to whether it is a true hormone. The regulation of DHEA is poorly understood and no specific receptor has been characterised. Despite this, the use of DHEA as an anti-ageing treatment outside medical supervision has been increasing over recent years as people attempt to restore the levels seen in early adulthood. DHEA has also been advocated as a possible treatment for menopause, with some practitioners even suggesting it as an alternative to standard hormone replacement therapy. The proponents of DHEA replacement therapy claim positive actions on cardiovascular and immune systems, together with beneficial effects on bone metabolism and mood. In fact, there have been very few well planned randomised, placebo-controlled, double-blind clinical trials and there is very little clinical evidence to support the hope invested in this hormone. Further clinical trials are urgently needed. [ABSTRACT FROM AUTHOR]

The author discusses the possibility of offering part time medical training to medical students in Great Britain. Topics explored include the positive acknowledgment of less than full time (LTFT) training by the British General Medical Council (GMC), the part time study options that universities may offer through distance or blended learning programs, and the lack of regulatory restrictions that would hinder part time training implementation.

It has previously been shown, by this laboratory and others, that adrenal cells actively secrete adrenomedullin. Here it is demonstrated that human adrenal cells also secrete the related peptide, proadrenomedullin N-terminal 20 peptide (PAMP). The actions of adrenomedullin and PAMP on adrenal steroid secretion were determined by measuring the aldosterone, cortisol and dehydroepiandrosterone (DHEA) content of cell culture medium after exposure of the human adrenal H295R cells to either PAMP or adrenomedullin. While PAMP was found to cause a dose-dependent increase in release of all the steroids into the medium, adrenomedullin only increased aldosterone and cortisol and had no effect on DHEA. These data suggest that both adrenomedullin and PAMP may be autocrine regulators of adrenal steroid secretion. [Copyright &y& Elsevier]

Adrenomedullin (AM) is a multifunctional peptide hormone, which plays a significant role in vasodilation and angiogenesis, implicating it in hypertension as well as in carcinogenesis. AM exerts its effects via the calcitonin receptor-like receptor (CRLR, now known as CL) complexed with either receptor activity modifying protein (RAMP) 2 or 3. We have investigated the effect of AM on immortalized human microvascular endothelial cells 1, since endothelial cells are a major source as well as a target of AM actions in vivo. Cells treated with AM showed elevated cAMP in a time (5-45 min)-dependent and dose (10(-6)-10(-14) M)-dependent manner. Pre-treatment with the AM receptor antagonist AM(22-52) partially suppressed the AM-induced increase in cAMP levels. An increase in extracellular signal-regulated kinase 1/2 phosphorylation was observed after 5 min of treatment with 10(-8) M AM. This phosphorylation was specific, since we were able to block the AM-induced effect with 1 microM U0126, a specific mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor. Using real-time PCR, we were able to show for the first time that AM upregulates peptide and mRNA expression of vascular endothelial growth factor (VEGF). However, AM treatment of cells did not result in increased cell proliferation. Instead, we observed that AM and VEGF induced cell migration, which could be inhibited by the AM(22-52) and anti-VEGF antibody respectively. AM also significantly elevated mRNA levels of CL (after 2 and 24 h treatment) and RAMP2 (after 1 and 24 h treatment). The upregulation of the AM receptor at two time points reflects possibly different cellular responses to short- and long-term exposure to AM.

Over recent years, increased attention has been paid to the possibility that dehydroepiandrosterone (DHEA) may have therapeutic benefits. Several clinical trials of DHEA have been conducted, investigating the use of this steroid in the treatment of conditions ranging from chronic inflammatory disease to psychiatric disorders. Possible replacement therapy with DHEA in adrenal insufficiency and in old age has also been investigated. This review evaluates our current understanding of the possible therapeutic value of DHEA. Evidence of beneficial effects is discussed and areas where further research is needed are highlighted. Possible adverse effects of long-term DHEA therapy are also considered.