SOX18 and the transcriptional regulation of blood vessel development

SOX18 is a transcription factor that is transiently expressed in nascent endothelial cells during embryonic development and adult neovascularization. This protein belongs to the SOX family of transcription factors, ih,which are proving to be some of the key regulators of cell-type specification in the vertebrate embryo. Natural mutations in the Sox18 gene have been shown to result to cardiovascular dysfunction, in some cases leading to death. Available evidence thus implicates Sox18 as an important regulator of vascular development, most likely playing a key role in endothelial cell specification. However; the genetic knockout of Sox18 in mice has produced a confounding result that complicates our understanding of the molecular mode of action of the SOX18 protein. We speculate that Sox18 inky act in a redundant fashion with closely related genes such as Sox7 and/or Sox17. (C) 2001, Elsevier Science Inc.

Cytokine regulation of syndecan-1 and-2 gene expression in human periodontal fibroblasts and osteoblasts

Cell-surface proteoglycans participate in several biological functions including interactions with a variety of growth factors and cytokines. Regulation of syndecan-1 and -2 gene expression was investigated in human periodontal ligament fibroblasts (PDLF), osteoblasts (OB) and gingival fibroblasts (GF), in response to platelet-derived growth factor (PDGF-BB), transforming growth factor (TGF-beta(1)), and interleukin (IL-1beta) by Northern blot analyses. We also compared the effect of PDGF-BB and TGF-beta(1), separately and in combination, in the prolonged presence of IL-1beta on the expression of both syndecan genes. The results demonstrated that the three cell lines regulated the expression of syndecan-1 and -2 in response to growth factors and cytokines in different manners. These cell lines increased syndecan-1 mRNA levels in response to either PDGF-BB or TGF-beta(1) and decreased levels in response to IL-1beta. The effect of IL-1beta on syndecan-1 mRNA synthesis was partially reversed after adding PDGF-BB and TGF-beta(1), separately or in combination, in the presence of IL-1beta. In contrast, syndecan-2 mRNA level was markedly upregulated in response to either TGF-beta(1) or IL-1beta in OB when compared with the other two cell lines. However, the stimulatory effect of TGF-beta(1) on syndecan-2 mRNA production in OB was abolished in the prolonged presence of IL-1beta. These findings lend support to the notion that syndecan-1 and syndecan-2 have distinct functions which correlate with their source and functions within the periodontium.

Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis

Background The mechanisms responsible for disturbed iron homoeostasis in hereditary haemochromatosis are poorly understood. However, results of some studies indicate a link between hepcidin, a liver-derived peptide, and intestinal iron absorption, suggesting that this molecule could play a part in hepatic iron overload. To investigate this possible association, we studied the hepatic expression of the gene for hepcidin (HAMP) and a gene important in iron transport (IREG1) in patients with haemochromatosis, in normal controls, and in Hfe-knockout mice. Methods We extracted total RNA from the liver tissue of 27 patients with HFE-associated haemochromatosis, seven transplant donors (controls), and Hfe-knockout mice. HAMP and IREG1 mRNA concentrations were examined by ribonuclease protection assays and expressed relative to the housekeeping gene GAPD. Findings There was a significant decrease in HAMP expression in untreated patients compared with controls (5.4-fold, 95% CI 3.3-7.5; p

The regulation of complementary health: sacrificing integrity?

In response to the increasing use of complementary and alternative medicine (CAM), governments are exploring ways to ensure patients' safety and respond to complaints. One solution is to establish registration boards and procedures based on the model of existing health practitioner Acts. Registration will require defined minimum standards for competence, which will have to be based on scientific evidence. As scientific evidence accumulates, these modalities are likely to lose their identities as alternative and become assimilated into Western medicine.

Naturopathic and Western herbal medicine practice in Australia - a workforce survey

Background: Despite substantial growth in the use of complementary medicine, no comprehensive national study has been undertaken of the naturopathic and Western herbal medicine component of the healthcare workforce in Australia. This study aimed to examine the nature of these practices and this currently unregulated workforce in Australia. Methods: A comprehensive survey questionnaire was developed in consultation with the profession and distributed nationally to all members of the naturopathic and Western herbal medicine workforce. Results: The practices of herbal medicine and naturopathy make up a sizeable component of the Australian healthcare sector, with approximately 1.9 million consultations annually and an estimated turnover of $AUD 85 million in consultations (excluding the cost of medicines). A large proportion of patients are referred to practitioners by word of mouth. Up to one third of practitioners work in multidisciplinary clinics with other registered sectors of the healthcare community. The number of adverse events associated with herbal medicines, nutritional substances and homoeopathic medicines recorded in Australia is substantial and the types of events reported are not trivial. Data suggest that practitioners will experience one adverse event every 11 months of full-time practice, with 2.3 adverse events for every 1000 consultations (excluding mild gastrointestinal effects). Conclusion: These data confirm the considerable degree of utilisation of naturopathic and Western herbal medicine practitioners by the Australian public. However, there is a need to examine whether statutory regulation of practitioners of naturopathy and Western herbal medicine is required to better protect the public. (C) 2004 Elsevier Ltd. All rights reserved.

Failure of normal glycaemic regulation in a patient with severe hypothermia

This report describes the case of an 88-year-old non-diabetic female who presented to the emergency department following a presumed hypoijtycaemic collapse due to self-neglect. Subsequent rewarming and resuscitation demonstrated a number of the significant consequences of severe hypothermia, including apparent secondary impairment of glycaemic autoregulation. The phenomenon of reversible inhibition of insulin secretion due to severe hypothermia has been documented previously in the field of cardiac surgery. The hyperglycaemia was not treated with any antihyperglycaernic agent, and her recovery was uneventful. Subsequent blood sugar level monitoring was normal. If insulin is administered to the hypothermic patient, intensive monitoring of blood glucose is essential due to the increase in endogenous insulin secretion on rewarming. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

A Research Agenda for Assessing the Potential Contribution of Genomic Medicine to Tobacco Control

This paper identifies research priorities in evaluating the ways in which "genomic medicine"-the use of genetic information to prevent and treat disease-may reduce tobacco-related harm by: (1) assisting more smokers to quit; (2) preventing non-smokers from beginning to smoke tobacco; and (3) reducing the harm caused by tobacco smoking. The method proposed to achieve the first aim is pharmacogenetics", the use of genetic information to optimise the selection of smoking-cessation programmes by screening smokers for polymorphisms that predict responses to different methods of smoking cessation. This method competes with the development of more effective forms of smoking cessation that involve vaccinating smokers against the effects of nicotine and using new pharmaceuticals (such as cannabinoid antagonists and nicotine agonists). The second and third aims are more speculative. They include: screening the population for genetic susceptibility to nicotine dependence and intervening (eg, by vaccinating children and adolescents against the effects of nicotine) to prevent smoking uptake, and screening the population for genetic susceptibility to tobacco-related diseases. A framework is described for future research on these policy options. This includes: epidemiological modelling and economic evaluation to specify the conditions under which these strategies are cost-effective; and social psychological research into the effect of providing genetic information on smokers' preparedness to quit, and the general views of the public on tobacco smoking.

The prediction of disease risk in genomic medicine

In recent years, the phrase 'genomic medicine' has increasingly been used to describe a new development in medicine that holds great promise for human health. This new approach to health care uses the knowledge of an individual's genetic make-up to identify those that are at a higher risk of developing certain diseases and to intervene at an earlier stage to prevent these diseases. Identifying genes that are involved in disease aetiology will provide researchers with tools to develop better treatments and cures. A major role within this field is attributed to 'predictive genomic medicine', which proposes screening healthy individuals to identify those who carry alleles that increase their susceptibility to common diseases, such as cancers and heart disease. Physicians could then intervene even before the disease manifests and advise individuals with a higher genetic risk to change their behaviour - for instance, to exercise or to eat a healthier diet - or offer drugs or other medical treatment to reduce their chances of developing these diseases. These promises have fallen on fertile ground among politicians, health-care providers and the general public, particularly in light of the increasing costs of health care in developed societies. Various countries have established databases on the DNA and health information of whole populations as a first step towards genomic medicine. Biomedical research has also identified a large number of genes that could be used to predict someone's risk of developing a certain disorder. But it would be premature to assume that genomic medicine will soon become reality, as many problems remain to be solved. Our knowledge about most disease genes and their roles is far from sufficient to make reliable predictions about a patient’s risk of actually developing a disease. In addition, genomic medicine will create new political, social, ethical and economic challenges that will have to be addressed in the near future.

The Rural Clinical Division: a student journey to rural medicine

Background: The University of Queensland has through an Australian Government initiative, established a Rural Clinical Division (RCD) at four regional sites in the southern and central Queensland. Over the fi rst four years of the existence of the RCD, an integrated package of innovative medical education has been developed. Method: The integrated aspects of the RCD program include: The Rural Medical Rotation: Every medical student undertakes an eight week rural rotation in Year 3. Year 3 and 4 MBBS - 100 students are currently spending one to two years in the rural school and demand is increasing. Interprofessional Education - Medical and Allied Health students attend lectures, seminars and workshops together and often share the same rural clinical placement. Rural health projects - allow students to undertake a project of benefi t to the rural community. Information Technology (IT) - the Clinical Discussion Board (CDB) and Personal Digital Assistants (PDA) demonstrate the importance of IT to medical students in the 21st century. Changing the Model of Medical Education - The Leichhardt Community Attachment Placement (LCAP), is a pilot study that resulted in the addition of three interns to the rural workforce. All aspects of the RCD are evaluated with surveys using both qualitative and quantitative free response questions, completed by all students regularly throughout the academic year. Results: Measures of impact include: Student satisfaction and quality of teaching surveys – 86-91% of students improved their clinical skills and understanding across all rotations. Academic results and progress – RCD students out-perform their urban colleagues. Intent to work in rural areas – 90% of students reported a greater interest in rural medicine. Intern numbers – rural / regional intern placements are increasing. Conclusions: The RCD proves to be a site for innovations all designed to help reach our primary goal of fostering increased recruitment of a rural medical workforce.