What is the future for rimonabant in the treatment of obesity

Orlistat and sibutramine only cause modest reductions in body weight. Rimonabant, a cannabinoid receptor 1 antagonist, is a new approach to weight reduction, but is it safe, efficacious, and better than the existing agents?

Clinical efficacy and safety of zoledronic acid in osteoporosis and Paget's disease

Osteoporosis and Paget’s bone disease are the most common diseases of the bone. In addition to glucocorticoid treatment, there are many other secondary causes of osteoporosis. Bisphosphonates are used to treat these bone conditions. Zoledronic acid is the most potent bisphosphonate at inhibiting bone resorption. In osteoporosis, zoledronic acid increases bone mineral density for at least 1 year following a single intravenous administration. The efficacy and safety of zoledronic acid in the treatment of osteoporosis and Paget’s bone disease are reviewed. This article also covers the studies of the effects of zoledronic acid in the bone loss associated with the secondary osteoporosis.

Resistance training for obese, type 2 diabetic adults: A review of the evidence

In both developed and developing countries, increased prevalence of obesity has been strongly associated with increased incidence of type 2 diabetes mellitus (T2DM) in the adult population. Previous research has emphasized the importance of physical activity in the prevention and management of obesity and T2DM, and generic exercise guidelines originally developed for the wider population have been adapted for these specific populations. However, the guidelines traditionally focus on aerobic training without due consideration to other exercise modalities. Recent reviews on resistance training in the T2DM population have not compared this modality with others including aerobic training, or considered the implications of resistance training for individuals suffering from both obesity and T2DM. In short, the optimal mix of exercise modalities in the prescription of exercise has not been identified for it benefits to the metabolic, body composition and muscular health markers common in obesity and T2DM. Similarly, the underlying physical, social and psychological barriers to adopting and maintaining exercise, with the potential to undermine the efficacy of exercise interventions, have not been addressed in earlier reviews. Because it is well established that aerobic exercise has profound effects on obesity and T2DM risk, the purpose of this review was to address the importance of resistance training to obese adults with T2DM.

Glycaemic load is associated with insulin resistance in older Australian women

Background: Diets with a high postprandial glycemic response may contribute to long-term development of insulin resistance and diabetes, however previous epidemiological studies are conflicting on whether glycemic index (GI) or glycemic load (GL) are dietary factors associated with the progression. Our objectives were to estimate GI and GL in a group of older women, and evaluate cross-sectional associations with insulin resistance. Subjects and Methods: Subjects were 329 Australian women aged 42-81 years participating in year three of the Longitudinal Assessment of Ageing in Women (LAW). Dietary intakes were assessed by diet history interviews and analysed using a customised GI database. Insulin resistance was defined as a homeostasis model assessment (HOMA) value of >3.99, based on fasting blood glucose and insulin concentrations. Results: GL was significantly higher in the 26 subjects who were classified as insulin resistant compared to subjects who were not (134±33 versus 114±24, P<0.001). In a logistic regression model, an increment of 15 GL units increased the odds of insulin resistance by 2.09 (95%CI 1.55, 2.80, P<0.001) independently of potential confounding variables. No significant associations were found when insulin resistance was assessed as a continuous variable. Conclusions: Results of this cross-sectional study support the concept that diets with a higher GL are associated with increased risk of insulin resistance. Further studies are required to investigate whether reducing glycemic intake, by either consuming lower GI foods and/or smaller serves of carbohydrate, can contribute to a reduction in development of insulin resistance and long-term risk of type 2 diabetes.

The contribution of different androgen receptor domains to receptor dimerization and signaling

The androgen receptor (AR) is a ligand-activated transcription factor of the nuclear receptor superfamily that plays a critical role in male physiology and pathology. Activated by binding of the native androgens testosterone and 5-dihydrotestosterone, the AR regulates transcription of genes involved in the development and maintenance of male phenotype and male reproductive function as well as other tissues such as bone and muscle. Deregulation of AR signaling can cause a diverse range of clinical conditions, including the X-linked androgen insensitivity syndrome, a form of motor neuron disease known as Kennedy’s disease, and male infertility. In addition, there is now compelling evidence that the AR is involved in all stages of prostate tumorigenesis including initiation, progression, and treatment resistance. To better understand the role of AR signaling in the pathogenesis of these conditions, it is important to have a comprehensive understanding of the key determinants of AR structure and function. Binding of androgens to the AR induces receptor dimerization, facilitating DNA binding and the recruitment of cofactors and transcriptional machinery to regulate expression of target genes. Various models of dimerization have been described for the AR, the most well characterized interaction being DNA-binding domain- mediated dimerization, which is essential for the AR to bind DNA and regulate transcription. Additional AR interactions with potential to contribute to receptor dimerization include the intermolecular interaction between the AR amino terminal domain and ligand-binding domain known as the N-terminal/C-terminal interaction, and ligand-binding domain dimerization. In this review, we discuss each form of dimerization utilized by the AR to achieve transcriptional competence and highlight that dimerization through multiple domains is necessary for optimal AR signaling.

The new epidemics

In developed countries we once thought that the scourge of infectious diseases was tamed. Antibiotics were controlling infection in individual patients, vaccines were preventing illness and great faith was placed in the capacity of science to confound the most cunning organism. However, things have changed and in the new millennium we are confronting a host of challenges to public health from infectious diseases. Epidemics mean an excess of cases in the community from that normally expected or the appearance of a new infection (Webber ####, 22) Chapter 11 outlined the background to infectious diseases and the individual strategies directed towards the control and management of infectious diseases. The aim of this chapter is to outline the impact that infectious diseases have on population health, to identify the risks of major outbreaks and to identify the strategies required to reduce the risk and to manage any possible outbreak.

The effects of exercise-induced weight loss on appetite-related peptides and motivation to eat

Context: The magnitude of exercise-induced weight loss depends on the extent of compensatory responses. An increase in energy intake is likely to result from changes in the appetite control system toward an orexigenic environment; however, few studies have measured how exercise impacts on both orexigenic and anorexigenic peptides. ---------- Objective: The aim of the study was to investigate the effects of medium-term exercise on fasting/postprandial levels of appetite-related hormones and subjective appetite sensations in overweight/obese individuals. ---------- Design and Setting: We conducted a longitudinal study in a university research center. ---------- Participants and Intervention: Twenty-two sedentary overweight/obese individuals (age, 36.9 ± 8.3 yr; body mass index, 31.3 ± 3.3 kg/m2) took part in a 12-wk supervised exercise programme (five times per week, 75% maximal heart rate) and were requested not to change their food intake during the study. ---------- Main Outcome Measures: We measured changes in body weight and fasting/postprandial plasma levels of glucose, insulin, total ghrelin, acylated ghrelin (AG), peptide YY, and glucagon-like peptide-1 and feelings of appetite. ---------- Results: Exercise resulted in a significant reduction in body weight and fasting insulin and an increase in AG plasma levels and fasting hunger sensations. A significant reduction in postprandial insulin plasma levels and a tendency toward an increase in the delayed release of glucagon-like peptide-1 (90–180 min) were also observed after exercise, as well as a significant increase (127%) in the suppression of AG postprandially. ---------- Conclusions: Exercise-induced weight loss is associated with physiological and biopsychological changes toward an increased drive to eat in the fasting state. However, this seems to be balanced by an improved satiety response to a meal and improved sensitivity of the appetite control system.

Ghrelin and obestatin concentrations during puberty: Relationships with adiposity, nutrition and physical activity

Ghrelin and obestatin are two peptides associated with appetite control and the regulation of energy balance in adults. It is intuitive that they have an important role in growth and development during puberty. Therefore, it is acknowledged that these peptides, in addition to others, form part of the substrate underlying energy homeostasis which in turn will contribute to body weight regulation and could explain changes in energy balance during puberty. Both peptides originate from the stomach; hence, it is intuitive that they are involved in generating signals from tissue stores which influence food intake. This could be manifested via alterations in the drive to eat (i.e. hunger), eating behaviors and appetite regulation. Furthermore, there is some evidence that these peptides might also be associated with physical activity behaviors and metabolism. Anecdotally, children and adolescents experience behavioral and metabolic changes during growth and development which will be associated with physiological changes.

Addressing childhood obesity through increased physical activity

Obesity is affecting an increasing proportion of children globally. Despite an appreciation that physical activity is essential for the normal growth and development of children and prevents obesity and obesity-related health problems, too few children are physically active. A concurrent problem is that today’s young people spend more time than previous generations did in sedentary pursuits, including watching television and engaging in screen-based games. Active behavior has been displaced by these inactive recreational choices, which has contributed to reductions in activity-related energy expenditure. Implementation of multifactorial solutions considered to offer the best chance of combating these trends is urgently required to redress the energy imbalance that characterizes obesity. The counterproductive ‘shame and blame’ mentality that apportions responsibility for the childhood obesity problem to sufferers, their parents, teachers or health-care providers needs to be changed. Instead, these groups should offer constant support and encouragement to promote appropriate physical activity in children. Failure to provide activity opportunities will increase the likelihood that the children of today will live less healthy (and possibly shorter)lives than their parents.