Lifestyle modifications to prevent and control hypertension. 4. Recommendations on physical exercise training. Canadian Hypertension Society,Canadian Coalition for High Blood Pressure Prevention and Control,Laboratory Centre for Disease Control at Health Canada,Heart and Stroke Foundation of Canada

OBJECTIVE: To provide updated, evidence-based recommendations for health care professionals concerning the effects of regular physical activity on the prevention and control of hypertension in otherwise healthy adults. OPTIONS: People may engage in no, sporadic or regular physical activity that may be of low, moderate or vigorous intensity. For sedentary people with hypertension, the options are to undertake or maintain regular physical activity and to avoid or moderate medication use; to use another lifestyle modification technique; to commence or continue antihypertensive medication; or to take no action and remain at increased risk of cardiovascular disease. OUTCOMES: The health outcomes considered were changes in blood pressure and in morbidity and mortality rates. Because of insufficient evidence, no economic outcomes were considered. EVIDENCE: A MEDLINE search was conducted for the period 1966-1997 with the terms exercise, exertion, physical activity, hypertension and blood pressure. Both reports of trials and review articles were obtained. Other relevant evidence was obtained from the reference lists of these articles, from the personal files of the authors and through contacts with experts. The articles were reviewed, classified according to study design and graded according to level of evidence. VALUES: A high value was placed on avoidance of cardiovascular morbidity and premature death caused by untreated hypertension. BENEFITS, HARMS AND COSTS: Physical activity of moderate intensity involving rhythmic movements with the lower limbs for 50-60 minutes, 3 or 4 times per week, reduces blood pressure and appears to be more effective than vigorous exercise. Harm is uncommon and is generally restricted to the musculoskeletal injuries that may occur with any repetitive activity. Injury occurs more often with jogging than with walking, cycling or swimming. The costs include the costs of appropriate shoes, garments and equipment, but these were not specifically measured. RECOMMENDATIONS: (1) People with mild hypertension should engage in 50-60 minutes of moderate rhythmic exercise of the lower limbs, such as brisk walking or cycling, 3 or 4 times per week to reduce blood pressure, (2) Exercise should be prescribed as an adjunctive therapy for people who require pharmacologic therapy for hypertension, especially those who are not receiving beta-blockers. (3) People who do not have hypertension should participate in regular exercise as it will decrease blood pressure and reduce the risk of coronary artery disease, although there is no direct evidence that it will prevent hypertension. VALIDATION: These recommendations agree with those of the World Hypertension League, the American College of Sports Medicine, the report of the US Surgeon General on physical activity and health, and the US National Institutes of Health Consensus Development Panel on Physical Activity and Cardiovascular Health. These guidelines have not been clinically tested. SPONSORS: The Canadian Hypertension Society, the Canadian Coalition for High Blood Pressure Prevention and Control, the Laboratory Centre for Disease Control at Health Canada, and the Heart and Stroke Foundation of Canada.     

One-dimensional isoelectric focusing and immunoblotting of bovine major histocompatibility complex (BoLA) class I molecules and correlation with class I serology

One-dimensional isoelectric focusing followed by immunoblotting and development of the immunoblots with the monoclonal antibody HC-10, raised against denatured HLA class I heavy chains, was used to demonstrate biochemical variation in cattle MHC (BoLA) class I molecules. The bands obtained correlated well with BoLA-A specificities. Two or three bands were identified for the specificities w7, w8, w16, w18, w21, cph43 and cph49, whereas no bands were observed for the specificity w2. Two serologically indistinguishable subtypes of specificity w18 were identified.     

BCL‐XL exerts a protective role against anemia caused by radiation‐induced kidney damage

Studies of gene‐targeted mice identified the roles of the different pro‐survival BCL‐2 proteins during embryogenesis. However, little is known about the role(s) of these proteins in adults in response to cytotoxic stresses, such as treatment with anti‐cancer agents. We investigated the role of BCL‐XL in adult mice using a strategy where prior bone marrow transplantation allowed for loss of BCL‐XL exclusively in non‐hematopoietic tissues to prevent anemia caused by BCL‐XL deficiency in erythroid cells. Unexpectedly, the combination of total body γ‐irradiation (TBI) and genetic loss of Bcl‐x caused secondary anemia resulting from chronic renal failure due to apoptosis of renal tubular epithelium with secondary obstructive nephropathy. These findings identify a critical protective role of BCL‐XL in the adult kidney and inform on the use of BCL‐XL inhibitors in combination with DNA damage‐inducing drugs for cancer therapy. Encouragingly, the combination of DNA damage‐inducing anti‐cancer therapy plus a BCL‐XL inhibitor could be tolerated in mice, at least when applied sequentially.     

TT232, A Novel Signal Transduction Inhibitory Compound in the Therapy of Cancer and Inflammatory Diseases

TT-232 is a structural analogue of somatostatin exhibiting strong and selective growth-inhibitory effects, inhibition of neurogenic inflammation, as well as general anti-inflammatory and analgesic potential without the wide-ranging endocrine side effects of the parent hormone and its “traditional” analogues. The anti-inflammatory action of TT-232 is mediated through the SSTR4 receptor, and its antitumor activity is mediated through the SSTR1 receptor and by the tumor-specific isoform of pyruvate kinase. Its mechanism of action is in line with a new era of molecular medicine called signal transduction therapy, where “false” intracellular or intercellular communication is inhibited or corrected without interfering with basic cell functions and machinery. TT232 has passed phase I clinical trials without toxicity and significant side effects, and phase II studies are running for oncological and anti-inflammatory indications, respectively. This compound has the perspective to become the first drug in molecularly targeted therapy of inflammation where a combined effect of anti-inflammatory, analgesic, and neurogenic inflammation-inhibiting activity can be achieved.     

Using a logical model to predict the growth of yeast

Background  

A logical model of the known metabolic processes in S. cerevisiae was constructed from iFF708, an existing Flux Balance Analysis (FBA) model, and augmented with information from the KEGG online pathway database. The use of predicate logic as the knowledge representation for modelling enables an explicit representation of the structure of the metabolic network, and enables logical inference techniques to be used for model identification/improvement.