Noncontact dipole effects on channel permeation. III. Anomalous proton conductance effects in gramicidin

Proton transport on water wires, of interest for many problems in membrane biology, is analyzed in side-chain analogs of gramicidin A channels. In symmetrical 0.1 N HCl solutions, fluorination of channel Trp(11), Trp-(13), or Trp(15) side chains is found to inhibit proton transport, and replacement of one or more Trps with Phe enhances proton transport, the opposite of the effects on K(+) transport in lecithin bilayers. The current-voltage relations are superlinear, indicating that some membrane field-dependent process is rate limiting. The interfacial dipole effects are usually assumed to affect the rate of cation translocation across the channel. For proton conductance, however, water reorientation after proton translocation is anticipated to be rate limiting. We propose that the findings reported here are most readily interpreted as the result of dipole-dipole interactions between channel waters and polar side chains or lipid headgroups. In particular, if reorientation of the water column begins with the water nearest the channel exit, this hypothesis explains the negative impact of fluorination and the positive impact of headgroup dipole on proton conductance.     

Pregnancy Weight Retention in Morbid Obesity

HUNT, STEVEN C, MARIA M DAINES, TED D ADAMS, EDWARD M HEATH AND ROGER R WILLIAMS. Pregnancy weight retention in morbid obesity. Obes Res. 1995;3:121–130. Recent hypotheses suggest that for women who develop morbid obesity, increases in weight associated with pregnancy may represent a significant contribution to their obesity status. The effects of multiple pregnancies on weight gain were studied in 96 morbidly obese women (<13.6 kg over ideal weight at ages 20–24 or before an earlier first pregnancy and currently >44.5 kg over ideal weight) and 115 random control women from the Utah population. Self-reported weights for each pregnancy included: prepregnancy, greatest during pregnancy, and 6 weeks following delivery, which were validated against available hospital records. Mean number of pregnancies in each group were similar (4.2 and 4.3), ranging from 1 to 9. Mean current age was 46 and mean weight gain since ages 20–24 was 46.0 kg in the morbidly obese and 14.1 kg in controls. Regression of current weight on total number of pregnancies, adjusting for weight at ages 20–24, showed a 1.3 kg/pregnancy increase in current weight (p=0.03) with no difference between groups (p=0.6). Weight gain subsequent to the last pregnancy was not related to the number of pregnancies (p=0.2). Morbidly obese women gained more weight during pregnancy than controls only for the first pregnancy. Gains were similar for all other pregnancies. Morbidly obese women had smaller weight losses after delivery than the controls, but these differences were not significant. For the first pregnancy, morbidly obese women had a net weight retention that was 4.0 kg greater than the controls at 6 weeks post-partum and an average of 1.6 kg/pregnancy greater retention for the remaining pregnancies. Pregnancy weight gains for each pregnancy subsequent to the first pregnancy were constant. These findings suggest: 1) women who develop morbid obesity have slightly less weight loss after delivery and greater between-pregnancy weight gains than controls; 2) the number of pregnancies does not affect the amount of weight gained after the last pregnancy; and 3) while multiparity may augment weight gain in morbidly obese women, it is probably not a primary factor in the later development of morbid obesity.     

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.