Present development concerning antimalarial activity of phospholipid metabolism inhibitors with special reference to in vivo activity

The systematic screening of more than 250 molecules against Plasmodium falciparum in vitro has previously shown that interfering with phospholipid metabolism is lethal to the malaria parasite. These compounds act by impairing choline transport in infected erythrocytes, resulting in phosphatidylcholine de novo biosynthesis inhibition. A thorough study was carried out with the leader compound G25, whose in vitro IC50 is 0.6 nM. It was very specific to mature parasites (trophozoïtes) as determined in vitro with P. falciparum and in vivo with P. chabaudi -infected mice. This specificity corresponds to the most intense phase of phospholipid biosynthesis activity during the parasite cycle, thus corroborating the mechanism of action. The in vivo antimalarial activity (ED50) against P. chabaudi was 0.03 mg/kg, and a similar sensitivity was obtained with P. vinckei petteri, when the drug was intraperitoneally administered in a 4 day suppressive test. In contrast, P. berghei was revealed as less sensitive (3- to 20-fold, depending on the P. berghei-strain). This difference in activity could result either from the degree of synchronism of every strain, their invasion preference for mature or immature red blood cells or from an intrinsically lower sensitivity of the P. berghei strain to G25. Irrespective of the mode of administration, G25 had the same therapeutic index (lethal dose 50 (LD50)/ED50) but the dose to obtain antimalarial activity after oral treatment was 100-fold higher than after intraperitoneal (or subcutaneous) administration. This must be related to the low intestinal absorption of these kind of compounds. G25 succeeded to completely inhibiting parasitemia as high as 11.2% without any decrease in its therapeutic index when administered subcutaneously twice a day for at least 8 consecutive days to P. chabaudi -infected-rodent model. Transition to human preclinical investigations now requires a synthesis of molecules which would permit oral absorption.

Daily physical activity assessment: what is the importance of upper limb movements vs whole body movements?

OBJECTIVE: The movement of the upper limbs (eg fidgeting-like activities) is a meaningful component of nonexercise activity thermogenesis (NEAT). This study examined the relationship between upper limb movements and whole body trunk movements, by simultaneously measuring energy expenditure during the course of the day. DESIGN: A cross-sectional study consisting of 88 subjects with a wide range in body mass index (17.3-32.5 kg/m(2)). The energy expenditure over a 24-h period was measured in a large respiratory chamber. The body movements were assessed by two uniaxial-accelerometers during daytime, one on the waist and the other on the dominant arm. The accelerometry scores from level 0 (=immobile) up to level 9 (=maximal intensity) were recorded. The activities of subjects were classified into eight categories: walking at two speeds on a horizontal treadmill (A & B), ambling (C), self-care tasks (D), desk work (E), meals (F), reading (G), watching TV (H). RESULTS: There was a significant relationship between the accelerometry scores from the waist (ACwaist) and that from the wrist (ACwrist) over the daytime period (R(2)=0.64; P<0.001). The ACwrist was systematically higher than the ACwaist during sedentary activities, whereas it was the reverse for walking activities. ACwrist to ACwaist ratio of activities E-H were above 1.0 and for walking activities (A-C) were below 1.0. A multiple regression analysis for predicting daytime energy expenditure revealed that the explained variance improved by 2% only when the ACwrist was added as a second predictor in addition to the ACwaist. This indicates that the effect of the ACwrist for predicting energy expenditure was of limited importance in our conditions of measurement. CONCLUSIONS: The acceleration of the upper limbs which includes fidgeting is more elevated than that of the whole body for sitting/lying down activities. However, their contribution to energy expenditure is lower than whole body trunk movements, thus indicating that the weight-bearing locomotion activities may be a key component of NEAT. However, its contribution may depend on the total duration of the upper limb movements during the course of the day.

Ireland on the move: Enhancing opportunities for physical activity in the built environment

The Institute of Public Health in Ireland recently hosted a seminar on physical activity. The seminar presentations were: Ms Teresa Lavin, IPH - Physical activity and the built environment in Ireland Prof James Sallis, Professor of Psychology at San Diego State University and Director of Active Living Research - Translating evidence from physical activity research into practice.

Get Ireland Active: The National Guidelines on Physical Activity for Ireland

The National Guidelines on Physical Activity for Ireland Click here to download PDF 3.1mb Consumer Leaflet PDF 932kb Fact Sheet for Adults PDF 667kb Fact Sheet for Parents and Guardians PDF 574kb Foldout Executive Summary PDF 699kb

Promoting physical activity at work: A guide for employers

This booklet is the second in a series of short guides aimed at promoting health in the workplace. It outlines to employers the benefits of promoting physical activity at work, how workplaces can be active places through simple activities and changes, what information and facilities can benefit employees,

30 minutes of physical activity a day is good for your health

This poster promotes the message that 30 minutes of moderate physical activity a day has substantial health benefits, and highlights the fact that you don’t have to do 30 minutes all in one go.

Barriers to health - Migrant health and wellbeing in Belfast

Over the last decade Belfast has experienced significant political, economic and social change. As a consequence, the population of greater Belfast has increased substantially over the past decade. This has been as a result of both natural change and net migration gain. This report covers the following issues legislation on immigration, work, health & social services and social security entitlements; health issues; migrant health priorities identified at the Stakeholder Workshop held in April 2010.

Social and economic inequalities in diet and physical activity

This briefing paper describes social and economic inequalities associated with two of the key determinants of obesity - diet and physical activity. The paper also explores possible explanations for these inequalities.

Obesity and the environment briefing: Increasing physical activity and active travel

This briefing has been written in conjunction with the Local Government Association (LGA). It is aimed at those who work in or represent local authorities. It addresses the issue of taking action to create environments where people are more likely to walk or cycle for short journeys. It summarises the importance of action on obesity and a specific focus on active travel, and outlines the regulatory and policy approaches that can be taken.

Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective

The goal of this Report is to review all the relevant research in order to generate a comprehensive series of recommendations on food, nutrition, and physical activity, designed to reduce the risk of cancer and suitable for all societies. This process is also the basis for a continuous review of the evidence.

Active East - A Physical Activity Framework for the East of England 2006

This document sets out the role of physical activity, not just in terms of its known health benefits (prevention of obesity), but also its wider social contribution. Physical activity is a cross cutting agenda and needs to involve a variety of organisations working in partnership with the health sector.

Statistics on Obesity, Physical Activity and Diet, England 2006

This is a statistical bulletin from the Information Centre which presents a range of information on obesity, physical activity and diet, drawn together from a variety of sources. The topics covered include: overweight and obesity prevalence among adults and children physical activity levels among adults and children trends in purchases and consumption of food and drink, and energy intake health outcomes of being obese hospital admissions and prescriptions dispensed related to obesity. The bulletin also summarises government plans and targets in this area, as well as providing sources of further information and links to relevant documents.

Statistics on obesity, physical activity and diet: England, January 2008

This statistical report from the Information Centre presents a range of information on obesity, physical activity and diet, drawn together from a variety of sources. The publication also summarises government plans and targets in this area, as well as providing sources of further information and links to relevant documents and key sources. There are several notable additions to this, The Information Centre's second report on obesity, physical activity and diet. Waist circumference analysis has been included where possible to reflect the importance of using this measurement in conjunction with Body Mass Index (BMI) in order to identify those at increased risk of health problems associated with obesity. More regional data is presented with a greater number of tables providing government office region and Strategic Health Authority breakdowns. Where possible information at a more local level has been reported on.

Statistics on Obesity, Physical Activity and Diet: England, 2010

This statistical report presents a range of information on obesity, physical activity and diet, drawn together from a variety of sources. The topics covered include: Overweight and obesity prevalence among adults and children; Physical activity levels among adults and children; Trends in purchases and consumption of food and drink and energy intake; and Health outcomes of being overweight or obese. refer to the resource