Thermogenesis and obisity

Adaptive reduction in thermogenesis and resistance to lose fat in obese men
Adaptive thermogenesis is defined as a greater than predicted change in energy expenditure in response to changes in energy balance. This issue is particularly relevant in the context of a weight-reducing programme in which diminished thermogenesis can be sufficient to compensate for a prescribed decrease in daily energy intake.
In the pilot study,described in this paper Tremblay and Chaput in British Journal of Nutrition investigated the adaptive reduction in thermogenesis in resting state that appears to favour resistance to further weight loss.
Eight obese men (mean BMI: 33•4kglm2, mean age: 38 years) participated in this repeated-measures, within-subject, clinical intervention. They were subjected to a weight-loss programme that consisted of a supervised diet (- 2930 kJ/d) and exercise clinical intervention.
The phases investigated were as follows: (i) baseline, (ii) after 5 (SE I) kg loss of body weight (phase 1), (iii) after 10 (SE 1) kg weight loss (phase 2) and (iv) at resistance to further weight loss (plateau).
At each phase of the weight-reducing programme, body weight and composition as well as Resting Metabolic Rate were measured. A regression equation was established in a control population of the same age to predict Resting Metabolic Rate obese men at each phase of the weight-loss programme. They observed that body weight and Fat Mass were significantly reduced (P<0•05), while fat-free mass remained unchanged throughout the programme.
In phase 1, measured Resting Metabolic Rate had fallen by 418kJ/d, more than predicted (P<0•05), and this difference reached 706kJ/d at plateau (P<0•05 v. phase 1). A positive associ¬ation (r 0•64, P< 0•05) was observed between the reduction in thermogenesis and the degree of Fat Mass depletion at plateau. The adaptive reduction in thermogenesis at plateau was substantial and represented 30•9 % of the compensation in energy balance that led to resistance to further lose body weight.
Tremblay and Chaput suggest that these results show that adaptive reduction in thermogenesis may contribute to the occurrence of resistance to lose fat in obese men subjected to a weight-reducing programme.

Tremblay and Chaput 2009 Adaptive reduction in thermogenesis and resistance to lose fat in obese men Brit J Nutrition vol 101 488-492

colorectal cancer

Epidemiology
In a review of colorectal cancer Cunningham et al March 20th Lancet 2010 discuss the risk factors in developing cancer of the colon. One million individuals world wide will develop cancer of the colon.
They state that most cases arise sporadically. Risk factors include age, male sex, previous colonic polyps, and environmental factors ( e.g. red meat, high fat diet, inadequate intake of fibre , obesity , sedentary life style, diabetes mellitus, smoking and high consumption of alcohol) . Inflammatory bowel disease ( ulcerative colitis ands Crohn’s) accounts for two thirds of the incidence , 18 % after 30 years ) .
In general, cancer of the colon is associated with chromosomal ( 85% ) and micro satellite instability ( 15%).Micro satellite is a repeating DNA segment.
Hereditary cause play a small but significant role. A germline mutation in a mismatch repair gene ( most commonly MLH1, MSH2, MSH6 )and is associated with cancer of the colon in a family.
Cunningham et al Colorectal Cancer 2010 Lancet vol 375 p 1030-103

new UK-WHO growth charts

In April 2006 the World Health Organisation published a new growth In April 2006 the World Health Organization published a new growth standard for children aged under 5 years. They were based on the growth patterns of healthy infants in United States, Norway, Oman, Brazil, India , Ghana, born at full term whose mothers were non-smoking , relatively affluent whose pregnancy was healthy. The results for each country were very consistent with the other countries..
The United Kingdom was one of the first developed coun¬tries to adopt it, and the Department of Health commis¬sioned the Royal College of Paediatrics and Child Health to design new growth charts and develop new evidence based instructions and supporting educational materials. These charts (known as the UK-WHO growth charts) are now in use for monitoring the growth of children aged under 4 years.
An article by Wright and colleagues discusses the use of these very user friendly charts which replace the previous charts. They give clear instructions on gestational corrections, and include a new chart for infants born before 3 weeks gestation.
The charts also contain a tool to determine body mass index from weight and height and an aid fo predicting adult height.
These charts for children aged 0-4 can be downloaded from the Royal College of Paediatics and Child Health web site.
Wright et al Using the UK-WHO growth charts. BMJ vol 340 pp647-650

vitamin A supplements in neonates

Andrew Prentice in the BMJ 20th March 2010 comments on a linked randomised controlled trial, where Benn and colleagues ( BMJ 20th March 2010 ) assess the effect of giving high dose vitamin A supplements to low birth weight neonates in Guinea-Bissau. They found no effect on infant mortality, although boys tended to benefit but a significantly harmful effect was seen on girls' survival.
In 1983 it was reported that young Indonesian children with mild xerophthalmia, Bitot's spots, and night blind¬ness, ie vitamin A deficiency had a higher mortality rate . A subsequent randomised controlled trial of vitamin A supplementation showed an impressive benefit on mortality. A meta-analysis of large scale trials in Asia and Africa showed that this cheap and simple intervention reduces child mortality by 30% in countries with evidence of at least marginal vitamin A deficiency. The World Health Organization recommended universal vitamin A supplementation of children aged six to 60 months, which is government policy in more than 60 countries. .
The question was than asked if it was better to give vitamin A to newborn babies or later to infants or children . Infant mortality is greatest in the first six months of life. Clinical trials of supplementing breast feeding mothers postpartum gave varying results and some infant complications eg acute bulging fontanelles after dosing. More trials were conducted and a meta-analysis found a mixed picture , no survival benefit, but evidence of benefit from Asian trials and evidence of no effect (or even harm) in two African trials eg previous one by Benn and colleagues in Guinea-Bissau.
Yet vitamin A supplementation has saved many thousands of lives. Benn has indicated no benefit and even harmful effect of vitamin A at birth that seemed to be confined to girls. Benn has shown repeated examples of how vaccines, micronutrients, and exposure to infections can strongly affect all cause mortality in regions with a high burden of infection. Sex differences in susceptibility to certain infections and in responses to vaccination have been recognised for decades,
WHO has commissioned three large trials in an attempt to resolve the possibility that neonatal vitamin A supplementation may be beneficial in Asia but not in Africa. These trials will assess mortality up to six months of age.
Prentice 2010 Vitamin A supplements and survival in children BMJ vol 340 pp 607-8
Benn et al 2010 Vitamin A supplementation and BCG vaccination at birth in two low birthweight neonates: two by two factorial randomised trial BMJ vol 340 p 636

ulcerative colitis and linoleic acid

Wood 2009 IBD: High dietary intake of linoleic acid more than doubles the risk of ulcerative colitis,Nature Reviews Gastroenterology and Hepatology 7, 65
A high dietary intake of linoleic acid—an essential n-6 polyunsaturated fatty acid found in red meats, polyunsaturated margarines and various cooking oils—more than doubles the risk of developing incident ulcerative colitis, according to the results of a new multicenter European study.Linoleic acid is converted to arachidonic acid, which is incorporated into the colonocyte cell membrane; once released from the cell membrane, arachidonic acid is metabolized to proinflammatory eicosanoids (including prostaglandin E2, leukotriene B4 and thromboxane A2).

grapes and cognitive impairment

Alzheimer's disease is the cause of 60 to 80 % of cases of dementia ,there are some 25 million cases Worldwide which are expected to rise. Mild cognitive impairment identifies individuals with elevated risk for dementia, and some 10% a year progress to Alzheimer's disease.
Even age-associated memory impairment, formally called benign forgetfulness, may be associated with very early neurodegeneration. Older adult with subjective memory complaints with age-associated memory impairment show degradation in the medial temporal lobe . There is a trebling of risk of Alzheimers’s disease in these individuals. Memory complaints and associated manifestations in everyday functioning are indicators of neurodegeneration. Preventive interventions begun at an early stage cannot be other than good.
Specific constituents of grape juice eg polyphenols have neuroprotective effects.
Epidemiological studies indicate that consumption of fruits and vegetables is associated with lower risk of neurodegenerative disorders and better cognitive performance in the elderly.
Concord grape juice contains polyphenol compounds, which have antioxidant and anti-inflammatory properties and influence neuronal signalling. Concord grape juice supplementation has been shown to reduce inflammation, blood pressure and vascular pathology in individuals with cardio vascular disease and consumption of such flavonoid-containing foods is associated with a reduced risk for dementia. In this initial investigation of neurocognitive effects, Krikorian and colleagues Brit J Nutrition 2010 vol 103 pp 730-734 enrolled twelve older adults with memory decline but not dementia in a randomised, placebo-controlled, double-blind trial with Concord grape juice supplementation for 12 weeks. Significant improvement was observed in verbal learning and non-Significant enhancement of verbal and spatial recall. There was no appreciable effect of the intervention on depressive symptoms and no effect on weight or waist circumference. A small increase in fasting insulin was observed for those consuming grape juice. These preliminary findings suggest that supplementation with Concord grape juice may enhance cognitive function for older adults with early memory decline and offers hope for future studies.

Krikorian et al 2010 Concord juice supplementation improves memory function in older adults with mild cognitive impairment, Brit J Nutrition vol 103 pp 730-734

mitochonria and post trauma illness

These are such ingenious and clever two papers
Serious physical injury, or trauma, is a major cause of morbidity and mortality worldwide, Patients who survive the initial trauma, despite medical and surgical care, often remain critically ill. One cause of this extension of danger is the systemic inflammatory response syndrome with shock and compromised function of several organs. The clinical symptoms of post-traumatic syndromes, fever, increased heart rate and low blood pressure (shock) are similar to the signs and symptoms of the systemic inflammatory response to severe infection, i.e. sepsis. The molecular mechanism of these severe problems has been poorly understood.
In Nature 4th March 2010 Zhang et al. identify one of the pathways that triggers trauma associated syndromes and links it to pathways implicated in sepsis-associated syndromes.
It was previously proposed that traumatic stress syndrome was due to bacterial escaping from the bowel and infecting the patient. Zhang et al suggest that mitochondria are the link. Mitochondria are believed to be organelles that originated from bacteria that parasitized eukaryotic cells and retain many similarities with bacteria. So during trauma these mitochondria pour out of the damaged tissues and cause a form of sepsis.
Calfee and Matthay 2010 Culprits with evolutionary ties Nature vol 464 pp 41-42
Zhang 2010 Circulating mitochondrial DAMPs cause inflammatory responses to injury Nature vol 464 pp 104-107

Mosquitos and human odours

The malaria mosquito, Anopheles gambiae, is involved in the deaths of about one million humans every year. The female mosquitoes feed on human blood and whilst sucking their victim's blood the mosquitoes unwittingly transmit the malaria causing parasite that threatens half of the world's population. The number of people world wide who get malaria each year is greater than the population of the United States.
Human derived odorants have a key role in the mosquito tracing their human food sources. Female mosquitoes find the odour of patients with malaria particularly attractive.
Some of the mosquito’s odorant receptors are tuned into human derived compounds eg indole , an important component of human sweat. The receptors respond to phenol, methylphenols and other aromatic compounds and 3–methylindole , an odorant that induces females of another mosquito species to lay eggs.
Leal WS , 2010, The treacherous scent of a human. Nature vol 464 2010
Carey et al 2010 Odorant reception in the malarial mosquito Anopheles gambiae , Nature vol 464 , 66-71