breast feeding

Hoddinott et al have written a very timely clinical review of breast feeding in the BMJ of 19th April 2008.
Breast feeding is crucial to infant health in developing countries, but there are possible longer term benefits to act against subsequent obesity, high blood pressure, cholesterol, and cancer.
The World Health Organization (WHO) recommends exclusive breast feeding, that is breast milk only , with no water, other fluids, or solids for six months, with supplemental breast feeding continuing for two years and beyond.
In the UK and the United States, breast feeding rates have been low for decades and can seem remarkably resistant to change.
Formula milk is just a food, whereas breast milk is a complex living nutritional fluid that contains anti-bodies, enzymes, and hormones, all of which have health benefits. In addition, some methods of delivering formula milk expose the baby to serious risks of infection. Early intake of colustrum, which is rich in antibodies, is especially important in developing countries, and the small volume of colostrum helps to prevent renal overload when the newborn baby is adjusting its fluid balance
In countries with poor services , contaminated drinking water , low immunisation rates and reduced immunity babies readily die. And each baby is born from a pregnancy where the mother is at risk. Exclusive breast feeding could prevent 1.3 million deaths in children under 5 years.
Good education and training for new mothers would make such a difference to the breast feeding rates
Breast fed babies may not grow at the same rate as bottle fed babies so new growth charts may need to be constructed to avoid unfavourable comparisons.
Hoddinott et al 2008 Breast feeding BMJ vol 336, 881-7

2015 Countdown for health

The Lancet for April 23 2008 is largely devoted to the Countdown programme for 2015. This initiative is so important for the poor countries of the world.
Of enormous importance for our world and the future of the populations.
The features of the Countdown Initiatives are
Country Focus Individual country profiles of coverage with selected information about the demographic and epidemiological contexts and key determinants of coverage.
68 priority countries 68 countries with the highest burden of maternal and child mortality, which represent more than 97% of all such deaths
Coverage of interventions within the continuum of care.
Tracking coverage of interventions with evidence of effects for maternal, newborn, and child survival, which tan be delivered within the continuum of care, the core of a functioning health system
Continuity Countdown will continue to report on progress until 2015, the target date for the Millennium Development Goals
Independence yet wide ownership
An effort, involving UN agencies and Civil society, individual researchers, and development worked from country, regional, and international levels
Action-oriented Countdown amalgamates the information needed to assess progress and spur country level action to accelerate progress towards reduction of maternal, newborn, and child mortality and improved nutrition

agricultural nitrate metabolism

Modern farming industry and other industries are causing a large amount of nitrogen to enter the soil at double the natural rate.
The nitrogen is in the form of nitrates and much elutes into streams, rivers and lakes. There is increased plant and bacterial growth in the water, a process known as eutrophication.
However some nitrate is retained by biological processes by plants and bacteria. Most importantly there are bacteria which convert the nitrate to molecular nitrogen and nitrous oxide. These bacteria persist in the sediment of streams and banks. However at higher concentrations of nitrate the efficiency of this process declines.
Seitzinger Out of reach Nature vol 452, pp162-3

ageing update

Ageing
It is painful to read Nutrition papers proposing that some element of the diet is affecting expectation of life and that in the olden golden days life expectation was better. This is palpably not the truth.
In developed countries the expectation of life has increased over the last 200 years from the late 40s to late 80s.
The benefits of sanitation, nutrition, better housing , and education have been central to this progress . More recently the benefits of improved medical care including vaccination and antibiotics have been very important.
Much of the improvement is due to most people surviving the former vicissitudes of diseases in youth and middle age.
Now the elderly live longer.
An extensively studied model of cellular ageing is the cultured human diploid fibroblast, which divides only a finite number of times before entering a state of ‘replicative senescence’ (this number is known as the Hayflick limit). Although senescence is commonly attributed to simple telomere erosion, there is remarkable cell-to-cell heterogeneity in division potential.
There is evidence that the rate of telomere shortening is strongly affected by oxidative stress, and that an important source of damage-inducing ‘free radicals’(reactive oxygen species) is the intracellular population of mitochondria, particularly those that are themselves damaged by random mutation. As a result, a mathematical model was developed that showed how the heterogeneity of cell senescence can be explained by the synergy of multiple mechanisms (oxidative damage, telomere shortening and the stochastic nature of mutation to mitochondrial and nuclear DNA). These modelling predictions prompted the experimental study of a role for mitochondrial dysfunction in senescence”,
Damage which may contribute to ageing
DNA damage (genome instability)
Somatic mutations (copying errors, imperfect repair)
Telomere shortening
Chromosome rearrangements
Mitochondrial-DNA mutations
Gene disruption by viruses, transposons etc
Aberrant epigenetic modifications RN A damage
Transcription errors
Aberrant splicing
Protein damage
Misfolding
Synthesis errors
Aberrant post-translational modifications
Aberrant aggregation
Impaired protein turnover (catabolism)
Membrane damage
Oxidation

Kirkwood 2008 a systematic look at an old problem Nature vol 451 pp 644-647

More water thoughts

The world is facing a real crisis in obtaining fresh water. This topic, central to any Population Nutrition economy has been discussed at length in a recent edition of Nature
1 billion people lack access to fresh drinkable water.
2 billion lack proper sanitation.
Whilst climate change is an important factor other factors are contributing to the problem. Growing populations and increasing energy requirements. India and China are prospering and consuming more meat. It takes 15,500 litres of water to produce 1 kilogram of beef. Which is 10 times the amount of water to produce 1 kg of wheat.
Cooling electricity plants requires fresh water, the United States uses more than 500 billion litres of fresh water a day to cool its power stations. Australia is struggling to obtain sufficient water to grow wheat.
Energy usage is increasing and the use of water will double.
To produce sufficient food we will need 12,000 cubic km of water , equal to the
Many of the world’s rivers are drying. volume of Lake Superior every year.
There is a need to use what is called blue water efficiently , rivers, lakes, reservoirs and underground aqueducts but also green water that is rain water.
Green water conservation means changes in agricultural techniques to ensure that rain is effectively used. Which is not universally the case currently
Desalination is an attractive option but is very energy costly. Polyamide membranes and reverse osmosis plants are more efficient than thermal distillation plants. At the present time 40 million cubic metres of water is produced a day world wide. The average cost is 3.5 times the cost of pumping from aquifer, though this varies with the locality. . Fouling of the filters is a real problem and costly.

Editorial Nature 2008, a fresh approach to water Nature vol 452 pp 254
Schiermeier 208 Purification with a pinch of salt Nature vol 452, pp 260-61
Water under pressure a News Feature 2008 Nature vol452. pp 269-316

Warburg effect explained

Otto Warburg demonstrated the difference between metabolism in cancer ceils and that in normal adult tissue. Cancer cells take up glucose at higher rates than normal tissue but use a smaller fraction of this glucose for oxidative phosphorylation. This effect is known as aerobic glycolysis or the Warburg effect Lewis Cantley and colleagues now report that the human M2 (fetal) isoform of pyruvate kinase (PKM2), an enzyme that is involved in glycolysis, is a phosphotyrosine-binding protein and promotes the Warburg effect.
Phosphotyrosine-peptide binding is specific to the M2 isoform. PKM2 contains a 56-amino-acid stretch, which forms an allsteric pocket unique to PKM2 that allows binding of its activator, fructose-1,6-bisphosphate (FBP). Binding of phosphotyrosine peptides toPKM2 results in release of the allosteric activator FBP and subsequent inhibition of enzymatic activity.
Tyrosine phosphorylation can regulate the activity of PKM2 in cells,. Of the the different pyruvate kinase isoforms, this effect is specific to the M2 isoform and requires the phosphotyrosine-peptide binding capability.
Cancer cell lines exclusively express PKM2, and knockdown of PKM2 expression in cancer cells results in reduced glycolysis and decreased cell proliferation. Further analysis of M2KE-mutant cells revealed reduced lactate production and increased oxygen consumption compared with wild-type cells. This finding indicates that tyrosine kinase regulation of PKM2 activity is involved in mediating the Warburg effect in tumour cells.
But how do tumour cells achieve this altered metabolic phenotype? The authors reasoned that tumour tissue switches pyruvvate kinase expression from an adult isoform to the embryonic M2 isoform.
In a breast cancer tumour model PKMi is the primary- isoform before tumour development, whereas PKM2 is the primary isoform in four independent tumours.. In vivo, PKM2 expression was found to provide a selective growth advantage for tumour.
What a wonderful piece of science.
The specialised metabolism of tumour cells is critical for tumorogenesis.
Kritikou 2008, Metabolism Warburg revisited Nature Reviews cancer vol 8 p 247A

experiencing pleasure

It would appear that pleasure can be mapped.
According to Plassmann el al., “...a basic assumption in economics is that experienced pleasantness from consuming a good depends only on its intrinsic properties and on the state of the individual” .
By contrast, it is known by so-called marketers that experienced pleasantness can be influenced by “...changing properties of Commodities, such as prices, that are unrelated to their intrinsic qualities or to the consumer’s state.”
To further elucidate these discrepancies, Plassmann and colleagues proceeded to investigate the neural associations of experienced pleasantness, by assessing both the subjectively reported perceived pleasure and the modulated blood-oxygen-level-dependent signal in the medial orbitofrontal cortex of the brain, an area of the brain in which activity is associated with the perception of experienced pleasantness.
Subjects randomly tasted three different wines in a series of six tastings, during which the price of each wine was varied. Not only did the price of the wine influence the subjectively reported experienced pleasantness, but also the activity in several areas of the brain associated with behavioral ratings for taste, odors and music. There were no changes in activity in the areas associated with primary taste
. These finding support the concept that experienced pleasantness is computed by the brain in a hierarchical manner that incorporates both actual sensory properties as well as expectations.
Stephen B Hanauer 2008 Experienced pleasantness. Nature Gastroenterology and hepatology vol 5,pp 119

A dog's life expectation and diet.

In a fascinating study Lawler and his colleagues review decade two of the lifetime diet restriction study of the dog. Labrador retrievers (n 48) were paired at age 6 weeks by sex and weight within each of seven litters, and assigned randomly within the pair to control-feeding (CF) or 25 % diet restriction (DR). Feeding began at age 8 weeks. The same diet was led to all dogs; only the quantity differed.
Major lifetime observations included I 8 years longer median lifespan among diet-restricted dogs, with delayed onset of late life diseases, especially osteoarthritis.
Long-term DR did not negatively affect skeletal maturation, structure or metabolism.
Among all dogs, high static fat mass and declining lean body mass predicted death, most strongly at 1 year prior. Fat mass above 25 % was associated with increasing insulin resistance, which independently predicted lifespan and chronic diseases. Metabolizable energy requirement/lean body mass most accurately explained energy metabolism due to diet restriction; diet-restricted dogs required 17 % less energy to maintain each lean kilogram.
It is hard with a domestic dog no to pamper , but farm dogs probably eat less and exercise more and live longer. There may be parallels for humans.
Dennis F. Lawler et al 2008, Diet restriction and ageing in the dog: major observations over two decades, Brit J Nutrition vol 99 pp793-805
Diet restriction: Dog: Ageing: Longevity

genetic variation and lung cancer

Variation in the human genome and the consequences for health are giving exciting result, largely through genome-wide association studies (GWAS). Such studies need to be large and repeatable.. Since early 2007, variations at nearly 100 regions of the genome have been associated with an increased risk for diseases with a complex genetic background, such as diabetes, inflammatory bowel disease, cancer (most notably breast, colorectal and prostate) and heart disease.
Lung cancer is associated with smoking and hence has a considerable environmental factor in its aetiology. Not everyone who smokes heavily gets lung cancer Three recent studies identify variation in the same region of the long arm of chromosome 15 (15q24/15q25.1) as having a key role in the aetiology of lung cancer. Among the genes in this region are those that encode subunits of nicotinic acetylcholine receptors, which have an affinity for nicotine. The genetic variation are as single nucleotide polymorphisms (SNPs, with DNA sequence variations that arise from the substitution of one nucleotide base for another, and contribute approximately 90% of common variation in the human genome.
The three studies are all large and appropriately replicated, but they differ on whether the connection is direct or mediated via smoking behaviour — that is, characteristics such as the duration and 'dose' of lifetime smoking, and/or the propensity for nicotine addiction. Previous studies 'had identified the genes encoding subunits of nicotinic acetylcholine receptors as strongly associated with smoking behaviour. The association between smoking and lung cancer is very strong , and any gene variant that is modestly linked with smoking behaviour will seem to be associated with lung cancer unless the matching of cancer cases and controls by smoking behaviour is close to perfect.
The reports vary in their interpretation of the results. One says that the association between the SNP variations is with the number of cigarettes smoked per day and a nicotine dependence scale. They argue that the link with cancer is though nicotine dependence.
The other two groups interpret their results as an association with lung cancer and not smoking.
These result s indicate the complexity of the subject. It is also indicates that it is easy to jump to conclusions about the aetiology of disease and environmental influences.
Nutrition studies are not sufficiently careful in this area.
Chanock and Hunter 2008 When the smokes clears Nature vol 452, pp 537-538

Should we be eating fish

Khursheed N Jeejeebhoy has reviewed the benefits and risks of a fish diet and should we be eating more or less?
Omega-3 fatty acids, eg eicosapentaenoic and docosahexaenoic acids which are plentiful in fish oils may preventing coronary artery disease. Eating three fish meals a week reduces risk in contrast to ineffectual high-fibre and low-fat diets did not have a significant reduction in mortality. Many trials have since shown the benefit of taking fish oil. This cardioprotective benefits is found with both wild and farmed fish.
. The consumption of as little as one fish meal weekly has been shown to be beneficial, with dose-dependent greater benefits up to about five fish meals per week.
The caveat to this simple diet change has been the suggestion of a risk of mercury poisoning of the central nervous system.
Mercury enters the atmesphere by combustion of waste and coal. The element then enters the oceans from the atmosphere where it is converted to methyl mercury by microorganisms and then taken up by marine life and concentrated in fish. As methyl mercury is not fat soluble, unlike dioxins, it does not accumulate in the fatty tissues. Methyl mercury is strongly neurotoxic.
The concentration of methyl mercury in fish b increased by fish eating other fish for food. Fish that are not predatory, such as sardines, salmon and shrimp, therefore have very low levels of methyl mercury. By contrast, predatory fish such as shark, tuna, swordfish and orange roughy have higher levels of methyl mercury. Farmed fish have the lowest levels of methyl mercury. Whilst methyl mercury per se is very neurotoxic, in fish methyl mercury is bound to cysteine, and this compound has a tenth of the toxicity of pure methyl mercury.
Whale meat is enriched with methyl mercury and is more neurotoxic..^
The conclusion is that in the amounts eaten in North America fish is very safe and the benefits large. That in pregnancy care should be taken with the eating o shark, tuna and sword fish.
Jeejeebhoy 2008, Benefits and risks of a fish diet-should we be eating more or less. Nature Gastroenterology and hepatology vol 5, pp 178-179