The study was conducted in mice, some of which were fed a normal diet of rodent chow and some a 16-week diet of fructose and sucrose-enriched drinking water and trans-fat solids. Their liver tissue was then analyzed for fat content, scar tissue formation (fibrosis), and the biological mechanism of damage. This was done by measuring reactive oxygen stress, inflammatory cell type and plasma levels of oxidative stress markers, which are known to play important roles in the development of obesity-related liver disease and its progression to end-stage liver disease.
The investigators found that mice fed the normal calorie chow diet remained lean and did not have fatty liver disease. Mice fed high calorie diets (trans-fat alone or a combination of trans-fat and high fructose) became obese and had fatty liver disease.
“Interestingly, it was only the group fed the combination of trans-fat and high fructose which developed the advanced fatty liver disease which had fibrosis,” says Dr. Kohli. “This same group also had increased oxidative stress in the liver, increased inflammatory cells, and increased levels of plasma oxidative stress markers.”
Dr. Kohli hopes to further investigate the mechanism of liver injury caused by high fructose and sucrose enriched drinking water and study a therapeutic intervention of antioxidant supplementation. Antioxidants are natural defenses against oxidative stress and may reverse or protect against advanced liver damage, according to Dr. Kohli.
The investigators also would like to use this model to better understand human fatty liver disease and perform clinical trials using novel therapeutic and monitoring tools.
“Our data suggest that supplementation with pharmaceuticals agents should be tested on our new model to establish whether one is able to reverse or protect against progressive liver scarring and damage,” says Dr. Kohli.
The study was supported by grants from the National Institutes of Health and the Children's Digestive Health and Nutrition Foundation.
The scientists looked for three nucleotides in breast milk (adenosine, guanosine and uridine), which excite or relax the central nervous system, promoting restfulness and sleep, and observed how these varied throughout a 24-hour period.
“You wouldn't give anyone a coffee at night, and the same is true of milk – it has day-specific ingredients that stimulate activity in the infant, and other night-time components that help the baby to rest”, explains Sánchez.
The benefits of breast milk
The World Health Organisation (WHO) says breast milk is the best food for the newborn, and should not be substituted, since it meets all the child's physiological requirements during the first six months of life. It not only protects the baby against many illnesses such as colds, diarrhoea and sudden infant death syndrome, but can also prevent future diseases such as asthma, allergies and obesity, and promotes intellectual development.
The benefits of breastfeeding also extend to the mother. Women who breastfeed lose the weight gained during pregnancy more quickly, and it also helps prevent against anaemia, high blood pressure and postnatal depression. Osteoporosis and breast cancer are also less common among women who breastfeed their children.
The factors instrumental in triggering latent tuberculosis (TB) infection to progress into active disease have long remained elusive to researchers. New insight into the mystery is provided by Professor David Russell, speaking at the Society for General Microbiology's spring meeting in Edinburgh today. His work could help develop innovative strategies for treating the disease.
Professor Russell and his group at Cornell University in New York, USA, have demonstrated that TB-causing bacteria are able to hijack fat metabolism in the host to drive the progression of the disease. The team's research shows that Mycobacterium tuberculosis (Mtb) is able to stimulate macrophages – the immune cells the bacterium infects – to accumulate fat droplets, turning them into “foamy” cells. This cellular transformation can trigger a reawakening of the TB infection from its latent state.
Following initial infection by Mtb, the infected immune cells in the body can clump together in the lungs in a cellular mass that is surrounded by a fibrous cuff. This containing structure, called a
tubercle, physically protects the bacteria from being destroyed by the immune system. This allows them to persist inside the host for years during a latent period in which the host shows no symptoms. The respiratory infection is reactivated only in a small percentage of individuals (often those who are immunosuppressed) in whom it progressively destroys lung tissue. Very little is known about the exact causes of reactivation and the relative roles of the host and the pathogen.
Professor Russell's group discovered that inside the tubercle, surface molecules of Mtb prompted host macrophage cells to take up vast quantities of cholesterol-type lipids from the surrounding blood
vessels. “We think that the lipids in the newly-formed foamy cell are then expelled into the cellular environment, which contributes to the collapse of the tubercle,” he said.
Once freed from their containing structure, the infectious bacteria are able to leak out into the airways where they can progressively destroy lung tissue. “If our model is correct, it has huge implications for
vaccines and chemotherapy programmes. A more detailed knowledge of the bacterium's life cycle and its host interactions will allow us to spot new targets for drugs – opening up new possibilities for treatment,” said Professor Russell.
Professor Latz has recently been recruited by the University of Bonn after working ten years in basic research in the United States. Here, he heads the new Institute for Innate Immunity (Institut für Angeborene Immunität), which has a research focus on the immune mechanisms that cause inflammatory reactions. The innate immune system forms part of the body's own defence mechanism and is able to respond rapidly and directly to a number of alarm signals that appear in the tissue environment. These triggers not only include viruses, bacteria and fungi but also certain crystals and other substances that occur during infections of in stress situations. The strength of the innate immune system is that it can respond very quickly to situations that are of danger to the host. The problem, however, is that it can also overshoot the mark. This type of overreaction is also seen in the case of pneumoconioses such as the black lung, a disease which frequently affects miners. In these lung diseases, a chronic inflammatory reaction is triggered by inhaled crystals made of silicates or asbestos. The molecular mechanisms of crystal recognition are similar to those triggered by cholesterol crystals in blood vessels.
Starting point for developing new drugs
There is still a piece of the jigsaw puzzle missing which researchers need to complete the overall picture. “We don't know precisely how the cholesterol crystals activate the inflammasome”, says Professor Latz. The findings of this study however, offer some starting points for developing new drug therapies. At present, statins are widely used in therapy. Statins reduce the synthesis of endogenous – i.e. the body's self-produced cholesterol and diminish the risk of heart attack or stroke, but they cannot inhibit the absorption of cholesterol from ones diet.
Estimates by the World Health Organization put the number of people now dying from cardiovascular diseases at almost 17 million per year. This means that one in four deaths worldwide is caused by atherosclerosis.
For pulmonary ailments, certain mediaeval physicians had a useful medical textbook on hand offering detailed information remarkably similar to those a modern doctor might use today. One of the fathers of medicine, the great Persian scholar Avicenna left a wealth of information in his many works. Iranian academics dust off one of these in an article published today in the SAGE journal Therapeutic Advances in Respiratory Disease, sharing in English details of Avicenna's work that still fascinate both physicians and historians of medicine alike.
Seyyed Mehdi Hashemi and Mohsen Raza dug deep into Avicenna's original ancient text, housed in the Central Library of the Tehran University of Medical Sciences in Iran, where they both work. In particular, they aimed to highlight Avicenna's work on respiratory diseases, which may be informative or interesting to physicians and pulmonologists today.
Avicenna discusses respiratory diseases in volume three of the Canon of Medicine, covering the functional anatomy and physiopathology of the pulmonary diseases that were known in his time in detail. His descriptions of the signs and symptoms of various respiratory diseases and conditions are remarkably similar to those found in modern pulmonary medicine. The topic is covered under five chapters: breathing, voice, cough and haemoptysis, internal wounds and inflammations and principles of treatments.
The authors also highlight both herbal and non-herbal treatments Avicenna recommends for respiratory diseases, and their signs and symptoms from the second volume of the Canon of Medicine. Avicenna suggested 21 herbs to treat respiratory disorders, and today we know that several of these herbs contain bioactive compounds with analgesic, antispasmodic, bronchodilatory or antimicrobial activities. For instance, Avicenna would have prescribed opium at that time for cough and haemoptysis, a practice which today has an established therapeutic basis.
“In the time of Avicenna, the presentation of respiratory diseases, their treatment and their prognosis was much different than in modern times,” says Hashemi. Mediaeval physicians had a greater reliance on history, physical examination (which was mostly based on visual observation), individual variation, environmental factors, diet, and so on, for diagnosis and treatment.
Even so, several of Avicenna's observations related to signs and symptoms, aggravating and relieving factors and the treatment of pulmonary disorders are still valid and can be explained by modern science. For example, one of the important symptoms in the diagnosis of asthma that Avicenna discusses is dyspnea during sleep that leads to awakening. Avicenna also observed plaster-like material in tuberculosis patients' sputum, which is now known as lithoptysis (stone spitting), where a patient coughs up calcified material due to perforated bronchial lymph node.
Despite many limitations and the lack of modern instruments in his day, Avicenna adopted a scientific approach to the diagnosis and treatment, not only of respiratory disorders, but also more generally to illnesses he treated and mentioned throughout the Canon of Medicine.
To examine this thesis, Froy and his colleagues, Ph.D. student Maayan Barnea and Zecharia Madar, the Karl Bach Professor of Agricultural Biochemistry, tested whether the clock controls the adiponectin signaling pathway in the liver and, if so, how fasting and a high-fat diet affect this control. Adiponectin is secreted from differentiated adipocytes (fat tissue) and is involved in glucose and lipid metabolism. It increases fatty acid oxidation and promotes insulin sensitivity, two highly important factors in maintaining proper metabolism.
The researchers fed mice either a low-fat or a high-fat diet, followed by a fasting day, then measured components of the adiponectin metabolic pathway at various levels of activity. In mice on the low-fat diet, the adiponectin signaling pathway components exhibited normal circadian rhythmicity. Fasting resulted in a phase advance. The high-fat diet resulted in a phase delay. Fasting raised and the high-fat diet reduced adenosine monophosphate-activated protein kinase (AMPK) levels. This protein is involved in fatty acid metabolism, which could be disrupted by the lower levels.
In an article soon to be published by the journal Endocrinology, the researchers suggest that this high-fat diet could contribute to obesity, not only through its high caloric content, but also by disrupting the phases and daily rhythm of clock genes. They contend also that high fat-induced changes in the clock and the adiponectin signaling pathway may help explain the disruption of other clock-controlled systems associated with metabolic disorders, such as blood pressure levels and the sleep/wake cycle.
New research from the University of Ulster today offered hope to millions of lupus sufferers worldwide. Dr Emeir Duffy, from the School of Biomedical Sciences, and Dr Gary Meenagh, from Musgrave Park Hospital, Belfast, have discovered new evidence to suggest that fish oil can greatly reduce the symptoms of the disease.
Systemic Lupus Erythematosus (SLE) or Lupus is a disorder of the Immune System, where the body harms its own healthy cells and tissues. The body tissues become damaged causing painful or swollen joints, unexplained fever, skin rashes, kidney problems, complications to the cardiovascular system and extreme fatigue. There are approximately 500 diagnosed cases of SLE in Northern Ireland and it is most common in women of child-bearing age.
At present there is no cure but a key to managing lupus is to understand the disease and its impact. Steroids are the main drug used in the treatment of lupus and they should be administered for the shortest period possible to reduce side-effects. But recently researchers have been looking specifically at its management through diet.
Fish oils contain long-chained polyunsaturated fatty acids which are essential for normal growth and development but also have anti-inflammatory and anti-autoimmune properties. Dr Duffy said: “We have been investigating how fish oil can improve the quality of life for lupus sufferers. “In lupus, the body's immune system does not work as it should. Antibodies, which help fight viruses, bacteria and other foreign substances, are not produced effectively. The immune system actually produces antibodies against the body's own healthy cells and tissues. These auto-antibodies contribute to inflammation and other symptoms of the disease.
“Participants in the study who were taking fish oil supplements, three times per day for twenty-four weeks, saw a reduction in disease activity, an improvement in quality of life and reported an overall feeling of improved health by the end of the study compared to those taking a placebo supplement. Participants taking the fish oil also showed a reduction in fatigue severity, the most debilitating symptom for lupus sufferers. “From our study and from other work, there is evidence that increasing dietary intake of the polyunsaturated fats found in fatty fish can have beneficial effects for lupus sufferers. Good examples of fatty fish include mackerel, lake trout, herring, sardines, tuna and salmon”.
In the survey, commissioned by Act Against Allergy, further impact on family life was revealed. As a direct result of having a child with CMA, half (49%) the respondents have missed work, over a third (38%) have argued with their partner and 39% said the lives of other children in the family have also been disrupted.1
These findings were no surprise to Natalie Hammond, from Hertfordshire, UK, whose son Joe was diagnosed with CMA when he was six months old. Joe was initially misdiagnosed and even underwent surgery for a twisted bowel before doctors finally discovered that CMA was the cause of his illness. Mrs. Hammond said: “It was heartbreaking and frightening seeing Joe so sick – he would vomit and had blood in his stools. We felt utterly powerless, and couldn't believe a simple food like milk could do this. It took a long time to get over this terrifying and stressful experience.”
Cows' milk is one of the European Union's 'big eight' allergy-inducing foods alongside gluten, eggs, fish, peanuts, soya, treenuts and shellfish. More serious than lactose intolerance, a true milk allergy presents in one or more of three organ systems:
– Gastrointestinal (vomiting, diarrhoea, abdominal cramps, bloating) – affecting 50-60% of those with CMA
– Skin (rashes, including eczema and atopic dermatitis) – 50-70%
– Respiratory (wheeze, cough, runny nose) – 20-30%3
For further information on cows' milk allergy, see: www.actagainstallergy.com
The researchers also looked at bone density and structure in the lower leg in around 360 19-year-old men who had previously done sports but had now stopped training. They found that men who had stopped training more than six years ago still had larger and thicker bones in the lower leg than those who had never done sports.
“This result is particularly important, because we know that a bone with a large circumference is more durable and resistant to fractures than a narrower bone,” says Nilsson.
The researchers also studied bone density throughout the body in around 500 randomly selected 75-year-old men. Those who had done competitive sports three or more times a week at some point between the ages of 10 and 30 had higher bone density in several parts of the body than those who had not.
The researchers have therefore established that there is a positive link between exercise while young and bone density and size. The connection is even stronger if account is taken of the type of sports done.
“The bones respond best when you're young, and if you train and load them with your own bodyweight during these years, it has a stimulating effect on their development,” says Nilsson. “This may be important for bone strength much later in life too, so reducing the risk of brittle bones.”
Led by researchers at Copenhagen University in Denmark, Robbins and an international team of colleagues analyzed the results of seven large clinical trials from around the world to assess the effectiveness of vitamin D alone or with calcium in reducing fractures among people averaging 70 years or older. The researchers could not identify any significant effects for people who only take vitamin D supplements.
Among the clinical trial results analyzed was Robbins' WHI research, which was part of a 15-year, national program to address the most common causes of death, disability and poor quality of life in postmenopausal women such as cardiovascular disease, cancer and osteoporosis. Those trials were primarily designed to study the effect of calcium and vitamin D supplementation in preventing hip fractures, with a secondary objective of testing the supplements on spine and other types of fractures, as well as on colorectal cancer. The results were published in the Feb. 16, 2006 edition of the New England Journal of Medicine.
Fractures are a major cause of disability, loss of independence and death for older people. The injuries are often the result of osteoporosis, or porous bone, a disease characterized by low bone mass and bone fragility. The National Osteoporosis Foundation estimates that about 10 million Americans have osteoporosis; 80 percent of them are women. Four of 10 women over age 50 will experience a fracture of the hip, spine or wrist in their lifetime, and osteoporosis-related fractures were responsible for an estimated $19 billion in health-related costs in 2005.
“This study supports a growing consensus that combined calcium and vitamin D is more effective than vitamin D alone in reducing a variety of fractures,” said Robbins. “Interestingly, this combination of supplements benefits both women and men of all ages, which is not something we fully expected to find. We now need to investigate the best dosage, duration and optimal way for people to take it.”