All Posts tagged tissue

Low vitamin D common in lung disease

Kinder and his colleagues assessed the prevalence of vitamin D deficiency in a cohort of patients with interstitial lung disease, who are often treated with corticosteroids. The detrimental effect of chronic use of corticosteroids on bone health has been well established, according to the researchers. Of the patients included in the study, 51 had interstitial lung disease and 67 had other forms of interstitial lung disease related to autoimmune connective tissue diseases.

A vitamin D insufficiency was defined as a serum level of less than 30 ng/mL. A level of less than 20 ng/mL was considered deficient. Both insufficient and deficient levels were prevalent in the study. In the overall sample, lower vitamin D levels were associated with reduced forced vital capacity (P=0.01). When the analysis was restricted to patients with connective tissue disease, both forced vital capacity and diffusing capacity of lung for carbon monoxide — a measure of the lung’s ability to transfer gases from the air to the blood — were significantly reduced (P<0.05 for both). After adjustment for several potential confounders — including age, corticosteroid use, race, and season, the presence of connective lung disease was a strong predictor of vitamin D insufficiency (OR 11.8, 95% CI 3.5 to 40.6).

According to the researchers, a pathogenic role of low vitamin D in the development of autoimmune diseases such as interstitial lung disease is plausible because of the immunoregulatory role of the biologically active form of vitamin D, 1,25-(OH)2D. “All cells of the adaptive immune system express vitamin D receptors and are sensitive to the action of 1,25-(OH)2D,” they wrote. “High levels of 1,25-(OH)2D are potent inhibitors of dendritic cell maturation with lower expression of major histocompatibility complex class II molecules, down-regulation of costimulatory molecules, and lower production of proinflammatory cytokines.” “A common theme in the immunomodulatory functions of vitamin D is that higher levels are immunosuppressive,” they continued, “which is consistent with a potential role for hypovitaminosis D in the pathogenesis of autoimmune disorders.”

In a statement, Len Horovitz, MD, a pulmonary specialist at Lenox Hill Hospital in New York City, commented that “vitamin D is known to promote wound healing, and to benefit the immune system. So it is not surprising to find that patients with immune lung disorders are vitamin D deficient.” He said that all of his patients are screened and treated for vitamin D deficiency with supplements. The study authors noted that further research is needed to determine whether supplementation is associated with improved outcomes. The study was limited, Kinder and his colleagues wrote, by its use of patients from a single center in Cincinnati.

In addition, the cross-sectional design of the study did not evaluate whether vitamin D supplementation is associated with any improved clinical outcomes. To examine that issue, the team called for prospective controlled interventional studies to determine whether vitamin D7 supplements can ameliorate symptoms and improve outcomes in connective tissue disease-related interstitial lung disease.

Source reference: Hagaman J, et al “Vitamin D deficiency and reduced lung function in connective tissue-associated interstitial lung diseases” Chest 2011; DOI: 10.1378/chest.10-0968.

More

Cause of Osteoporosis in Celiac patients

People with celiac disease may develop osteoporosis due to immune-system attacks on bone tissue (N Engl J Med. 2009; 361:1459-1465). Although osteoporosis is a known complication of celiac disease, scientists have always believed that it occurred because celiac patients cannot properly absorb calcium and vitamin D from their diet and were therefore unable to maintain healthy bone tissue.

At the heart of this development is the protein osteoprotegerin, which plays a crucial role in maintaining bone health by controlling the rate at which bone tissue is removed. Researchers from the United Kingdom's University of Edinburgh and University of Liverpool detected autoantibodies against osteoprotegerin in several patients with celiac disease.

“Such autoantibodies may be associated with the development of high-turnover osteoporosis, but whether autoantibodies against osteoprotegerin commonly contribute to the pathogenesis of osteoporosis in patients with celiac disease remains to be determined,” the investigators conclude.

More

High Levels of Fructose, Trans Fats Lead to Significant Liver Disease

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.

More

Fat clue to TB awakening

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.

More

Brown Rice and Cardiovascular Protection

Brown Rice and Angiotensin II

The subaleurone layer of Japanese rice, which is located between the white center of the grain and the brown fibrous outer layer, is rich in oligosaccharides and dietary fibers, making it particularly nutritious. However, when brown rice is polished to make white rice, the subaleurone layer is stripped away and the rice loses some of its nutrients. The subaleurone layer can be preserved in half-milled (Haigamai) rice or incompletely-milled (Kinmemai) rice. These types of rice are popular in Japan because many people there believe they are healthier than white rice.

The Temple team and their colleagues at the Wakayama Medical University Department of Pathology and the Nagaoka National College of Technology Department of Materials Engineering in Japan sought to delve into the mysteries of the subaleurone layer and perhaps make a case for leaving it intact when rice is processed. Because angiotensin II is a perpetrator in such lethal cardiovascular diseases, the team chose to focus on learning whether the subaleurone layer could somehow inhibit the wayward protein before it wreaks havoc.

First, the team removed the subaleurone tissue from Kinmemai rice. Then they separated the tissue's components by exposing the tissue to extractions of various chemicals such as ethanol, methanol and ethyl acetate. The team then observed how the tissue affected cultures of vascular smooth muscle cells. Vascular smooth muscle cells are an integral part of blood vessel walls and are direct victims of high blood pressure and atherosclerosis.

During their analysis, the team found that subaleurone components that were selected by an ethyl acetate extraction inhibited angiotensin II activity in the cultured vascular smooth muscle cells. This suggests that the subaleurone layer of rice offers protection against high blood pressure and atherosclerosis. It could also help explain why fewer people die of cardiovascular disease in Japan, where most people eat at least one rice-based dish per day, than in the U.S., where rice is not a primary component of daily nutrition.

“Our research suggests that there is a potential ingredient in rice that may be a good starting point for looking into preventive medicine for cardiovascular diseases,” said Dr. Eguchi. “We hope to present an additional health benefit of consuming half-milled or brown rice [as opposed to white rice] as part of a regular diet.”

More

Indian Spice May Delay Liver Damage

Curcumin, one of the principal components of the Indian spice turmeric, seems to delay the liver damage that eventually causes cirrhosis, suggests preliminary experimental research in the journal Gut. Curcumin, which gives turmeric its bright yellow pigment, has long been used in Indian Ayurvedic medicine to treat a wide range of gastrointestinal disorders.

Previous research has indicated that it has anti-inflammatory and antioxidant properties which may be helpful in combating disease. The research team wanted to find out if curcumin could delay the damage caused by progressive inflammatory conditions of the liver, including primary sclerosing cholangitis and primary biliary cirrhosis.

Both of these conditions, which can be sparked by genetic faults or autoimmune disease, cause the liver's plumbing system of bile ducts to become inflamed, scarred, and blocked. This leads to extensive tissue damage and irreversible and ultimately fatal liver cirrhosis.

The research team analysed tissue and blood samples from mice with chronic liver inflammation before and after adding curcumin to their diet for a period of four and a period of eight weeks.

The results were compared with the equivalent samples from mice with the same condition, but not fed curcumin.

The findings showed that the curcumin diet significantly reduced bile duct blockage and curbed liver cell (hepatocyte) damage and scarring (fibrosis) by interfering with several chemical signalling pathways involved in the inflammatory process.

These effects were clear at both four and eight weeks. No such effects were seen in mice fed a normal diet.

The authors point out that current treatment for inflammatory liver disease involves ursodeoxycholic acid, the long term effects of which remain unclear. The other alternative is a liver transplant.

Curcumin is a natural product, they say, which seems to target several different parts of the inflammatory process, and as such, may therefore offer a very promising treatment in the future.

 

Source: Anna Baghdasaryan, Thierry Claudel, Astrid Kosters, Judith Gumhold, Dagmar Silbert, Andrea Thüringer, Katharina Leski, Peter Fickert, Saul J Karpen, Michael Trauner. Curcumin improves sclerosing cholangitis in Mdr2-/- mice by inhibition of cholangiocyte inflammatory response and portal myofibroblast proliferation. Gut, 2010; 59: 521-530

More

Blackcurrants show anti-asthma potential

Study details

Led by Dr Roger Hurst, the New Zealand-based researchers examined the effects of the anthocyanidin-rich blackcurrant extract on cells from lung tissue. The researchers focussed on a compound called eotaxin-3 or CCL26, which is expressed in the lungs after stimulation of the cells by cytokine interleukin-4 (IL-4). According to their findings, epigallocatechin (EGC) worked in conjunction with other natural immune responses to suppress CCl26 expression, and therefore inflammation. Furthermore, these actions were distinct from the inflammation-reducing activity of anthocycanins, said the researchers.

“The bioavailability of plant-derived phytochemicals, although not the focus of this particular study, is an important consideration in the design of a functional food,” wrote Dr Hurst and his co-workers. “In particular, blackcurrant- derived proanthocyanidins mainly (480 per cent) consist of high molecular weight polymers, however, recent findings show that these large proanthocyanidins can be broken down by chemical, enzymatic and/or resident microflora in various regions of the digestive tract to release small oligomers and monomers that are easily absorbed, such as EGC and epicatechin. “Therefore, it is feasible that blackcurrant metabolites, such as EGC, may be able to modulate eotaxin expression in lung tissue,” they added.

Plant & Food Research's Dr Roger Hellens, Genomics Science Group Leader, will be presenting at the upcoming NutraIngredients Antioxidants 2010 Conference in Brussels on the subject of super Vegetables. 

Source: Molecular Nutrition and Food Research
“Blackcurrant proanthocyanidins augment IFN-gamma-induced suppression of IL-4 stimulated CCL26 secretion in alveolar epithelial cells”
Authors: S.M. Hurst, T.K. McGhie, J.M. Cooney, D.J. Jensen, E.M. Gould, K.A. Lyall, R.D. Hurst

More