Injection of human umbilical cord blood helps the aging brain

Injection of human umbilical cord blood helps the aging brain Monday, 10 March 2008 When human umbilical cord blood cells (UCBC) were injected into aged laboratory animals, researchers at the University of South Florida (USF) found improvements in the microenvironment of the hippocampus region of the animals’ brains and a subsequent rejuvenation of neural stem/progenitor cells. Published online at BMC Neuroscience, the research presented the possibility of a cell therapy aimed at rejuvenating the aged brain. “Brain cell neurogenesis decreases dramatically with increasing age, mostly because of a growing impoverishment in the brain’s microenvironment,” said co-author Alison Willing, PhD, of the USF Center of Excellence for Aging and Brain Repair. “The increase in neurogenesis we saw after injecting UCBCs seemed to be due to a decrease in inflammation.” According to lead author Carmelina Gemma, Ph.D., of the James A. Haley Veterans Administration Medical Center (VA) and USF, the decrease in neurogenesis that accompanies aging is a result of the decrease in proliferation of stem cells, not the loss of cells. “In the brain, there are two stem cell pools, one of which resides in the hippocampus,” explained graduate student and first author Adam Bachstetter. “As in other stem cell pools, the stem cells in the brain lose their capacity to generate new cells. A potent stressor of stem cell proliferation is inflammation.” Prior to this study, the research team led by Paula C. Bickford, Ph.D., of the VA and USF found that reducing neuroinflammation in aged rats by blocking the synthesis of the pro-inflammatory cytokine IL1B rescued some of the age-related decrease in neurogenesis and improved cognitive function. “We think that UCBCs may have a similar potential to reduce inflammation and to restore some of the lost capacity of stem/progenitor cells to proliferate and differentiate into neurons,” said Dr. Bickford. The study found that the number of proliferative cells increased within 24 hours following the UCBC injections into the aged laboratory rats and that the increased cell proliferation continued for at least 15 days following a single treatment. “We have shown that injections of UCBCs can reduce neuroinflammation,” concluded co-author Paul R. Sanberg, Ph.D. D.Sc. director of the Center of Excellence for Aging and Brain Repair. “Our results raise the possibility that a cell therapy could be an effective approach to improving the microenvironment of the aged brain and restoring some lost capacity.” ......... ZenMaster

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Cardiovascular benefits of omega-3 fatty acids

Cardiovascular benefits of omega-3 fatty acids Monday, 10 March 2008 Thousands of research studies have documented how the oils known as omega-3 fatty acids can benefit the cardiovascular system, particularly among people diagnosed with coronary artery disease. The incredible volume of research on this topic creates difficulty for many physicians and patients to stay current with findings and recommendations related to these oils. In the March issue of Mayo Clinic Proceedings, contributors briefly summarize current scientific data on omega-3 fatty acids and cardiovascular health, focusing on who benefits most from their protective effects, recommended guidelines for administration and dosing, and possible adverse effects associated with their use. Two omega-3 fatty acids that have been associated with cardiovascular benefit, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are found in fish oils. The best source for DHA and EPA are fatty coldwater fish such as herring, mackerel, salmon and tuna. Fish oil supplements or algae supplements also can provide omega-3 fatty acids. Author James O’Keefe, M.D., a cardiologist from the Mid America Heart Institute in Kansas City, Mo., cites the results of several large trials that demonstrated the positive benefits associated with omega-3 fatty acids, either from oily fish or fish oil capsules. “The most compelling evidence for the cardiovascular benefit provided by omega-3 fatty acids comes from three large controlled trials of 32,000 participants randomized to receive omega-3 fatty acid supplements containing DHA and EPA or to act as controls,” explains Dr. O’Keefe. “These trials showed reductions in cardiovascular events of 19 percent to 45 percent. Overall, these findings suggest that intake of omega-3 fatty acids, whether from dietary sources or fish oil supplements, should be increased, especially in those with or at risk for coronary artery disease.” How much fish oil should people attempt to incorporate into their diets? According to Dr. O’Keefe, people with known coronary artery disease should consume about 1 gram per day, while people without disease should consume at least 500 milligrams (mg) per day. “Patients with high triglyceride levels can benefit from treatment with 3 to 4 grams daily of DHA and EPA,” says Dr. O’Keefe. “Research shows that this dosage lowers triglyceride levels by 20 to 50 percent.” About two meals of oily fish can provide 400 to 500 mg of DHA and EPA, so patients who need to consume higher levels of these fatty-acids may choose to use fish oil supplements to reach these targets. Dr. O’Keefe also notes that research supports the effectiveness of combining the consumption of fish oil with the use of cholesterol-lowering medications called statins. Combination therapy with omega-3 fatty acids and a statin is a safe and effective way to improve lipid levels and cardiovascular health beyond the benefits provided by statin therapy alone. Blood DHA and EPA levels could one day be used to identify patients with deficient levels and to individualize therapeutic recommendations. Dr. O’Keefe found little evidence of serious adverse effects associated with fish oil consumption. “In prospective placebo-controlled trials, no adverse effects were observed to occur at a frequency of more than 5 percent, and no difference in frequency was noted between the placebo and omega-3 fatty acid groups,” he says. The most commonly observed side effects include nausea, upset stomach and a “fishy burp.” Taking the supplement at bedtime or with meals, keeping fish oil capsules in the freezer or using enteric-coated supplements may help reduce burping and upset stomach symptoms. ......... ZenMaster

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Genetic Research Unveils Common Origins for Distinct Clinical Diagnoses

Genetic Research Unveils Common Origins for Distinct Clinical Diagnoses Monday, 10 March 2008 Researchers at Johns Hopkins have discovered that two clinically different inherited syndromes are in fact variations of the same disorder. Reporting in the April issue of Nature Genetics, the team suggests that at least for this class of disorders, the total number and “strength” of genetic alterations an individual carries throughout the genome can generate a range of symptoms wide enough to appear like different conditions. “We’re finally beginning to blur the boundaries encompassing some of these diseases by showing that they share the same molecular underpinnings,” says Nicholas Katsanis, Ph.D., an associate professor of ophthalmology at the McKusick-Nathans Institute of Genetic Medicine at Hopkins. “This is important progress for several reasons. First, knowing what’s going on molecularly and being able to integrate rarer conditions under common mechanisms allows us to potentially help more people at once. Second, clinicians can finally begin to offer more accurate diagnoses based on what really matters: the state of affairs at the cellular/biochemical level. In time, this will empower genetic counselling and much improved patient management.” Katsanis’s team studies Bardet-Biedl syndrome (BBS), a rare so-called ciliopathy that is characterized by a combination of vision loss, obesity, diabetes, extra digits and mental defects and caused by faulty cilia, tiny hair-like projections found on almost every cell of the body. Recently they started looking at another disease, Meckel-Gruber syndrome (MKS), which also shows cilia dysfunction but is clinically distinct from BBS and generally associated with prenatal or newborn death. “While these two groups of patients exhibit such different clinical outcomes, the genes associated with both syndromes all seemed to be pointing at the same culprit: cilia,” says Katsanis. “So we wondered if BBS and MKS might actually represent different flavours of the same disease.” The researchers sequenced the MKS genes from 200 BBS patients and found six families that, in addition to carrying BBS genetic mutations, also carried mutations in MKS genes. To figure out what, if any, effect these MKS mutations have on BBS, the team used a system they previously developed in zebrafish. Knocking out BBS genes in zebrafish generates short fish with even shorter tails, among other malformations. Injecting normal BBS genes into these fish rescues them, resulting in normal looking fish. The researchers reasoned that if MKS and BBS are indeed the same condition, then fish with the MKS genes knocked out should mimic the BBS knockout fish. They did. The team then went on to test mutant versions of MKS genes in BBS fish and found that three genes originally attributed to MKS do indeed cause BBS or render the BBS defects more pronounced, increasing the number of BBS genes to 14 in total. “From a clinical perspective, these two syndromes look nothing alike, but molecularly, the genes involved clearly participate in the same fundamental processes,” says Katsanis. “This means that Meckel-Gruber and Bardet-Biedel actually represent a continuum of one disease. This never would have been discovered in the clinic-only molecular analysis can reveal these things.” But what does this mean for clinicians and the diagnosis and treatment of these syndromes? Katsanis hopes that the growing body of molecular data will help move medicine away from symptom-defined syndromes, which can leave clinicians struggling with ambiguous diagnoses, to approaching disorders from a molecular standpoint. “We now have the possibility of merging several rare disorders,” he says. “And their gross sum now turns out to be fairly common; hopefully this will now put them on the radar for drug development and other therapies.” Authors on the paper are Carmen Leitch, Norann Zaghloul, Erica Davis and Katsanis, all of Hopkins; Corrine Stoetzel and Helene Dollfus of Université Louis Pasteur, Strasbourg, France; Anna Diaz-Font, Suzanne Rix and Philip Beales of University College London, UK; Majid Al-Fadhel and Wafaa Eyaid of King Fahad Hospital, Riyadh, Saudi Arabia; Richard Alan Lewis of Baylor College of Medicine, Houston, Texas.; Eyal Banin of Hadassah-Hebrew University Hospital, Jerusalem, Israel; and Jose Badano, previously of Hopkins and now at the Institut Pasteur de Montevideo, Uruguay. ......... ZenMaster

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