What's Hot

What's Hot

January 2001

What's Hot Archive

January 31, 2000

Iron likely plays causative role in Parkinson's and Multiple System Atrophy

In research conducted by the National Institute of Child Health and Human Development (NICHD) to be published in the February 2000 issue of the journal Nature Genetics, the discovery was made that genetically engineered mice lacking the gene for iron regulatory protein 2 develop iron deposits in the brain and Parkinson's disease symptoms. Iron regulatory protein 2, or IRP2, regulates how much iron is in the cell by governing the actions of other proteins involved in iron metabolism, protecting the cell from iron overload. IRP2 is found most abundantly in the brain. Mice engineered to lack this protein developed normally, but later developed difficulty with walking and movement similar to that found in humans with Parkinson's disease and the disease Multiple System Atrophy, also known as Parkinson's Plus. The mice were found to have iron deposits in the cerebellum and basal ganglia of their brains, areas of the brain involved in movement and the same areas as those in the human brain affected by multiple system atrophy. Excess iron in the brain has been observed with Parkinson's disease as well, but the areas of the brain affected are different, which leads researchers to believe that although IRP2 is not involved in Parkinson's, other genes involved in iron metabolism could be implicated in the disease.

NICHD Director Duane Alexander MD, stated, "Researchers have long debated whether the characteristic iron deposits of these diseases are the cause or the result of the disease process. This is a strong clue that iron may play a causative role in Parkinson's and similar disorders."

Senior Investigator Tracy A Rouault, MD is seeking Multiple System Atrophy patients for participation in a study to test for IRP2 defects. Those with Parkinson's symptoms are also encouraged to participate because Parkinson's disease can be mistaken for Multiple System Atrophy. Prospective participants' physicians may contact Dr. Rouault at Rouault@mail.nih.gov.

—D Dye


January 26, 2001

Vitamin E improves immune function, reduces oxidative stress in humans

December 2000's Journal of Nutrition was the site of a report detailing the effects of vitamin E on oxidation and immune function in an Asian population. Although studied in animals, elderly humans and in vitro, vitamin E's effect on immune cell subsets has not been well characterized in a young, healthy adult population. Immune system cells produce free radicals in order to destroy invading organisms, but the immune system itself is damaged by oxidants such as oxygen free radicals, diminishing its response.

The study recruited men and women living in Hong Kong between the ages of 25 and 35 who were free of chronic diseases, intestinal malabsorption, obesity, smoking, vitamin supplement use and certain pharmaceutical drug use which could effect outcome. Participants were given 400 iu synthetic vitamin E per day for one month. Blood and urine samples were taken at the beginning and end of the study. Plasma vitamin E levels rose at the end of the study from what were considered deficient levels. Plasma malondialdehyde, a marker of lipid oxidation, and urinary 8-OHDG, which measures DNA damage, decreased from starting levels, demonstrating vitamin E's known antioxidant ability. The oxidative stress of T-lymphocytes decreased by 44% at the conclusion of the study, and when challenged in vitro remained lower at the end of the study than at the beginning. Analysis of lymphocytes after vitamin E supplementation showed total-T, T-helper/inducer cells and the CD4/CD8 ratio to be enhanced while natural killer cells and interleukin-2 receptors remained unaffected.

The authors conclude that short term vitamin E supplementation can reduce oxidative stress and improve cell-mediated immunity in a healthy Chinese population, and suggest a specific requirement for vitamin E in the proliferation of total-T and T-helper cells.

—D Dye


January 24, 2001

Hormonal link found between diabetes and obesity

The long-sought connection between diabetes and obesity appears to have been discovered by researchers in a series of experiments conducted at the University of Pennsylvania School of Medicine. Obesity affects over 80% of people with type 2 diabetes, the form of the disease characterized by resistance to insulin. Increased storage of fat molecules in adipose tissue causes insulin resistance, but until now, its ability to cause the same in other tissues such as the muscles and liver remained unknown.

The researchers found that a protein released by the fat cells called resistin, for "resistance to insulin" is higher in diabetic mice, and that the antidiabetic drug rosiglitazone reduces resistin levels. Mice with both genetic and diet-induced obesity have higher resistin levels. Normal mice given resistin exhibited impaired glucose tolerance and insulin action. Antiresistin antibody administration improves the action of insulin when administered to mice on a high fat diet. It was furthermore found that a gene that codes for resistin is expressed only in fatty tissue and this gene is switched off by antidiabetic drugs. The research was published in the January 18, 2001 issue of the journal Nature. Jeffrey Flier of Beth Israel Deaconess Medical Center in Boston, author of a "News and Views" article on the subject in the same issue commented, "Some of the effects were rather small. But they all point in the same direction: that the protein is an important link between obesity and diabetes."

The researchers in this study suggest that new drugs targeting resistin could bring relief from diabetes, if human resistin proves to be similar to mouse resistin. This would be an important breakthrough for the 5% of the US population with type 2 diabetes.

—D Dye


January 22, 2001

Longterm vitamin C intake not a strong factor in iron absorption

Studies have shown that vitamin C taken with a single meal containing iron greatly enhanced iron absorption. Although this may be of benefit for some populations, life extensionists have avoided excessive iron because of the correlation between high iron levels and heart disease, cancer and Parkinson's disease. Thankfully, other research has shown that prolonged supplementation with vitamin C has a negligible effect on iron absorption. In one study, two grams of vitamin C supplemented for one year did not increase iron stores. A study published in January 2001's American Journal of Clinical Nutrition confirms that finding and presents evidence that vitamin C's ability to enhance iron absorption may be valid only in the setting of a single meal preceded by fasting used in clinical studies.

In this study, participants consumed meals which included one item containing iron that was tagged in order to measure its absorption, and were free to chose the remainder of their diets for one period, followed by diets containing higher or lower amounts of vitamin C for the second and third periods of the study. There was no difference in iron absorption found among study participants, despite widely varying vitamin C intakes. Further analysis of the data showed that phosphorous had an inhibiting effect on iron absorption, while vitamin C appeared only to weakly enhance it. This contrasts strongly with studies in which fasting subjects are tested with an isolated meal and found to have their iron absorption
strongly enhanced in the presence of vitamin C. Various factors were proposed by the authors to account for this difference, including the possibility that food residues in the digestive tracts of nonfasting subjects may dampen the influence of dietary factors. The study provides further reassurance to the many people who supplement several times a day with vitamin C that they are not contributing to iron overload.

—D Dye


January 19, 2001

Leukemia breakthrough

In an article published in recent issue of Hammersmith Research, researchers from the Hammersmith Hospital and Imperial College School of Medicine in London reported the successful engineering of immune cells that seek out and destroy leukemia cells. Over six years of research has identified the overexpression a single gene, WT-1, in cells that cause leukaemia. The identification of this gene enabled the researchers to develop immune cells that recognize the WT-1 on cancerous cells and destroy them, while ignoring normal cells of the same type. The research was originally published in the April 1 2000 issue of the journal, Blood.

Research team leader, Dr Hans Stauss, of Imperial College School of Medicine stated, "The principle we have developed can be applied to almost all forms of leukemia and could signal a huge step forward in how we treat the disease. What makes this work even more exciting is that our findings can also be applied to solid cancers, such as breast or lung cancer, where there is similar over expression of WT-1. The possibilities for new treatments are enormous."

The project is expanding to join researchers from Hamersmith Hospital's Hematology Department and clinical trials are planned to take place within the next two years. Professor Robert Winston, Director of Research and Development at the Hammersmith Hospitals NHS Trust commented, "To the best of our knowledge, this is the first time in the world that anyone has identified a target which allows T-cells to selectively destroy cells that cause leukaemia. Such a breakthrough underlines the vital importance of long-term academic research, in the production of new and desperately needed treatments."

—D Dye


January 17, 2001

Further evidence linking homocysteine and dementia

A letter published in the January 2001 issue of American Journal of Clinical Nutrition, provided more evidence of a correlation between elevated homocysteine levels and dementia. Hyperhomocysteinemia has been recently identified as a risk factor for atherosclerosis and Alzheimer's disease, and folic acid, vitamin B6 and B12 have been recommended to lower homocysteine levels. An Austrian study of thirty-one patients with cognitive decline found an elevation of homocysteine compared to controls and in some patients other vascular disease risk factors were noted. An inverse correlation was found between test scores that measured cognitive skills and serum homocysteine levels, as well as between folic acid and homocysteine levels. Higher folic acid levels were associated with better test scores.

When nine of the patients were treated with 50 mg vitamin B1, 50 mg vitamin B6, 5 mg folic acid and 50 micrograms vitamin B12, all of the patients experienced a lowering of homocysteine to normal levels.

This study confirms several others that have shown a link between B vitamin status, homocysteine and brain function. Authors of other studies have mentioned that these vitamins are often deficient in elderly populatoins, and that deficiencies can result in brain ischemia, through occlusive vascular disease, stroke or blood clots. The author of this study pointed out that vascular disease risk factors such as hypertension have been recognized in Alzheimer's disease. It is also interesting to note that nonsteroidal antiinflammatories have been shown to be helpful in preventing both vascular disease and Alzheimer's disease. The authors of this study conclude that vascular disease risk factors may contribute to the pathophysiology of Alzheimer's disease.

—D Dye


January 15, 2001

New Alzheimer's target found

In yet another exciting recent discovery in the field of Alzheimer's disease, Gladstone Institute of Neurological Disease and University of California San Francisco researchers have found that a protein called alpha1-antichymotrypsin or ACT, a serine protease inhibitor that prevents protease enzymes from digesting proteins, can significantly increase the amount of amyloid plaque in the brains of mice. It had been known that Alzheimer's patients have increased production of ACT, which is found in the amyloid plaques characteristic of this disease, but researchers were unaware of whether the presence of ACT combatted or enhanced the buildup of these plaques. It has recently been discovered that the plaques are most likely the cause of Alzheimer's disease symptoms (see What's Hot, Jan 3, 2001).

The researchers in this study, published in the December 2000 issue of the American Journal of Pathology, crossed mice genetically engineered to produce human amyloid protein precursors in their brains and amyloid beta in their neurons with mice engineered to produce human ACT. The mice engineered to produce ACT alone did not produce plaques, however the mice who produced both amyloid and ACT had twice as much amyloid plaque as mice engineered to produce amyloid without ACT.

Lead author Lennart Mucke, MD, of the Gladstone Institute of Neurolgoical Disease stated, "We speculate that reducing or inhibiting the plaque-enhancing activity of ACT could help prevent the accumulation of plaques in the brain. There's a sneakiness to this protein. While the association of ACT with plaques has been known for more than ten years, the true nature of its activity in the brain has remained elusive for all this time. Our study now demonstrates that ACT insidiously increases the plaque burden in the aging brain . . . The amyloid-enhancing effect of ACT we demonstrated in our study suggests that
ACT might be an interesting target for therapeutic interventions. Our next step will be to explore the mechanism through which this factor acts. Possibilities include that it promotes the assembly of amyloid proteins and that it prevents their degradation and clearance from the brain."

—D Dye


January 12, 2001

Mechanism of action found for aspirin in cancer cell apoptosis

The November/December 2000 issue of the journal Neoplasia published a research article which explained the discovery of how aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) induce apoptotic cell death in cancer, a process that had heretofore been unknown. It has been believed that aspirin and other NSAIDs exerted their known colon cancer preventive effects by inhibiting cyclooxygenase (COX) activity, but recently researchers have proposed that NSAIDs' anticancer ability lies in their induction of apoptosis, the process whereby programmed cell death occurs. There are several possible pathways by which apoptosis ocurs. The researchers studied a cultured cancer cell line and found that aspirin acts via a pathway which involves the release of cytochrome c from the mitochondria of the cell to bind with Apaf-1 or apoptotic protease activating factor. This complex activates caspase proteases, enzymes that cause cellular destruction. Cells lacking Apaf-1 proved to be resistant to apoptosis stimulated by aspirin, as were cells that overexpressed the antiapoptotic protein Bcl-2, known to prevent the release of cytochrome c.

When asked about the possibility of a destructive effect of aspirin on noncancerous cells, lead study author Katja C Zimmermann told the Life Extension Foundation, "The common side effects of cancer drugs and treatments are their damage of healthy high-proliferative cells (e.g hair cells, hematopoetic cells and gastric mucosa cells) . . . Regarding the apoptosis inducing effect this will be especially crucial for cells with a high turn over like cancer cells. A recent study by Elder et al. (Cancer Research, 1996) found that colorectal carcinoma cells - which are at a later stage of neoplastic progression - are significantly more sensitive to the apoptosis-inducing effect of salicylates than colorectal adenoma cell lines. In this study salicylate failed to induce significant apoptosis in two of the four adenoma cell lines studied."

This study confirmed that the release of cytochrome C is an important part of aspirin's apoptotic mechanism, which will aid in understanding its ability to fight cancer.

—D Dye


January 10, 2001

Melatonin may protect against Parkinson's disease

The theory that Parkinson's disease has an environmental cause has recently gained credence. A study published in the December 2000 issue of the journal Nature Neuroscience demonstrated that the pesticide Rotenone caused Parkinson's symptoms when administered to rats. The article indicated that Rotenone may cause the mitochondria, which are the power plants of the cells, to produce free radicals, thereby causing the damage that leads to Parkinson's disease.

In a study published in the January 1, 2001 issue of the Federation of American Societies for Experimental Biology or FASEB journal, researchers injected the neurotoxin 6-hydroxydopamine (6-OHDA) into the right substantia nigra of the brains of rats. This neurotoxin produces a loss of dopaminergic cells, thereby creating an experimental model of Parkinson's in the right hemisphere of the brain of the rats who received the injection, as Parkinson's disease is characterized by a loss of these cells. The rats exhibited a postural assymetry which causes rotation away from the the undamaged side of the body, seen as circling behavior. Rats given melatonin prior to administration of 6-OHDA did not demonstrate this behavior. Analysis of the affected brain tissue in rats receiving 6-OHDA who were not protected with melatonin showed a loss of complex 1 activity of mitochondrial phosphorylation enzymes, a reduction of which has been observed in the substantia nigra of Parkinson's disease patients. However, the melatonin-treated rats were protected against this loss. The researchers conclude that a deficit in mitochondrial complex 1 could cause free radical-induced cell death in Parkinson's disease, both directly and by decreased ATP synthesis and energy failure, and that melatonin may be useful in the treatment of neurodegenerative disorders in which free radicals play a role.

—D Dye


January 8, 2001

Human proteome database completed

Another genetic landmark was passed on January 4 when it was announced by Large Scale Biology Corporation (LSBC) that it had completed the initial version of its proprietary human proteome database, the Human Protein Index(tm) version 1.0, or HPI v1.0. The database provides a complete inventory of all human proteins A summary of the research will be published in the January 18 2001 issue of the journal Proteomics.

Robert Erwin, CEO of Large Scale Biology Corporation commented, "With the completion of the HPI v1.0, we now have a comprehensive process for analyzing the proteins encoded by human genes. Diseases are caused by changes in proteins that are not always predictable by gene analysis alone, and we believe HPI v1.0 provides an important new baseline for determining the roles of both genes and proteins in health and disease. We expect the protein discoveries for medical applications enabled by HPI v1.0 to drive a major shift in pharmaceutical research and development from genes to proteins . . . "

The company estimates that the database currently covers the protein products of 18,000 human genes. Future versions are expected to expand the database. They predict that it will be used in the discovery of new drugs and drug targets as well as in diagnostics.

Leigh Anderson, President of LSBC's proteomics subsidiary stated, "The HPI v1.0 gives us a first look at the protein components of all the major tissues of the human body. Our initial analysis of the HPI has turned up new candidate diagnostic markers of tissue damage, as well as fascinating insights into the differences between tissues, for example, in different regions of the brain. We believe that over the long term, the HPI provides a unique foundation for our ongoing investigations of specific diseases."

—D Dye


January 5, 2001

Long-sought stroke prevention in diabetes with ramipril

The January 2 2001 issue of American Heart Association (AHA) journal Circulation and the January issue of AHA's Stroke published a comprehensive article entitled "Primary Prevention of Ischemic Stroke : A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association" which, among other important guidelines, recommended the use of the drug ramipril, or Altace R to diabetics to prevent stroke. These latest recommendations are based on the findings of the HOPE Trial, which stands for Heart Outcomes Prevention Evaluation which showed that diabetics taking the drug can reduce the risk of stroke by a third. The findings of the HOPE trial were published in the January 20, 2000 issue of the New England Journal of Medicine.

Diabetes is a major risk factor for cardiovascular disease, which is the number one killer of diabetics and diabetics are two to four times more likely to suffer a stroke than nondiabetics. Of 9541 patients enrolled in the HOPE trial, a substudy 3577 diabetics with at least one other cardiovascular risk factor were give ramipril or a placebo. Jeffrey Probstfield, M.D., professor of medicine, University of Washington and Investigator of the HOPE study commented, "In patients with diabetes who took Altace, the risk reduction for stroke was 33 percent . . . The HOPE results also showed that Altace protects people with diabetes beyond just reducing risk of events. Patients treated with Altace have a 22 percent reduction in the need for laser eye therapy and a 16 percent lower risk of permanent kidney damage."

Dr Probstfield also noted that, "The incidence of diabetes greatly increases with age. More than one in six Americans age 65 and over has diabetes. Because the risk of cardiovascular disease also increases with age, the threat of cardiovascular disease should be a particular concern for older adults with diabetes."

—D Dye


January 3, 2001

Alzheimer's plaques probable cause, not effect

The Journal of Neuroscience (volume 21, 2001) published a report of research conducted by the National Institute of Environmental Health Sciences (NIEHS) that the plaques found in the brains of Alzheimer's patients disrupt brain signals which may contribute to the memory loss experienced by this group. These plaques contain a protein called beta-amyloid and their presence is confirmative of an Alzheimer's diagnosis upon autopsy of the brain. The beta-amyloid peptide has been found in the brains of both humans and animals. Although it had been frequently speculated, it had not been known whether these plaques were causative of the disease's symptoms.

Working with rats, the NIEHS team of Jerrel L. Yakel, PhD, Diana L. Pettitt, Ph.D., and Zuoyi Shao, Ph.D, working from NIEHS' headquarters and laboratory in Research Triangle Park, North Carolina, discovered that beta-amyloid binds to the nicotinic acetylcholine receptor, a key signalling receptor in the brain's hippocampus, which is the area of the brain involved in emotion, memory and motivation. This blocks the transmission of signals involved in learning and memory. According to the researchers this is the first time that a link between Alzheimer's plaques and failed brain function has been established.

Although several treatments are available which can temporarily relieve some of the symptoms Alzheimer's disease, there is no cure, and with a longer-lived population the disease's incidence in the U.S. is on the rise. Dr Yakel stated, "Knowing how the disease process works makes it more likely that medical science can find ways to slow, halt or even reverse the process." He predicted that improved therapies could result from finding chemicals that prevent the binding of beta-amyloid to the nicotinic acetylcholine receptor.

—D Dye



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