|December 2002 |
Stem cells viable after fifteen years in deep freeze
The December 30 2002 issue of Proceedings of the National Academy of Sciences (www.pnas.org) announced the finding that human stem cells from human umbilical cord blood that were cryogenically stored for fifteen years are nearly as viable as those from fresh blood. Long-term freezing is critical for cord blood banking, an option currently pursued over 100,000 individuals in anticipation of the future need of the donor's own stem cells to treat genetic diseases, immune system disorders or childhood cancers. The current recommendation advised only a three to five year period as optimal for the usage of frozen stem cells
Following the successful thawing of five and ten year old stem cells from cord blood, researchers funded by the National Institutes of Health and led by Hal Broxmeyer, of the Department of Microbiology and Immunology at Indiana University School of Medicine in Indianapolis, attempted to determine the viability of fifteen year old samples. The samples were tested for recovery and results compared to values obtained prior to freezing. It was found that 83 to 95 percent of the stem cells were viable upon thawing and that they maintained their capacity to reproduce. When the thawed cells were transplanted into mice, the cells were able to reproduce for over eleven weeks.
The authors state that final proof of the long-term engrafting capability of cord-blood will require successful engraftment in humans, but they conclude that their results "are highly suggestive that cord blood can be stored for at least fifteen years with highly efficient recovery of viable and highly functional hematopoietic stem cells and hematopoietic progenitor cells needed for successful cord blood transplantation."
Modified citrus pectin inhibits cancer growth and metastasis in mice
The Journal of the National Cancer Institute, December 18 2002 issue, published an article on the findings of researchers from Wayne State University in Detroit that oral administration of modified citrus pectin suppresses the growth of cancer and prevents it from metastasizing both in vivo and in vitro. Pectin is a fiber that when modified, acts as an inhibitor of galectin-3, a carbohydrate-binding protein involved with tumor growth and metastasis.
In one experiment, mice were injected with a human metastatic breast cancer cell line. Twenty mice were provided with drinking water containing 1 percent modified citrus pectin one week before receiving the injections, and 20 controls received regular water. Tumor volume was calculated twice per week for seven weeks for ten mice from each group who then had primary tumors removed, following which they continued to receive the modified citrus pectin or water for eight weeks. The remainder of the mice were euthanized after thirty-three days, and tumors were removed and examined.
In a second experiment, 10 mice received modified citrus pectin-enhanced drinking water prior to and following injections of human colon cancer cells and ten control mice did not receive pectin. After six weeks the animals were examined for tumors.
In the first experiment, mice who received modified citrus pectin experienced a significant reduction in tumor growth rate and metastasis compared to the controls. When the tumors were examined, those from the modified citrus pectin-treated group were found to have one third fewer blood vessels than those of the controls, demonstrating an antiangiogenic effect. When modified citrus pectin was tested in vitro on human umbilical vein endothelial cells, angiogenesis was found to be impaired. The pectin-treated mice who received colon cancer cells also had smaller tumors and fewer metastases than the controls.
These data suggest that modified citrus pectin may reduce breast and colon cancer growth by inhibiting angiogenesis.
High homocysteine associated with hippocampal, cortical atrophy in elderly population
The January 2003 issue of the journal Brain, published the findings of researchers in the Netherlands that elevations in homocysteine levels are correlated with atrophy of the cortical and hippocampus regions of the brains of older individuals without dementia. Atrophy of the hippocampus and amygdala, as well as global brain atrophy as determined by magnetic resonance imaging, has been suggested as an early marker for Alzheimer's disease.
Participants included 1077 men and women without dementia, aged 60 to 90, selected from the ongoing Rotterdam and the Zoetermeer Studies. All subjects underwent MRIs to the brain which visualized global cortical brain atrophy. Additionally, 511 participants recruited from the Rotterdam Study received MRIs that measured measured hippocampal and amygdalar volumes. At the same time, blood samples were taken and plasma total homocysteine levels determined.
Homocysteine levels were found to increase with age, and were higher in men than women. It was observed that the 61 participants who reported multivitamin use had lower homocysteine levels than subjects who did not report vitamin use. Seven participants who had extreme plasma homocysteine values were excluded from the analyses, leaving 1031 participants for the analyses on global atrophy and 505 for those of the hippocampus and amygdala.
It was found that subjects with higher homocysteine levels had greater cortical and hippocampal atrophy. Plasma homocysteine did not appear to be associated with atrophy of the amygdala.
The authors noted that a recent study showed that low levels of folate may be predictive of brain neocortical atrophy and that homocysteine may be responsible. Also noted were several current large-scale trials with folic-acid based vitamins to lower homocysteine levels, some of them assessing cognitive function and, like the current study, including MRI findings.
Statin drug saves no more lives than usual care in large study
A study of patients with controlled hypertension and moderately high cholesterol published in in the December 18 issue of The Journal of the American Medical Association, showed that the drug Pravastatin was not superior to usual care in reducing deaths or coronary heart disease incidence. The study involved a subset of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). The current trial (ALLHAT-LLT), enrolled 10,355 participants 55 years of age or older with elevated low density lipoprotein (LDL) levels, well-controlled high blood pressure and at least one other heart disease risk factor. Pravastatin was assigned to 5,170 subjects and 5,185 received usual care. Subjects were followed for an average of 4.8 years.
Follow-up visits occurred at three, six, nine, and twelve months following the beginning of the trial, then at every four months, during which participants were questioned concerning cardiovascular events, such as heart attack. Total cholesterol levels and electrocardiograms were obtained at the beginning of the trial and every two years thereafter. After four years, pravastatin was found to reduce cholesterol levels by 17% while usual care only reduced total cholesterol by 8%. Low density lipoprotein levels dropped 28% with pravastatin in a random sampling taken, compared to 11% usual care. Nevertheless, all-cause mortality was similar for those taking the drug and those who were not taking it, and coronary heart disease event rates were not significantly different. However, the authors write that this study should be viewed in light of other studies that have found a reduction in coronary heart disease events and all-cause mortality with statins.
More evidence that cardiovascular disease is inflammatory
In a study published in the online version of the journal Circulation in advance of its publication in the January 23 2003 issue, San Francisco Veterans Administration Medical Center researchers have found high levels of the inflammatory marker C-reactive protein to be associated with exercise-induced cardiac ischemia, strengthening the link believed to exist between cardiovascular disease and inflammation. The study involved 229 subjects from the ongoing Heart and Soul Study, which enrolled participants from three medical centers in the San Francisco Bay area to determine the effect of psychosocial factors on heart disease. In the current study, researchers utilized frozen serum samples from 118 participants with exercise-induced ischemia (which occurs when blood flow to the heart is reduced during exercise) and 111 subjects without the condition, to determine levels of C-reactive protein.
The researchers found that while 75% of participants in the top one-fifth of serum C-reactive protein levels had exercise-induced ischemia, only 45% of those in the lower four-fifths had experienced the condition. When patients taking statins or beta blockers were excluded from the analysis, individuals with exercise-induced ischemia composed 95% of the top level of C-reactive protein.
"Our study supports the idea that heart disease is more of a systemic disease rather than just a plumbing problem," study coauthor Mary S. Beattie, MD, summarized.
Senior author Mary A. Whooley, MD, added, "It's hard to know whether ischemia or inflammation comes first. It may be that inflammation causes ischemia by increasing the degree of blockage in people's coronary arteries, or it may be that ischemia causes inflammation by damaging the heart tissue. We will try to sort this out by following patients over time to determine whether CRP predicts future events independent of baseline ischemia."
Coenzyme Q10 lowers blood pressure and improves glycemic control in diabetics
In the November 2002 European Journal of Clinical Nutrition, researchers from Royal Perth Hospital, in Perth, Western Australia, demonstrated that a daily regimen of coenzyme Q10 lowered systolic and diastolic blood pressure and improved glycemic control in subjects with type 2 diabetes who were dyslipidemic (defined as an elevation in serum triglycerides or a high total cholesterol to HDL cholesterol ratio), and who had blood pressure in the high-normal range.
Participants included sixty-one men and nineteen women aged 31 to 75, who were randomized to receive 100 milligrams coenzyme Q10 twice per day, 200 milligrams of the lipid-lowering drug fenofibrate, both substances or a placebo, for twelve weeks. Blood pressure was measured and blood samples collected at the beginning and conclusion of the study. The subjects' blood was measured for cholesterol, triglycerides, insulin, glucose, coenzyme Q10 levels and glycated hemoglobin, a measure of longterm glycemic control. In addition, plasma F2-isoprostane levels were determined in order to assess oxidative stress.
While fenofibrate did not affect blood pressure or glycemic control, coenzyme Q10 was found to significantly decrease systolic and diastolic blood pressure as well as reduce glycated hemoglobin indicating improved glycemic control, while not changing fasting plasma glucose and insulin concentrations. Although coenzyme Q10 has reduced LDL oxidation in vitro, the lack of reduction of F2-isoprostane in the group receiving the nutrient led the researchers to suggest that the improvements noted in this study were not due to a reduction in oxidative stress. However, the authors note that F2-isoprostanes are only one marker of oxidative stress, and that if the effects of coenzyme Q10 are specific at the cellular level, a reduction in oxidative stress could occur without changing F2-isoprostane concentrations.
N-acetyl-cysteine may help with cocaine withdrawal
At the American College of Neuropsychopharmacology's annual meeting, David A Baker PhD, from the laboratory of Peter W Kalivas at Medical University of South Carolina announced the finding that the amino acid N-acetyl-cysteine could reduce the cravings that accompany withdrawal from cocaine.
Inactivity has greater impact on mortality than obesity
Grape-seed extract aids healing
A study funded by the National Institutes of Health, published in the October 12, 2002 issue of Free Radical Biology and Medicine, has found that an extract of grape seed helps regenerate damaged blood vessels and destroy bacteria in wounds, thus aiding in the healing process. Researchers at Ohio State University tested a topical grape seed proanthocyanidin solution on mice who each received two small puncture wounds. Proanthocyanidins are potent antioxidants found in grape seeds and other plants. One wound received an application of the grape seed extract, while the other wound received a saline solution, following which both wounds were left to heal for five days. When the wound areas were examined at the end of this period, skin samples were obtained and examined.
Study coauthor and Ohio State University Heart and Lung Research Institute Laboratory of Molecular Medicine Director Chandan Sen summarized the results: "We saw the healing effects grape-seed extract had on wounds from day one. It seemed to enhance the formation of epidermal tissue as well as the deposition of connective tissue. The skin treated with grape-seed extract was further along in the healing process compared to the saline-treated tissue. The extract-treated skin showed signs of healing faster and the newly formed tissue was denser, meaning that its structure was stronger."
Although proanthocyanidins act as an antioxidant when ingested, they can have a pro-oxidant effect when applied to wounds. This provides an antibacterial action, and was observed in a second study utilizing the compound. When human skin cells were treated with grape seed extract the researchers found more free radicals, which at low levels increase cell proliferation, connective tissue formation, and the creation of new blood vessels through enhanced vascular endothelial growth factor expression.
Men: Do you hear your biological clock ticking?
At the yearly American Society for Reproductive Medicine meeting held in Seattle, Charles Muller of the University of Washington Department of Urology presented more evidence that men, like women, have a reproductive clock that slows with age. The research teams' findings resulted from a study of the sperm of sixty men, ages twenty-two to sixty. Computerized semen analysis looked for breaks in sperm cell DNA as well as for signs of apoptosis, the programmed cell death that occurs when the body attempts to protect itself by eliminating damaged cells. It was found that men over 35 years of age had more double strand breaks in their DNA and fewer apoptotic cells than the younger men in the study. This could mean more genetically-induced damage in offspring.