Antioxidant vitamins prevent progression of hypertension in spontaneously hypertensive rats
In a study published in Hypertension: Journal of the American Heart Association, researchers from the University of Montreal and Sungkyunkwan University in Seoul, Korea, demonstrated the ability of vitamins C and E to prevent the progression of hypertension in rats given a 4% sodium chloride diet. High sodium diets are notorious for raising blood pressure, and salt reduction is a frequent recommendation given by physicians to their hypertensive patients.
Stroke-prone spontaneous hypertensive rats were divided into groups who received diets containing 1000 mg ascorbic acid per day, 1000 international units vitamin E per day or a diet supplemented with neither vitamin. The rats were studied for six weeks and had their blood pressure measured weekly. At twenty-two weeks of age the animals were euthanized and blood samples drawn. Small arteries were examined for the ability to relax, and thoracic aortas were examined for the presence of the pro-oxidant superoxide and the antioxidant superoxide dismutase (SOD).
While hypertension progressed in the animals receiving the nonsupplemented high sodium diet, the condition only increased marginally in the animals receiving vitamin C or E, while body weights of all groups did not differ. The media to lumen ratio and media thickness of the arteries of the supplemented rats were significantly lower than that of controls. Vitamins C and E increased the ability of the arteries to relax, indicating improved endothelial function. They also lowered superoxide activity by decreasing the activity of NADPH oxidase, and increasing that of SOD in the vasculature of the animals studied.
The researchers concluded that vitamins C and E lower blood pressure by improving vasodilation as well the structure of the arteries, by decreasing oxidative stress and increasing antioxidants. They comment that in addition to the known free radical scavenging properties of these vitamins, they appear to also prevent free radical generation.
Latest: Fountain of Youth not in Florida
Researchers at the University of Illinois at Chicago have identified a gene that enables tissue to grow at the rate of a younger animal. The research, published in the September 25 2001 issue of the journal Proceedings of the National Academy of Science, demonstrated the ability of a gene known as forkhead box M1B, or FoxM1B, to enable mouse liver cells to regenerate in a manner comparable to that of young mice.
The forkhead box family play a role in regulating cellular proliferation and transformation, differentiation and longevity. Recent studies have shown that age-related cellular proliferation defects are associated with a decrease in the expression of FoxM1B transcription factor. The gene is known to be involved in the control of liver cell division during regeneration of this organ. The researchers increased the activity of FoxM1B in the livers of aged mice and after removing part of the liver, observed the pronounced increase in DNA replication and cell division characteristic of young animals. Other genes involved in cell division were increased as well. The authors suggest that FoxM1B controls the transcriptional network of genes necessary for cell division and that reduced expression of the FoxM1B transcription factor contributes to the decline in cell division associated with aging. FoxM1B also controls the completion of cell division which prevents defects that can cause cancer.
Study author, Robert Costa, Robert Costa, professor of molecular genetics at the University of Illinois Chicago College of Medicine, summarized, "Ponce de Leon was looking in the wrong place for the fountain of youth. He should have been looking for the FoxM1B gene. FoxM1B clearly regulates the expression of a whole network of genes that are required for cells to multiply."
Antioxidants may be treatment of choice for hypertension
The September 2001 issue of International Kidney published an article in which the hypothesis was submitted that severe regional hypertension may be due to inactivation of nitric oxide by a type of free radical known as reactive oxygen species. Nitric oxide is a substance produced in the body which aids in the relaxation of the blood vessels, helping to maintain normal blood pressure. The researchers acted on the finding that in rats with a severe narrowing of the aorta above the renal arteries, nitric oxide synthase is upregulated in the heart, chest and brain, which may be caused by nitric oxide inactivation by free radicals.
The researchers in this study banded the aortas of rats above the renal artery to mimic a condition found in humans in which elevated blood pressure exists in the vasculature above a narrowed site. Another group of rats were sham-operated as controls. Nitrotyrosine, a marker of nitric oxide interaction with reactive oxygen species, and intra-arterial pressure were measured after three weeks. The banded rats experienced a significant rise in arterial pressure as well as increases in nitrotyrosine in the aorta above the band as well as in the heart and brain compared to controls. In the aorta segment below the bands where there was no change in blood pressure, nitrotyrosine levels remained the same.
Author Dr Nick Naziri stated, ""Nitric oxide inactivation was seen in restricted arteries with high pressure but not in open arteries. This indicates that this circle of inactivation and pressure is made worse by the mechanical pressure and not by genetic or hormonal interactions affecting the body as a whole. Free radicals and other such molecules, then, play a much stronger role in high blood pressure than has been previously assumed. These molecules may hold the key to controlling excessively high pressure and perhaps to better treatments using antioxidants and other chemicals to keep pressure normal."
Vitamins protect the lungs
The September 2001 issue of American Journal of Respiratory and Critical Care Medicine, a journal of the American Thoracic Society, published a study demonstrating that antioxidant supplementation protects the lungs from damage by ozone. Ozone is a gas found in smog which causes oxidative damage to the cells of the lungs, leading to inflammatory changes and decreases lung function.
Thirty-one nonsmoking men and women aged 18 to 35 were placed on an antioxidant restricted diet for three weeks. Upon following the diet for one week, participants were exposed to filtered air while moderately exercising for two hours and were tested for pulmonary function. This was followed by lung airway washout to obtain cell specimens. They were then were divided into two groups: one receiving 250 milligrams vitamin C, 50 international units of vitamin E and 12 ounces of vegetable cocktail and the other a placebo, for the remaining two weeks of the study. At this time, subjects were exposed to air containing four-tenths parts per million ozone for two hours, again followed by bronchoalveolar wash out.
Blood samples taken the day of exposure to ozone showed that those supplemented with antioxidants predictably had higher plasma levels of vitamin C, tocopherols and carotenoids than the group receiving a placebo. Two tests of pulmonary function revealed that the antioxidant supplement group had 30% and 24% less decline in function caused by ozone, although airway inflammatory response as determined by examination of the washout fluid was the same for both groups. Nevertheless, antioxidants appear to protect lung function against the effects of ozone. This is particularly important in light of a study previously reported in What's Hot, in which decreased lung function was found to be associated with all-cause mortality.
Middle age aerobic decline reversible
Two studies that appeared in the September 18, 2001 issue of Circulation: Journal of the American Heart Association, showed that a six month endurance training program was able to reverse three decades worth of decline in aerobic function in a small group of men. The study is one of the longest to examine the effects of age and fitness on the heart.
Participants in their early twenties were studied in 1966 as part of the Dallas Bed Rest and Training Study, and were reexamined in 1996. The original study sought to determine the adverse effects of a twenty day period of bedrest on fitness. The current studies evaluated the effect of the thirty year interval on body composition and cardiovascular response to exercise as measured by maximal oxygen uptake. Subjects completed a training program consisting of walking, cycling or jogging for four or five times per week. By the end of the program, participants were exercising a total of four and one half hours per week. Maximal oxygen uptake was measured during treadmill exercise before the endurance program and at its conclusion.
The men were found to have a 25% gain in body weight after thirty years, in the form of fat. Maximal oxygen update declined an average of 11%. Following the exercise program, maximal oxygen uptake increased an average of 14% to a level observed in the participants thirty years earlier.
Lead author Darren McGuire MD summarized, "First, twenty days of bed rest - which is the ultimate 'sedentary' state - in these subjects when they were 20 years old had a more profound negative impact on their cardiovascular fitness than did 30 years of aging. Second, an endurance training program using a relatively modest intensity of training was able to reverse 100 percent of the loss of cardiovascular capacity, returning the group to their 1966 baseline levels of aerobic power."
Another reason why women live longer
Research published in the September 2001 issue of the journal Clinical and Experimental Immunology and summarized in New Scientist has established that the stronger immune system of women could be a reason why they live longer in modern societies. A team at the Imperial College School of Medicine in London discovered that women have higher levels of new T lymphocytes than men of equal age.
T cells are immune system cells that are made by the thymus, a gland that shrinks 3% every year after birth until middle age, after which it shrinks 1% yearly. The researchers in this study measured the amount of new T cells in forty-six men and women aged 20 to 62. They also examined statistics regarding deaths from influenza and pneumonia in the UK between 1993 and 1998. What they found is that peripheral blood samples from males contained significantly lower levels of a marker for recent thymic emigrants than females of the same age, although both levels declined with age, and that more men than women died of the infections during the period studied, with the risk of death of infection for men and women correlated with their differences in thymic activity.
The discrepancy between men and women's lifespans has often been attributed to greater risk-taking behavior on the part of men. In a quote in New Scientist, research team member Dr Richard Aspinall stated, "Risk can explain anything from number of car crash deaths to deaths from colon cancer. But there are probably other factors that contribute to the difference in longevity."
The researchers write that this finding could explain the immunologic differences between men and women noted in earlier studies.
Aspirin use associated with lower all-cause mortality
Although studies have shown an association between the use of aspirin and a reduction in cardiovascular mortality, a reduction in mortality from all causes has not been established. A study published in the September 12 2001 issue of the Journal of the American Medical Association followed 6,174 men and women with known or suspected heart disease who received stress echocardiography testing at the Cleveland Clinic Foundation in Cleveland, Ohio between 1990 and 1998. Patients younger than thirty years of age, those with significant valvular disease, patients being referred for arrhythmia evaluation or consideration of heart transplant, or those with a prior heart transplant were not included in the study. Data concerning aspirin use, defined as an aspirin daily or every other day, medical history and cardiovascular risk factors were collected at the study's onset.
Cooling helps MS patients
In a study that appeared in the September 11 2001 issue of the journal Neurology, researchers from the Netherlands reported on the benefits of wearing a cooling vest and cap in patients with multiple sclerosis. Acting on reports from multiple sclerosis patients that their symptoms improve with cooler temperatures and worsen in warmer ones, researchers have developed garments that are cooled through an attachment that pumps coolant fluid through them. Ten patients with a history of temperature-sensitive symptoms took part in the study, in which half the patients received what is termed "active cooling", with the coolant set at 45 degrees, while the other half received "sham" cooling, with the coolant set at 79 degrees, which created a sensation of a cool contact. After one week, the patients alternated treatments. Participants were tested for balance, muscle strength, fatigue, and white blood cell production of nitric oxide before the treatment and three hours after. Nitric oxide levels were also tested in twelve healthy volunteers. Nitric oxide has been implicated in MS symptoms through its ability to block conduction in demyelinated cells.
Environment, not estrogen, more important in heart disease
A paper published in the September 8, 2001 issue of British Medical Journal, demonstrated that the long held belief that estrogen accounts for the differences between male and female coronary heart disease deaths may be erroneous. Trials conducted several decades ago in which high doses of estrogen were administered to men failed to reveal a protective benefit. Researchers at the University of Bristol in England used national and international data sources to examine mortality trends from coronary heart disease and found that environment may be responsible for the discrepancy.
The researchers found that from 1921 to 1949 deaths from heart disease in England and Wales were lower in women, but the pattern of change was similar for both, with a constant sex ratio of 1.5. Heart disease mortality in men rose markedly after 1949 and peaked in the early 1970s while the rates for women were stable or even decreased, increasing the sex ratio of men to women. Similar trends were observed in other western countries and Japan, but not in less developed countries. Trends in fat consumption showed a similar pattern to that of male heart disease mortality and that of the increasing sex ratio. Mean per capita alcohol consumption was also correlated with the sex ratio in coronary heart disease mortality.
The researchers state that the preventive benefit of estrogen by itself does not explain the results because estrogen levels in women have not changed dramatically over the past one hundred years, nor do they vary among women of different countries. They conclude that the differences are due to environmental factors that affect only males. If environmental factors are the culprit in men's earlier deaths from heart disease, this is good news for men, because these factors are controllable. With appropriate preventive measures taken by men, coronary deaths could be reduced to levels found in women.
Vitamin C enhances arsenic's action against myeloma
The August 1 2001 issue of the journal Blood published the results of a study showing that vitamin C enhances the ability of arsenic trioxide to cause programmed cell death, or apoptosis, in human multiple myeloma cell lines. Multiple myeloma is a form of cancer in which cancerous plasma cells infiltrate bone and bone marrow.
Arsenic was approved by the US Food and Drug Administration a year ago for another cancer involving bone marrow cells, acute promyelocytic leukemia, after having been demonstrated to cause complete remission of the disease with few side effects. The researchers in this study added vitamin C to arsenic, because ascorbic acid metabolism is associated with a decrease in glutathione, a peptide which can inhibit arsenic's ability to cause cancer cell death. Patients with myeloma usually become resistant to treatment, leading to a median survival of three years, so any new treatment would be welcome.
Researchers from H Lee Moffitt Cancer Center at the University of South Florida and Sylvester Cancer Center at University of Miami tested the combination of arsenic trioxide and ascorbic acid on four multiple myeloma cell lines, and on multiple myeloma cells freshly taken from patients with the disease. Vitamin C was found to inhibit glutathione and increase arsenic's ability to cause apoptosis in all lines tested. The effects were not seen when the combination was tested on normal bone marrow cells. Study coauthor Lawrence H Boise of University of Miami School of Medicine stated, "We have initiated a National Cancer Institute-sponsored phase I/II trial to determine the safety and efficacy of the combination therapy in patients with refractory multiple myeloma. The early results look very encouraging."
Virus kills cancer cells
In a letter published in the August 30 2001 issue of the journal, Nature, researchers from the Swiss Institute for Cancer Research in Epallinges, Switzerland, have found a new way to target and kill cancer cells. Acting on the knowledge that the gene p53 is mutated in half of human cancers, the research team found that the human adeno-associated virus was able to cause the death of cells with this mutation.
The gene p53 has been called the guardian of the genome because it prevents cells with damaged DNA from progressing from a resting phase in their cycle of cell division to a replicating phase. Cells with a normal p53 gene are able to manufacture the p53 tumor suppressor protein which halts cell division, while those with a mutated gene lose this capability, ensuring tumor progression. It has not been possible to find a way to inhibit mutated tumor suppressor genes because in some instances the gene itself has been deleted. The researchers in this study infected cells in vitro with adeno-associated virus, whose gene structure mimics damaged DNA. Cells with normal p53 were able to pause in their cell cycle to successfully combat the virus. Cells without functional p53 were not able to do so, and began a process of nuclear division leading to their death. Adeno-associated viruses that were engineered to lack all genes and contained only DNA ends were also able to induce cell death in cells with mutated p53. Additionally, the virus was shown to shrink tumors when injected into mice.
A drug that could target cells lacking a functional p53 enzyme could treat almost every type of cancer. In an accompanying "News and Views" article in Nature (http://www.nature.com/nature/), authors Vogelstein and Kinzler of Johns Hopkins Oncology Center enthused, "Continued research into the structure of p53 . . . has the potential to benefit millions."