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Query: UMLS:C0038454 (stroke)
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General behavioral patterns of rats or mice fed 5 wt% safflower oil (75% linoleate [n-6] and less than 0.1% alpha-linolenate [n-3]) for two generations were significantly different from those of animals fed 5 wt% perilla oil (15% n-6 and 55% n-3). Also, brightness-discrimination learning ability and retinal function were higher in the perilla group than in the group fed 5 wt% soybean oil (53% n-6 and 4.7% n-3) or safflower oil, indicating that the requirement of n-3 for the maximum responses of the nervous system is above 0.6 en% when there is 6.8 en% linoleate n-6. Perilla oil has been found to be beneficial for the suppression of carcinogenesis, allergic hyperreactivity, thrombotic tendency, apoplexy, hypertension, and aging in animals, as compared with soybean oil and safflower oil. These results are against a lipid peroxide theory of aging, carcinogenesis, and chronic diseases. Animal experiments and epidemiological studies lead to a recommendation that the intake of n-6 should be decreased to as low as 2-4 en% and that of n-3 be increased to levels higher than linoleate n-6 for the prevention of chronic diseases prevailing in the industrialized countries.
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PMID:Minimum requirements of n-3 and n-6 essential fatty acids for the function of the central nervous system and for the prevention of chronic disease. 157 78

Several F1 mouse hybrids were used in a chronic bioassay to determine whether such an experimental design would provide greater statistical power than using only the B6C3F1 hybrid. For this purpose, the dose response of formation of hepatocellular and bladder tumors after 30 mo of feeding 2-acetylaminofluorene (2-AAF) in the diet was assessed in 4 F1 mouse hybrids, including the B6C3F1 hybrid. No strain background-related differences in frequency of bladder neoplasms between any F1 hybrids were detected. Bladder tumors occurred only at the highest 2-AAF dose in female mice. In males the lowest dose was already sufficient to induce bladder neoplasms with incidences of 25-48% adjusted for different nontumor mortality patterns across doses. No marked strain-related differences in hepatocellular tumor rates were apparent in either sex. Higher frequencies of hepatocellular neoplasms were observed among the untreated control males of the B6C3, AY, and CVA F1 hybrids than among the comparable females. Among treated mice, the lowest 2-AAF dose increased liver tumor incidence, more so among the females than among the males. The different background genomes resulted in somewhat different risk assessments for liver tumor formation in males due to differences in the time-to-tumor curves. Except for the much higher background liver tumor rate in the CVY mice, the adjusted liver tumor incidences were similar across the four hybrids. Hence, the levels of statistical significance obtained for dose-response trends and comparisons of treated and control groups were similar using 48 animals per dose groups with B6C3 mice, or combinations of 24 animals per dose from 2 genotypes, or 12 animals per dose from the 4 hybrid genotypes. Estimates of carcinogenic potency for bladder tumors were similar, within a factor of two, across the four hybrids. However, estimates of liver tumor potency across genotypes varied by a factor of two and six for females and males, respectively. Thus, the mean of cancer potency estimates across these genotypes would be more representative for mice than results from any single genotype. As in chronic carcinogenesis studies with other test agents, neoplasms developed in only a certain proportion, rather than in all, of the genetically identical animals exposed to a given dose of the toxicant for the same length of time under the same controlled environmental conditions. This phenotypic variability in toxic responses may reflect differential regulation of gene expression among the genetically identical test animals.
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PMID:Bladder and liver tumorigenesis induced by 2-acetylaminofluorene in different F1 mouse hybrids: variation within genotypes and effects of using more than one genotype on risk assessment. 185 80

Even though oxygen is necessary for aerobic life, it can also participate in potentially toxic reactions involving oxygen free radicals and transition metals such as Fe that damage membranes, proteins, and nucleic acids. Oxygen free radical reactions and oxidative damage are in most cases held in check by antioxidant defense mechanisms, but where an excessive amount of oxygen free radicals are produced or defense mechanisms are impaired, oxidative damage may occur and this appears to be important in contributing to several pathological conditions including aging, carcinogenesis, and stroke. Several newer methods, such as in vivo spin-trapping, have become available to monitor oxygen free radical flux and quantitate oxidative damage. Using a combination of these newer methods collectively focused on one model, recent results show that oxidative damage plays a key role in brain injury that occurs in stroke. Subtle changes, such as oxidative damage-induced loss of glutamine synthetase activity, may be a key event in stroke-induced brain injury. Oxygen free radicals may play a key role in carcinogenesis by mediating formation of base adducts, such as 8-hydroxyguanine, which can now be quantitated to very low levels. Evidence is presented that a new class of free radical blocking agents, nitrone spin-traps, may help not only to clarify if free radical events are involved, but may help prevent the development of injury in certain pathological conditions.
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PMID:Role of oxygen free radicals in carcinogenesis and brain ischemia. 218 75

Lipid peroxidation is a radical induced chain reaction which is fundamentally linked to cellular destruction in the secondary injury process which is initiated by head and spinal injury and stroke. Injuries such as these begin a series of molecular events which lead to gradual vascular and neuronal degeneration. This process ultimately precludes neurological recovery. The secondary damage process is a combination of lipid peroxidation, calcium influx, arachidonic acid release and metabolism, transition metal redox reactions and tissue pH. Although CNS cells are particularly susceptible to lipid peroxidation, the process is common to many biological processes (e.g. inflammation, carcinogenesis, aging, radiation damage, transplant rejection, etc.).
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PMID:Lipid peroxidation and the role of oxygen radicals in CNS injury. 312 21

Although no absolute certainty exists about the role of nutrition in the etiology of cancer, many facts in favor of the relationship became available during the last decades. Correlation studies, experimental work and to a lesser extent case-control studies made it possible to clarify the role of certain nutrients and foods in carcinogenesis. The most important cancer sites where nutrition could play a role are esophagus, stomach, colon, rectum, prostate and breast. Esophageal cancer is of a very complex etiology, in which alcohol intake plays an important role, at least in western countries. The cancer-promoting properties of alcohol intake are enhanced by smoking. Three factors from nutrition are probably related to stomach cancer, namely salt, nitrate/nitrite and vitamin C. Salt is caustic to the stomach mucosa, resulting in atrophic gastritis. Salt is also co-carcinogenic and stomach cancer-promoting in experimental animals. Nitrate is probably important at the stage of atrophic gastritis, where bacterial overgrowth, due to the high pH, converts nitrates in nitrites, making the loco synthesis possible of potent nitrosocarcinogens. Vitamin C inhibits the latter step. The epidemiological evidence for the role of those factors is provided. The most important among them is the strong and consistent association of stomach cancer mortality with stroke. Rectum, colon, prostate and breast cancer are related in some way to fat intake. They all seem positively related to saturated fat intake, whereas breast cancer is probably also promoted by polyunsaturated fat intake. However, polyunsaturated fat seems to be without effect on rectum cancer. Colon and prostate cancer are probably also influenced by polyunsaturated fat but to a lesser degree than breast cancer. An important argument for this are the positive ecological correlations between changes in rectum, colon and breast cancer mortality from 1968 on, and changes occurring in coronary heart diseases, stroke and diabetes mortality. Those six types of mortality are decreasing, or only slightly increasing in the USA, Belgium, France, the Netherlands, etc. They are strongly increasing in East European countries. The intake of saturated fat has generally decreased in the first group of countries, and has markedly increased in the second group.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Nutrition and cancer. 353 16

Iron deficiency is an important nutritional problem in third world countries because it diminishes work performance. In meat-eating countries, iron excess may be more important than iron deficiency. Heme iron is more efficiently absorbed from the diet than inorganic iron, and iron excess can produce cellular oxidation in association with superoxide dismutase. Metal ion catalysis is linked to aging, coronary artery disease, stroke, carcinogenesis, neurodegenerative disorders, and inflammatory disorders. Prudence is advised in the excessive consumption of meat and iron supplementation of the diet until this process is more thoroughly investigated.
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PMID:Ironic catastrophes: one's food--another's poison. 819 51

Cancers of many types are major chronic diseases with a high fatality rate and a high cost to society. In the USA, the Delaney Clause was implemented in 1958 because the public believed that many cancers stem from food additives and food contaminants. In the intervening years, research has provided key information about the mechanisms of carcinogenesis and demonstrated that there are two major classes of carcinogens, genotoxic and non-genotoxic. Two case reports are presented, of sodium saccharin and ethylenebisdithiocarbamates that were banned based on the Delaney Clause in an unjustified manner, based on the underlying mechanisms not relevant for non-genotoxic carcinogens. Also, the causes of major cancers have been discovered. Most cancers are associated with lifestyle, specifically tobacco and excessive alcohol use, inappropriate nutritional traditions, and lack of exercise. These lifestyle components involve now known genotoxic carcinogens and importantly, non-genotoxic carcinogens. The effect of non-genotoxic carcinogens is highly dose dependent and also reversible upon lowering the dose below a threshold. Thus, it is quite possible to lower human cancer risk, and also the risk of related chronic diseases such as coronary heart disease, hypertension and stroke, adult on-set diabetes, by proper lifestyle adjustments. Clearly, the Delaney Clause plays no role in disease prevention.
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PMID:Human protection against non-genotoxic carcinogens in the US without the Delaney Clause. 867 78

Oxidative modification of DNA, proteins and lipids by reactive oxygen species (ROS) plays a role in aging and disease, including cardiovascular, neurodegenerative and inflammatory diseases and cancer. Extracts of fresh garlic that are aged over a prolonged period to produce aged garlic extract (AGE) contain antioxidant phytochemicals that prevent oxidant damage. These include unique water-soluble organosulfur compounds, lipid-soluble organosulfur components and flavonoids, notably allixin and selenium. Long-term extraction of garlic (up to 20 mo) ages the extract, creating antioxidant properties by modifying unstable molecules with antioxidant activity, such as allicin, and increasing stable and highly bioavailable water-soluble organosulfur compounds, such as S-allylcysteine and S-allylmercaptocysteine. AGE exerts antioxidant action by scavenging ROS, enhancing the cellular antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase, and increasing glutathione in the cells. AGE inhibits lipid peroxidation, reducing ischemic/reperfusion damage and inhibiting oxidative modification of LDL, thus protecting endothelial cells from the injury by the oxidized molecules, which contributes to atherosclerosis. AGE inhibits the activation of the oxidant-induced transcription factor, nuclear factor (NF)-kappa B, which has clinical significance in human immunodeficiency virus gene expression and atherogenesis. AGE protects DNA against free radical--mediated damage and mutations, inhibits multistep carcinogenesis and defends against ionizing radiation and UV-induced damage, including protection against some forms of UV-induced immunosuppression. AGE may have a role in protecting against loss of brain function in aging and possess other antiaging effects, as suggested by its ability to increase cognitive functions, memory and longevity in a senescence-accelerated mouse model. AGE has been shown to protect against the cardiotoxic effects of doxorubicin, an antineoplastic agent used in cancer therapy and against liver toxicity caused by carbon tetrachloride (an industrial chemical) and acetaminophen, an analgesic. Substantial experimental evidence shows the ability of AGE to protect against oxidant-induced disease, acute damage from aging, radiation and chemical exposure, and long-term toxic damage. Although additional observations are warranted in humans, compelling evidence supports the beneficial health effects attributed to AGE, i.e., reducing the risk of cardiovascular disease, stroke, cancer and aging, including the oxidant-mediated brain cell damage that is implicated in Alzheimer's disease.
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PMID:Antioxidant health effects of aged garlic extract. 1123 7

The idea that diseases such as cardiovascular disease and cancer can be prevented by taking a 'pill' is attractive to many people. Chemoprevention is an established method in the primary and secondary prevention of cardiovascular disease such as myocardial infarct and stroke. Clinical trials have demonstrated beyond reasonable doubt that both fatal and non-fatal coronary events and strokes can be prevented. Antihypertensive drugs have been shown to be effective through clinical trials in preventing myocardial infarctions, stroke and other cardiovascular morbidity and mortality. Statins are commonly used to lower the blood cholesterol concentration, and aspirin is widely used to prevent occlusive vascular disease. Aspirin and other non-steroidal antiinflammatory agents have shown promise in the chemoprevention of colorectal cancer. While observational epidemiological studies have consistently suggested that diets rich in antioxidants such as beta-carotene might be useful in preventing coronary heart disease and cancer, the published reports of randomized trials clearly indicate that beta-carotene supplements are of no value in persons of high risk for such conditions. Although the chemoprevention of cancer is decades behind that of cardiovascular disease, there is no reason to believe that progress in cancer chemoprevention will differ substantially from that in cardiovascular disease. Better understanding of the molecular steps critical to carcinogenesis should open new avenues for cancer chemoprevention.
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PMID:Prevention of disease with pharmaceuticals. 1124 5

Recent studies have reported that estrogen replacement therapy (ERT) reduces the risk of cardiovascular diseases in postmenopausal women. However, mechanisms responsible for this effect are not yet completely understood, and ERT is associated with carcinogenic side effects in women and feminizing effects in men. Because soybean isoflavones, a group of natural phytoestrogens, have only weak estrogenic activity and are not known to have side effects such as carcinogenesis and feminization, we evaluated the effects of genistein, daidzein and glycitein on the growth and DNA synthesis of aortic smooth muscle cells (SMC) from stroke-prone spontaneously hypertensive rats (SHRSP). SMC were cultured in dishes and proliferated on 10% dextran-coated charcoal/fetal bovine serum, and then treated with 0.1-30 micromol/L of genistein, daidzein or glycitein to investigate cell proliferation (cell number) and DNA synthesis (cell proliferation ELISA system), respectively. We also studied their effects on platelet-derived growth factor (PDGF)-BB (20 microg/L)-induced SMC proliferation. Soybean isoflavones inhibited proliferation and DNA synthesis of SMC from SHRSP in a concentration-dependent manner. Inhibition was significant at 3 micromol/L of genistein and 10 micromol/L of both daidzein and glycitein. For significant inhibition of PDGF-BB-induced SMC proliferation, concentrations as low as 0.1 micromol/L of each isoflavone were effective. These isoflavones, with their inhibitory effects on natural and PDGF-BB-induced SMC proliferation, may be useful in attenuatating such proliferation, a basic mechanism involved in atherosclerotic vascular change, thereby preventing atherosclerotic cardiovascular diseases.
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PMID:Genistein, daidzein and glycitein inhibit growth and DNA synthesis of aortic smooth muscle cells from stroke-prone spontaneously hypertensive rats. 1128 18


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