Instruct: Given a question, retrieve passages that answer the question.
Query: Paleolithic Lessons
Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.
Domoic acid is a potent neurotoxin that is naturally produced by several diatom species of the genus Pseudo-nitzschia. The toxin acts as a glutamate agonist and is excitotoxic in the vertebrate central nervous system and other glutamate receptor-rich organs. Human exposure to domoic acid occurs via the consumption of contaminated shellfish that have accumulated the toxin while filter feeding on toxigenic phytoplankton during blooms. The first reported human domoic acid poisoning event occurred in Canada in 1987 during which clinical signs of acute toxicity such as gastrointestinal distress, confusion, disorientation, memory loss, coma and death were observed. The illness was named amnesic shellfish poisoning (ASP) and due to effective seafood monitoring programs there have been no documented ASP cases since 1987. However, domoic acid poisoning has a significant effect on marine wildlife and multiple poisoning events have occurred in marine birds and mammals over the last few decades. Currently, domoic acid producing diatom blooms are thought to be increasing in frequency world wide, posing an increasing threat to wildlife and human health. Of particular concern are the potential impacts of long-term low-level exposure in "at risk" human populations. The impacts of repetitive low-level domoic acid exposure are currently unknown. This review provides a basic description of the mechanism of action of domoic acid as well as a synthesis of information pertaining to domoic acid exposure routes, toxin susceptibility, and the importance of effective monitoring programs. The importance of investigating the potential human health impacts of long-term low-level domoic acid exposure in "at risk" human populations is also discussed. Published by Elsevier Ltd.
The Yanomamo Indians are an unacculturated tribe inhabiting the tropical equatorial rain forest of northern Brazil and southern Venezuela who do not use salt in their diet. The group therefore presented an unusual opportunity to study the hormonal regulation of sodium metabolism in a culture with life-long extreme restriction of dietary sodium, with parallel observations on blood pressure. Blood pressures increased from the first to second decade but, in constrast to civilized populations, do not systematically increase during subsequent years of life. In twenty-four hour urine collections on adult male Indians, excretion of sodium averaged only 1 plus or minus 1.5 (SD) mEq. Simultaneous plasma renin activities were elevated and comparable to those of civilized subjects placed for brief periods on 10 mEq sodium diets. Similarly, excretion rates of aldosterone equaled those of acculturated subjects on low sodium diets. The findings suggest that the hormonal adjustments to life-long low sodium intakes are similar to those achieved in acute sodium restriction of civilized man. Parenthetically, these elevated levels of aldosterone and renin were probably the norm for man during much of human evolution and suggest that the values observed in civilized controls are depressed by an excessive salt intake in contemporary diets.
It is likely that plant food consumption throughout much of human evolution shaped the dietary requirements of contemporary humans. Diets would have been high in dietary fiber, vegetable protein, plant sterols and associated phytochemicals, and low in saturated and trans-fatty acids and other substrates for cholesterol biosynthesis. To meet the body's needs for cholesterol, we believe genetic differences and polymorphisms were conserved by evolution, which tended to raise serum cholesterol levels. As a result modern man, with a radically different diet and lifestyle, especially in middle age, is now recommended to take medications to lower cholesterol and reduce the risk of cardiovascular disease. Experimental introduction of high intakes of viscous fibers, vegetable proteins and plant sterols in the form of a possible Myocene diet of leafy vegetables, fruit and nuts, lowered serum LDL-cholesterol in healthy volunteers by over 30%, equivalent to first generation statins, the standard cholesterol-lowering medications. Furthermore, supplementation of a modern therapeutic diet in hyperlipidemic subjects with the same components taken as oat, barley and psyllium for viscous fibers, soy and almonds for vegetable proteins and plant sterol-enriched margarine produced similar reductions in LDL-cholesterol as the Myocene-like diet and reduced the majority of subjects' blood lipids concentrations into the normal range. We conclude that reintroduction of plant food components, which would have been present in large quantities in the plant based diets eaten throughout most of human evolution into modern diets can correct the lipid abnormalities associated with contemporary eating patterns and reduce the need for pharmacological interventions.
Dietary restriction (DR) and reduced growth factor signaling both elevate resistance to oxidative stress, reduce macromolecular damage, and increase lifespan in model organisms. In rodents, both DR and decreased growth factor signaling reduce the incidence of tumors and slow down cognitive decline and aging. DR reduces cancer and cardiovascular disease and mortality in monkeys, and reduces metabolic traits associated with diabetes, cardiovascular disease and cancer in humans. Neoplasias and diabetes are also rare in humans with loss of function mutations in the growth hormone receptor. DR and reduced growth factor signaling may thus slow aging by similar, evolutionarily conserved, mechanisms. We review these conserved anti-aging pathways in model organisms, discuss their link to disease prevention in mammals, and consider the negative side effects that might hinder interventions intended to extend healthy lifespan in humans.
Experimentation involving children is not a new phenomenon. Children have been used as research subjects in a diverse set of experiments, including the trials of new vaccines and sera, in efforts to understand normal pediatric anatomy and physiology and in the development of new drugs and procedures. Concern about child participants in research is also not a new development. For more than a century, critics of medical research have called attention to the fact that children and other vulnerable populations--pregnant women, prisoners, the mentally ill--have too often served as the unwitting and unwilling subjects of medical experiments. This paper looks at several early cases in which children participated, including the first trial of cowpox vaccine, the first human trial of rabies vaccine, and the first treatment of Listerian wound antisepsis. The history of concern for children, especially institutionalized children, in medical research is considered along with the development of regulations or guidelines, including the Declaration of Helsinki (1964).
OBJECTIVE: Obesity results from protracted energy imbalance. Whether this comprises excessive energy intake, lowered physical activity or both, remains disputed. DESIGN: Physical activity energy expenditure, evaluated in three different ways from daily energy expenditure (DEE) measured using doubly labelled water, was examined for trends over time. Data included subjects in Europe (Maastricht, the Netherlands) and North America extending back to the 1980s. These data were compared with measures from the third world, and measures made on wild terrestrial mammals. RESULTS: Physical activity expenditure in Europe (residual of the regression of DEE on basal energy expenditure (BEE)) has slightly but significantly increased since the 1980s. There was no trend over time in physical activity level (PAL=DEE/BEE), or in the residual variance in DEE once mass, sex and age were accounted for. This latter index of physical activity expenditure also significantly increased over time in North America. DEE of individuals in Europe and North America was not significantly different from individuals measured in the third world. In wild terrestrial mammals, DEE mostly depended on body mass and ambient temperature. Predicted DEE for a 78 kg mammal living at 20 degrees C was 9.2 MJ per day (95% CI: 7.9-12.9 MJ per day), not significantly different from the measured DEE of modern humans (around 10.2-12.6 MJ per day). CONCLUSION: As physical activity expenditure has not declined over the same period that obesity rates have increased dramatically, and daily energy expenditure of modern man is in line with energy expenditure in wild mammals, it is unlikely that decreased expenditure has fuelled the obesity epidemic.
In this third installment of the series, we point out that the absence of an explicit, detailed and plausible hypothesis linking hypercholesterolemia to the events in the artery wall was probably an important reason for continuing skepticism and for failure to treat elevated blood cholesterol levels. The rapid advances in understanding of lipoprotein metabolism in the 1950s and 1960s and the application of modern cellular biology in the 1970s provided the context for a modern consensus on pathogenetic mechanisms of atherogenesis.
A method for culturing cysticerci that allows successful evagination and growth of scolexes from metacestodes of Taenia solium was used to study the survival of cysticerci subjected to low temperatures. Refrigeration of pork muscle infested with cysticerci at temperatures above 0 degrees C did not affect the parasites' survival in culture. Conversely, freezing of meat prevented survival of cysts. A practical procedure to kill cysticerci is the storage of pork muscle for four days at -5 degrees C, three days at -15 degrees C, or one day at -24 degrees C. These simple measures would help prevent the most frequent parasitosis of man's central nervous system.
The Kuna Indians who reside in an archipelago on the Caribbean Coast of Panama have very low blood pressure levels, live longer than other Panamanians, and have a reduced frequency of myocardial infarction, stroke, diabetes mellitus, and cancer -- at least on their death certificates. One outstanding feature of their diet includes a very high intake of flavanol-rich cocoa. Flavonoids in cocoa activate nitric oxide synthesis in healthy humans. The possibility that the high flavanol intake protects the Kuna against high blood pressure, ischemic heart disease, stroke, diabetes mellitus, and cancer is sufficiently intriguing and sufficiently important that large, randomized controlled clinical trials should be pursued.
The anti-genotoxic effect of Ocimum sanctum L. extract was studied against the genotoxic effect induced by a synthetic progestin cyproterone acetate, on human lymphocytes using chromosomal aberrations, mitotic index, sister chromatid exchanges and replication index as a parameters. About 30 microM of cyproterone acetate was treated with O. sanctum L. infusion, at dosages of 1.075 x 10(-4), 2.125 x 10(-4) and 3.15 x 10(-4) g/ml of culture medium. A clear dose-dependent decrease in the genotoxic damage of cyproterone acetate was observed, suggesting a possible modulating role of the plant infusion. The results of the present study suggest that the plant infusion per se does not have genotoxic potential, but can modulate the genotoxicity of cyproterone acetate on human lymphocytes in vitro.
Human gammadeltaT lymphocytes are a subset of T cells and are a first line of defense against microbes and tumors. These gammadeltaT cells can be primed by nitrogen-containing bisphosphonates, and certain short-chain alkylamines. These primed gammadeltaT cells have an enhanced capacity to proliferate and to secrete cytokines upon ex vivo exposure to a wide variety of microbes and tumor cells. The largest dietary source of alkylamines is L-theanine, an amino acid unique to tea beverages that is catabolized to ethylamine. Supplementation of subjects with capsules containing L-theanine and catechins has recently been shown to decrease the incidence of cold and flu symptoms, while enhancing gammadeltaT cell function.
Background. There are places around the world where people live longer and they are active past the age of 100 years, sharing common behavioral characteristics; these places (i.e., Sardinia in Italy, Okinawa in Japan, Loma Linda in California and Nicoya Peninsula in Costa Rica) have been named the “Blue Zones”. Recently it was reported that people in Ikaria Island, Greece, have also one of the highest life expectancies in the world, and joined the “Blue Zones”. The aim of this work work was to evaluate various demographic, lifestyle and psychological characteristics of very old (>80 years) people participated in Ikaria Study. Methods. During 2009, 1420 people (aged 30+) men and women from Ikaria Island, Greece, were voluntarily enrolled in the study. For this work, 89 males and 98 females over the age of 80 yrs were studied (13% of the sample). Socio-demographic, clinical, psychological and lifestyle characteristics were assessed using standard questionnaires and procedures. Results. A large proportion of the Ikaria Study's sample was over the age of 80; moreover, the percent of people over 90 were much higher than the European population average. The majority of the oldest old participants reported daily physical activities, healthy eating habits, avoidance of smoking, frequent socializing, mid-day naps and extremely low rates of depression. Conclusion. Modifiable risk factors, such as physical activity, diet, smoking cessation and mid-day naps, might depict the “secrets” of the long-livers; these findings suggest that the interaction of environmental, behavioral together with clinical characteristics may determine longevity. This concept must be further explored in order to understand how these factors relate and which are the most important in shaping prolonged life.
One outbreak of food poisoning associated with ingestion of the liver of a large lutjanid fish was investigated in this study. The symptoms in three patients primarily included headache, nausea, vomiting, fever, vertigo, and visual disorientation and later included peeling of the skin. The species of fish implicated in this incident was Etelis carbunculus (family Lutjanidae) as determined by direct sequence analysis and PCR plus restriction fragment length polymorphism analysis for detection of the cytochrome b gene. Subsequently, several specimens of E. carbunculus of different body weights were collected, and the level of vitamin A in the muscle and liver was determined by high-performance liquid chromatography. The average level of vitamin A in E. carbunculus muscle was 12 +/- 2 IU/g and that in the liver was 9,844 +/- 7,812 IU/g. Regression models indicate that E. carbunculus with higher body weight and liver weight will have higher levels of vitamin A levels in the liver.
Previously used standards for the diagnosis of precocious puberty in girls no longer appear to be appropriate in the USA, in that a significant number of girls are being seen in paediatricians' offices with breast budding before 8 years of age. The timing of menarche, however, has changed little over the past few decades. Early maturing girls are more likely to become obese in adolescence and adulthood than normal or late maturing girls. Early maturing white girls are heavier at the onset of puberty, but this is not the case for African-American girls or boys of either race. Boys and girls with premature pubarche may be more hyperinsulinaemic than normal children, and girls with premature pubarche more likely to develop functional ovarian and adrenal hyperandrogenism. Early menarche is preceded by prepubertal hyperinsulinaemia. It is proposed that pubertal onset, although not necessarily the tempo of puberty, is influenced by hyperinsulinaemia and insulin resistance. If this hypothesis is correct, insulin resistance may be more prevalent in US children than previously recognized. An advance in timing of onset of puberty has not been noted in other countries, although it is likely that this phenomenon may become more prevalent as other countries adopt a more American lifestyle and diet.
The idea that normal constituents of the diet can influence visual function is not new. As early as 1782, Buzzi identified the yellow of the macula and Schulze (1866) specifically postulated that the yellow pigments led to improvements in human vision. These pigments were later found to be derived from dietary lutein and zeaxanthin that are known to be oxygenated carotenoids (xanthophylls). Walls and Judd (1933) postulated that these yellow intraocular pigments could improve visual performance by absorbing light scattered both within (for example, glare) and outside of the eye (increasing visual range by absorbing blue light scattered in the atmosphere), and by improving spatial vision through enhancing contrast and reducing chromatic blur. In this article, evidence for these ideas is reviewed with particular emphasis towards more recent data on glare effects.
In November 2007 a novel neuropathy, immune-mediated polyradiculoneuropathy (IP), was identified among workers at a Minnesota swine abattoir where a unique compressed air technique was used to remove porcine brains. An epidemiologic investigation at another abattoir in Indiana that also uses this process was launched to evaluate workers self-reporting neurologic illness compatible with IP. A nested case-control study was performed to identify cases and risk factors. Six confirmed, one probable, and three possible IP cases were detected. IP cases were 28-52 years old, of Latino origin, and 62.5% female. Onset dates ranged from April 2005-December 2007; 60% were hospitalized. IP cases at this plant were similar in clinical presentation and exposure risks to those detected in Minnesota. Swine abattoirs using similar brain extraction methods should discontinue this process.
STUDY DESIGN: A histologic study on age-related changes of the human lumbar intervertebral disc was conducted. OBJECTIVES: To investigate comprehensively age-related temporospatial histologic changes in human lumbar intervertebral disc, and to develop a practicable and reliable classification system for age-related histologic disc alteration. SUMMARY OF THE BACKGROUND DATA: No comprehensive microscopic analysis of age-related disc changes is available. There is no conceptual morphologic framework for classifying age-related disc changes as a reference basis for more sophisticated molecular biologic analyses of the causative factors of disc aging or premature aging (degeneration). METHODS: A total of 180 complete sagittal lumbar motion segment slices obtained from 44 deceased individuals (fetal to 88 years of age) were analyzed with regard to 11 histologic variables for the intervertebral disc and endplate, respectively. In addition, 30 surgical specimens (3 regions each) were investigated with regard to five histologic variables. Based on the semiquantitative analyses of 20,250 histologic variable assessments, a classification system was developed and tested in terms of validity, practicability, and reliability. The classification system was applied to cadaveric and surgical disc specimens not included in the development of the classification system, and the scores were assessed by two additional independent raters. RESULTS: A semiquantitative analyses provided clear histologic evidence for the detrimental effect of a diminished blood supply on the endplate, resulting in the tissue breakdown beginning in the nucleus pulposus and starting in the second life decade. Significant temporospatial variations in the presence and abundance of histologic disc alterations were observed across levels, regions, macroscopic degeneration grades, and age groups. A practicable classification system for age-related histologic disc alterations was developed, resulting in moderate to excellent reliability (kappa values, 0.49-0.98) depending on the histologic variable. Application of the classification system to cadaveric and surgical specimens demonstrated a significant correlation with age ( < 0.0001) and macroscopic grade of degeneration ( < 0001). However, substantial data scatter caution against reliance on traditional macroscopic disc grading and favor a histology-based classification system as a reference standard. CONCLUSIONS: Histologic disc alterations can reliably be graded based on the proposed classification system providing a morphologic framework for more sophisticated molecular biologic analyses of factors leading to age-related disc changes. Diminished blood supply to the intervertebral disc in the first half of the second life decade appears to initiate tissue breakdown.
Salicylic acid (SA), which is central to defense mechanisms in plants and the principal metabolite of aspirin, occurs naturally in man with higher levels of SA and its urinary metabolite salicyluric acid (SU) in vegetarians overlapping with levels in patients on low-dose aspirin regimens. SA is widely distributed in animal blood. Fasting for major colorectal surgery did not cause disappearance of SA from plasma, even in patients following total proctocolectomy. A 13C6 benzoic acid load ingested by six volunteers led, between 8 and 16 h, to a median 33.9% labeling of urinary salicyluric acid. The overall contribution of benzoic acid (and its salts) to the turnover of circulating SA thus requires further assessment. However, that SA appears to be, at least partially, an endogenous compound should lead to reassessment of its role in human (and animal) pathophysiology.
The strategy of "manufacturing uncertainty" has been used with great success by polluters and manufacturers of dangerous products to oppose public health and environmental regulation. This strategy entails questioning the validity of scientific evidence on which the regulation is based. While this approach is most identified with the tobacco industry, it has been used by producers of asbestos, benzene, beryllium, chromium, diesel exhaust, lead, plastics, and other hazardous products to avoid environmental and occupational health regulation. It is also central to the debate on global warming. The approach is now so common that it is unusual for the science not to be challenged by an industry facing regulation. Manufacturing uncertainty has become a business in itself; numerous technical consulting firms provide a service often called "product defense" or "litigation support." As these names imply, the usual objective of these activities is not to generate knowledge to protect public health but to protect a corporation whose products are alleged to have toxic properties. Evidence in the scientific literature of the funding effect--the close correlation between the results of a study desired by a study's funder and the reported results of that study--suggests that the financial interest of a study's sponsors should be taken into account when considering the study's findings. Similarly, the interpretation of data by scientists with financial conflicts should be seen in this light. Manufacturing uncertainty is antithetical to the public health principle that decisions be made using the best evidence currently available.
The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.
Fundamental studies of the laxative action of wheat bran were undertaken in the United States in the early decades of the 20th century. Walker in South Africa extended these studies among African blacks and later suggested that cereal fiber protected them against certain metabolic disorders. Trowell in Uganda elaborated this concept with regard to the rarity of common noninfective diseases of the colon. Another stream of inquiry stemmed from the hypothesis of Cleave who postulated that the presence of refined sugar, and to a lesser extent white flour, caused many metabolic diseases, while the loss of fiber caused certain colonic disorders. Meanwhile Burkitt had collected massive evidence of the rarity of appendicitis and many venous disorders in rural Africa and parts of Asia. In 1972 Trowell proposed a new physiological definition of fiber in terms of the residue of plant foods that resisted digestion by alimentary enzymes of man. Southgate has proposed chemical methods to analyze the components of dietary fiber: cellulose, hemicellulose, and lignin.
Left subclavian arterioesophageal fistula resulting from chicken bone ingestion is a rare occurrence. The authors report the death of a 42-year-old Thai female with mental retardation who presented to the hospital with severe hematemesis and arrested Death occurred about 24 hours after laparotomy due to hypovolemic shock Postmortem examination revealed a chicken bone embedded in middle part of esophagus with fistula between the esophagus and the left subclavian artery.
In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.
To determine whether realistic snacks containing added sugar evoke excessive insulin responses, 10 healthy subjects consumed four different snack meals, similar in fat and total energy content. Two snacks were based on sugary, manufactured products (chocolate-coated candy bar; cola drink with crisps) and two on whole foods (raisins and peanuts; bananas and peanuts). After the processed-food snacks, plasma-glucose levels tended to rise higher and to fall lower than after the whole-food snacks. The area under the plasma insulin curve was 70% greater after the manufactured snacks than after the raisin-peanut snack. The banana-peanut snack evoked an intermediate insulin response. One subject had pathological insulinaemia after both manufactured snacks but normal responses after both whole-food snacks. These findings suggest that foods and drinks containing added fiber-depleted sugars stress and sometimes overwhelm homeostatic mechanisms but also suggest that the insulin response to food is influenced by the physical state of the food.