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Nutrition--mechanisms of immunosuppression.

Nutritionists must formulate diets that supply adequate amounts of nutrients from five major groups. These are carbohydrate, protein (amino acids), fat, minerals and vitamins. Carbohydrate is usually a cheaper source of energy than fat, but fat is often used to increase the caloric concentration of the diet. Variations in energy intake which may effect immunocompetence usually result from management practices rather than diet formulation. Feed restriction for broiler breeders and withholding feed in forced molting practices may affect immunocompetence. Feed restriction causes higher plasma corticosterone levels, which are known to decrease the immune response, possibly through effects on cytokines. Excessive feed, through forced feeding, may also have short-term effects on indicators of humoral immunity. Protein and amino acid nutrition have been studied in relation to immunocompetence. The level of dietary amino acid needed to maximize growth and feed efficiency will also generally maximize measures of immunocompetence. The level of amino acids needed for maximum growth is lower in chicks which have been immunologically stressed than in chicks which have not. An immune response changes metabolism so that less growth occurs, thereby decreasing the need for amino acids. Dietary levels of minerals can affect immunocompetence. While deficient levels of sodium and chloride decrease humoral immunity, levels of these nutrients which supported maximum growth also supported maximal humoral immunity. Low dietary zinc levels did not affect indicators of immunocompetence in the chick. The effect of fat soluble vitamin levels on the immune system has been studied. Vitamin A is needed to maintain epithelial tissue and prevent infection. Cellular immune response is decreased when the chick is deficient in this nutrient. Several indicators of immune responsiveness are depressed when chicks are vitamin E and/or selenium deficient. Since these nutrients serve as antioxidants, cellular integrity may be affected by a deficiency. Cellular integrity is very important for receiving, and responding to the messages needed to coordinate an immune response. High levels of vitamin E (greater than 10 times the required level) have been found to be immunostimulatory.

Animal Nutritional Physiological Phenomena↗

Drug-nutrient interactions and their implications for safety evaluations.

In order to assess the relevance of the drug-nutrient interactions described in this chapter to routine toxicologic studies, the range of nutrient concentrations within which these interactions may occur must be compared to the range of nutrient concentrations found in routinely used rodent diets. While obviously deficient levels of some nutrients were supplied to demonstrate some of the interactions, others occur when the nutrients are present in adequate or excess levels, such as might be found in commercially available diets. These diets are known to vary from batch to batch in nutrient content. A lifetime toxicity/carcinogenicity bioassay using rodents may last longer than 2 years, during which time several batches of diet will be used. The variation in diet composition, coupled with inadequate diet description, makes nutrient-toxin interactions not only possible, but difficult to recognize. These considerations raise the practical and philosophical question as to what type of diet is most appropriate for rodents used for safety evaluation of drugs and chemicals. Is it appropriate to use diets that vary unpredictably in nutrient content, that infer a degree of protection against chemical carcinogenesis and which supply some nutrients such as protein in great excess of dietary needs? Is the increase in sensitivity to chemical carcinogens of animals fed purified diets desirable or does this increased sensitivity of the bioassay exceed that required to assess the risk of human exposure? In other words, is the use of purified diets likely to increase the number of false positive results? Proper interpretation and extrapolation of safety evaluation studies requires adequate description of the test system. Given the profound influence of diet on the response to some toxins, the composition of the diet should, ideally, be defined with the same rigor as are the test compound and the strain, age, sex, and housing conditions of the animals. It is likely, however, that natural ingredients diets will continue to be the diets of choice in safety evaluation studies. This is largely due to economic reasons. It is possible, however, to use these diets with greater confidence if open-formula diets are used and the concentration of each nutrient is reported. Consideration should also be given to preparing diets for use in adult and aging rodents, diets in which protein content is reduced.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Feed↗

An alternative pathogenetic pathway for oral submucous fibrosis (OSMF).

Oral submucous fibrosis is a potent pre-cancerous condition which occurs almost exclusively in Indians but cases have been reported from several countries. The definite aetiology of OSMF is still unknown and there is no known treatment for it. Chilles, tobacco use, vitamin deficiencies and betel quid chewing have been implicated. Ramanathan is of the view that OSMF seems to be the Asian version of sideropenic dysphagia. He suggests that OSMF appears to be an altered oral mucosa following prolonged period of chronic deficiency of iron and/or vitamin "B" complex especially folic acid. This changed state of the oral mucosa subsequently appears to develop more easily a hypersensitivity to oral irritants such as spices especially chillies and to the betel quid. We hold that the hypersensitivity caused by local irritants and the resultant persistent juxta epithelial inflammatory response noted in OSMF (in a host system already primed by an intrinsic genetic defect) act as the initiating factor leading to a defective inflammatory--reparative response, culminating in fibrotic healing. The role of iron and "B"complex together with others may be contributory (promotor) to this pre-existing pathologic response of the lamina propria.

Anemia↗

Rat embryo culture to detect nutritional deficiency in women with poor reproductive histories.

The cause of habitual early pregnancy loss is not known for most affected couples. It has been proposed that a deficiency of amino acids or other nutrients may contribute to early embryo loss, and an assay based on culture of rat embryos in human serum has been proposed to evaluate women with poor reproductive histories. We tested this assay in women with unexplained infertility (n = 27), habitual abortion (n = 15), and normal midtrimester pregnancies (n = 10) by examining the ability of subject's serum to support the normal development of rat embryos in culture with and without supplemental vitamins and amino acids. Nonpregnant women with nutrient deficiencies identified in this manner were given oral supplements or placebo and were retested. A similar proportion of women in each group had serum that was unable to support the normal development of rat embryos without supplemental vitamins and amino acids. When oral supplements were used, most sera were able to support normal embryo growth. There were no seroconversions on placebo. In spite of the apparent success in producing seroconversions on oral supplementation, only two women conceived, one on the placebo treatment and one on nutritional supplements. Because serum nutrient deficiencies identified by rat embryo culture could not distinguish normal pregnant women from women with unexplained infertility or habitual abortion, and because of the low pregnancy rates, we could not confirm the utility of this assay for the general population of women with habitual abortion.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Habitual↗

Clinical aspects of vitamin and trace element metabolism.

An adequate provision of all micronutrients, vitamins and essential trace elements is necessary for maintenance of normal tissue function. In patients requiring nutritional support, these factors are essential for optimal utilization of the major nutrients and play a role in all aspects of intermediary metabolism. In this chapter, some of the main features of the micronutrients have been described, together with suggestions regarding their provision enterally or parenterally. For most of these nutrients, diagnostic methods are not available to permit accurate assessment of status and hence the level of provision necessary for optimal results. However, there is now sufficient understanding of nutritional requirements such that few patients should now develop clinical or biochemical signs of under- or overprovision of micronutrients.

Avitaminosis↗

Lipid quinones.

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Animals↗

Nutritional aspects of alcoholic liver disease.

Development of ethanol-induced fatty liver, alcoholic hepatitis, and cirrhosis has been attributed in part to nutritional deficiencies for many years. Special attention must be focused on treating alcohol-induced liver disease while providing replacement of deficient amino acids, vitamins, minerals, and other nutrients. Avoidance of alcohol intake is required to eliminate progressive liver disease in alcoholics. This is best achieved by using educational and social programs to convince patients and their caretakers of the great necessity to eliminate alcohol intake.

Avitaminosis↗

Effects of vitamin restriction and supplementation on rat intestinal epithelial cell apoptosis.

Diet influences intestinal growth and function and vitamins modulate intestinal cell turnover. We have assessed the effects of chronic, moderate (50% of control) vitamin restriction and supplementation on intestinal epithelial cell (IEC) apoptosis and the relevance of this to alterations in tissue oxidative stress and antioxidant status. Feeding a vitamin-restricted diet to male, weanling WNIN rats for 20 weeks significantly increased IEC apoptosis, but only in the villi region, as evident from increased annexin V staining, M30 positivity, histological observations, DNA ladder formation, and reduced expression of Bcl-2. This was associated with elevated levels of lipid peroxides and protein carbonyls in the intestinal mucosa despite the increased activities of superoxide dismutase, catalase, and glutathione peroxidase. Consistent with the increased oxidative stress and apoptosis, structural and functional integrity of the villi were compromised as evident from the lowered ratio of villus height:crypt depth and the decreased activities of the membrane marker enzymes alkaline phosphatase and Lys-Ala dipeptidyl aminopeptidase. These changes were reversed by supplementation with a vitamin mixture or vitamin E alone, whereas riboflavin or folic acid supplementation reduced the apoptotic rates, but only partially. Further, oxidative stress was the least in vitamin E- or vitamin mixture-supplemented rats and correlated well with their IEC apoptotic rates. Increased tissue oxidative stress seems to mediate the vitamin-restriction-induced apoptosis of the IECs in rats.

Animals↗

Serum fat-soluble vitamin deficiency and abnormal calcium metabolism after malabsorptive bariatric surgery.

Weight loss after biliopancreatic diversion or duodenal switch is due to decreased calorie absorption secondary to fat malabsorption. Fat malabsorption may also cause essential fat-soluble vitamin deficiencies, which may have severe clinical consequences and alter calcium metabolism. Serum vitamins A, D, E, and K, zinc, parathyroid hormone, corrected calcium, and alkaline phosphatase levels were measured in a cohort of patients who had previously undergone biliopancreatic diversion. Two bariatric surgery units were involved in the study: New York University School of Medicine (New York, NY), and the Wesley Medical Center (Brisbane, Australia). A total of 170 patients completed the study. The incidence of vitamin A deficiency was 69%, vitamin K deficiency 68%, and vitamin D deficiency 63% by the fourth year after surgery. The incidence of vitamin E and zinc deficiency did not increase with time after surgery. The incidence of hypocalcemia increased from 15% to 48% over the study period with a corresponding increase in serum parathyroid hormone values in 69% of patients in the fourth postoperative year. There is a progressive increase in the incidence and severity of hypovitaminemia A, D, and K with time after biliopancreatic diversion and duodenal switch. Calcium metabolism is affected with an increasing incidence of secondary hyperparathyrodisim and evidence of increased bone resorption in 3% of patients. Long-term nutritional monitoring is necessary after malabsorptive operations for morbid obesity.

Adolescent↗

Preoperative nutritional status of patients undergoing Roux-en-Y gastric bypass for morbid obesity.

Few data exist concerning preoperative nutritional status in patients undergoing bariatric surgery. We retrospectively analyzed the preoperative values of serum albumin, calcium, 25-OH vitamin D, iron, ferritin, hemoglobin, vitamin B12, and thiamine in 379 consecutive patients (320 women and 59 men; mean body mass index 51.8 +/- 10.6 kg/m2; 25.8% white, 28.4% African American, 45.8% Hispanic) undergoing bariatric surgery between 2002 and 2004. Preoperative deficiencies were noted for iron (43.9%), ferritin (8.4%), hemoglobin (22%; women 19.1%, men 40.7%), thiamine (29%), and 25-OH vitamin D (68.1%). Low ferritin levels were more prevalent in females (9.9% vs. 0%; P = 0.01); however, anemia was more prevalent in males (19.1% vs. 40.7%; P < 0.005). Patients younger than 25 years were more likely to be anemic than patients over 60 years (46% vs. 15%; P < 0.005). This correlated with iron deficiency, which was more prevalent in younger patients (79.2% vs. 41.7%; P < 0.005). Whites (78.8%) and African Americans (70.4%) had a higher prevalence of vitamin D deficiency than Hispanics (56.4%), P = 0.01. Whites were the least likely group to be thiamine deficient (6.8% vs 31.0% African Americans and 47.2% Hispanics; P < 0.005). Nutritional deficiencies are common in patients undergoing Roux-en-Y gastric bypass, and these deficiencies should be detected and corrected early to avoid postoperative complications.

Adult↗

Mineral and vitamin deficiencies can accelerate the mitochondrial decay of aging.

Mitochondrial oxidative decay, which is a major contributor to aging, is accelerated by many common micronutrient deficiencies. One major mechanism is inhibition of the pathway of heme biosynthesis in mitochondria, which causes a deficit of heme-a. Heme-a, only found in Complex IV, is selectively diminished, resulting in oxidant leakage and accelerated mitochondrial decay, which leads to DNA damage, neural decay, and aging. We emphasize those deficiencies, which appear to cause damage through this mechanism, particularly minerals such as iron (25% of menstruating women ingest <50% of the RDA) or zinc (10% of the population ingest <50% of the RDA). Several vitamin deficiencies, such as biotin or pantothenic acid, also increase mitochondrial oxidants through this mechanism. Additionally, other minerals such as magnesium and manganese that play a role in mitochondrial metabolism, but do not affect heme directly, are discussed. An optimum intake of micronutrients could tune up metabolism and give a marked increase in health, particularly for the poor, elderly, and obese, at little cost.

Aging↗

Nutritional disorders in the elderly.

Undernutrition is common in older people and has serious adverse effects. Weight loss and low body weight are key markers. Correctable causes, such as depression, are common and should be sought. Structured efforts to encourage food intake, together with nutritional supplements, often are of benefit. It is hoped that a better understanding of the underlying mechanisms will lead to targeted treatments. Overweight and obesity also are common in older people, and are associated with morbidity and impaired function. It is probably appropriate to recommend weight loss to obese older people who have associated comorbidities, particularly reduced mobility, but seldom, if ever, for increased weight alone.

Aged↗

Arguments for a lower carbohydrate-higher fat diet in patients with a short small bowel.

Short small bowel patients suffer from malabsorption due to a strongly reduced small bowel surface. These patients usually get a high caloric high carbohydrate-low fat diet at oral or enteral feeding. At several points our studies demonstrate that the effect of this formula is doubtful. In these patients the intestinal flora has strongly been changed and even become characteristic due to abundant presence of lactobacilli (up to nearly 100%). In many patients with a high carbohydrate-low fat diet these bacteria both produce massive amounts of d-lactic acid and gaseous CO2, and they destroy the primary bile acids that are necessary for uptake of lipids. Thus, they cause (i) an increased risk of D-lactic acidosis and D-lactic acid-associated encephalopathy, (ii) flatulence, abdominal pain and non-infectious diarrhoea, and (iii) low uptake of fat and lipophilic vitamins. It is argued that by gradually converting the diet to a low carbohydrate-high fat diet growth of the characteristic lactobacilli can be strongly reduced and so also the mentioned inconveniences.

Acidosis, Lactic↗

Chronic low intake of protein or vitamins increases the intestinal epithelial cell apoptosis in Wistar/NIN rats.

OBJECTIVE: Malnutrition decreases antioxidant defense and increases oxidative stress in the intestine. We studied the effects of long-term restriction of food, protein, and vitamins on intestinal epithelial cell (IEC) apoptosis and the underlying mechanisms. METHODS: Weanling, Wistar/NIN male rats were fed ad libitum with a control diet, 75% protein-restricted diet, or 50% vitamin-restricted diet for 20 wk. The food-restricted group received 50% of the diet consumed by control rats. IEC apoptosis was monitored by morphometry, Annexin V binding, M30 CytoDeath assay, and DNA fragmentation. Structural and functional integrity of the villus were assessed by the ratio of villus height to crypt depth, and alkaline phosphatase and lys, ala-dipeptidyl aminopeptidase activities, respectively. Oxidative stress parameters, caspase-3 activity, and expression of Bcl-2 and Bax were determined to assess the probable mechanisms of altered apoptosis. RESULTS: Protein and vitamin restrictions but not food restriction significantly increased IEC apoptosis and only vitamin restriction altered structural and functional integrity of villi. Increased levels of protein carbonyls, thiobarbituric acid reactive substances, and caspase-3 activity along with decreased glutathione levels and Bcl-2 expression were observed in IECs of these rats, whereas food restriction did not affect these parameters. CONCLUSIONS: Protein restriction increased only IEC apoptosis, whereas vitamin restriction also affected the structure and function of villi. Modulation of the pathway mediated by mitochondria through increased oxidative stress appears to be the probable mechanism underlying this effect.

Animals↗