Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003123 (anorexia)
 13,794 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anorexia and reduced energy intake contribute to worsen the prognosis of patients suffering from a number of chronic diseases, by promoting skeletal muscle wasting, leading to the development of malnutrition and eventually cachexia. The pathogenesis of cancer anorexia is still matter of debate. Many possible mediators, including hormones, peptides, and neurotransmitters, appear to be involved. However, consistent animal and clinical data suggest that brain tryptophan and serotonin may represent a common final pathway shared by many contributing factors. Supporting this hypothesis, recent data showed that the manipulation of brain tryptophan availability ameliorates anorexia and food intake in cancer patients.
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PMID:Role of brain tryptophan and serotonin in secondary anorexia. 1520 36

Cytokines contribute to anorexia of diseases. Tumor Necrosis Factor (TNF) and/or interleukin-1 (IL-1) stimulate leptin release, but not insulin. Both affect hypothalamus to decrease food intake (FI). Hypothalamic serotonin (5HT) decreases FI. Its synthesis depends on brain availability of precursor, tryptophan (TRP), which depends on plasma free TRP. Purpose is to test involvement of plasma leptin, insulin, TRP, and thus hypothalamic 5HT in cytokine-induced anorexia in rats. In male rats, IL-1alpha (10 mg/kg/d; n=9), TNFalpha (30 mg/kg/d; n=9), Il-1alpha+TNFalpha (10:30 mg/kg/d; n=9), TRP (100 mg/kg/d, n=8) and saline (n=8; Control) were injected sc for 2 days. FI, BW, plasma free and total TRP, leptin and insulin, and body fat were measured. Data analyzed via ANOVA. IL-1alpha and IL-1alpha+TNFalpha vs others decreased FI and BW. TNFalpha and TRP did not change FI and BW. Plasma total TRP was higher in TRP vs IL-1alpha, TNFalpha, and IL-1alpha+TNFalpha. Plasma free TRP was higher in IL-1alpha and IL-1alpha+TNFalpha vs Control. IL-1alpha and IL-1alpha+TNFalpha decreased leptin and body fat. Insulin in Control was lower than others. Data suggest: i) IL-1alpha increases plasma free TRP, but not total TRP, thus increases hypothalamic 5HT synthesis, resulting in anorexia; ii) leptin does not mediate anorexia, but; iii) insulin may contribute to anorexia induced by cytokines.
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PMID:Plasma leptin, insulin and free tryptophan contribute to cytokine-induced anorexia. 1520 37

Pellagra is a systemic disturbance caused by a cellular deficiency of niacin, resulting from inadequate dietary nicotinic acid and/or its precursors, the essential amino-acid tryptophan. In Europe and North America cases of pellagra are rarely encountered, but in some developing countries this disease is frequent, and is the most frequent clinical feature of nutritional deficiency of adult. The principal causes of pellagra are: nutritional niacin deficiency; chronic alcoholism; gastro-intestinal malabsorption; some medications (5-fluoro-uracil, isoniazid, pyrazinamide ehtionamide, 6-mercaptopurine, hydantoins, phenobarbital and chloramphenicol). The diagnosis of pellagra is based on the patient's history and the presence of "3 D syndrome": dermatitis, diarrhea, and dementia. The dermatitis caused by pellagra is a bilaterally symmetrical erythema at the sites of solar exposure. The dermatitis begins in the form of an erythema with acute or intermittent onset gradually changing to an exsudative eruption on the dorsa of the hand, face, neck, and chest with pruritus and burning. Acute dermatitis of pellagra resembles sunburn in the first stages, sometimes with vesicles and bullae. The gastro-intestinal disturbances are: anorexia, nausea, epigastric discomfort and chronic or recurrent diarrhea. Anorexia and malabsorbative diarrhea lead to a state of malnutrition and cachexia. Stools are typically watery, but occasionally can be bloody and mucoid. Neuropsychologic manifestation included photophobia, asthenia, depression, hallucinations, confusions, memory loss and psychosis. As pellagra advances, patient become disoriented, confused and delirious; then stuporous and finally die. Pathological changes in the skin is non-specific, there are no chemical tests available to definitively diagnose pellagra. However low levels of urinary excretion of N-methylnicotinamide and pyridone indicates niacin deficiency. The treatment of pellagra consisted to exogenous administration of niacin or nicotinamide cures. Topical management of skin lesions with emollients may reduce discomfort. The therapy should also include other B vitamins, zinc and magnesium as well as a diet rich in calories. The prevention is based in the nutritional education (food sources of niacin: eggs, bran, peanuts, meat, poultry, fish, red meat, legumes and seeds), and the eviction of alcohol.
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PMID:[Pellagra]. 1620 85

In this double-blind prospective study, the authors examined the effect of an oral supplement consisting of a branched-chain amino acid (BCAA) mixture or an isonitrogenous placebo on food intake in anorexic cancer patients (n = 28). For all patients, biochemical indices of nutritional status were within the normal range before and after the study. BCAA supplement (3 times 4.8 g/d for 7 consecutive days) increased BCAA concentrations in plasma (+121% on day 7 vs day 0) and decreased the tryptophan/large neutral amino acids (LNAA) ratio by 40%. Meanwhile, incidence of anorexia decreased in the BCAA-treated group (100% prior vs. 45% at the end of the study) but not in the placebo group (84% at the end of the study). The authors conclude that oral BCAA supplement can be safely used in the treatment of cancer-induced anorexia.
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PMID:Effects of administration of oral branched-chain amino acids on anorexia and caloric intake in cancer patients. 1684 68

The immune and neuroendocrine systems are closely involved in the regulation of metabolism at peripheral and central hypothalamic levels. In both physiological (meals) and pathological (infections, traumas and tumors) conditions immune cells are activated responding with the release of cytokines and other immune mediators (afferent signals). In the hypothalamus (central integration), cytokines influence metabolism by acting on nucleus involved in feeding and homeostasis regulation leading to the acute phase response (efferent signals) aimed to maintain the body integrity. Peripheral administration of cytokines, inoculation of tumor and induction of infection alter, by means of cytokine action, the normal pattern of food intake affecting meal size and meal number suggesting that cytokines acted differentially on specific hypothalamic neurons. The effect of cytokines-related cancer anorexia is also exerted peripherally. Increase plasma concentrations of insulin and free tryptophan and decrease gastric emptying and d-xylose absorption. In addition, in obesity an increase in interleukin (IL)-1 and IL-6 occurs in mesenteric fat tissue, which together with an increase in corticosterone, is associated with hyperglycemia, dyslipidemias and insulin resistance of obesity-related metabolic syndrome. These changes in circulating nutrients and hormones are sensed by hypothalamic neurons that influence food intake and metabolism. In anorectic tumor-bearing rats, we detected upregulation of IL-1beta and IL-1 receptor mRNA levels in the hypothalamus, a negative correlation between IL-1 concentration in cerebro-spinal fluid and food intake and high levels of hypothalamic serotonin, and these differences disappeared after tumor removal. Moreover, there is an interaction between serotonin and IL-1 in the development of cancer anorexia as well as an increase in hypothalamic dopamine and serotonin production. Immunohistochemical studies have shown a decrease in neuropeptide Y (NPY) and dopamine (DA) and an increase in serotonin concentration in tumor-bearing rats, in first- and second-order hypothalamic nuclei, while tumor resection reverted these changes and normalized food intake, suggesting negative regulation of NPY and DA systems by cytokines during anorexia, probably mediated by serotonin that appears to play a pivotal role in the regulation of food intake in cancer. Among the different forms of therapy, nutritional manipulation of diet in tumor-bearing state has been investigated. Supplementation of tumor bearing rats with omega-3 fatty acid vs. control diet delayed the appearance of tumor, reduced tumor-growth rate and volume, negated onset of anorexia, increased body weight, decreased cytokines production and increased expression of NPY and decreased alpha-melanocyte-stimulating hormone (alpha-MSH) in hypothalamic nuclei. These data suggest that omega-3 fatty acid suppressed pro-inflammatory cytokines production and improved food intake by normalizing hypothalamic food intake-related peptides and point to the possibility of a therapeutic use of these fatty acids. The sum of these data support the concept that immune cell-derived cytokines are closely related with the regulation of metabolism and have both central and peripheral actions, inducing anorexia via hypothalamic anorectic factors, including serotonin and dopamine, and inhibiting NPY leading to a reduction in food intake and body weight, emphasizing the interconnection of the immune and neuroendocrine systems in regulating metabolism during infectious process, cachexia and obesity.
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PMID:Hypothalamic integration of immune function and metabolism. 1687 87

Man ingests food to mitigate hunger (mediated by physiological and biochemical signals), satisfy appetite (subjective sensation) and because of psychosocial reasons. Satiation biomarkers (stop feeding) are gastric distention and hormones (CCK, GLP-1) and satiety biomarkers (induce feeding) are food-induced thermogenesis, body temperature, glycaemia and also hormones (insulin, leptin and ghrelin). Oxidative metabolism/body composition, tryptophan/serotonin and proinflammatory cytokines are also implicated on hunger physiology. At the present time, ghrelin is the only known circulating orexigenic with potential on hunger/body weight regulation. It is a neuropeptide (endogenous ligand for the GH secretagogue) recently isolated from the oxyntic mucosa and synthesized mainly in the stomach. Its blood concentration depends on diet, hyperglucemia and adiposity/leptin. It is secreted 1-2 hours preprandially and its concentration decreases drastically during the postprandium. Ghrelin acts on the lateral hypothalamus and theoretically inhibits proinflammatory cytokine secretion and antagonizes leptin. Ghrelin physiologically increases food intake and stimulates adipogenesis, gastrointestinal motility and gastric acid secretion, and has other hormonal and cardiovascular functions. Ghrelin blood concentration is reduced in massive obesity, non-alcoholic steatohepatitis, polycystic ovary syndrome, acromegaly, hypogonadism, ageing, short bowel syndrome and rheumatoid arthritis; and increased in primary or secondary anorexia, starvation, chronic liver disease and celiac disease. Cerebral and peritoneal ghrelin administration (rats) and systemic administration (rats and healthy volunteers, cancer patients or patients on peritoneal dialysis) promotes food consumption and increases adiposity, of utmost importance in the treatment of patients with anorexia.
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PMID:[Ghrelin: beyond hunger regulation]. 1705 87

Neuropsychiatric symptoms are commonly related to interferon alpha treatment. The paper summarises the current knowledge about their aetiology, course, and treatment. Interferon alpha is a cytokine with antiviral and antineoplasmatic activity. It is commonly used in the treatment of chronic hepatitis C and B, malignant melanoma, Kaposi sarcoma, renal cancers, and some haematological malignancies. Treatment with interferon alpha is associated with depressive symptoms, cognitive disturbances, chronic fatigue syndrome, dysphoria, anxiety symptoms, anorexia, mania and psychotic states. Up to a half of the patients need psychiatric consultations, 10-25% of them need psychiatric treatment. Neuropsychiatric symptoms are the results of direct affection of CNS by interferon and induced cytokines. They increase hypothalamic-pituitary-adrenal (HPA) activity, alter thyroid function and lead to a behavioural syndrome called 'sickness behaviour'. Moreover interferon induces the activity of 2, 3 indoloamine dioxygenase, the enzyme which converts tryptophan into kynurenine, leads to a reduced level of tryptophan, and thus to a reduced level of central serotonin and to an increased level of neurotoxic kynurenine metabolites. Interferon also affects central opioid receptors and changes dopaminergic and noradrenergic neurotransmission. Serotonin selective reuptake inhibitors (SSRI), other antidepressants i.e. nortriptyline, benzodiazepines, naltrexone, and neuroleptics (for maniac and psychotic states) are used to treat interferon associated psychiatric symptoms. Psychological therapy may also be useful, as well as psychoeducation and behavioural interventions.
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PMID:[Neuropsychiatric symptoms related to interferon alpha]. 1706 50

This article reviews current knowledge about mechanisms responsible for uremic events, especially those that involve the central nervous system (CNS). Anorexia is a frequent complication of the uremic syndrome that contributes to malnutrition in patients on dialysis. Uremic anorexia has been associated with many factors. Traditionally, anorexia in dialysis patients has been regarded as a sign of uremic toxicity; therefore, 2 hypotheses have been proposed: the "middle molecule" and "peak concentration" hypotheses; both of these remain unproved. Recently, our group has proposed the tryptophan-serotonin hypothesis, which is based on a disorder in the amino acid profile that may be acquired when the patient is in uremic status. It is characterized by low concentrations of large neutral and branched chain amino acids in the cerebrospinal fluid. This situation permits a high level of tryptophan transport across the blood-brain barrier and enhances the synthesis of serotonin (the final target responsible for inhibiting appetite). The role of inflammation in the genesis of anorexia-malnutrition is also emphasized. In summary, in the CNS, factors associated with uremic anorexia include high levels within the cerebrospinal fluid of proinflammatory cytokines, leptin, and free tryptophan and serotonin (hyperserotoninergic-like syndrome), along with deficiency of neural nitric oxide (nNO) and disorders in various receptors such as melanocortin receptor-4 (MC4-R). Uremic anorexia is a complex complication associated with malnutrition and high levels of morbidity and mortality. Several uremia-acquired disorders in the CNS such as high cerebrospinal fluid levels of anorexigen substances and disorders in appetite regulator receptors may explain the lack of appetite.
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PMID:Brain activation in uremic anorexia. 1719 34

The general consensus is that brain serotonin (5-HT) inhibits feed intake in teleost fishes and other vertebrates. Dietary manipulations with the 5-HT precursor tryptophan (TRP) have, however, yielded contradictory effects on feed intake, while studies of the endocrine response to stress indicate that the effects of TRP-enriched feed are context dependent. A characteristic behavioural response to stress is a reduction in feed intake, and in the present study we investigated whether pre-treatment with TRP-enriched feed affected stress-induced changes in feeding behaviour in brown trout (Salmo trutta). After acclimatisation in observation aquaria, isolated fish were fed control or TRP-supplemented feed for 7 d, whereupon they were transferred to a novel environment, in which all fish were fed control feed. Transfer to a new environment resulted in decreased feeding in both the TRP pre-treated and the control-treated group. However, this decrease was more pronounced in the control-treated group. Previous experiments have concluded that stimulation of brain 5-HT systems by TRP enhancement does not affect feed intake in salmonid fishes, but in these studies food intake was observed in unstressed animals only. The present study suggests that pre-treatment with dietary TRP attenuates stress-induced anorexia. Hence, it appears that the effect of dietary manipulations of TRP on feeding behaviour is dependent on the stress levels experienced by experimental animals. These behavioural data are discussed in the context of the involvement of 5-HT in appetite regulation.
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PMID:Attenuation of stress-induced anorexia in brown trout (Salmo trutta) by pre-treatment with dietary l-tryptophan. 1734 93

Peripheral administration of interleukin-1 (IL-1) reduces food intake and affects brain serotonergic activity, suggesting a causal relationship. Furthermore, IL-1 increases the brain concentrations of the serotonin precursor, tryptophan (TRP), by unclear mechanism(s). We aimed at confirming the link between IL-1 administration, raised brain TRP concentrations and the development of anorexia, and at investigating the mechanisms of TRP entry into the brain. Thirty adult, overnight fasted Sprague-Dawley rats were randomly assigned to i.p. injections of 1 mug/kg BW of IL-1 alpha (n=10) or vehicle (n=10), or to pair-feeding with IL-1 animals (n=10). After 2 h, food intake, blood plasma concentrations of total TRP, free TRP, large neutral amino acids (LNAA; competing with TRP for brain entry) were measured. Cerebral spinal fluid (CSF) TRP concentrations were also measured. TRP brain availability was assessed by calculating the plasma ratio free TRP/LNAA. Following IL-1 injection, food intake significantly declined in IL-1 rats, which was paralleled by decreased plasma free TRP and increased plasma LNAA. Despite a decrease in the free TRP/LNAA ratios in plasma, IL-1 significantly increased concentrations of TRP in CSF. These data show that the acute peripheral administration of IL-1 induces anorexia and raises CSF TRP levels. Considering the possible role of the raised CSF TRP in influencing brain serotonin activity, it is postulated that increased serotonergic neurotransmission could be involved in IL-1 induced anorexia.
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PMID:Free tryptophan/large neutral amino acids ratios in blood plasma do not predict cerebral spinal fluid tryptophan concentrations in interleukin-1-induced anorexia. 1804 69


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