Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with anorexia nervosa (AN) often show normal to elevated physical activity levels despite severe weight loss and emaciation. This is seemingly in contrast to the loss of energy and fatigue characteristic of other starvation states associated with weight loss. Despite the fact that historical accounts and clinical case studies of AN have regularly commented on the elevated activity levels, the behavior has become only recently the subject of systematic study. Because rodents and other species increase their activity upon food restriction leading to weight loss when given access to an activity wheel--a phenomenon referred to as activity-based anorexia or semi-starvation-induced hyperactivity (SIH)-it has been proposed that the hyperactivity in AN patients may reflect the mobilization of phylogenetically old pathways in individuals predisposed to AN. Exogeneous application of leptin in this animal model of AN has recently been shown to suppress completely the development of SIH. Hypoleptinemia, as a result of the food restriction, may represent the initial trigger for the increased activity levels in AN patients and in food-restricted rats. In the first and second parts of our review, we will summarize the relevant findings pertaining to hyperactivity in AN patients and in the rat model, respectively. We conclude with a synopsis and implications for future research.
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PMID:Hyperactivity in patients with anorexia nervosa and in semistarved rats: evidence for a pivotal role of hypoleptinemia. 1281 7

Sleep research on eating disorders has addressed two major questions: (1) the effects of chronic starvation in anorexia nervosa and of rapidly fluctuating eating patterns in bulimia nervosa on the sleep regulating processes and (2) the search for a significant neurobiological relationship between eating disorders and major depression. At present, the latter question appears to be resolved, since most of the available evidences clearly underline the notion that eating disorders (such as anorexia and bulimia nervosa) and affective disorders are two distinct entities. Regarding the effects of starvation on sleep regulation, recent research in healthy humans and in animals demonstrates that such a condition results in a fragmentation of sleep and a reduction of slow wave sleep. Although several peptides are supposed to be involved in these regulatory processes (i.e. CCK, orexin, leptin), their mode of action is still poorly understood. In opposite to these experimentally induced sleep disturbances are the findings that the sleep patterns in eating disorder patients per se do not markedly differ from those in healthy subjects. However, when focusing on the so-called restricting anorexics, who maintain their chronic underweight by strictly dieting, the expected effects of malnutrition on sleep can be ascertained. Furthermore, at least partial weight restoration results in a 'deepening' of nocturnal sleep in the anorexic patients. However, our knowledge about the neurobiological systems (as well as their circadian pattern of activity) that transmit the effects of starvation and of weight restoration on sleep is still limited and should be extended to metabolic signals mediating sleep.
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PMID:Sleep in eating disorders. 1503 50

Cachexia is among the most debilitating and life-threatening aspects of cancer and is more common in children and elderly patients. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. This process results from a failure of the adaptive feeding response seen in simple starvation and includes cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. Cytokines play a pivotal role in long-term inhibition of feeding by mimicking the hypothalamic effect of excessive negative feedback signaling from leptin, a hormone secreted by adipose tissue, which is an integral component of the homeostatic loop of body weight regulation. This could be caused by persistent inhibition of the feeding-stimulatory circuitry including neuropeptide Y. Cachexia should be suspected in patients with cancer if an involuntary weight loss of greater than five percent of premorbid weight occurs within a 3-6-month period. The two major options for pharmacological therapy have been either progestational agents or corticosteroids. However, knowledge of the mechanisms of cancer anorexia-cachexia syndrome has led to, and continues to lead to, effective therapeutic interventions for several aspects of the syndrome. These include antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids, eicosapentanoic acid, cannabinoids, melatonin, and thalidomide all of which act on the feeding-regulatory circuitry to increase appetite and inhibit tumor-derived catabolic factors to antagonize tissue wasting and/or host cytokine release. Because weight loss shortens the survival time of cancer patients and decreases performance status, effective therapy would extend patient survival and improve quality of life.
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PMID:[Pathogenesis and treatment of cancer anorexia-cachexia, with special emphasis on aged patients]. 1551 19

Anorexia nervosa is an eating disorder defined by a symptomatic triad, anorexia, emaciation and amenorrhoea. This disease mainly affects young women. Besides these three symptoms, hyperactivity is often associated with anorexia nervosa. Hyperactivity can be considered as a strategy to lose weight, but studies on animal models have shown that it could be explained by more complicated mechanisms. Hyperactivity is defined by an excess of physical activity, which can induce social, professional and family consequences. Hyperactivity can take different forms, most striking is the restless one. Patients with anorexia nervosa are not all hyperactive. Brewerton et al. have compared patients with anorexia nervosa and hyperactivity to patients without hyperactivity. Hyperactive patients are more dissatisfied by their body image, they use less means of purging (laxatives, vomiting), and they start starving earlier than patients without hyperactivity. Many factors can promote the emergence and maintenance of hyperactivity, especially social and cultural requirements, sports environment, family influences. Various models can explain the links between excessive exercise and anorexia nervosa. Epling and Pierce have exposed a behavioural model which shows how hyperactivity can lead to starvation, creating a self-maintained cycle. Eisler and Le Grande have described four models to explain the links between hyperactivity and anorexia nervosa. First, excessive exercise can be considered as a symptom of anorexia nervosa. It can also promote the development of eating disorders. Anorexia nervosa and hyperactivity can be a manifestation of an other psychiatric disorder. At least, hyperactivity can be a variant of anorexia nervosa, which has the same effects, as weight loss. Hyperactivity can also be considered as a kind of obsessive compulsive disorder. Hyperactivity and obsessive compulsive disorders actually share some clinical and neurochemical characteristics. An other model consists in comparing excessive exercise in anorexia nervosa to an addictive behaviour. Self-starvation exacerbated by hyperactivity can be considered as an addiction to endogenous opioid. Few studies are carried out in order to estimate the prevalence of high level exercise in the eating disorders. Davis et al. have achieved a prevalence study. The results indicate that a large majority of patients with anorexia nervosa (80,8%) were exercising excessively during an acute phase of the disorder. Research on animals, specially on rats, brings us an interesting model explaining interactions between anorexia nervosa and hyperactivity. With animal models, we have noticed that, when rats with access to a running wheel, are restricted in their food intake, they become excessively active, and paradoxically reduce food consumption. Many searchers have tried to explain this phenomenon. Morse et al. have pointed from animal models that the level of hyperactivity was linked to the severity of food restriction. This result can be explained by a failure of a part of the brain involved in rest and activity regulation. Animal research brings us explanations about the effects of starvation on the endocrine system and the neurotransmitters. Broocks et al. have shown that corticosterone concentration in plasma was synergistically increased by semi starvation and exercise, and the reduction of triiodothyronine by semi starvation was significantly greater in the running wheel group. An other study of Broocks et al. has revealed an increased hypothalamic serotonin metabolism with the combined effect of hyperactivity and food restriction. Tryptophan, an amid acid involved in serotonin synthesis, can also play a role in the maintenance of anorexia nervosa. In starvation conditions, opioid releasing caused by physical exercise would decrease food intake. Exner's study and Adan's one have shown that leptin would be involved in semi starvation induced hyperactivity mechanisms. In spite of animal models can not be entirely generalized to human, they are useful to try to explain biological supports of hyperactivity. Hyperactivity is not only a strategy to lose weight, but also a specific symptom which completes the clinical triad. Animal studies have led to promising results; we might use medicine, such as serotonin reuptake inhibitors or opioid antagonists in the treatment of hyperactivity in anorexia nervosa.
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PMID:[Hyperactivity and anorexia nervosa: behavioural and biological perspective]. 1562 53

Ghrelin is a peptidic hormone composed of 28 aminoacid residues. It is produced by enteroendocrine cells of stomach and intestine. It is also produced in pancreas, kidney, placental tissue, thyroid gland, hypothalamus, and hypophysis. Gastrectomy leads to 65-80% decrease of plasma levels of ghrelin. In human organism, ghrelin stimulates secretion of growth hormone, prolactin, and ACTH. Ghrelin also has orexigenic activity (increases food intake), influences the sleep/wake cycle, gastric motility and secretion, cardiovascular functions, regulates endocrine function of pancreas and metabolism of glucose and shows an antiproliferative effect. Ghrelin is an important regulatory part of the homeostasis of the organism, and iterconnects neuroendocrine and metabolic response of the organism to starvation, and it is considered as a counterpart to leptin. Ghrelin was discovered by Japanese scientists in 1999 as a natural ligand of an "orphan" receptor GHS1a, which is specific for a group of synthetic peptides (growth hormone secretagogues--GHS) stimulating secretion of growth hormone. Plasma levels of ghrelin reflect short-time changes of food intake, as well as long-time changes of the nutritional state of the organism. Plasma levels of ghrelin are decreased after food intake and in obese humans, and they are increased during starvation and in patients with mental anorexia. Plasma levels of ghrelin in humans correlate negatively with body mass index, amount of body fat, size of adipocytes, and plasma levels of insulin, glucose, and leptin. Thus, ghrelin probably plays a role as a metabolic signal of hunger.
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PMID:[Ghrelin--structure, function and clinical applications]. 1570 43

Cachexia is among the most debilitating and life-threatening aspects of cancer, and is more common in children and elderly patients. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. This process results from a failure of the adaptive feeding response seen in simple starvation and includes cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. Cytokines play a pivotal role in long-term inhibition of feeding by mimicking the hypothalamic effect of excessive negative feedback signaling from leptin, a hormone secreted by adipose tissue, which is an integral component of the homeostatic loop of body weight regulation. This could be done by persistent inhibition of feeding-stimulatory circuitry including neuropeptide Y. Cachexia should be suspected in patients with cancer if an involuntary weight loss of greater than five percent of premorbid weight occurs within a 3-6-month period. The two major options for pharmacological therapy have been either progestational agents or corticosteroids. However, knowledge of the mechanisms of cancer anorexia-cachexia syndrome has led to, and continues to lead to, effective therapeutic interventions for several aspects of the syndrome. These include antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids, eicosapentanoic acid, cannabinoids, melatonin, and thalidomide-all of which act on the feeding-regulatory circuitry to increase appetite and inhibit tumor-derived catabolic factors to antagonize tissue wasting and/or host cytokine release. The outcomes of drug studies in cancer cachexia should focus on the symptomatic and quality-of-life advantages rather than simply on nutritional end points, since the survival of cachexia cancer patients may be limited to weeks or months due to the incurable nature of the underlying malignancy. Communication among physicians and other health care professionals provides the patient with a multidisciplinary approach to care. The patient record will be an excellent resource to document a plan of care and patient responses to treatment. Psychological distress and psychiatric disorders are common among cancer patients. These problems are also as common among the family members of people with cancer. The use of psychological and behavioral interventions in cancer is increasing, and recent studies have suggested that some of these techniques may affect quality of life and, perhaps, survival rates. Evaluations of relaxation, hypnosis, and short-term group psychotherapy have suggested some benefit with regard to anorexia and fatigue, although the population most likely to benefit from these interventions has not yet been determined. Because weight loss shortens the survival time of cancer patients and decreases performance status, effective therapy would extend patient survival and improve quality of life.
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PMID:[Recent development in research and management of cancer anorexia-cachexia syndrome]. 1598 10

Anorexia (anx) is a recessive mutation that causes lethal starvation in homozygous mice. Studies of anx/anx mice hypothalamus have shown abnormalities in the orexigenic (NPY/AGRP neurons) and the anorexigenic (POMC/CART neurons) pathways. By gene expression profiling using cDNA and oligonucleotide microarrays, we have shown that a surexpression of genes involved in inflammatory process occurred in anx mice hypothalamus. This inflammatory process could be the cause of the anorexia phenotype observed in these mice.
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PMID:Gene expression profiling reveals an inflammatory process in the anx/anx mutant mice. 1600 7

The cachectic syndrome, characterized by a marked weight loss, anorexia, asthenia, and anemia is invariably associated with the presence and growth of the tumor and leads to a malnutrition status due to the induction of anorexia or decreased food intake. In addition, the competition for nutrients between the tumor and the host leads to an accelerated starvation state, which promotes severe metabolic disturbances in the host, including hypermetabolism, which leads to an increased energetic inefficiency. Although the search for the cachectic factor(s) started a long time ago, and although many scientific and economic efforts have been devoted to its discovery, we are still a long way from knowing the whole truth. Present investigation is devoted to revealing the different signaling pathways, in particular transcriptional factors involved in muscle wasting. The main aim of the present review is to summarize and evaluate the different molecular mechanisms and catabolic mediators (both humoral and tumoral) involved in cancer cachexia since they may represent targets for future promising clinical investigations.
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PMID:Mediators involved in the cancer anorexia-cachexia syndrome: past, present, and future. 1604 25

The progressive deterioration in nutrition status frequently seen in cancer patients is often referred to as cancer cachexia. Unlike starvation, in which fat stores from adipose are depleted and protein is spared from skeletal muscle, neither fat nor protein is spared in cachexia. Cachexia affects nearly half of cancer patients, causing the clinical manifestations of anorexia, muscle wasting, weight loss, early satiety, fatigue, and impaired immune response. Cachexia does not only impede the response to chemotherapy but also is a major cause of morbidity and mortality. According to clinical studies, increasing caloric intake does not necessarily reverse cachexia. The pathophysiology of cachexia involves more complex mechanisms than simply caloric deficiency. The process appears to be mediated by circulating catabolic factors, either secreted by the tumor alone or in concert with host-derived factors, such as tumor necrosis factor-alpha (TNF-alpha), interleukins (IL-1 and IL-6), interferon (IFN-y), and leukemia inhibitory factor (LIF). The successful reversal of this process will require in-depth knowledge of the mechanisms involved, which will then enable the development of effective pharmacologic interventions that may not only improve quality of life, but more importantly, improve survival among cancer patients.
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PMID:The cancer cachexia syndrome: a review of metabolic and clinical manifestations. 1620 77

When rats are given access to a running-wheel in combination with food restriction, they will become hyperactive and decrease their food intake, a paradoxical phenomenon known as activity-based anorexia (ABA). Little is known about the regulation of the hypothalamic neuropeptides that are involved in the regulation of food intake and energy balance during the development of ABA. Therefore, rats were killed during the development of ABA, before they entered a state of severe starvation. Neuropeptide mRNA expression levels were analysed using quantitative real-time PCR on punches of separate hypothalamic nuclei. As is expected in a state of negative energy balance, expression levels of agouti-related protein (AgRP) and neuropeptide Y (NPY) were increased 5-fold in the arcuate nucleus (ARC) of food-restricted running ABA rats vs 2-fold in sedentary food-restricted controls. The co-regulated expression of AgRP and NPY strongly correlated with relative body weight and white adipose tissue mass. Arcuate expression of pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) was reduced 2-fold in the ABA group. In second-order neurons of the lateral hypothalamic area (LHA), melanin-concentrating hormone (MCH) mRNA expression was upregulated 2-fold in food-restricted running rats, but not in food-restricted sedentary controls. Prepro-orexin, CART and corticotropin-releasing hormone expression levels in the LHA and the paraventricular nucleus (PVN) were unchanged in both food-restricted groups. From this study it was concluded that during the development of ABA, neuropeptides in first-order neurons in the ARC and MCH in the LHA are regulated in an adequate response to negative energy balance, whereas expression levels of the other studied neuropeptides in secondary neurons of the LHA and PVN are unchanged and are probably regulated by factors other than energy status alone.
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PMID:Hypothalamic neuropeptide expression following chronic food restriction in sedentary and wheel-running rats. 1621 17


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