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)

In summary, the vitamin pantothenic acid is an integral part of the acylation carriers, CoA and acyl carrier protein (ACP). The vitamin is readily available from diverse dietary sources, a fact which is underscored by the difficulty encountered in attempting to induce pantothenate deficiency. Although pantothenic acid deficiency has not been linked with any particular disease, deficiency of the vitamin results in generalized malaise clinically. In view of the fact that pantothenate is required for the synthesis of CoA, it is surprising that tissue CoA levels are not altered in pantothenate deficiency. This suggests that the cell is equipped to conserve its pantothenate content, possibly by a recycling mechanism for utilizing pantothenate obtained from degradation of pantothenate-containing molecules. Although the steps involved in the conversion of pantothenate to CoA have been characterized, much remains to be done to understand the regulation of CoA synthesis. In particular, in view of what is known about the in vitro regulation of pantothenate kinase, it is surprising that the enzyme is active in vivo, since factors that are known to inhibit the enzyme are present in excess of the concentrations known to inhibit the enzyme. Thus, other physiological regulatory factors (which are largely unknown) must counteract the effects of these inhibitors, since the pantothenate-to-CoA conversion is operative in vivo. Another step in the biosynthetic pathway that may be rate limiting is the conversion of 4'-phosphopantetheine (4'-PP) to dephospho-CoA, a step catalyzed by 4'-phosphopantetheine adenylyl-transferase. In mammalian systems, this step may occur in the mitochondria or in the cytosol. The teleological significance of these two pathways remains to be established, particularly since mitochondria are capable of transporting CoA from the cytosol. Altered homeostasis of CoA has been observed in diverse disease states including starvation, diabetes, alcoholism, Reye syndrome (RS), medium-chain acyl CoA dehydrogenase deficiency, vitamin B12 deficiency, and certain tumors. Hormones, such as glucocorticoids, insulin, and glucagon, as well as drugs, such as clofibrate, also affect tissue CoA levels. It is not known whether the abnormal metabolism observed in these conditions is the result of altered CoA metabolism or whether CoA levels change in response to hormonal or nonhormonal perturbations brought about in these conditions. In other words, a cause-effect relation remains to be elucidated. It is also not known whether the altered CoA metabolism (be it cause or result of abnormal metabolism) can be implicated in the manifestations of a disease. Besides CoA, pantothenic acid is also an integral part of the ACP molecule.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pantothenic acid in health and disease. 174 61

Infection-induced malnutrition, the most common form of cytokine-induced malnutrition, results from the actions of proinflammatory cytokines, ie, tumor necrosis factor (TNF) and interleukins 1,6, and 8 (IL-1, IL-6, and IL-8). During acute generalized infections, these cytokines initiate the acute-phase reaction. This reaction is quite stereotyped, and includes fever, malaise, myalgia, headaches, cellular hypermetabolism, and multiple endocrine and enzyme responses. In addition, there is heightened catabolism of muscle proteins and many amino acids; flux of free amino acids into the liver; hepatic synthesis of acute-phase plasma proteins; sequestration of iron and zinc; gluconeo-genesis; insulin resistance; impaired cellular uptake of fatty acids from plasma triglycerides; sizable losses of body nitrogen, potassium, magnesium, phosphate, and zinc; retention of body salt and water; heightened metabolic degradation and/or loss of vitamins; and an activation of the immune system. The pathogenesis of cytokine-induced malnutrition is thus vastly different from the malnutrition caused by uncomplicated starvation. Cytokine-induced malnutrition can have a devastating effect on the immune system and its functions. Although proinflammatory cytokines are found in mucosal fluids, where they contribute to the pathogenesis of inflammatory bowel diseases, it is not known whether cytokines play a role in toxigenic, secretory diarrheas such as cholera, which cause huge losses of body water, electrolytes, and bicarbonate while exhibiting no systemic manifestations of an acute-phase reaction.
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PMID:Herman Award Lecture, 1995: infection-induced malnutrition--from cholera to cytokines. 757 15

Hypothalamic obesity, or intractable weight gain after hypothalamic damage, is one of the most pernicious and agonizing late effects of CNS insult. Such patients gain weight even in response to caloric restriction, and attempts at lifestyle modification are useless to prevent or treat the obesity. The pathogenesis of this condition involves the inability to transduce afferent hormonal signals of adiposity, in effect mimicing a state of CNS starvation. Efferent sympathetic activity drops, resulting in malaise and reduced energy expenditure, and vagal activity increases, resulting in increased insulin secretion and adipogenesis. Pharmacologic treatment is difficult, consisting of adrenergics to mimick sympathetic activity, or suppression of insulin secretion with octreotide, or both. Recently, bariatric surgery (Roux-en-Y gastric bypass, laparoscopic gastric banding, vagotomy) have also been attempted with variable results. Early and intensive management is required to stave off the obesity and its consequences.
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PMID:Hypothalamic obesity: causes, consequences, treatment. 1920 8

Neurons in the arcuate nucleus that produce AgRP, NPY, and GABA (AgRP neurons) promote feeding. Ablation of AgRP neurons in adult mice results in Fos activation in postsynaptic neurons and starvation. Loss of GABA is implicated in starvation because chronic subcutaneous delivery of bretazenil (a GABA(A) receptor partial agonist) suppresses Fos activation and maintains feeding during ablation of AgRP neurons. Moreover, under these conditions, direct delivery of bretazenil into the parabrachial nucleus (PBN), a direct target of AgRP neurons that also relays gustatory and visceral sensory information, is sufficient to maintain feeding. Conversely, inactivation of GABA biosynthesis in the ARC or blockade of GABA(A) receptors in the PBN of mice promote anorexia. We suggest that activation of the PBN by AgRP neuron ablation or gastrointestinal malaise inhibits feeding. Chronic delivery of bretazenil during loss of AgRP neurons provides time to establish compensatory mechanisms that eventually allow mice to eat.
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PMID:Loss of GABAergic signaling by AgRP neurons to the parabrachial nucleus leads to starvation. 1956 47

Obesity is a common complication after craniopharyngioma therapy, occurring in up to 75% of survivors. Its weight gain is unlike that of normal obesity, in that it occurs even with caloric restriction, and attempts at lifestyle modification are useless to prevent or treat the obesity. The pathogenesis of this condition involves the inability to transduce afferent hormonal signals of adiposity, in effect mimicking a state of CNS starvation. Efferent sympathetic activity drops, resulting in malaise and reduced energy expenditure, and vagal activity increases, resulting in increased insulin secretion and adipogenesis. Lifestyle intervention is essentially useless in this syndrome, termed "hypothalamic obesity." Pharmacologic treatment is also difficult, consisting of adrenergics to mimic sympathetic activity, or suppression of insulin secretion with octreotide, or both. Recently, bariatric surgery (Roux-en-Y gastric bypass, laparoscopic gastric banding, truncal vagotomy) have also been attempted with variable results. Early and intensive management is required to mitigate the obesity and its negative consequences.
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PMID:Hypothalamic obesity after craniopharyngioma: mechanisms, diagnosis, and treatment. 2265 17

Of the problems that complicate child-bearing, hyperemesis gravidarum (HG), or severe nausea and vomiting of pregnancy (NVP), is likely one of the most painful with unrelenting retching and vomiting that can lead to measurable injuries such as Mallory-Weiss Syndrome and esophageal rupture, and/or subtle maternal cognitive impairments related to starvation and dehydration. Recognized hallmarks of HG include dehydration, ketonuria, weight loss over 5%, and electrolyte abnormalities not attributable to other causes. Historically providers regarded the hyperemetic as a difficult to treat patient with potentially underlying psychological problems. Sick patients who experience pain and suffering present challenges to care, not excepting NVP. Ill patients can be demanding and agitated. Agitation can be one of the early signs of delirium or altered mental status (AMS). AMS can include previously diagnosed psychiatric conditions as well as new onset of Wernicke's encephalopathy, deliria, insomnia, hallucinations and autoscopy, resulting from various etiologies including and not limited to medications, pain including pain from hunger, vomiting and retching, constipation, dehydration, altered electrolytes, hypoglycemia, malnutrition and sleep deprivation. AMS may have a subtle waxing and waning trajectory, making the condition difficult to diagnosis in early stages. What have not been well elucidated in AMS are subjective images and/or experiences. Whether all AMS experiences are similar is unknown. We believe there may be a transient alteration of cognitive status or "altered sensorium gestosis" (ASG), attributed to the direct insults of hyperemesis gravidarum which will be discussed herein. How prevalent ASG might be is unknown and needs further investigation.
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PMID:Hyperemesis gravidarum: a case of starvation and altered sensorium gestosis (ASG). 2461 34

New tools for mapping and manipulating molecularly defined neural circuits have improved the understanding of how the central nervous system regulates appetite. Studies that focused on Agouti-related protein neurons, a starvation-sensitive hypothalamic population, have identified multiple circuit elements that can elicit or suppress feeding behavior. Distinct axon projections of this neuron population point to different circuits that regulate long-term appetite, short-term feeding, or visceral malaise-mediated anorexia. Here, we review recent studies examining these neural circuits that control food intake.
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PMID:Agouti-related protein neuron circuits that regulate appetite. 2540 52

The ketogenic diet, which has become an increasingly popular diet, severely restricts carbohydrate intake to shunt metabolism towards fatty acid oxidation and production of ketones as a fuel source. There have been many studies illustrating the positive effects of a ketogenic diet in weight loss and other benefits; however, the long-term effects and potential adverse events of a ketogenic diet have not been well studied or documented in literature. There are a few case reports of ketogenic diet resulting in hypoglycemia. We report a case of hypoglycemia with a blood glucose of 39 mg/dL and ketosis in a 69-year-old woman who strictly followed a ketogenic diet for nearly one year. She presented with malaise, sugar cravings, and mental fogginess, and after intake of alcoholic beverages, was admitted to the hospital with hypoglycemia. She had elevated beta-hydroxybutyrate, and low insulin and C-peptide, all consistent with a starvation ketosis. This case illustrates that adherence to a ketogenic diet for a prolonged period of time, in combination with alcohol intake, can disrupt normal glucose homeostatic mechanisms and result in a significant degree of hypoglycemia. This pattern of hypoglycemia may not present with classic symptoms, most likely partly due to effects of the ketogenic diet on brain function. This case provides insight that supports the need to counsel patients about alcohol intake while on the ketogenic diet. More information is needed on long-term complications of the ketogenic diet on glucose homeostasis in the body as well as in the brain.
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PMID:A Case of Hypoglycemia Associated With the Ketogenic Diet and Alcohol Use. 3253 39