Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Crospovidone is an insoluble polymer of N-vinyl-2-pyrrolidone that is used as a disintegrant in pharmaceutical tablets. It can potentially embolize to the lung when aqueous tablet suspensions are injected intravenously. In this report, we identified embolized crospovidone in autopsy-derived lung tissue from three adult IV drug users, 1 man and 2 women, whose ages respectively were 27, 38, and 40 years. Suspected crospovidone was compared with pharmaceutical-grade crospovidone by means of histochemical stains, transmission electron microscopy, and infrared spectroscopy. Similar particles were also observed by light microscopy in a 4-mg tablet of hydromorphone, a preparation prescribed to two of the patients. Two patients had sickle cell disease and were taking methadone and/or hydromorphone for pain management; the third was receiving parenteral hyperalimentation after small bowel resection. Crospovidone appeared as deeply basophilic, coral-like particles within pulmonary arteries and in extravascular foreign-body granulomas. Intrapulmonary crospovidone stained similarly to the pure substance, including intense staining with mucicarmine, Congo red, and Masson trichrome. With Movat pentachrome stain, both intravascular and purified crospovidone appeared orange-yellow, whereas most interstitial particles associated with giant cells stained blue-green. Alcian blue failed to stain intravascular or purified crospovidone but strongly decorated some phagocytized particles. Ultrastructurally, both purified powder and tissue deposits of crospovidone appeared as irregular, electron dense, laminated, and finely granular material. Intrapulmonary crospovidone was associated with inflammatory cells and exhibited degenerative changes. By infrared spectroscopy, crospovidone in tissue had the same spectral characteristics as pharmaceutical grade crospovidone and the library reference, polyvinylpyrrolidone (PVP). We conclude that crospovidone contributes to pulmonary vascular injury in some persons who illicitly inject pharmaceutical tablets. It is readily identifiable histologically and distinguishable from other tablet constituents, such as cornstarch, talc, and microcrystalline cellulose. The variable staining with Alcian blue and Movat suggests that crospovidone is altered in vivo by the inflammatory response.
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PMID:Embolized crospovidone (poly[N-vinyl-2-pyrrolidone]) in the lungs of intravenous drug users. 1269 92

A byproduct of the aging of the population has been a dramatic rise in patients with dementia. The aim of the present study is to clarify the use of aggressive and palliative treatments, artificial nutrition and sedation in long-term care hospitals in Japan. We assessed 123 deaths in people aged 65 and older who died in two long-term care hospitals in and around Nagoya from January 2001 to December 2002. All deceased were divided into two groups according to their diagnosis of dementia. Data on the particular characteristics of the deceased, diagnosis of dementia, aggressive treatments (including CPR, intubation, mechanical ventilation, the use of systemic antibiotics and blood transfusion), palliative treatments (including oxygen, narcotic and nonnarcotic pain medication) artificial nutrition (including hyperalimentation and tube feeding) and sedation during the last six months of their lives were collected from medical charts. The prevalence of aggressive and palliative interventions did not vary significantly with the diagnosis of dementia except for the use of vasopressors. Artificial nutrition was prevalent and few patients received sedatives in either group. Patients with and without dementia received similar treatments in the end-stage. A greater understanding of the course of dementia is needed to further discussions on the terminal care of people with dementia. A national consensus on how to treat end-stage demented patients is also needed.
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PMID:[Terminal care for elderly patients with dementia in two long-term care hospitals]. 1499 24

A questionnaire that assessed a broad range of eating-related characteristics for unselected, normal subjects was factor analyzed in a two-step process proposed by Comrey (1984). Twelve "factored homogeneous item dimensions" were identified first and yielded three primary-level factors in a second factor analysis: Predisposition to Obesity (including Dieting and Preoccupation with, and Fear Of, Gaining Weight), Uncontrollable Urges to Eat (including Eating Momentum Beyond Control, Food a Panacea and Constant Temptation, and Secret Binging), and Predisposition to Anorexia (including Insufficient Eating Obvious to Others, Food Phobia, Inability to Eat, and Vomiting After Meals). The three primary-level factors were positively intercorrelated and exhibited significant positive, though weak, correlations with a measure of trait arousability. Also, weak results tentatively indicated that individuals with more pleasant and/or more arousable temperaments were less likely to be overweight. Subjects reported sharply higher levels of food consumption when feeling "depressed" (i.e., bored, lonely, sad) than when feeling "distressed" (i.e., uncomfortable, anxious, in pain). Uncontrollable Urges to Eat correlated positively and significantly with self-reports of food consumption while depressed, showing that those lacking control over eating ate especially more while feeling bored, lonely, or sad. Predisposition to Obesity correlated negatively and significantly with self-reports of food consumption while distressed, showing that those tending more toward obesity ate less while upset or anxious.
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PMID:Measures of eating-related characteristics for the general population: relationships with temperament. 1636 30

Obesity is highly prevalent among patients with schizophrenia and is associated with detrimental health consequences. Although excessive consumption of fast food and pharmacotherapy with such second-generation antipsychotic agents (SGAs) as clozapine and olanzapine has been implicated in the schizophrenia/obesity comorbidity, the pathophysiology of this link remains unclear. Here, we propose a mechanism based on brain reward function, a relevant etiologic factor in both schizophrenia and overeating. A comprehensive literature search on neurobiology of schizophrenia and of eating behavior was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) energy homeostasis, (2) food reward and hedonics, (3) reward function in schizophrenia, and (4) metabolic effects of the SGAs. A mesolimbic hyperdopaminergic state may render motivational/incentive reward system insensitive to low salience/palatability food. This, together with poor cognitive control from hypofunctional prefrontal cortex and enhanced hedonic impact of food, owing to exaggerated opioidergic drive (clinically manifested as pain insensitivity), may underlie unhealthy eating habits in patients with schizophrenia. Treatment with SGAs purportedly improves dopamine-mediated reward aspects, but at the cost of increased appetite and worsened or at least not improved opiodergic capacity. These effects can further deteriorate eating patterns. Pathophysiological and therapeutic implications of these insights need further validation via prospective clinical trials and neuroimaging studies.
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PMID:Food intake and reward mechanisms in patients with schizophrenia: implications for metabolic disturbances and treatment with second-generation antipsychotic agents. 1698 Sep 85

Histamine H3 receptors (H3Rs) are autoreceptors that negatively regulate the release of histamine and other neurotransmitters such as norepinephrine, dopamine, and acetylcholine in the central nervous system (CNS). Consistent with the wide-spread projection of histaminergic neurons from the lateral hypothalamus, H3Rs are widely distributed in the CNS and are believed to play a variety of physiological roles, including regulation of feeding, arousal, cognition, pain, and endocrine systems. To further understand the physiological roles of H3Rs in vivo, we produced H3R knockout (H3R-/-) mice and found that H3R-/- mice displayed hyperphagia and late-onset obesity associated with hyperinsulinemia and leptinemia, the fundamental marks of metabolic syndromes. A series of non-imidazole H3R antagonists/inverse agonists with improved selectivity and potency have been developed and were found to regulate feeding and body weight gain in laboratory animals. Taken together, these observations suggest that H3Rs are involved in the regulation of feeding behavior and body weight. Several H3R inverse agonists targeting cognitive disorders and dementia have entered clinical trials. These trials will give critical information about the physiological functions of H3Rs in humans.
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PMID:Recent advances in molecular pharmacology of the histamine systems: physiology and pharmacology of histamine H3 receptor: roles in feeding regulation and therapeutic potential for metabolic disorders. 1664 67

In the present article, we review the pharmacological properties of KDS-4103 (URB597), a highly potent and selective inhibitor of the enzyme fatty-acid amide hydrolase (FAAH), which catalyzes the intracellular hydrolysis of the endocannabinoid anandamide. In vitro, KDS-4103 inhibits FAAH activity with median inhibitory concentrations (IC(50)) of 5 nM in rat brain membranes and 3 nM in human liver microsomes. In vivo, KDS-4103 inhibits rat brain FAAH activity after intraperitoneal (i.p.) administration with a median inhibitory dose (ID(50)) of 0.15 mg/kg. The compound does not significantly interact with other cannabinoid-related targets, including cannabinoid receptors and anandamide transport, or with a broad panel of receptors, ion channels, transporters and enzymes. By i.p. administration to rats and mice KDS-4103 elicits significant, anxiolytic-like, antidepressant-like and analgesic effects, which are prevented by treatment with CB1 receptor antagonists. By contrast, at doses that significantly inhibit FAAH activity and substantially raise brain anandamide levels, KDS-4103 does not evoke classical cannabinoid-like effects (e.g., catalepsy, hypothermia, hyperphagia), does not cause place preference, and does not produce generalization to the discriminative effects of the active ingredient of cannabis, Delta9-tetrahydrocannabinol (Delta9-THC). These findings suggest that KDS-4103 acts by enhancing the tonic actions of anandamide on a subset of CB(1) receptors, which may normally be engaged in controlling emotions and pain. KDS-4103 is orally available in rats and cynomolgus monkeys. Sub-chronic repeated dose studies (1,500 mg/kg, per os) in these two species have not demonstrated systemic toxicity. Likewise, no toxicity was noted in bacterial cytotoxicity tests in vitro and in the Ames test. Furthermore, no deficits were observed in rats on the rotarod test after acute i.p. treatment with KDS-4103 at doses up to 5 mg/kg or in a functional observation battery after oral doses up to 1,500 mg/kg. The results suggest that KDS-4103 will offer a novel approach with a favorable therapeutic window for the treatment of anxiety, depression and pain.
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PMID:Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597). 1683 56

This study examined arthritis self-efficacy and self-efficacy for resisting eating as predictors of pain, disability, and eating behaviors in overweight or obese patients with osteoarthritis (OA) of the knee. Patients (N=174) with a body mass index between 25 and 42 completed measures of arthritis-related self-efficacy, weight-related self-efficacy, pain, physical disability, psychological disability, overeating, and demographic and medical information. Hierarchical linear regression analyses were conducted to examine whether arthritis self-efficacy (efficacy for pain control, physical function, and other symptoms) and self-efficacy for resisting eating accounted for significant variance in pain, disability, and eating behaviors after controlling for demographic and medical characteristics. Analyses also tested whether the contributions of self-efficacy were domain specific. Results showed that self-efficacy for pain accounted for 14% (p=.01) of the variance in pain, compared to only 3% accounted for by self-efficacy for physical function and other symptoms. Self-efficacy for physical function accounted for 10% (p=.001) of the variance in physical disability, while self-efficacy for pain and other symptoms accounted for 3%. Self-efficacy for other (emotional) symptoms and resisting eating accounted for 21% (p<.05) of the variance in psychological disability, while self-efficacy for pain control and physical function were not significant predictors. Self-efficacy for resisting eating accounted for 28% (p=.001) of the variance in eating behaviors. Findings indicate that self-efficacy is important in understanding pain and behavioral adjustment in overweight or obese OA patients. Moreover, the contributions of self-efficacy were domain specific. Interventions targeting both arthritis self-efficacy and self-efficacy for resisting eating may be helpful in this population.
Pain 2008 Jun
PMID:Arthritis self-efficacy and self-efficacy for resisting eating: relationships to pain, disability, and eating behavior in overweight and obese individuals with osteoarthritic knee pain. 1776 44

Mutations in the tyrosine kinase receptor trkB or in one of its natural ligands, brain-derived neurotrophic factor (BDNF), lead to severe hyperphagia and obesity in rodents and/or humans. Here, we show that peripheral administration of neurotrophin-4 (NT4), the second natural ligand for trkB, suppresses appetite and body weight in a dose-dependent manner in several murine models of obesity. NT4 treatment increased lipolysis, reduced body fat content and leptin, and elicited long-lasting amelioration of hypertriglyceridemia and hyperglycemia. After treatment termination, body weight gradually recovered to control levels in obese mice with functional leptin receptor. A single intrahypothalamic application of minute amounts of NT4 or an agonist trkB antibody also reduced food intake and body weight in mice. Taken together with the genetic evidence, our findings support the concept that trkB signaling, which originates in the hypothalamus, directly modulates appetite, metabolism, and taste preference downstream of the leptin and melanocortin 4 receptor. The trkB agonists mediate anorexic and weight-reducing effects independent of stress induction, visceral discomfort, or pain sensitization and thus emerge as a potential therapeutic for metabolic disorders.
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PMID:TrkB agonists ameliorate obesity and associated metabolic conditions in mice. 1806 76

Nociceptin/orphanin FQ (N/OFQ), an endogenous ligand for opioid receptor-like 1 (ORL1), is involved in various central functions, such as pain, psychological stress, locomotor activity, learning and memory, and feeding regulation. Of these functions, the role of N/OFQ in the regulation of feeding has been suggested by the fact that the central administration of N/OFQ leads to feeding behavior. However, the manner in which N/OFQ influences body weight control and subsequent obesity is unclear. To clarify the involvement of N/OFQ in the development of obesity, we evaluated the effects of intracerebroventricular infusion of N/OFQ on food intake and body weight in C57BL/6J mice that were fed a regular chow diet or moderately high-fat (MHF) diet (32.6% kcal fat). N/OFQ significantly increased food intake and body weight both in the regular diet- and MHF diet-fed mice, and these changes were more apparent in the MHF diet-fed mice. When we performed a pair-feeding study in N/OFQ intracerebroventricularly infused mice, N/OFQ did not cause body weight gain but increased white adipose tissue weight and plasma leptin, insulin, and cholesterol levels. N/OFQ reduced rectal temperature in pair-fed mice, in keeping with decreased UCP1 mRNA expression in brown adipose tissue. These results suggest that N/OFQ contributes to the development of obesity not only by inducing hyperphagia but also by decreasing energy expenditure.
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PMID:Chronic intracerebroventricular infusion of nociceptin/orphanin FQ produces body weight gain by affecting both feeding and energy metabolism in mice. 1919 98

Animals eat rather than react to moderate pain. Here, we examined the behavioral, hedonic, and neural requirements for ingestion analgesia in ad libitum fed rats. Noxious heat-evoked withdrawals were similarly suppressed during self-initiated chocolate eating and ingestion of intraorally infused water, sucrose, or saccharin, demonstrating that ingestion analgesia does not require feeding motivation, self-initiated food procurement, sucrose, or calories. Rather, food hedonics is important because neither salt ingestion nor quinine rejection elicited analgesia. During quinine-induced nausea and lipopolysaccharide (LPS)-induced illness, conditions when chocolate eating was presumably less pleasurable, analgesia accompanying chocolate consumption was attenuated, yet analgesia during water ingestion was preserved in LPS-injected rats who showed enhanced palatability for water within this context. The dependence of ingestion analgesia on the positive hedonics of an ingestate was confirmed in rats with a conditioned taste aversion to sucrose: after paired exposure to sucrose and LPS, rats no longer showed analgesia during sucrose ingestion but continued to show analgesia during chocolate consumption. Eating pauses tended to occur less often and for shorter durations in the presence of ingestion analgesia than in its absence. Therefore, we propose that ingestion analgesia functions to defend eating from ending. Muscimol inactivation of the medullary raphe magnus blocked the analgesia normally observed during water ingestion, showing the involvement of brainstem endogenous pain inhibitory mechanisms in ingestion analgesia. Brainstem-mediated defense of the consumption of palatable foods may explain, at least in part, why overeating tasty foods is so irresistible even in the face of opposing cognitive and motivational forces.
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PMID:Analgesia accompanying food consumption requires ingestion of hedonic foods. 1982 18


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