Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is considerable potential for translating knowledge of aquaporin structure, function and physiology to the clinic. One area is in aquaporin-based diagnostics. The discovery of AQP4 autoantibodies as a marker of the neuromyelitis optica form of multiple sclerosis has allowed precise diagnosis of this disease. Other aquaporin-based diagnostics are possible. Another area is in aquaporin-based genetics. Genetic diseases caused by loss-of-function mutations in aquaporins include nephrogenic diabetes insipidus and cataracts, and functionally significant aquaporin polymorphisms are beginning to be explored. Perhaps of greatest translational potential is aquaporin-based therapeutics. Information largely from aquaporin knockout mice has implicated key roles of aquaporin-facilitated water transport in transepithelial fluid transport (urinary concentrating, gland fluid secretion), water movement into and out of the brain, cell migration (angiogenesis, tumor metastasis, wound healing) and neural function (sensory signaling, seizures). A subset of aquaporins that transport both water and glycerol, the 'aquaglyceroporins', regulate glycerol content in epidermal, fat and other tissues, and are involved in skin hydration, cell proliferation, carcinogenesis and fat metabolism. Aquaporin-based modulator drugs are predicted to be of broad potential utility in the treatment of edematous states, cancer, obesity, wound healing, epilepsy and glaucoma. These exciting possibilities and their associated challenges are reviewed.
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PMID:Aquaporins: translating bench research to human disease. 1944 80

Central obesity have an important impact on the development of risk factors for coronary heart disease, including dyslipidemia, glucose intolerance, insulin resistance and hypertension. These factors contribute to building cardiovascular (CV) disease as a major cause of death. The approach to obesity therapy should be designed to reduce CV risk and mortality. Diet and lifestyle changes remain the cornerstones of therapy for obesity, but the resultant weight loss is often small and long-term success is uncommon and disappointing. Drug therapy is considered for individuals with a body mass index greater than 30 kg/m(2) or ranging from 25 to 30 kg/m(2) if they have comorbid conditions. Antiobesity agents can be helpful to some patients in achieving and maintaining meaningful weight loss, but yet our pharmaceutical tools are of limited effectiveness considering the magnitude of the problem. At the present, only two drugs, orlistat and sibutramine, are approved for long-term treatment of obesity and promote no more than 5 to 10% of weight loss. Rimonabant, a cannabinoid-1 receptor antagonist, was withdrawn from the market because of concerns about its safety, including risk of suicidal and seizures, although very effective in promoting clinically meaningful weight loss, reduction in waist circumference, and improvements in several metabolic risk factors, rimonabant, a cannabinoid-1 receptor antagonist was withdrawn from the market because it concerns about its safety, including risk of suicidal and seizures. Fortunately, recent fundamental insights into the neuroendocrine mechanisms regulating body weight provide an expanding list of molecular targets for novel, rationally designed antiobesity drugs. In this review, the therapeutic potential of some antiobesity molecules in the development will be analyzed based on an understanding of energy homeostasis.
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PMID:Emerging drugs for obesity therapy. 1946 20

Youth inactivity and inappropriately high weight is a problem in the United States, Canada, and much of the industrialized world. Physiological and behavioral changes associated with the Youth Fit For Life protocol, a physical activity and nutrition education treatment based on self-efficacy theory, were assessed in 7- to 12-yr.-olds (N - 43) from Calgary, Alberta, Canada. Body Mass Index, strength, and cardiorespiratory endurance significantly improved over a 12-wk. period when contrasted with changes based on normative data. Significant within-group improvements in measures of self-efficacy, vegetable intake, and voluntary moderate-to-vigorous physical activity were also found over 12 wk. Multiple regression analysis indicated that score changes in measures of self-regulatory and task self-efficacy, and general self, accounted for changes in voluntary physical activity. Implications for use of behaviorally based methods for large-scale obesity prevention treatments in preadolescents were discussed.
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PMID:Effects of the Youth Fit for Life protocol on physiological, psychological, and behavioral factors at YMCA Calgary after-school care sites. 1970 15

Topiramate is biochemically classified as a fructopyranose sulphamate. Discovered as early as 1979, during middle 1980's it was approved in many countries for the treatment of epilepsies and migraine prevention. More recently, in the experimental stage, possible new indications have been disclosed: treatment of obesity, bipolar disorder, also cessation of smoking, neuropathic pain, cerebral pseudotumour, bulimia, periventricular leucomalatia in preterm infants and alcohol addiction. Most epileptologists consider it to be the first choice antiepileptic drug in severe pharmacoresistant epilepsies. A substantial corpus of evidence in paediatric population has been accumulated that confirms its efficiency in the treatment of generalised tonic-clonic seizures, Lenox-Gestaut syndrome, partial, absence and combined seizures. Having a unique monosaccharide chemical structure among other anticonvulsant drugs, characterizes it with special pharmacokinetic features. This substance exhibits a low interindividual variability in plasma levels and hence it features predictable pharmacokinetics. A steady state plasma concentration of topiramate increases linearly with higher dosages. Serum protein binding is approximately 15%, and biologic half-life in healthy volunteers is considered to range from 20 to 30 hours. Mean expected distribution volume rates from 0.55-0.8 l/kg, and accordingly, the drug shows a low and saturable binding capacity toward erythrocytes. It has not been present at the market for a sufficiently long time that would enable us to speak about a significant accumulation of data on its metabolism based on post-registration 4th stage clinical trials. For this purpose, we have done a literature review in order to summarise so far reported experience on topiramate pharmacokinetics in patients and healthy adults. Deeper understanding of its pharmacokinetic profile could enable a better technological design of the produced drug and the choice of the adequate route of its administration, and accordingly a more rational treatment of severe epilepsies resistant to other drugs.
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PMID:[Current clinical evidence on topiramate pharmacokinetics]. 1976 3

As exergames are increasingly being used as an interventional tool to fight the obesity epidemic in clinical studies, society is absorbing their impact to a more intense degree. Interactivity and immersion are key factors that attract exergame consumers. This research asks, What are the effects of priming the actual self versus the ideal self on users' perceived interactivity and immersion in avatar-based exergame playing? and What are important moderators that play a role in exergame users' self-concept perception? To answer these research questions, this study leveraged the Wii's avatar-creating function (Mii Channel) and exergame feature (Wii Fit) in a controlled, randomized experimental design (N = 126). The results of a 2 x 2 factorial design experiment demonstrated the significant main effect of self-priming on interactivity and the moderating role of the actual-ideal self-concept discrepancy in influencing immersion during exergame playing. Game players who created an avatar reflecting the ideal self reported greater perceived interactivity than those who created a replica avatar mirroring the actual self. A two-way ANOVA demonstrated the moderating role of the actual-ideal self-concept discrepancy in determining the effects of the primed regulatory focus on immersion in the exergame play. The underlying theoretical mechanism is derived from and explained by Higgins's self-concept discrepancy perspective. Practical implications for game developers and managerial implications for the exergame industry are discussed.
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PMID:Avatars mirroring the actual self versus projecting the ideal self: the effects of self-priming on interactivity and immersion in an exergame, Wii Fit. 1978 81

In the N-end rule pathway of protein degradation, the destabilizing activity of N-terminal Asp, Glu or (oxidized) Cys residues requires their conjugation to Arg, which is recognized directly by pathway's ubiquitin ligases. N-terminal arginylation is mediated by the Ate1 arginyltransferase, whose physiological substrates include the Rgs4, Rgs5 and Rgs16 regulators of G proteins. Here, we employed the Cre-lox technique to uncover new physiological functions of N-terminal arginylation in adult mice. We show that postnatal deletion of mouse Ate1 (its unconditional deletion is embryonic lethal) causes a rapid decrease of body weight and results in early death of approximately 15% of Ate1-deficient mice. Despite being hyperphagic, the surviving Ate1-deficient mice contain little visceral fat. They also exhibit an increased metabolic rate, ectopic induction of the Ucp1 uncoupling protein in white fat, and are resistant to diet-induced obesity. In addition, Ate1-deficient mice have enlarged brains, an enhanced startle response, are strikingly hyperkinetic, and are prone to seizures and kyphosis. Ate1-deficient males are also infertile, owing to defects in Ate1(-/-) spermatocytes. The remarkably broad range of specific biological processes that are shown here to be perturbed by the loss of N-terminal arginylation will make possible the dissection of regulatory circuits that involve Ate1 and either its known substrates, such as Rgs4, Rgs5 and Rgs16, or those currently unknown.
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PMID:Ablation of arginylation in the mouse N-end rule pathway: loss of fat, higher metabolic rate, damaged spermatogenesis, and neurological perturbations. 1991 79

The severity of many diseases varies across the day and night. For example, adverse cardiovascular incidents peak in the morning, asthma is often worse at night and temporal lobe epileptic seizures are most prevalent in the afternoon. These patterns may be due to the day/night rhythm in environment and behavior, and/or endogenous circadian rhythms in physiology. Furthermore, chronic misalignment between the endogenous circadian timing system and the behavioral cycles could be a cause of increased risk of diabetes, obesity, cardiovascular disease and certain cancers in shift workers. Here we describe the magnitude, relevance and potential biological basis of such daily changes in disease severity and of circadian/behavioral misalignment, and present how these insights may help in the development of appropriate chronotherapy.
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PMID:Influence of the Circadian System on Disease Severity. 2016 Nov 49

Despite widespread uptake of bariatric procedures for severe obesity, changes in pharmacodynamics after surgery are poorly understood. We report an epileptic patient who had a seizure following gastric bypass, although he had been asymptomatic for 30 years and without any change in his treatment. Phenytoin levels were undetectable despite a high dose. Drugs with a narrow therapeutic range such as phenytoin should be prescribed with caution after bariatric surgery.
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PMID:Reduced phenytoin levels in an epileptic patient following Roux-En-Y gastric bypass for obesity. 2018 78

Vagus nerve stimulation (VNS) for medically refractory seizures has been an approved therapy by the Food and Drug Administration since 1997, with additional approval as an adjunct therapy for major depression granted in 2005. Potential applications for VNS therapy in obesity, neuropsychiatric disorders, and chronic pain syndromes are under investigation. Bradyarrhythmias, including asystole, may occur during VNS device placement or as a delayed complication. A peritracheal hematoma may develop following VNS device placement, necessitating emergent management. Other respiratory complications may include vocal cord movement abnormalities with potential for aspiration. Vagus nerve stimulation results in sleep-related breathing pattern changes, with an associated increase in the number of obstructive apneas and hypopneas in both children and adults, which may impact perioperative care.
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PMID:Intraoperative and perioperative complications with a vagus nerve stimulation device. 2040 10

Recently, a truncating mutation of the UBE2A gene has been observed in a family with X-linked mental retardation (XLMR) (1). The three affected males had similar phenotypes, including seizures, obesity, marked hirsutism and a characteristic facial appearance. Here, we report on two families with a total of seven patients and a clinically very similar syndromic form of XLMR. Linkage analysis was performed in the larger of these families, and screening several positional candidate genes revealed a G23R missense mutation in the UBE2A gene. Subsequent UBE2A screening of a phenotypically similar second family revealed another missense mutation, R11Q, again affecting an evolutionarily conserved amino acid close to the N-terminus of the protein. SIFT and PolyPhen analyses suggest that both mutations are pathogenic, which is supported by their absence in 168 healthy controls. Thus, both missense and truncating mutations can give rise to a specific, syndromic form of XLMR which is identifiable in a clinical setting.
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PMID:Novel missense mutations in the ubiquitination-related gene UBE2A cause a recognizable X-linked mental retardation syndrome. 2041 11


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