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)

Despite numerous experiments showing that administration of neuropeptide Y (NPY) to rodents stimulates feeding and obesity, whereas acute interference with NPY signaling disrupts feeding and promotes weight loss, NPY-null mice have essentially normal body weight regulation. These conflicting observations suggest that chronic lack of NPY during development may lead to compensatory changes that normalize regulation of food intake and energy expenditure in the absence of NPY. To test this idea, we used gene targeting to introduce a doxycycline (Dox)-regulated cassette into the Npy locus, such that NPY would be expressed until the mice were given Dox, which blocks transcription. Compared with wild-type mice, adult mice bearing this construct expressed approximately 4-fold more Npy mRNA, which fell to approximately 20% of control values within 3 days after treatment with Dox. NPY protein also fell approximately 20-fold, but the half-life of approximately 5 days was surprisingly long. The biological effectiveness of these manipulations was demonstrated by showing that overexpression of NPY protected against kainate-induced seizures. Mice chronically overexpressing NPY had normal body weight, and administration of Dox to these mice did not suppress feeding. Furthermore, the refeeding response of these mice after a fast was normal. We conclude that, if there is compensation for changes in NPY levels, then it occurs within the time it takes for Dox treatment to deplete NPY levels. These observations suggest that pharmacological inhibition of NPY signaling is unlikely to have long-lasting effects on body weight.
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PMID:Modulation of neuropeptide Y expression in adult mice does not affect feeding. 1633 12

Zonisamide is an antiepileptic drug used as adjunctive therapy for refractory partial seizures in adults. Because of the multiple mechanisms of action, it shows a broad spectrum of anticonvulsant activity and has been effective in several types of seizures, including partial and generalized seizures, tonic-clonic seizures and absence seizures in patients unresponsive to other anticonvulsants. Myoclonic epilepsy, Lennox-Gastaut syndrome and infantile spasms have also been treated effectively with zonisamide. Recent clinical studies have demonstrated additional potential for therapeutic use in neuropathic pain, bipolar disorder, migraine, obesity, eating disorders and Parkinson's disease. Despite adverse events, zonisamide is relatively safe and well tolerated in patients, and shows low discontinuation rate. It has a good pharmacokinetic profile and a low drug interaction potential. Zonisamide is considered as a drug that effectively reduces the frequency of partial seizures.
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PMID:Zonisamide: review of its use in epilepsy therapy. 1634 Dec 90

Valproate is commonly used for treatment of a variety of seizure types in both children and adults. However, if the medication is started before the age of 20 years, it may affect reproductive endocrine functions. In order to investigate the possible role of valproate treatment in the development of obesity, hyper-insulinism and polycystic ovaries, we studied metabolic parameters and ovarian morphology/size in prepubertal girls with epilepsy. Our study included 14 girls with epilepsy and 15 healthy age-matched controls. The age of the patients ranged from 7 years to 13 years. Mean body weight, fasting serum insulin and glucose levels and HOMA index of girls in the study group were significantly greater than those of the control girls (p < 0.05). Serum androstenedione, prolactin and free testosterone were significantly lower in the VPA-treated girls than in the controls, whereas SHBG level was higher (p < 0.05). There was no difference between the groups for ovarian morphology. In conclusion, our findings showed that valproate treatment may lead to hyperinsulinemia and hypoandrogenism during the prepubertal period. This emphasizes that a mature adult endocrine system may not be necessary for the development of VPA-related hyperinsulinemia.
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PMID:Valproate-induced insulin resistance in prepubertal girls with epilepsy. 1635 11

The medical records of 54 dogs presented to the Hebrew University Veterinary Teaching Hospital and diagnosed with heat stroke were retrospectively reviewed. Data abstracted included history, clinical and clinicopathological signs at admission, treatment, disease progression, and outcome. Exertional and environmental heat stroke were present in 63% (34 of 54) and 37% (20 of 54) of the dogs, respectively, and 78% (42 of 54) were examined between June and August. The mean temperature and heat discomfort index in the particular days of heat stroke were significantly increased (P < .001, P < .001, respectively) compared with their corresponding average daily values. In 27 dogs the body temperature was > or = 41 degrees C (105.8 degrees F). Belgian Malinois (15%, odds ratio [OR] = 24, 95% confidence interval [CI95%] 8.2-64.5), Golden and Labrador Retrievers (21%, OR = 2.08, CI95% 0.95-4.2), and brachycephalic breeds (25%, OR = 1.7, CI95%], 0.81-3.21) were overrepresented, whereas small breeds (<8 kg) were underrepresented (2%, OR = 0.08, CI95%, 0.002-0.48). Thrombocytopenia (45 of 54 dogs) and prolongation of the prothrombin (PT) and activated thromboplastin (aPTT) times (27 of 47 dogs) were recorded during hospitalization. Disseminated intravascular coagulation (P = .013) and acute renal failure (P = .008), diagnosed in 28 of 54 and 18 of 54 of the cases, respectively, were risk factors for death. The overall mortality rate was 50%. Hypoglycemia (<47 mg/dL, P = .003), prolonged PT (>18 seconds, P = .05), and aPTT (>30 sec, P < .001) at admission were associated with death. Serum creatinine >1.5 mg/dL (P = .003) after 24 hours, delayed admission (>90 minutes, P = .032), seizures (P = .02), and obesity (P = .04) were also risk factors for death. Heat stroke in dogs results in serious complications and high fatality rate despite appropriate treatment.
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PMID:Heat stroke in dogs: A retrospective study of 54 cases (1999-2004) and analysis of risk factors for death. 1649 21

New generation antiepileptic medications have improved seizure outcome in patients with intractable epilepsy. We studied the efficacy and side effect profile of vigabatrin (VGB) in pediatric patients with intractable seizure disorder. We reviewed the database of our short-term video-EEG monitoring laboratory to screen patients with intractable epilepsy who were on VGB either alone or in combination for three months or more. We subsequently reviewed the medical records of these patients to abstract clinical information regarding age, sex, seizure type, epilepsy syndrome, efficacy and side effects of VGB. Of 111 patients, 75 (68%) were male and 36 (32%) female. Seizure onset was during the newborn period in 12 patients (11%), during the first year of life beyond the newborn period in 47 patients (42%), between 1-5 years in 23 patients (21%), and above five years in the remaining 29 patients (26%). Fifty-four patients (48.6%) had partial onset seizures with or without secondary generalization; 49 patients (44.1%) had primary generalized seizures; 8 patients (7.2%) had two or more types of seizure. Fifty-three percent of patients had mental retardation, and 35% had abnormal findings on physical/ neurological examination. Of 98 patients, 70 (71.4%) had abnormal magnetic resonance imaging (MRI) findings. Ninety-seven percent of patients had been on polytherapy before VGB was added to treatment. VGB reduced seizure frequency by at least 50% in 33.3% of patients with partial seizures, and in 30.6% of patients with primary generalized seizures. Six of the responders with partial seizures had complete resolution of their seizures. Most common side effects included visual field defects, increased appetite and obesity. Vigabatrin seems to be more effective in partial seizures in childhood intractable epilepsy. Patients should be closely monitored regarding side effects of VGB.
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PMID:Vigabatrin in pediatric patients with refractory epilepsy. 1656 82

The literature on the health of adults with disabilities focuses on one disability compared to a comparison group. This study allows cross disability comparisons with the hypothesis. Adults with disabilities had higher odds of having common health conditions, compared to adults without disability in the same practice. A retrospective record review of 1449 patients with disability and 2084 patients without disability included individuals with sensory impairments (n = 117), developmental disabilities (n = 692), trauma-related impairments (n = 155) and psychiatric impairments (n = 485). The only two health conditions with statistically significantly increased odds for all groups with disabilities were dementia and epilepsy. Patients with developmental disabilities were less likely to have coronary artery disease, cancer, and obesity. Those with sensory impairments had increased odds for congestive heart failure, diabetes, transient ischemic attacks and death. Patients with trauma disabilities had increased odds for chronic obstructive pulmonary disease, and depression. Finally, psychiatric patients had increased odds for most of the investigated condition. In conclusion, there were many similarities in the risk for common health conditions such as asthma, cancer, coronary artery disease, depression, hypertension, and obesity, among patients with and without disability. Some of the conditions with increased odds ratios, including depression, seizures, and dementia are secondary to the primary disability.
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PMID:Variation in health conditions among groups of adults with disabilities in primary care. 1683 May 4

We report two 71-year-old female monozygotic twins presenting with advanced hyperostosis frontalis interna, obesity, shortness and cognitive impairment. They both have suffered from generalized seizures since their early adulthood. Moreover, the patients showed some additional conditions only occurring in one individual or the other such as migraine, marked recurrent depressive disorder or polyarthrosis. The symptoms common to both twins appear to correspond to the Morgagni-Stewart-Morel syndrome and indicate a genetic basis of this disorder as these features occur in genetically identical patients.
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PMID:Evidence of a genetic basis of Morgagni-Stewart-Morel syndrome. A case report of identical twins. 1690 48

Neuropeptide Y (NPY) is one of the most prominent and abundant neuropeptides in the mammalian brain where it interacts with a family of G-protein coupled receptors, including the Y(1) receptor subtype (Y(1)R). NPY-Y(1)R signalling plays a prominent role in the regulation of several behavioural and physiological functions including feeding behaviour and energy balance, sexual hormone secretion, stress response, emotional behaviour, neuronal excitability and ethanol drinking. Y(1)R expression is regulated by neuronal activity and peripheral hormones. The Y(1)R gene has been isolated from rodents and humans and it contains multiple regulatory elements that may participate in the regulation of its expression. Y(1)R expression in the hypothalamus is modulated by changes in energetic balance induced by a wide variety of conditions (fasting, pregnancy, hyperglycaemic challenge, hypophagia, diet induced obesity). Estrogens up-regulate responsiveness to NPY to stimulate preovulatory GnRH and gonadotropin surges by increasing Y(1)R gene expression both in the hypothalamus and the pituitary. Y(1)R expression is modulated by different kinds of brain insults, such as stress and seizure activity, and alteration in its expression may contribute to antidepressant action. Chronic modulation of GABA(A) receptor function by benzodiazepines or neuroactive steroids also affects Y(1)R expression in the amygdala, suggesting that a functional interaction between the GABA(A) receptor and Y(1)R mediated signalling may contribute to the regulation of emotional behaviour. In this paper, we review the state of the art concerning Y(1)R function and gene expression, including our personal contribution to many of the subjects mentioned above.
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PMID:Physiology and gene regulation of the brain NPY Y1 receptor. 1698 96

Laron-type dwarfism is an autosomal recessive disorder caused by deletions or mutations of the growth hormone receptor gene. It is characterized by high circulating levels of growth hormone (GH) and low levels of insulin-like growth factor I (IGF-I). Patients are refractory to both endogenous and exogenous GH, and present severe growth retardation and obesity. Therapy with recombinant human insulin-like growth factor-I (rhIGF-I) accelerates linear growth. We describe a 2-year old girl with Laron syndrome, who presented with postnatal growth failure and hypoglycaemic seizures. Her evaluation disclosed high GH values during a glucagon test (peak GH value 170 ng/ml) and very low IGF I value (0.1 ng/ml) with no rise following GH administration. The growth velocity improved considerably with the administration of IGF I. Molecular analysis showed a heterozygous mutation on exon 4 of the GH receptor gene, inherited from the mother, a rather puzzling finding considering the clinical findings in mother and infant. This case constitutes the first report of Laron syndrome from Greece.
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PMID:Laron syndrome. First report from Greece. 1700 11

We report a female patient with a de novo balanced translocation, 46,X,t(X;2)(p11.2;q37)dn, who exhibits seizures, capillary abnormality, developmental delay, infantile hypotonia, and obesity. The 2q37 breakpoint observed in association with the seizure phenotype is of particular interest, because it lies near loci implicated in epilepsy in humans and mice. Fluorescence in situ hybridization mapping of the translocation breakpoints showed that no known genes are disrupted at Xp11.2, whereas diacylglycerol kinase delta (DGKD) is disrupted at 2q37. Expression studies in Drosophila and mouse suggest that DGKD is involved in central nervous system development and function. Electroencephalographic assessment of Dgkd mutant mice revealed abnormal epileptic discharges and electrographic seizures in three of six homozygotes. These findings implicate DGKD disruption by the t(X;2)(p11.2;q37)dn in the observed phenotype and support a more general role for DGKD in the etiology of seizures.
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PMID:Disruption of diacylglycerol kinase delta (DGKD) associated with seizures in humans and mice. 1735 84


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