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)

Due to the increased interest of the medical community in sleep disorders an experts meeting was called to establish common criteria for diagnosis, treatment and management of these disorders. Adult prevalence of sleep apnea/hypopnea syndrome (SA/HS) is about 2-4% and increases in the elderly. Snoring and excessive daytime somnolence (EDS) are habitual symptoms. Increased risk to cardiovascular disorders and traffic accidents are the major complications. Increased upper airways resistance syndrome is a recently described syndrome which also involves EDS. A standardized questionnaire was developed and its use was recommended in order to evaluate patients with respiratory sleep disorders (RSD). Polysomnography was established as gold standard in the diagnosis of RSD. Minimal requirement of split night studies and screening studies was also standardized and specific indications were summarized. Medical treatment of obesity in relationship to RSD was analyzed. Nasal continuous positive airways pressure (CPAP) was established as the first choice treatment of SA/HS. Titration of CPAP was standardized. Oral appliances with mandibular advancement could be considered in the treatment of snoring patients without SA/HS and in patients with increased upper airways resistance syndrome. Uvulopalatopharingoplasty can only be performed in snoring patients in whom the presence of SA/HS has been dismissed by polysomnography. Management of patients must include periodic clinical control. EDS must be determined by Epworth test. In order to evaluate CPAP compliance the use of time-controlled devices is highly recommended.
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PMID:[Argentine consensus on sleep-related respiratory disorders]. 1147 86

A progressive decrease in androgen production is common in aging men. The physiological causes for this phenomenon seem to be multifactorial. The magnitude of the decline in testosterone with age and the prevalence of older men with low testosterone levels have not been well established. The extent to which an age-dependent decline in androgen levels leads to health problems that might affect or alter the quality of life remains under debate. In men older than middle age, total testosterone levels may be misleading because of an increase in sex hormone-binding globulin levels. The mechanism of the age-associated decrease of the endocrine testicular function is also essentially due to primary testicular failure, but important changes occur at the hypothalamopituitary level. The most prominent endocrinological alterations with aging are related to the sex steroids, but others, such as growth hormone, melatonin cortisol, and thyroxine, are also affected. The clinical picture of andropause syndrome is characterized by diminished sexual desire and erectile capacity, decrease in intellectual activity, fatigue, depression, decrease in lean body mass, skin alterations, decrease in body hair, decrease in bone mineral density that results in osteoporosis, and increase in visceral fat and obesity. Current medical treatments for androgen supplementation include oral tablets, intramuscular injections, and scrotal and nonscrotal patches. Unfortunately, none of these preparations mimic the circadian rhythm, even if some of them may approximate the circadian rhythm by dose adjustments. Moreover, the androgen supplementation could have adverse effects on different organs, namely, the liver, lipid profile, cardiovascular disease, prostate, sleep disorders, and emotional behavior. Clinical response is a better guide to dose requirements, regardless of serum testosterone levels. This important field must be actively investigated by the medical, behavioral, and social sciences.
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PMID:Male andropause: myth, reality, and treatment. 1215 25

The medical findings from a population-based study of Prader-Willi syndrome (PWS) are discussed (in which birth incidence of PWS was estimated at 1:22,000 and death rate at over 3% per annum). In this study the prevalence of specific medical disorders that might account for a shortened life expectancy were investigated. Of all people with a possible diagnosis of PWS, only those meeting clinical criteria and/or with a confirmed genetic diagnosis were included in the study. Sixty-six individuals, 40 males and 26 females with a mean age of 19 years (range of 0 to 46 years) agreed to participate in the population-based study group. A prevalence rate of 25% for non-insulin dependent diabetes mellitus (NIDDM) was found in adults. Mean age at onset was 20 years. Those with NIDDM had a higher past maximum body weight and a greater likelihood of positive family history. Nearly 50% across the age groups reported a history of recurrent respiratory infections. High rates of fractures (29%), leg ulceration (22% in adults), sleep disorders (20%), and severe scoliosis (15% in childhood) were also reported. It is postulated that hypotonia is a possible contributory factor to the risk of strabismus, scoliosis, and respiratory infections. Other causes of morbidity, in particular the high rates of NIDDM, may be due to a failure to manage over-eating resulting in severe obesity. Early diagnosis and clear guidance to families about these risks and how they might be prevented is recommended. It is hypothesized that the high pain threshold may result in the presence of some illness not being apparent.
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PMID:Prevalence of, and risk factors for, physical ill-health in people with Prader-Willi syndrome: a population-based study. 1199 93

Sleep and sleep disorders play a prominent role in hormone regulation. Given that sleep disordered breathing (SDB) and diabetes mellitus (DM) are thought to result from obesity, it has been assumed that when the two coexist, the diabetes was caused by the obesity. However, new data has shed light on the effects that SDB, sleep deprivation, and snoring have on glucose regulation. It now appears that in addition to causing daytime drowsiness, cardiovascular disease, mood and memory disturbances, impotence, and car wrecks, obstructive sleep apnea (OSA) also promotes insulin resistance. Though data is still sketchy on the optimum management of coexisting DM and OSA, large-scale studies will most likely prove that homeostatic glucose control in patients with sleep apnea will require aggressive treatment of their SDB.
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PMID:Sleep and the endocrine system: new associations to old diseases. 1239 57

The mouse is a proven model for studying human disease. Many strains exist that exhibit either natural or engineered genetic variation and thereby enable the elucidation of pathways involved in the development of cardiovascular disease. Although those mouse models have been fundamental to advancing our knowledge base, we are still at an early stage in understanding how genes contribute to complex disorders. There remains a need for new animal models that closely represent human disease. To expedite their development, we have established the Center for New Mouse Models of Heart, Lung, Blood, and Sleep Disorders at The Jackson Laboratory. We are using a phenotype-driven approach to identify mutations leading to atherosclerosis, hypertension, obesity, blood disorders, lung dysfunction, thrombosis, and disordered sleep. Our high-throughput, comprehensive phenotyping draws from two sources for new models: 1) the natural variation among over 40 inbred mouse strains and 2) chemically induced, whole-genome mutagenized mice. Here, we review our cardiovascular screens and present some hypertensive, obese, and cardiovascular models identified with this approach.
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PMID:Invited review: Identifying new mouse models of cardiovascular disease: a review of high-throughput screens of mutagenized and inbred strains. 1262 79

Presynaptic histamine H(3) receptors (H(3)R) regulate neurotransmitter release in the central nervous system, suggesting an important role for H(3) ligands in human diseases such as cognitive disorders, sleep disturbances, epilepsy, or obesity. Drug development for many of these human diseases relies upon rodent-based models. Although there is significant sequence homology between the human and rat H(3)Rs, some compounds show distinct affinity profiles. To identify the amino acids responsible for these species disparities, various mutant receptors were generated and their pharmacology studied. The N-terminal portion was shown to determine the species differences in ligand binding since a chimeric H(3)R containing N-terminal human and C-terminal rat receptor sequences exhibited similar pharmacology to the human receptor. Sequence analysis and molecular modeling studies suggested key amino acids at positions 119 and 122 in transmembrane region 3 play important roles in ligand recognition. Mutant receptors changing amino acids 119 or 122 of the human receptor to those in the rat improved ligand binding affinities and functional potencies of antagonist ligands, confirming the significant role that these amino acids play in species-related pharmacological differences. A model has been developed to elucidate the ligand receptor interactions for H(3)Rs, and pharmacological aspects of this model are described.
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PMID:Molecular modeling and pharmacological analysis of species-related histamine H(3) receptor heterogeneity. 1268 76

Obstructive sleep apnea (OSA) is an increasingly recognized, common chronic disease in the developed nations and is a complex disease that has high social and economic costs. OSA and its associated 'intermediate' phenotypes-craniofacial structure, body fat distribution and metabolism, and neurological control of the upper airway muscles and of sleep and circadian rhythm-are under a substantial degree of genetic control. Investigating the genetic aetiology of OSA offers a means of better understanding its pathogenesis, with the goal of improving preventive strategies, diagnostic tools and therapies. Molecular studies of OSA itself are in their infancy, but considerable effort and expense has already been expended in attempts to detect genetic loci contributing to OSA-associated intermediate phenotypes, such as obesity. However, many of the fundamental questions relating to the genetic epidemiology of OSA and associated factors remain unanswered. This chapter reviews the current state of knowledge of the genetics of OSA, with a focus on genomic approaches to understanding sleep disorders.
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PMID:Genomic approaches to understanding obstructive sleep apnea. 1280 19

Breathing-related sleep disorders, particularly obstructive sleep apnea, have been largely undiagnosed in people with cardiovascular disease, probably due to limited health care provider awareness of the association between the two conditions. Solid evidence is emerging that the apneic events that occur during sleep lead to acute and chronic hemodynamic changes during wake time, including elevated sympathetic tone, decreased stroke volume and cardiac output, increased heart rate, and changes in circulating hormones that regulate blood pressure, fluid volume, vasoconstriction, and vasodilation. Obstructive sleep apnea is associated with known cardiovascular risk factors such as obesity and hyperlipidemia, and is considered by many sleep clinicians to be an independent risk factor for hypertension. Additionally, sleep apnea has been implicated in the pathogenesis of heart failure and stroke. Treatment with positive airway pressure during sleep eliminates the apneic events and the ensuing acute hemodynamic changes. Improvements in daytime blood pressure and left ventricular function also have been noted in persons with hypertension and heart failure. Because effective treatment is available for sleep apnea, this condition needs to be diagnosed and treated in persons with cardiovascular disease.
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PMID:Sleep-disordered breathing and the association with cardiovascular risk. 1501 52

Twelve to twenty-five percent of human population suffer from sleep disorders and sleep-related breathing disorders have a frequency of 5-10%. The association between sleep-related breathing disorders and several diseases, mainly cardiovascular and dysmetabolic, is well known. The aim of this study was to assess the prevalence of this association in a group of 620 patients, aged between 18 and 78 years and referred to the Laboratory of Respiratory Pathophysiology of the Umberto I Hospital of Rome. All patients had a clinical history of a sleep-related breathing disorder and answered a specific questionnaire. One-hundred-and-thirty-seven patients (120 males and 17 females, mean age 64 years), whose questionnaire was suggestive of a sleep-related breathing disorder, underwent clinical assessment including blood tests, lung function tests, blood-gas analysis, ECG and nocturnal polysomnography, either as in- or as out-patients. The main associated pathologies were: arterial hypertension (54.7%), chronic obstructive pulmonary disease (17.9%), obesity (63.1%), dyslipidemia (41%), type 2 diabetes mellitus (6.3%), gastroesophageal reflux (27.3%) and cardiac arrhythmias (4.2%); 95 patients with obstructive sleep apnea syndrome were treated, on the basis of the polysomnography outcomes and according to the Italian Association of Sleep Medicine Guidelines, either with preventive strategies for risk factor reduction, or with medical (positive pressure ventilation, oxygen, assessment of the best drug medication) and/or ear, nose end throat surgical therapies. In most patients, the improvement in the sleep-related breathing disorder was associated with an improvement in their systemic pathology, in particular cardiovascular disease, suggesting the need of a deeper consideration and comprehension of nocturnal apneas.
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PMID:[Relationship between the obstructive sleep apnea syndrome and internal medicine]. 1517 2

Evidence exists to implicate the monoamine histamine in the control of arousal and cognitive functions. Antagonists of H(3) receptors are postsynaptic and presynaptic modulators of neural transmission in a variety of neuronal circuits relevant to cognition. Accumulating neuroanatomical, neurochemical, pharmacological, and behavioral data support the idea that H(3) receptor antagonists may function to improve cognitive performances in disease states (e.g., Alzheimer's disease and mild cognitive impairment states). Thus, H(3) receptor antagonists have been shown to increase performance in attention and memory tests in nonhuman experiments and prevent the degradation in performances produced by scopolamine, MK-801, or age. In contrast, agonists of the H(3) receptor generally produce cognitive impairing effects in animal models. The role of H(3) receptors in these behavioral effects is substantiated by data indicating a central origin for their effects, the selectivity of some of the H(3) receptor antagonists studied, and the pharmacological modification of effects of H(3) receptor antagonists by selective H(3) receptor agonists. Data and issues that challenge the potential role for H(3) receptor antagonists in cognitive processes are also critically reviewed. H(3) receptor antagonists may also have therapeutic value in the management of obesity, pain, sleep disorders, schizophrenia, and attention deficit hyperactivity disorder.
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PMID:Selective histamine H3 receptor antagonists for treatment of cognitive deficiencies and other disorders of the central nervous system. 1525 Dec 26


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