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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sleep is an important modulator of cardiovascular function, both in physiological conditions and in disease states. In individuals without a primary sleep disorder, sleep may exert significant effects on the autonomic nervous system, systemic hemodynamics, cardiac function, endothelial function, and coagulation. Some of these influences can be directly linked to specific modulatory effects of sleep stages per se; others result from the natural circadian rhythm of various physiological processes. There is a temporal association between physiological sleep and occurrence of vascular events, cardiac arrhythmias, and sudden death. Epidemiological and pathophysiological studies also indicate that there may be a causal link between primary sleep abnormalities (sleep curtailment, shift work, and sleep-disordered breathing) and cardiovascular and metabolic disease, such as hypertension, atherosclerosis, stroke, heart failure, cardiac arrhythmias, sudden death, obesity, and the metabolic syndrome. Finally, sleep disturbances may occur as a result of several medical conditions (including obesity, chronic heart failure, and menopause) and may therefore contribute to cardiovascular morbidity associated with these conditions. Further understanding of specific pathophysiological pathways linking sleep disorders to cardiovascular disease is important for developing therapeutic strategies and may have important implications for cardiovascular chronotherapeutics.
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PMID:Sleep and cardiovascular disease. 1630 Oct 95

The serotonin (5-hydroxytryptamine) 5-HT2 receptor subfamily consists of three members, 5-HT2A, 5-HT2B, and 5-HT2C. These receptors share high homology in their amino acid sequence, have similar signaling pathways, and have been indicated to play important roles in feeding, anxiety, aggression, sexual behavior, mood, and pain. Subtype-selective agonists and antagonists have been explored as drugs for hypertension, Parkinson's disease, sleep disorders, anxiety, depression, schizophrenia, and obesity. In this study, we report the development of homogeneous agonist binding assays in a scintillation proximity assay (SPA) format to determine the high-affinity binding state of agonist compounds for the human 5-HT2C, 5-HT2A, and 5-HT2B receptors. The 5-HT2 agonist 1-(4- [125I]iodo-2,5-dimethoxyphenyl)-2-aminopropane ([125I]DOI) was used to label the high-affinity sites for the 5-HT2A and 5-HT2C receptors. The high-affinity sites for the 5-HT2B receptor were labeled with [3H]lysergic acid diethylamide. Total receptor expression was determined with the 5-HT2 antagonist [3H]mesulergine for the 5-HT2B and 5-HT2C receptors, and [3H]ketanserin for the 5-HT2A receptor. The agonist high-affinity binding sites accounted for 2.3% (5-HT(2C) receptor), 4.0% (5-HT2A receptor), and 22% (5-HT2B receptor) of the total receptor population. Competition binding studies using known agonists indicated high Z' values of the agonist binding assays in SPA format (Z' > 0.70). The Ki values of 5-HT, (R)(-)DOI, and VER-3323 for the 5-HT2A, 5-HT2B, and 5-HT2C receptors by SPA format were equivalent to published data determined by filtration binding assays. These results indicate that agonist binding assays in SPA format can be easily adapted to a high throughput assay to screen for selective 5-HT2C receptor agonists, as well as for selectivity profiling of the compounds.
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PMID:Development of homogeneous high-affinity agonist binding assays for 5-HT2 receptor subtypes. 1643 60

Sleep complaints are very common among the general population and are usually accompanied by significant medical, psychological and social disturbances (Redline S, Strohl K, Otolaryngol Clin North Am, 132:303, 1999). A higher prevalence of sleep complaints has been described in the elderly (Vgontzas AN, Kales A, Annu Rev Med, 50:387-400, 1999). It is manifested by breathing disturbances during sleep, loud snoring, difficulties maintaining sleep, fatigue, daytime sleepiness, mood effects and impairment of daily activities (Lugaresi E, Cirignotta F, Zucconi M et al., Good and poor sleepers: an epidemiological survey of the San Marino population, Raven, New York, pp 1-12, 1983; Kales A, Soldatos CR, Kales JD, Am Fam Physician, 22:101-108, 1980). It has been associated with cardiovascular, endocrine and neurocognitive manifestations. Growing interest in early diagnosis and treatment has been noted in recent years based on emerging knowledge about the potential health consequences when the disease goes untreated (Nanen AM, Dunagan DP, Fleisher A et al., Chest, 121:1741, 2002). The veteran population in the mainland has a higher tendency for obesity, high blood pressure (HBP), sleep disorders and chronic alcohol consumption (Mustafa M, Erokwu N, Ebose I, Strohl K, Sleep Breath, 9:57-63, 2005). The Hispanic veteran population has never been studied in detail for sleep disorders and related conditions. We used previously validated screening tools for sleep disturbance breathing. Two hundred and forty-five questionnaires were administered. We found a higher prevalence of Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) in our population compared with data from the mainland (USA). The mean age was 64 years (+/-11). Ninety seven per cent were males. The mean body mass index was 25 kg/cm(2); mean Epworth Sleepiness Scale score was 8. Thirty-four per cent met high-risk criteria for sleep apnea, 53% for insomnia, 13% for symptoms suggestive of narcolepsy and 13% for those suggestive of restless leg syndrome. There were high incidences of alcohol consumption (37.6%), diabetes (32.7%), hypercholesterolemia (31.8%), depression (31.8%), hypertension (39.6%) and post-traumatic stress disorder (PTSD) (9.8%).
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PMID:The veteran population: one at high risk for sleep-disordered breathing. 1649 17

The histamine H3 receptor is an attractive G protein-coupled receptor drug target that regulates neurotransmission in the central nervous system and plays a role in cognitive and homeostatic functions. Drug discovery efforts by numerous pharmaceutical companies have focused on the preclinical development of H3 receptor antagonists for the potential treatment of attention-deficit hyperactivity disorder, dementias, schizophrenia, as well as obesity and sleep disorders. This receptor exhibits molecular, pharmacological, and functional heterogeneity that informs the preclinical development of effective antagonists. Herein, we describe the biological and chemical implications for developing H3 receptor antagonists and their therapeutic potential as disclosed through animal models of cognition, sleep, and obesity.
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PMID:Histamine H3 receptor antagonists: preclinical promise for treating obesity and cognitive disorders. 1656 70

Depriving healthy subjects of sleep has been shown to acutely increase blood pressure and sympathetic nervous system activity. Prolonged short sleep durations could lead to hypertension through extended exposure to raised 24-hour blood pressure and heart rate, elevated sympathetic nervous system activity, and increased salt retention. Such forces could lead to structural adaptations and the entrainment of the cardiovascular system to operate at an elevated pressure equilibrium. Sleep disorders are associated with cardiovascular disease, but we are not aware of any published prospective population studies that have shown a link between short sleep duration and the incidence of hypertension in subjects without apparent sleep disorders. We assessed whether short sleep duration would increase the risk for hypertension incidence by conducting longitudinal analyses of the first National Health and Nutrition Examination Survey (n=4810) using Cox proportional hazards models and controlling for covariates. Hypertension incidence (n=647) was determined by physician diagnosis, hospital record, or cause of death over the 8- to 10-year follow-up period between 1982 and 1992. Sleep durations of < or =5 hours per night were associated with a significantly increased risk of hypertension (hazard ratio, 2.10; 95% CI, 1.58 to 2.79) in subjects between the ages of 32 and 59 years, and controlling for the potential confounding variables only partially attenuated this relationship. The increased risk continued to be significant after controlling for obesity and diabetes, which was consistent with the hypothesis that these variables would act as partial mediators. Short sleep duration could, therefore, be a significant risk factor for hypertension.
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PMID:Short sleep duration as a risk factor for hypertension: analyses of the first National Health and Nutrition Examination Survey. 1658 9

The prevalence of gastroesophageal reflux disease (GERD) is increasing in Japan. Symptoms of GERD negatively affect their quality of life and sleep. There are several reasons for sleep disorder with GERD as follows. Nocturnal GERD symptoms sometimes directly avoid sleeping. Sleep apnea syndrome and GERD are sometimes concomitant. The both are sharing similar risk factor such as obesity and cause sleep disorder. When untypical symptoms of GERD are not diagnosed, patients are severely anxious about their physical condition. Then they feel stressful and sometimes get secondary depressive state including sleep disorder. We had better take care about patients' psychosocial factors and treat symptoms of GERD and sleep disorder together with holistic approach.
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PMID:[GERD and sleep disorder]. 1683 62

The sleep-wake cycle is under the control of the circadian clock. Recent advances in rhythm biology have identified molecular clocks and their key regulating genes. Circadian clock genes (Clock, Per) were first isolated in Drosophila, and their homologous counterparts have been found in mammals. Some of the circadian master genes have been shown to influence sleeping behavior. For instance, a point mutation in a human clock gene (Per2) was shown to produce the rare advanced sleep phase syndrome, whereas a functional polymorphism in Per3 is associated with the more frequent delayed sleep phase syndrome. Furthermore, a study examining the association between Clock gene polymorphisms and insomnia revealed a higher recurrence of initial, middle, and terminal insomnia in patients homozygous for the Clock genotype. Other genes have been shown to contribute to sleep pathologies. A point mutation in the prion protein gene appears to be the cause of fatal familial insomnia. A missense mutation has been found in the gene encoding the GABA-A beta 3 subunit in a patient with chronic insomnia. In both animal models and humans, a deficiency in the hypocretin/orexin system was proposed to be responsible for narcolepsy. Selective destruction of hypocretin neurons is the most probable culprit in humans. These findings suggest that the genetic contribution to sleep disorders and wake determinants is more important than originally thought. Beyond sleep, light/dark cycles and sleep deprivation appear also to be associated with eating habits, and epidemics of obesity have to be evaluated in the context of shortened sleep duration.
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PMID:Genetics of the sleep-wake cycle and its disorders. 1697 29

Migraine is a chronic-recurrent disorder that progresses in some individuals. Transformed migraine is the result of this progression. Since migraine does not progress in most patients, identifying the risk factors for progression has emerged as a very important public health priority. If risk factors can be identified, that might provide a foundation for more aggressive preventive intervention. Risk factors for progression may be divided into non-remediable (gender, age, race) and remediable categories. In this paper, we focus on several already identified remediable risk factors, including frequency of migraine attacks, obesity, acute medication overuse, caffeine overuse, stressful life events, depression, and sleep disorders. We present the evidence for each risk factor and discuss possible interventions to address them.
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PMID:Modifiable risk factors for migraine progression. 1704 Mar 31

In spite of a progressive fall in the incidence of traditional risk factors of cardiovascular morbidity (cigarette smoking, high blood pressure, and hyperlipidemia), there is an upward trend in the prevalence of obesity and chronic kidney disease (CKD). Furthermore, there is a strong correlation between body mass indices and the relative risk of progression of CKD. The close biophysiological interaction between obesity and CKD is evident by a similar occurrence of comorbidities including insulin resistance, hyperlipidermia, endothelial dysfunction, and sleep disorders. Truncal obesity is a primary component of metabolic syndrome; unlike peripheral fat, the visceral adipocytes are more resistant to insulin. In addition, lipolysis results in a release of free fatty acid and TG, whereas hypertriglycedemia is potentiated by uremic activation of fatty acid synthase. Hypertriglycedemia and low HDL cholesterol increase the relative risk of progression of CKD. Furthermore, endothelial inflammation and premature atherosclerosis are promoted by hyperhomocysteinemia and oxidation of LDL, both of which are commonly observed in CKD and obesity. Predominance of oxidative stress in both obesity and azotemia stimulate synthesis of angiotensin II, which in turn increases TGF-B and plasminogen activator inhibitor-1, thereby propagating glomerular fibrosis. Furthermore, local synthesis of angiotensinogen by adipocytes, leptin activation of sympathetic nervous system, and hyperinsulinemia contribute to the development of hypertension in obesity and CKD. In addition, increased renal tubular expression of Na-K-ATPase and a blunted response to natiuretic hormones in obesity promote salt and water retention. Glomerular hyperfiltration from systemic volume load and hypertension results in mesangial cellular proliferation and progressive renal fibrosis. In addition, maternal nutritional deprivation increases the incidence of obesity, hypertension, and diabetes in adulthood. Reduced fetal protein synthesis contributes to oxidative glomerular injury and impairment of renal morphogenesis. Thus, kidneys are poorly equipped to handle physiologic stress that may result from the rapid body growth and programmed metabolic dysfunction later in life. Finally, in order to minimize morbidity of obesity-related kidney disease, preventive strategy must include optimal maternal health care, promotion of healthy nutrition and routine physical exercise, and early detection of CKD.
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PMID:The role of obesity and its bioclinical correlates in the progression of chronic kidney disease. 1704 21

The post-tsunami health and nutritional statuses of survivors were surveyed three months after the disaster struck. Non-participant observations and questionnaires were used to study the effects of the disaster on their lifestyles and health while residing in temporary shelters provided by the government and private donors. Anthropometrics were measured and dietary surveys conducted to elicit nutritional status. Our findings indicated good management of drinking water in the temporary shelters. Toilet construction and water supply were adequate, but wastewater and sewage systems were poorly managed. The study group still suffered from injuries after the disaster, and complained of back pain, stress, and sleep disorders. Most in the study group had unsatisfactory health behaviors, and obesity was an increasing problem among female participants.
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PMID:Health and nutrition survey of tsunami victims in Phang-Nga Province, Thailand. 1712 3


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