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

The histamine H(3) receptor is involved in the central and peripheral regulation of levels of histamine and other neurotransmitters (e.g., acetylcholine, noradrenaline, dopamine, serotonin and GABA), which sets it up as a target in the treatment of various CNS (e.g., depression, schizophrenia, ADHD, dementia, neuropathic pain and sleep disorders), metabolic syndrome (e.g., obesity) and allergic disorders. Novel chemical series from the most recent 2 years of patent literature have been reviewed. While overall structural diversity is moderate, these represent or relate to some of the compounds progressing through clinical trials (e.g., GSK-189254). However, an H(3) receptor drug still has yet to reach the market. Patenting activity is likely to remain high in the near future, bolstered by the commercial promise of potential H(3) receptor drugs.
 ...
PMID:Recent advances in the development of histamine H3 antagonists. 2014 64

Although sleep disorders such as insomnia and obstructive sleep apnea are common in both children and adults, the clinical features and treatments for these conditions differ considerably between these two populations. Whereas an adult with obstructive sleep apnea typically presents with a history of obesity, snoring, and prominent daytime somnolence, a child with the condition is more likely to present with normal body weight, tonsillar hypertrophy, and inattentiveness during school classes. The adult with suspected sleep apnea almost always undergoes a baseline polysomnogram and proceeds to treatment only if this test confirms the diagnosis, while many children with suspected sleep apnea are treated empirically with adenotonsillectomy without ever receiving a sleep study to verify the diagnosis. This article reviews sleep disorders in children, with a particular focus on age-related changes in sleep, conditions that primarily affect children, and disorders for which clinical manifestations and treatment differ substantially from the adult population.
 ...
PMID:Sleep disorders in children. 2014 88

Obstructive sleep apnea syndrome (OSAS) is an often underestimated sleep disorder that has been associated with cardiovascular disease. OSAS is characterized by cycles of apnea and/or hypopnea during sleep caused by the collapse of the upper airways. Intermittent hypoxia deriving from the cycles of apnea/arousals (to retrieve the ventilation) plays a pivotal role in the pathogenesis of the disease. Obesity is the most frequent predisposing condition of OSAS. Recent evidence suggests that OSAS could be considered as a pro-atherosclerotic disease, independently of visceral fat amount. Oxidative stress, cardiovascular inflammation, endothelial dysfunction, and metabolic abnormalities in OSAS could accelerate atherogenesis. The present review is focused on the possible pathophysiological mediators which could favor atherosclerosis in OSAS.
 ...
PMID:Inflammation accelerates atherosclerotic processes in obstructive sleep apnea syndrome (OSAS). 2019 12

Elucidation of the cellular and molecular mechanisms of the circadian clock, along with the realization that these mechanisms are operative in both central and peripheral tissues, has revolutionized circadian biology. Further, these observations have resulted in an explosion of interest in the health implications of circadian organization and disorganization at both molecular and physiological levels. Thus, recent research has implicated mutations and polymorphisms of circadian clock genes in diabetes and obesity, cardiovascular disease, and cancer. At the neuro-behavioral level, circadian clock genes have also been implicated in sleep disorders, drug and alcohol addiction, and other psychiatric conditions. While such findings are frequently described as revealing "non-circadian" effects of clock genes, it remains possible that most of these non-circadian effects are in fact secondary to the loss of cellular and systemic rhythmicity. This review summarizes the evidence linking circadian clock genes to biobehavioral dysregulation, and considers criteria for defining a pleiotropic clock gene effect as non-circadian.
 ...
PMID:Circadian clock genes: non-circadian roles in sleep, addiction, and psychiatric disorders? 2030 70

Mutations in the prokineticin 2 peptide (PROK2) and its seven-transmembrane domain type 2 receptor PROKR2 are newly identified molecular culprits in autosomal Kallmann syndrome (KS). Prok2 and prokr2 gene knockout mice both have agenesis or hypoplasia of the olfactory bulbs, associated with hypogonadotropic hypogonadism linked to abnormal GnRH neuron migration. Prok2-/- and prokr2-/- mice are the first murine models of this human disease. KS patients of both sexes have a variety of point mutations, missense mutations, frameshifts and nonsense mutations in the PROK2 and PROKR2 genes that lead to a loss of peptide or receptor function. When only one allele is affected, penetrance of the two main clinical features of KS may be incomplete: subjects with only one mutant allele may have (1) no symptoms, with normal olfaction and complete pubertal development, (2) congenital isolated (idiopathic) hypogonadotropic hypogonadism (IHH) but normal olfaction, (3) anosmia/hyposmia but normal pubertal development and gonadal function or (4) the two cardinal clinical KS signs, anosmia and IHH. These phenotypic dissociations can be seen in family members with the same PROK2/PROKR2 mutations. By contrast, patients with two mutant alleles almost always have the cardinal signs of KS. Even when monoallelic PROK2/PROKR2 mutations are associated with full-blown KS, the reproductive phenotype in males is less severe than in KS associated with biallelic mutations, evidenced by significantly lower frequency of cryptorchidism and micropenis, greater testicular volume, and higher serum levels of LH, FSH and testosterone. Moreover, at least some of these monoallelic cases are in fact digenic, in that they also carry mutations of other KS/IHH genes. Overall, these observations point towards a combination of mendelian autosomal recessive transmission, with more complex oligogenic transmission. Patients with this genetic form of KS have been reported to have a possible increased prevalence of obesity and sleep disorders, which may be related to the role of PROK2 and PROKR2 in food intake and circadian rhythms. However, diurnal variation of serum cortisol levels appears to be physiologically maintained.
 ...
PMID:Kallmann syndrome caused by mutations in the PROK2 and PROKR2 genes: pathophysiology and genotype-phenotype correlations. 2038 90

The field of sleep medicine has grown exponentially worldwide. Sleep apnea is linked to the obesity epidemic, which, in some regions of the United States, affects more than one-third of the population. Sleep alterations increase the risk of cardiovascular and cerebrovascular pathology through a diversity of direct and indirect mechanisms. Recent investigations have found a clinical correlation between sleep disorders and diabetes. Obese pregnant women are at high risk for development of sleep apnea and preeclampsia. New studies have uncovered that restless legs syndrome and periodic limb movements may increase the risk of hypertension and vascular disease. Sudden death in sleep may be preventable if conditions that lead to sudden death are investigated. New neuroimaging techniques during sleep in patients with insomnia have uncovered metabolic overactivity in areas of the brain related to maintenance of wakefulness. Sleep neuroimaging promises to have research and clinical diagnostic applications.
 ...
PMID:A review of frontiers in clinical sleep medicine. 2041 Aug 57

Migraine is a prevalent, disabling, undiagnosed and undertreated disease in neurological practice. It is a chronic, recurrent disorder with episodic manifestations that are progressive in some individuals with clinical, physiological and anatomical bases. Progression may be due to mechanisms generating the migraine attacks or to the activation generated by the attacks. Potentially remediable risk factors for chronification include frequency of migraine attacks, obesity, excessive use of medications, caffeine overuse, stressful life events, depression, sleep disorders and cutaneous allodynia.
 ...
PMID:Pathophysiology of migraine chronification. 2046 76

Obstructive sleep apnoea (OSA) is a sleep disorder characterized by recurrent episodes of oxygen desaturation during sleep, representing an independent risk factor for cardiovascular disease, such as myocardial infarction, stroke, congestive heart failure and resistant hypertension. Several neurohormonal mechanisms have been suggested to account for blood pressure increases, such as sympathetic nervous system hyperactivity, oxidative stress, renin-angiotensin-aldosterone system (RAAS) activation, endothelin system activation, and endothelial dysfunction. The aim of this study was to evaluate the behaviour of RAAS and the presence of primary aldosteronism (PA) in these patients and possible correlations between RAAS and the severity of OSA. From October 2007 to November 2008 we studied 325 consecutive newly diagnosed hypertensive patients; 71 patients (21.8%) presented with clinical signs of sleep disorders, evaluated also through a specific questionnaire (Epworth Sleepiness Scale). In hypertensive patients with sleep disorders, 53 patients were affected by OSA; in this group 18 patients were affected by PA (five with aldosterone-producing adenoma (APA) and 13 with bilateral hyperplasia (IHA)); obesity was also demonstrated (BMI > 30 kg/m(2)). Overall, in patients with OSA PRA levels correlated positively with apnoea/hypopnoea index (AHI; r = 0.35; p<0.01), and in all groups the waist circumference and the neck circumference were correlated positively with AHI (r = 0.3 p<0.02 and r = 0.3 p<0.03, respectively). We revealed a high prevalence of PA in patients with OSA, and we can conclude that patients with hypertension and OSA, especially those who are newly diagnosed, must be evaluated for PA.
 ...
PMID:Renin-angiotensin-aldosterone system in patients with sleep apnoea: prevalence of primary aldosteronism. 2048 24

The importance of sleep on health has only been recently recognized, and the general public and the medical community are not yet fully knowledgeable about this issue. The great majority of sleep research has been performed in whites of European descent and to a lesser extent in African Americans, making generalization of the findings to other ethnic and racial groups difficult. Very little sleep research has been done in U.S. Hispanics. However, based on the available literature and the high prevalence of risk factors in Hispanics, such as obesity, diabetes, living in the inner city, and use of alcohol, the prevalence of such important sleep disorders such as obstructive sleep apnea and sleep habits such as poor sleep hygiene are suspected to be high. There is also some evidence that acculturation to the U.S. life style may lead to worse sleep habits in Hispanics, including fewer hours of sleep. Two current large NIH sponsored studies of sleep in U.S. Hispanics promise to significantly add to the literature on various sleep disorders such as sleep disordered breathing, insomnia, restless legs syndrome, periodic limb movement disorder, and sleep habits such as short sleep duration and sleep hygiene.
 ...
PMID:Sleep health in U.S. Hispanic population. 2061 56

Sleep medicine is evolving rapidly. This Journal Conference summarizes recent and upcoming developments in sleep-monitoring technology, our understanding of the underlying physiology of sleep disorders and the relationships of sleep disorders to other health problems, the treatment of sleep disorders, and regulatory matters in sleep medicine. Sleep medicine is a growing field, partly because of the obesity epidemic and partly because of an increasing recognition of how sleep disorders cause and/or exacerbate serious conditions such as heart disease, and how poor sleep increases societal costs (eg, decreased work/school productivity, and motor vehicle accidents from hypersomnolence). Some key questions that remain to be answered include: What are the best metrics for diagnosing the severity of sleep apnea? What outcomes are most relevant to evaluate the efficacy of therapy? What is the best type of positive airway pressure (PAP) therapy for each category of sleep disorder? What is the best approach to treatment when positive airway pressure does not work? How often should sleep studies be repeated? What are the indications for re-titration of the PAP level? What will happen to sleep laboratories, especially if reimbursement is reduced and portable unattended sleep studies gain in popularity? Could non-sleep-specialists interpret sleep studies? What is the role of increased nasal resistance in producing upper-airway obstruction? What is the influence of chronic sinusitis on adherence to PAP therapy? How do gender differences affect the incidence, morbidity, and outcomes of sleep apnea? What are the needs of special populations with sleep disorders, such as children, patients with mental impairment, psychiatric patients, and ICU patients?
 ...
PMID:Sleep disorders: diagnosis and treatment. 2087 64


<< Previous 1 2 3 4 5 6 7 8 9 10