Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overproduction of corticotropin-releasing hormone (CRH) and stress system abnormalities are seen in psychiatric diseases such as depression, anxiety, eating disorders, and addiction. Investigations of CRH type 1 receptor (CRHR1) nonpeptide antagonists suggest therapeutic potential for treatment of these and other neuropsychiatric diseases. However, overproduction of CRH in the brain and on its periphery and disruption of the hypothalamic-pituitary-adrenal axis are also found in 'somatic' disorders. Some rare forms of Cushing's disease and related pituitary/adrenal disorders are obvious applications for CRHR1 antagonists. In addition, however, these antagonists may also be effective in treating more common somatic diseases. Patients with obesity and metabolic syndrome who often have subtle, but chronic hypothalamic-pituitary-adrenal hyperactivity, which may reflect central dysregulation of CRH and consequently glucocorticoid hypersecretion, could possibly be treated by administration of CRHR1 antagonists. Hormonal, autonomic, and immune aberrations are also present in chronic inflammatory, autoimmune, and allergic diseases, with considerable evidence linking CRH with the observed abnormalities. Furthermore, autonomic dysregulation is a prominent feature of common gastrointestinal disorders, such as irritable bowel syndrome and peptic ulcer disease. Patients with irritable bowel syndrome and other gastrointestinal disorders frequently develop altered pain perception and affective symptoms. CRH acts peripherally to modulate bowel activity both directly through the autonomic system and centrally by processing viscerosensory and visceromotor neural signals. This review presents clinical and preclinical evidence for the role of CRH in the pathophysiology of these disorders and for potential diagnostic and therapeutic applications of CRHR1 antagonists. Recognition of a dysfunctional stress system in these and other diseases will alter the understanding and treatment of 'psychosomatic' disorders.
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PMID:Nonpeptide corticotropin-releasing hormone receptor type 1 antagonists and their applications in psychosomatic disorders. 1552 86

Cannabis sativa L. preparations have been used in medicine for millenia. However, concern over the dangers of abuse led to the banning of the medicinal use of marijuana in most countries in the 1930s. Only recently, marijuana and individual natural and synthetic cannabinoid receptor agonists and antagonists, as well as chemically related compounds, whose mechanism of action is still obscure, have come back to being considered of therapeutic value. However, their use is highly restricted. Despite the mild addiction to cannabis and the possible enhancement of addiction to other substances of abuse, when combined with cannabis, the therapeutic value of cannabinoids is too high to be put aside. Numerous diseases, such as anorexia, emesis, pain, inflammation, multiple sclerosis, neurodegenerative disorders (Parkinson's disease, Huntington's disease, Tourette's syndrome, Alzheimer's disease), epilepsy, glaucoma, osteoporosis, schizophrenia, cardiovascular disorders, cancer, obesity, and metabolic syndrome-related disorders, to name just a few, are being treated or have the potential to be treated by cannabinoid agonists/antagonists/cannabinoid-related compounds. In view of the very low toxicity and the generally benign side effects of this group of compounds, neglecting or denying their clinical potential is unacceptable--instead, we need to work on the development of more selective cannabinoid receptor agonists/antagonists and related compounds, as well as on novel drugs of this family with better selectivity, distribution patterns, and pharmacokinetics, and--in cases where it is impossible to separate the desired clinical action and the psychoactivity--just to monitor these side effects carefully.
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PMID:Cannabinoids in health and disease. 1828 1

Ghrelin is an orexigenic peptide hormone secreted into the systemic circulation predominantly by the X/A-like cells in the mucosa of the stomach. In addiction to central effects on food intake and growth hormone release, ghrelin has also important vascular and metabolic actions. Our laboratory has shown that administration of exogenous ghrelin acutely improves endothelial function by increasing nitric oxide bioavailability and normalizing the alterate balance between endothelin 1/nitric oxide (ET-1/NO) within the vasculature of individuals with metabolic syndrome. Additionally, in endothelial cell cultures, it has been shown that ghrelin directly stimulates NO production using a signaling pathway that involves GHSR-1a, PI 3-kinase, Akt, and eNOS. Other cardiovascular effects of ghrelin include lowering of peripheral resistance, improvement of contractility and cardiac output. In addition ghrelin plays a significant role in the regulation of glucose homeostasis, lipid profiles and body composition. Importantly, ghrelin has antinflammatory and antiapoptotic effects both in vivo and in vitro. This review focuses on the physiological roles of ghrelin in regulating metabolic and endothelial function and on the potential of ghrelin as the therapeutic target to treat metabolic and cardiovascular disorders.
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PMID:Cardiovascular and metabolic effects of ghrelin. 2045 93

Rates of fructose consumption continue to rise nationwide and have been linked to rising rates of obesity, type 2 diabetes, and metabolic syndrome. Because obesity has been equated with addiction, and because of their evolutionary commonalities, we chose to examine the metabolic, hedonic, and societal similarities between fructose and its fermentation byproduct ethanol. Elucidation of fructose metabolism in liver and fructose action in brain demonstrate three parallelisms with ethanol. First, hepatic fructose metabolism is similar to ethanol, as they both serve as substrates for de novo lipogenesis, and in the process both promote hepatic insulin resistance, dyslipidemia, and hepatic steatosis. Second, fructosylation of proteins with resultant superoxide formation can result in hepatic inflammation similar to acetaldehyde, an intermediary metabolite of ethanol. Lastly, by stimulating the "hedonic pathway" of the brain both directly and indirectly, fructose creates habituation, and possibly dependence; also paralleling ethanol. Thus, fructose induces alterations in both hepatic metabolism and central nervous system energy signaling, leading to a "vicious cycle" of excessive consumption and disease consistent with metabolic syndrome. On a societal level, the treatment of fructose as a commodity exhibits market similarities to ethanol. Analogous to ethanol, societal efforts to reduce fructose consumption will likely be necessary to combat the obesity epidemic.
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PMID:Fructose: metabolic, hedonic, and societal parallels with ethanol. 2170 74

As obesity, type 2 diabetes (T2DM) and the metabolic syndrome sweep across the research and the clinical landscape of medical care, effective pharmacologic remedies for the treatment of obesity have become imperative. The complexities of nutrient impact on neurotransmitter and endocrine modulating chemistry have become increasingly better characterized as have the basic neurochemical pathways that mediate their effects. Food addiction has emerged as an important phenomenon that may help to explain and improve our capabilities of rendering bench lab research into impactful clinical intervention. Against this challenging backdrop of current research and study we introduce the notion that food may in fact, itself, represent a type of drug. In this review chapter of food as a drug, we outline some of the emerging science that argues how proteins, carbohydrates and fats operating on three basic levels of organismic functioning may constitute the most powerful drugs we have available to effectuate weight loss or weight gain over time. In addition, certain foods may not only be more addictive than others, but may actually have a direct effect on pro-inflammatory mediators that determine both metabolic dysfunction as well as overall neuropsychiatric function and well-being.
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PMID:Food as a bariatric drug. 2149 82

'Globesity' is a descriptive term for the obesity epidemic now facing the U.S. and indeed, the world. Hyperphagia (i.e. overeating) can lead to metabolic syndrome which in turn can lead to Type 2 diabetes mellitus, heart disease, stroke and some cancers. The World Health Organization even states that more people die each year from the consequences of obesity than from hunger. Something must be done to stem the tsunami of obesity and its resultant medical complications. Our work and that of others suggests that new obesity treatments and anti-obesity medications should be based on those already successful in treating other addictions. This paper looks at empirical evidence linking addictions to food and to drugs such as tobacco, alcohol, cannabis, amphetamines, and cocaine. Hypotheses are put forth as to why hyperphagia is so difficult to treat. Additionally, prenatal programming for addiction is explored. Lessons from successful drug treatment are elucidated and potential pharmaceutical targets for hyperphagia and obesity are suggested.
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PMID:Drug withdrawal and hyperphagia: lessons from tobacco and other drugs. 2149 91

Here the dramatic and rapid response of a 54-year-old obese hypertensive man with poorly controlled insulin-dependent diabetes with a 33 year history of high dose heroin use, a 1 year history of refractory ulceration of his hands, ankles and feet, treated coronary artery disease, and the metabolic syndrome, to implantation with long-acting naltrexone implants is presented. In particular his hyperlipidaemia, hyperglycaemia, proinflammatory state, evidence of hepatic and renal insufficiency, arterial stiffness, and extensive and chronic cutaneous ulceration all improved dramatically over just 13 weeks, in association with complete control of his heroin, benzodiazepine, tobacco and cannabis use. The metabolic and vascular benefits were all highly statistically significant. The case is the first to document dramatic and rapid metabolic, immune and vascular improvements in association with clinical naltrexone therapy and are consistent with its likely effects in restoring addiction-related stem cell and immunological deficits.
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PMID:Improved parameters of metabolic glycaemic and immune function and arterial stiffness with naltrexone implant therapy. 2168 46

The circadian clock is based on a molecular oscillator, which simulates the external day within nearly all of a body's cells. This "internalized" day then defines activity and rest phases for the cells and the organism by generating precise rhythms in the metabolism, physiology, and behavior. In its perfect state, this timing system allows for the synchronization of an organism to its environment and this may optimize energy handling and responses to daily recurring challenges. However, nowadays, we believe that desynchronization of an organism due to its lifestyle or problems with its circadian clock not only causes discomfort but also may aggravate conditions such as depression, metabolic syndrome, addiction, or cancer. In this review, we focus on one simple cogwheel of the mammalian circadian clock, the PERIOD2 (PER2) protein. Originally identified as an integral part of the molecular mechanism that yields overt rhythms of about 24h, more recently multiple other functions have been identified. In essence, the PER proteins, in addition to their important function within the molecular oscillator, can be seen not only as integrators on the input side of the circadian clock but also as mediators of clock output. This diversity in their function is possible, because the PER proteins can interact with a multitude of other proteins transferring oscillator timing information to the latter. In this fashion, the circadian clock synchronizes many rhythmic processes.
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PMID:The circadian clock component PERIOD2: from molecular to cerebral functions. 2287 69

The senior patient and/or the geriatrician are confronted with a confusing literature describing how patients interested in combating metabolic syndrome, diabesity (diabetes plus obesity) or simple obesity might best proceed. The present paper gives a brief outline of the basic disease processes that underlie metabolic pro-inflammation, including how one might go about devising the most potent and practical detoxification from such metabolic compromise. The role that dietary restriction plays in pro-inflammatory detoxification (detox), including how a modified fast (selective food abstinence) is incorporated into this process, is developed. The unique aspects of geriatric bariatric medicine are elucidated, including the concepts of sarcopenia and the obesity paradox. Important caveats involving the senior seeking weight loss are offered. By the end of the paper, the reader will have a greater appreciation for the challenges and opportunities that lie ahead for geriatric patients who wish to overcome food addiction and reverse pro-inflammatory states of ill-heath. This includes the toxic metabolic processes that create obesity complicated by type 2 diabetes mellitus (T2DM) which collectively we call diabesity. In that regard, diabesity is often the central pathology that leads to the evolution of the metabolic syndrome. The paper also affords the reader a solid review of the neurometabolic processes that effectuate anorexigenic versus orexigenic inputs to obesity that drive food addiction. We argue that these processes lead to either weight gain or weight loss by a tripartite system involving metabolic, addictive and relational levels of organismal functioning. Recalibrating the way we negotiate these three levels of daily functioning often determines success or failure in terms of overcoming metabolic syndrome and food addiction.
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PMID:Food addiction: detox and abstinence reinterpreted? 2326 44

Smoking is an important cardiovascular risk factor, however, use of smokeless tobacco has not been well studied. Smokeless tobacco use is high in countries of South and Southeast Asia, Africa and Northern Europe. Meta-analyses of prospective studies of smokeless tobacco users in Europe reported a relative risk for fatal coronary heart disease of 1.13 (confidence intervals 1.06-1.21) and fatal stroke of 1.40 (1.28-1.54) while in Asian countries it was 1.26 (1.12-1.40). Case-control studies reported significantly greater risk for acute coronary events in smokeless tobacco users (odds ratio 2.23, 1.41-3.52), which was lower than smokers (2.89, 2.11-3.96), and subjects who both chewed and smoked, had the greatest risk (4.09, 2.98-5.61). There is a greater prevalence of hypertension and metabolic syndrome in users of smokeless tobacco. Smokeless tobacco use leads to accelerated atherothrombosis similar to smoking. There is an urgent need for public health and clinical interventions to reduce smokeless tobacco addiction.
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PMID:Smokeless tobacco and cardiovascular disease in low and middle income countries. 2399 97


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