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)

Arteriosclerosis obliterance (ASO) is defined as the ischemic status of lower extremity produced by a stenotic and/or occlusive lesion of lumens of major arterial stress based on the pathology of atherosclerotic change. The sign and symptom of ASO are usually thought to be progressed slowly by natural progression process of atherosclerosis, however, in certain occasion, the progression of clinicopathological status of leg ischemia is acute as well as grave, so as to manifest rest pain or necrosis of the lower extremity. The basic mechanism of acute exacerbation of lower leg ischemia is attributed to the acute extended thrombus formation in arterial lumen. The factors influencing to the thrombus formation are represented as Virchow's Trias such as the changes in arterial wall, the stasis of blood flow and the coagulability of blood. One of the characteristic feature associated with massive and extended ischemia of lower leg is myonephropathic metabolic syndrome proposed by Haimovich in 1960. This syndrome is particularly seen immediately following the restoration of blood flow to the severely damaged leg and characterized by renal as well as systemic organs disorder. The relationship between the extent of muscle damage and the duration of ischemia is analysed through our data.
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PMID:[The clinico-pathological aspects of acute exacerbation of arteriosclerosis obliterance]. 880 10

Diabetes mellitus is very common in older persons. Changes in exercise habits, body habitus, leptin, amylin, tumor necrosis factor alpha, and nitric oxide all play a role in the pathogenesis of age-related insulin resistance. In older persons elevated glucose levels not only produce retinopathy, neuropathy, and nephropathy but also decrease quality of life, pain tolerance, cognition, and functional status and increase injurious falls, nocturia, incontinence, pressure ulcers, and orthostatic hypotension. The availability of multiple new therapies has enhanced the ability of physicians to improve glycemic control in older persons without unacceptable levels of hypoglycemia. Caregivers play an important role in the management of older diabetics. Depression increases mortality rate and hospital admissions in older diabetics. In many nursing homes the quality of diabetic care is marginal. A new causative theory of the metabolic syndrome involving cytokines and nitric oxide-the NO cytokine theory-is proposed.
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PMID:An overview of diabetes mellitus in older persons. 1033 29

Functional and organic abnormalities in small unmyelinated C fibers are the hallmark of type 2 diabetes. These may be silent clinically or present with burning feet, neurovascular abnormalities, wherein warm, cold, and heat pain thresholds are disturbed in association with impairment in skin blood flow and loss of PGP 9.5 immunostaining nerves in the skin. There is a dysfunctional phase preceding organic structural damage to the neurovascular unit. It coexists with elements of the metabolic syndrome, particularly insulin resistance (IR), elevated systolic blood pressure, and diabetic dyslipidemia i.e. dysfunction of the neurovascular unit may contribute to IR due to compromised blood flow with decreased delivery of fuels to their target tissues. If this proves to be the case, it will become important to re-focus energies on the defective neuropeptidergic regulation of blood flow as an approach to ameliorating diabetes. Because there is a functional phase that precedes structural damage, reversibility of the defect is achievable.
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PMID:Small fiber neuropathy and neurovascular disturbances in diabetes mellitus. 1146 May 91

A 60-year-old man had sudden chest pain and right lower extremity pain. A diagnosis of acute aortic dissection (Stanford type A) with right lower extremity ischemia was made. An emergency ascending aortic and total arch replacement, right axillo-femoral bypass, and coronary artery bypass grafting was performed for acute aortic dissection, acute right iliac arterial occlusion, and acute myocardial infarction. Myonephropathic metabolic syndrome (MNMS) occurred 2 days after operation. The serum creatine kinase value increased over 68,000 U/l, hemodiafiltration was started on the 2nd postoperative day (POD). The patient fell into anuric state and hemodiafiltration was performed 3 times a week. Urination was obtained over 1,000 ml/day from the 25th POD and hemodiafiltration was not necessary any more. We emphasize that prompt operation including revascularization of ischemic leg should be performed in acute aortic dissection with extremity ischemia and also prompt hemodiafiltration to improve the prognosis of these disastrous lesion.
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PMID:[A successful treatment for myonephropathic metabolic syndrome after operation of acute aortic dissection (Stanford type A) with multiple organ ischemia]. 1263 18

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

Diabetic polyneuropathy (DPN) is the most common complication of diabetes and may frequently be the presenting symptom in type 2 diabetes mellitus (T2DM). Metabolic syndrome and T2DM are associated with multiple metabolic toxicities. These substrate toxicities support the formation of reactive oxygen species (ROS), which are so damaging to cells, tissues and organs and play an important role in the development of multiple diabetic complications. The importance of redox stress (ROS) and their effect on the neuronal unit are discussed. There are at least 5 major pathways involved in the development of DPN: metabolic, vascular, immunologic-autoimmune, neurohormonal growth factor deficiency, and extracellular matrix neuronal unit remodeling. Each of these five pathways are reviewed and related to neural redox stress and the role of ROS. The identification of the toxic substrates (A-FLIGHT acronym), earlier diagnosis of T2DM at the stage of impaired glucose tolerance or impaired fasting glucose, and aggressive global risk reduction with the use of a simple RAAS acronym will assist the clinician in slowing the natural progressive history, and possibly preventing the complications associated with DPN. The pain, foot ulceration, limb loss, organ dysfunction, and the associated morbidity and financial burden all contribute to the need for a better understanding of DPN and the role of redox stress and global risk reduction.
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PMID:Neural redox stress and remodeling in metabolic syndrome, type 2 diabetes mellitus, and diabetic neuropathy. 1556 93

Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis, health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute-phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro- versus anti-inflammatory and T helper (Th)1 versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic 'overshooting' with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-alpha and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the 'systemic anti-inflammatory feedback' and/or 'hyperactivity' of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases.
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PMID:Cytokine dysregulation, inflammation and well-being. 1616 5

The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB(1) receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB(1) receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB(2) receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients' need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy.
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PMID:The endocannabinoid system as an emerging target of pharmacotherapy. 1696 47

In the present study, we tested the effect of a Mediterranean-style diet on sexual function in women with the metabolic syndrome. Women were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of female sexual dysfunction (FSD) associated with a diagnosis of metabolic syndrome, a complete follow-up in the study trial and an intervention focused mainly on dietary changes. Fifty-nine women met the inclusion/exclusion criteria; 31 out of them were assigned to the Mediterranean-style diet and 28 to the control diet. After 2 years, women on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain and olive oil as compared with the women on the control diet. Female sexual function index (FSFI) improved in the intervention group, from a mean basal value of 19.7+/-3.1 to a mean post-treatment value of 26.1+/-4.1 (P=0.01), and remained stable in the control group. C-reactive protein (CRP) levels were significantly reduced in the intervention group (P<0.02). No single sexual domain (desire, arousal, lubrication, orgasm, satisfaction, pain) was significantly ameliorated by the dietary treatment, suggesting that the whole female sexuality may find benefit from lifestyle changes. A Mediterranean-style diet might be effective in ameliorating sexual function in women with metabolic syndrome.
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PMID:Mediterranean diet improves sexual function in women with the metabolic syndrome. 1767 36

G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors in humans. They convey extracellular signals into the cell interior by activating intracellular processes such as heterotrimeric G protein-dependent signaling pathways. They are widely distributed in the nervous system, and mediate key physiological processes including cognition, mood, appetite, pain and synaptic transmission. With at least 30% of marketed drugs being GPCR modulators, they are a major therapeutic target in the pharmaceutical industry's drug discovery programs. This review will survey recently patented ligands for GPCRs implicated in CNS disorders, in particular the metabotropic glutamate, adenosine and cannabinoid receptors. Metabotropic glutamate receptors regulate signaling by glutamate, the major excitatory brain neurotransmitter, while adenosine is a ubiquitous neuromodulater mediating diverse physiological effects. Recent patents for ligands of these receptors include mGluR5 antagonists and adenosine A(1) receptor agonists. Cannabinoid receptors remain one of the most important GPCR drug discovery target due to the intense interest in CB(1) receptor antagonists for treating obesity and metabolic syndrome. Such small molecule ligands are the outcome of the continuing focus of many pharmaceutical companies to identify novel GPCR agonist, antagonist or allosteric modulators useful for CNS disorders, for which more effective drugs are eagerly awaited.
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PMID:GPCR drug discovery: novel ligands for CNS receptors. 1822 Dec 21


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