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)

Centrally acting imidazoline I(1)-receptor agonists such as moxonidine and rilmenidine induce peripheral sympathoinhibition via the stimulation of hypothetical I(1)-receptors in the rostral ventrolateral medulla. Because of a rather weak affinity for alpha(2)-adrenoceptors, the use of these agents is associated with a lower incidence of adverse reactions, such as sedation and dry mouth, compared with classic centrally acting alpha(2)-adrenoceptor agonists (clonidine, guanfacine, methyldopa). The antihypertensive efficacy of moxonidine and rilmenidine is well documented, and they display a favorable hemodynamic profile. Their tolerability is better than that of the aforementioned centrally acting antihypertensive agents. However, long-term outcome data for moxonidine and rilmenidine are not available, and neither is a quantitative evaluation of their adverse effects. There exists some uncertainty with respect to the identity of the imidazoline I(1)-receptor, which has so far not been cloned. Furthermore, it would be desirable to develop highly selective I(1)-receptor agonists as successor drugs to moxonidine and rilmenidine. Although available data indicate that I(1)-receptor agonists are effective in patients with hypertension, comparative data versus agents such as beta-blockers, diuretics, calcium channel antagonists and ACE inhibitors are required to establish their position in the treatment of hypertension. Finally, I(1)-receptor agonists have potential in the treatment of patients with CHF and those with the metabolic syndrome; syndrome X.
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PMID:Centrally acting imidazoline I1-receptor agonists: do they have a place in the management of hypertension? 1472 14

Rheumatoid arthritis (RA) associates with increased cardiovascular mortality. This appears to be predominantly due to ischaemic causes, such as myocardial infarction and congestive heart failure. The higher prevalence of cardiac ischaemia in RA is thought to be due to the accelerated development of atherosclerosis. There are two main reasons for this, which might be inter-related: the systemic inflammatory load, characteristic of RA; and the accumulation in RA of classical risk factors for coronary heart disease, which is reminiscent of the metabolic syndrome. We describe and discuss in the context of RA the involvement of local and systemic inflammatory processes in the development and rupture of atherosclerotic plaques, as well as the role of individual risk factors for coronary heart disease. We also present the challenges facing the clinical and scientific communities addressing this problem, which is receiving increasing attention.
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PMID:Inflammation and atherosclerosis in rheumatoid arthritis. 1587 61

Central imidazoline (I(1))-receptors have been recognised as targets of a new class of centrally acting antihypertensives. The stimulation of these I(1)-receptors induces peripheral sympatho-inhibition and a reduction of (elevated) blood pressure. Moxonidine and rilmenidine are the prototypes of this new class of centrally acting antihypertensives. These imidazoline receptor stimulants are effective antihypertensives with a haemodynamic profile which is attractive from a pathophysiological point of view. Since both moxonidine and rilmenidine have a much weaker affinity for central (2)-adrenoceptors than classic centrally acting drugs, for example, clonidine and alpha-methyl-DOPA, the side-effects profile of the I(1)-receptor stimulants is significantly better. The imidazoline (I(1))-receptor stimulants are the subject of the current survey. They appear to offer the possibility of developing centrally acting antihypertensives with the same attractive haemodynamic characteristics as the classic alpha(2)-adrenoceptor stimulants, but with clearly better tolerability. Their potential use in the treatment of congestive heart failure and the metabolic syndrome is subject to clinical investigation.
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PMID:Antihypertensive drugs interacting with central imidazoline (I1)-receptors. 1599 29

Type 2 diabetes mellitus is a public health problem of epidemic proportions and its prevalence is on the rise. The typical American born today has a one in three chance of developing type 2 diabetes. This diagnosis is associated with an adverse cardiovascular prognosis and is considered the risk equivalent of established coronary disease. Many risk factors, including the metabolic syndrome, have been implicated in its development. Even in high-risk individuals, type 2 diabetes is a preventable disease. Diet and exercise have been consistently shown to decrease the incidence of diabetes in large randomized controlled studies. Additionally, new-onset diabetes was reduced by several oral pharmacologic anti-diabetic agents including metformin, acarbose and troglitazone in randomized trials which studied patients with impaired glucose tolerance. More interestingly, multiple large prospective studies have also reported a reduction in the development of type 2 diabetes in patients treated with anti-hypertensive agents, predominantly angiotensin converting enzyme inhibitors and angiotensin receptor blockers. In this review, we will discuss some of these important trials and the speculative mechanisms whereby those medications prevent type 2 diabetes. Such observations, if proven to be true, may represent preventive strategies which can be considered in patients with pre-diabetic conditions such as the metabolic syndrome, hypertension, impaired fasting glucose, family history of diabetes, obesity, congestive heart failure or other risks for the development of type 2 diabetes.
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PMID:Strategies to prevent type 2 diabetes. 1600 80

The paraventricular nucleus of the hypothalamus (PVN) is a complex effector structure that initiates endocrine and autonomic responses to stress. It receives inputs from visceral receptors, circulating hormones such as angiotensin II, and limbic circuits and contains neurons that release vasopressin, activate the adrenocortical axis, and activate preganglionic sympathetic or parasympathetic outflows. The neurochemical control of the different subgroups of PVN neurons is complex. The PVN has been implicated in the pathophysiology of congestive heart failure and the metabolic syndrome.
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PMID:Paraventricular nucleus, stress response, and cardiovascular disease. 1603 78

Disease epidemics have influenced world history throughout time. Although disease patterns such as the plague and smallpox historically have been infectious in nature, chronic diseases such as cardiovascular disease, stroke, congestive heart failure, and end-stage renal disease have become the new global epidemics. The effects of these conditions affect nearly all populations of the world. Although high blood pressure has been implicated as the common link of these pandemic patterns only for less than half a century, the impact of hypertension treatment and control has become a documented population-based response with the greatest potential for global impact. For example, an estimated 45% of the deaths among African-American men could be prevented with treatment of high blood pressure to goal level. However, population demographics and risk factors predict a worsening effect as the populations of the world increase in age, racial disparities in access to medical care widen, and comorbid conditions such as obesity and metabolic syndrome continue to increase at epidemic rates. The economic impact of hypertension-related conditions, end-stage renal disease, and congestive heart failure is staggering, such that health care delivery systems will fail if the current trends are not changed. Hospitalization rates of hypertension-related conditions are increasing along with an aging population. The number of at-risk individuals in the population also is increasing. As the definition of hypertension changes with lower levels of blood pressure, the proportion of the population considered to have hypertension increases substantially. These trends and disease patterns clearly identify the essential need to implement population and clinical strategies for high blood pressure prevention, treatment, and control.
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PMID:Systemic hypertension: an endemic, epidemic, and a pandemic. 1620 91

The thiazolidinediones have been in clinical use for the management of type 2 diabetes for the past five years. These agents reduce insulin resistance by acting as ligands that regulate gene expression related to the proliferation and differentiation of adipose tissue. Overall, data from several clinical studies suggest that their hypoglycaemic efficacy is slightly less than sulphonylureas and metformin but greater than acarbose and the glinides. In the short term, treatment with thiazolidinediones is associated with weight gain, expansion of plasma volume, fluid retention, peripheral oedema, an increased risk of congestive heart failure when combined with insulin, and an idiosyncratic hepatotoxic reaction to troglitazone. The long term consequences of these effects are not known. Contrary to expectations, despite being insulin sensitisers these agents do not favourably influence the other components of the metabolic syndrome that are believed to be aggravated by insulin resistance. Dyslipidaemia and elevated blood pressure, which are major risk factors of cardiovascular disease in type 2 diabetes, are not favourably improved with thiazolidinedione treatment. Unlike the sulphonylureas and metformin, which have been shown in recent long term randomised studies to reduce cardiovascular risk substantially, there is no data on the long term cardiovascular safety of the thiazolidinediones. At present, in the absence of long term data, the thiazolidinediones in clinical use are moderately effective hypoglycaemic drugs with no particular advantage over existing treatments in type 2 diabetes.
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PMID:Thiazolidinediones in type 2 diabetes--have they lived up to expectations? 1622 62

Thiazolidinediones (TZDs) are peroxisomal proliferator-activated receptor (PPAR)-gamma agonists. They increase insulin action through several mechanisms including: stimulation of the expression of genes that increase fat oxidation and lower plasma free fatty acid levels; increased expression, synthesis and release of adiponectin; and stimulation of adipocyte differentiation resulting in more and smaller fat cells. TZDs lower blood sugar comparably to sulfonylureas and metformin. The clinical use of TZDs is limited due to the long duration of time required before they reach their full blood sugar-lowering action (3-4 months) and adverse effects such as fluid retention, resulting in excessive weight gain and occasionally in peripheral and/or pulmonary oedema and congestive heart failure. Troglitazone, a TZD that has since been removed from the market because of hepatoxicity, has been demonstrated to decrease the progression from normal or impaired glucose tolerance to overt Type 2 diabetes mellitus. Pioglitazone, another TZD, marginally decreased the incidence of cardiovascular complications in patients with Type 2 diabetes mellitus (PROactive trial). Other, as yet, unapproved uses of TZDs include: non-alcoholic fatty liver disease, in which TZDs reduced hepatic fat accumulation and improved liver function tests; polycystic ovary syndrome, where TZDs improved ovulation, hirsutism and endothelial dysfunction; and lipodystrophies, where TZDs increased body fat (marginally) and decrease liver size. Lastly, because PPAR-alpha and -gamma agonists improve atherosclerotic vascular disease and insulin sensitivity, respectively, dual PPAR-alpha/gamma agonists, which are currently undergoing clinical trials, may be useful in treating patients with the metabolic syndrome.
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PMID:Recent findings concerning thiazolidinediones in the treatment of diabetes. 1650 61

Hyperuricemia is a frequent finding in diseases in which the clinical manifestations are thought to be secondary to a state of generalized vascular endothelial dysfunction and related to the cardiovascular disease present in conditions associated with the metabolic syndrome, such as hypertension or diabetes. Traditionally, uric acid has not been given an active role in the pathologic process underlying these conditions. However, there is now a growing body of experimental and clinical evidence that points to a mechanistic role for uric acid in cardiovascular disease. The mechanisms that are most often thought to link uric acid and endothelial dysfunction involve inflammation and generation of oxidative stress in the vasculature. These observations allowed new clinical applications and formulations of therapies, such as the introduction of xanthine oxidase inhibitors in the management of congestive heart failure.
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PMID:Uric acid and the vasculature. 1667 43

It is not surprising that cardiovascular diseases such as congestive heart failure and coronary insufficiency can give rise to varying degrees of sleep impairment; it is less readily appreciated that certain physiologic events occurring during sleep-as well as long-term unsatisfactory sleep-may cause or increase the risk of cardiovascular conditions such as hypertension, atherosclerosis, stroke, and cardiac arrythmias. Heart rate abnormalities during sleep in normotensive subjects predict later cardiovascular disease, and their early identification alerts the physician to undertake preventive measures. Maneuvers, such as induction of hypoxia, can elicit abnormal blood pressure responses during sleep, and such responses have been used to identify impending cardiovascular problems that could become therapeutic targets. The spontaneously hypertensive rat has been used to examine the effect of sympathetic nervous system (SNS) activity on the heart under a variety of experimental conditions, including quiet and paradoxical sleep. The results have disclosed significant differences between the responses of spontaneously hypertensive rats and normal rats to SNS stimulation. Exploration of other pathophysiologic pathways affected by exposure to light and dark, including those responsive to the cyclic production of melatonin, will improve our understanding of the effect of disruptions of the circadian cycle on cardiovascular function. There is growing evidence that melatonin can influence important processes such as fluid, nitrogen, and acid-base balance. Human subjects whose nocturnal arterial blood pressure fails to show the "normal" decrement during sleep ("nondippers") are also prone to sleep poorly, exhibit increased SNS activity during sleep, and have an increased risk of total and cardiovascular disease mortality. Chronic sleep deficit is now known to be a risk factor for obesity and may contribute to the visceral form of obesity that underlies the metabolic syndrome. The rising prevalence of obstructive sleep apnea and central sleep apnea is linked to the modern-day epidemic of obesity. Obstructive sleep apnea is associated with an enhanced risk of having a new stroke or a transient ischemic attack.
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PMID:Sleep and vascular disorders. 1697 27


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