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

Artery calcification occurring in atherosclerosis is connected with a high risk of cardiovascular events. Quantitative calcification evaluation using electron beam tomography indicated a correlation between artery calcification and well-known cardiovascular risk factors, i.e. smoking, obesity, and hyperlipidemia. Elevated calcium scores are especially observed in diabetic patients, which may even explain the higher mortality in this group. Calcification leads to increased blood vessel rigidity and, consequently, elevated arterial vascular resistance and left ventricular hypertrophy. An increased risk of plaque rupture in relation to calcium-rich atherosclerotic lesions was not proved. Plaque rupture and thromboembolitic complications are probably higher in the case of lipid-rich lesions. Atherosclerotic calcification is an active process in which many cells (monocytes/macrophages, vascular smooth muscle cells, and endothelial cells) participate. Many substances and transcription factors normally participating in the bone remodeling process are found in calcified atherosclerotic lesions (e.g. Cbfa-1, osteocalcin, alkaline phosphatase, BMP-2, osteopontin, osteoprotegrin, and RANKL). On monocytes, cells playing an important role in atherosclerosis progression, the presence of a calcium-sensing receptor (CaR) has been demonstrated. Increase in monocyte chemotaxis and increased interleukin 6 secretion in response to extracellular calcium were observed. Monocytes also directly and indirectly enhance vascular calcification. Immune cells and cytokines participating in vascular calcification are connected in one pathogenetic mechanism, i.e. atherosclerosis as an inflammatory disease and calcification.
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PMID:[The role of calcium ions in the pathomechanism of the artery calcification accompanying atherosclerosis]. 1576 85

The population pharmacokinetics of efalizumab was characterized in patients with moderate to severe plaque psoriasis. The study included 1088 subjects who received 1 or 2 mg/kg/wk subcutaneous efalizumab for 12 weeks from a phase I (64 subjects) and 3 phase III studies with day 42 and/or day 84 trough levels (1024 patients). Due to the limitation of the data, a 1-compartment model with first-order absorption and elimination was used to fit the data. The population means for V/F, Ka, and CL/F were 9.13 L, 0.191 day(-1), and 1.29 L/d, respectively, for a typical subject receiving a 1-mg/kg dose. Interindividual variability in CL/F was 48.2%. Body weight has the largest influence on CL/F. Other covariates (obesity, baseline lymphocyte counts, Psoriasis Area and Severity Index score, and age) had only modest effects. Subjects in the 2-mg/kg dose group had a 24.0% lower CL/F, consistent with nonlinear pharmacokinetics of efalizumab. The results of this analysis support the current body weight-adjusted dosing strategy.
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PMID:Population pharmacokinetics of efalizumab (humanized monoclonal anti-CD11a antibody) following long-term subcutaneous weekly dosing in psoriasis subjects. 1577 28

The purpose of the study was to determine clinical importance of high serum levels of ferritin, fibrinogen and C-reactive protein (CRP) in patients with various forms of coronary heart disease (CHD) such as stable angina, painless myocardial ischemia (PMI) and instable angina (IA). The subjects of the study were 60 patients with CHD, whose clinical variant (stable angina, PMI or IA) had been determined by stress echocardiography. The control group consisted of 20 patients, not suffering from CHD, but having cardiovascular risk factors (arterial hypertension, dyslipoproteinemia, male gender, obesity, elderly age). All patients underwent routine clinical examination and biochemical blood tests. Serum levels of CRP, fibrinogen and ferritin were highest in the patients with IA and significantly differed from those in the control group. The difference in serum iron levels and total iron-binding capacity in serum (TIBC) between the groups were insignificant. Correlations between serum level of iron, TIBC and ferritin level were found neither in CHD patients (r = 0.1) nor in the control group (r = 0.15). No correlation between serum level of ferritin and CRP level was observed in the control group, but in all CHD groups this correlation was significant. The strongest correlation between these values was observed in the patients with IA. Besides, correlations between serum levels of ferritin and CRP (r = 0.46, p < 0.02) and between ferritin and fibrinogen levels (r = 0.39, p < 0.05) were found in the patients with IA. In patients with CHD, especially those who have IA, serum ferritin should be considered among acute phase proteins, reflecting destabilization of atherosclerotic plaque.
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PMID:[Ferritin and other acute phase proteins in various forms of coronary heart disease]. 1580 27

In recent years, the concepts of the pathogenesis of atherosclerosis and cardiovascular events have broadened from a lipid-centric view of etiology to the appreciation of the importance of the inflammatory processes. Although obesity, oxidized lipids, and other factors are known to contribute to cardiovascular inflammation, the role of infection is believed to serve as a critical inflammatory stimulus that contributes to both atherogenesis and acute events via plaque destabilization. This inflammatory process can involve the vasculature directly by interaction of the organisms or bacterial by-products with the vessel wall or indirectly via modulation of hemostasis or hepatic activation of the acute phase response that leads to increased circulating levels of acute-phase reactants such as C-reactive protein (CRP). Epidemiological studies have suggested a significant moderate association between periodontal infection and cardiovascular risk adjusting for traditional risk factors. The potential role of periodontal disease as a possible chronic source of infection and inflammation is supported by findings indicating an association of periodontal disease with elevated serum CRP and interleukin 6. Recently, periodontal therapy studies have shown a lowering of CRP and interleukin 6, and in this issue, a new report of an improvement of endothelial function, as measured by flow-mediated dilation. These studies raise the possibility that periodontal disease may represent a modifiable risk factor that merits further study.
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PMID:A perspective on the potential cardioprotective benefits of periodontal therapy. 1597 71

Obesity is a chronic disease, whose incidence is alarmingly growing, affecting not only adults but also children and adolescents. It is associated with severe metabolic abnormalities and increased cardiovascular morbidity and mortality. Adipose tissue secretes a great number of hormones and cytokines that not only regulate substrate metabolism but may deeply and negatively influence endothelial physiology, a condition which may lead to the formation of the atherosclerotic plaque. In this review, the physiology of the endothelium is summarised and the mechanisms by which obesity, through the secretory products of adipose tissue, influences endothelial function are explained. A short description of methodological approaches to diagnose endothelial dysfunction is presented. The possible pathogenetic links between obesity and cardiovascular disease, mediated by oxidative stress, inflammation and endothelial dysfunction are described as well.
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PMID:Mechanisms of endothelial dysfunction in obesity. 1598 46

Carotid stenosis is an important cause of transient ischaemic attacks and stroke. The cause of carotid stenosis is most often atherosclerosis; contributing to the pathogenesis of the lesion are endothelial injury, inflammation, lipid deposition, plaque formation, fibrin, platelets and thrombin. Carotid stenosis accounts for 10-20% of cases of brain infarction, depending on the population studied. Despite successful treatment of selected patients who have had an acute ischaemic stroke with tissue plasminogen activator and the promise of other experimental therapies, prevention remains the best approach to reducing the impact of ischaemic stroke. High-risk or stroke-prone patients can be identified and targeted for specific interventions. At this juncture, treatment of carotid stenosis is a well established therapeutic target and a pillar of stroke prevention. There are two main strategies for the treatment of carotid stenosis. The first approach is to stabilise or halt the progression of the carotid plaque through risk factor modification and medication. Hypertension, diabetes mellitus, smoking, obesity and high cholesterol levels are closely associated with carotid stenosis and stroke; control of these factors may decrease the risk of plaque formation and progression. The second approach is to eliminate or reduce carotid stenosis through carotid endarterectomy or carotid angioplasty and stenting. Carotid endarterectomy, which is the mainstay of therapy for severe carotid stenosis, is beyond the scope of this review. Anticoagulants seem to play little role (if any) in the medical (i.e. non-surgical) treatment of carotid stenosis. Adoption of a healthy lifestyle combined with the reduction of risk factors has been shown to lead to a reduction in the extent of carotid stenosis. The medical treatment of carotid stenosis should be based on the triad of the reduction of risk factors, patient education, and use of antiplatelet agents.
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PMID:Place of drug therapy in the treatment of carotid stenosis. 1598 96

The ability to restore myocardial perfusion in ischaemic heart disease has been one of the triumphs of surgery. Alternative, less invasive catheter-based methods have now taken the lead as favoured treatment. The resultant threat to surgical practice, as well as societal and organisational issues that impact on the life of surgeons, have caused many to question the future role of surgery in ischaemic heart disease. In spite of general awareness of risk factors, there is little to suggest that coronary disease will soon disappear; rather, obesity and unfavourable life-style of many will continue to recruit further patients and, additionally, an epidemic of heart failure is anticipated. At the same time, rapid advance in knowledge of the underlying disease is opening the prospect for more effective intervention for unstable coronary plaque. Of great relevance to the surgeon are recent advances in knowledge and technology that will lead to gene and cell-based therapy for ischaemic heart disease. The ability to modify or augment activity of myocytes in heart failure, and to promote angiogenesis, offers hope for repair of ischaemically damaged hearts undreamed of only a few years ago. Tissue engineering, encompassing gene and cell-based therapy, holds promise of reconstruction of the myocardium and its vasculature. Temporary cardiovascular support to enable application of these techniques will very likely provide one role for surgery. More importantly, the need to ensure optimal anatomic and functional repair will surely give rise to a new generation of surgeons with much expanded scientific and technical support to draw upon, and will ensure an important role for surgery in ischaemic heart disease for decades to come.
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PMID:The future role of surgery in ischaemic heart disease. 1689 45

The purpose of these studies was to test the hypothesis that Randall's plaque develops in unique anatomical sites of the kidney and that its formation is conditioned by specific stone-forming pathophysiologies. To test this hypothesis, we performed intraoperative mapping studies with biopsies of papilla from the kidneys of 15 idiopathic calcium oxalate (CaOx) stone formers, four intestinal bypass for obesity patients and ten brushite stone formers, and obtained papillary specimens from four non-stone formers after nephrectomy. Both light and electron microscopic examination of tissue changes along with infrared and electron diffraction analyses of mineral composition were performed. Distinct patterns of mineral deposition and papillary pathology were discovered in each of the three different stone forming groups. CaOx stone formers had predictable sites of interstitial apatite crystals beginning at the thin loops of Henle and spreading to the urothelium. These plaque areas are termed Randall's plaque and are thought to serve as sites for stone attachment. The papilla and medullary tubules appeared normal. The intestinal bypass patients only had intraluminal sites of crystalline material in the medullary collecting ducts. The brushite stone formers had the most severe form of cortical and medullary changes with sites of Randall's plaque, and yellowish intraluminal deposits in medullary collecting ducts. All deposits were determined to be apatite. The metabolic and surgical pathologic finding in three distinct groups of stone formers clearly shows that "the histology of the renal papilla from a stone former is particular to the clinical setting". It is observations like these that we believe will provide the insights to allow the stone community to generate better clinical treatments for kidney stone disease, as we understand the pathogenesis of stone formation for each type of stone former.
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PMID:Insights on the pathology of kidney stone formation. 1607 85

Fibric acid is a synthetic ligand of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-alpha that is highly expressed in skeletal muscle and heart, where it promotes beta-oxidation of fatty acids to mediate hypolipidemic actions. PPAR-alpha regulates expression of key proteins involved in atherogenesis, vascular inflammation, plaque instability, and thrombosis. Thus, PPAR-alpha may exert direct antiatherogenic actions in the vascular wall. Endothelial dysfunction associated with the metabolic syndrome and other insulin-resistant states is characterized by impaired insulin-stimulated nitric oxide production from the endothelium and decreased blood flow to skeletal muscle. Thus, improvement in insulin sensitivity leads to improved endothelial function. This may be an additional mechanism whereby fibrates decrease the incidence of coronary heart disease. Adiponectin is a protein secreted specifically by adipose cells that may couple regulation of insulin sensitivity with energy metabolism and serve to link obesity with insulin resistance. In this review, we discuss the mechanisms underlying the vascular and metabolic effects of fibrates that may act synergistically to prevent or regress atherosclerosis and coronary heart disease.
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PMID:Beneficial vascular and metabolic effects of peroxisome proliferator-activated receptor-alpha activators. 1623 May 15

The peroxisome proliferator-activated receptors (PPARs) are nuclear fatty acid receptors, which contain a type II zinc finger DNA binding motif and a hydrophobic ligand binding pocket. These receptors are thought to play an important role in metabolic diseases such as obesity, insulin resistance, and coronary artery disease. Three subtypes of PPAR receptors have been described: PPARalpha, PPARdelta/beta, and PPARgamma. PPARalpha is found in the liver, muscle, kidney, and heart. In the liver, its role is to up-regulate genes involved in fatty acid uptake (beta-oxidation and omega-oxidation). PPARdelta/beta is involved in fatty acid oxidation in muscle. PPARgamma has high expression in fat, low expression in the liver, and very low expression in the muscle. The thiazolidinediones (TZD) are synthetic ligands of PPARgamma. By activating a number of genes in tissues, PPARgamma increases glucose and lipid uptake, increases glucose oxidation, decreases free fatty acid concentration, and decreases insulin resistance. There is a sound rationale for the use of TZDs in patients with type 2 diabetes mellitus and promising preliminary data in patients with patients with pre-diabetes. In patients with type 2 diabetes, thiazolidinediones had been shown to decrease mean HbA(1c)by 1.5% and lower HbA(1c) to less than 7% in 30% of patients. Decreased muscle insulin resistance primarily mediates the glucose lowering effect. In addition, there are several nonhypoglycemic effects of TZDs which may be beneficial to both diabetics and patients with pre-diabetes. These include effects on lipid metabolism, blood pressure, endothelial function, atherosclerotic plaque, coagulation, and albuminuria. In a pilot study, we recently demonstrated that insulin sensitizers such as thiazolidinediones appear to be associated with better clinical outcomes compared to insulin providers in diabetic patients presenting with acute coronary syndromes. In another study, we showed that the prediabetic state is a marker for worse prognosis in patients with acute coronary syndromes. In this article, we review the existing literature on the effectiveness of PPAR-gamma agonists in patients with either overt diabetes or a prediabetic state.
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PMID:Role of PPAR- gamma agonist thiazolidinediones in treatment of pre-diabetic and diabetic individuals: a cardiovascular perspective. 1624 30


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