Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intermittent claudication (IC), the symptom of exercise-induced muscle ischemia of peripheral arterial disease (PAD), afflicts and limits the activities of a significant number of patients. Incidence and prevalence of IC depends on the population studied and the diagnostic instruments used. In large studies, prevalence has ranged from 3% to 10%, with a sharp increase in those aged > or =70 years. Over the next 20 years, the total number of patients affected is expected to increase significantly due to anticipated demographic changes. Analysis of the natural history of IC demonstrates that the risk of cardiovascular morbidity and mortality far exceeds that of severe limb ischemia or limb loss. In fact, only 2% to 4% of all patients with IC will require a major amputation in their lifetime. However, life expectancy is approximately 10 years less than that of an age-matched cohort. By now, PAD is well recognized as a marker of systemic atherosclerosis. The cornerstone of patient evaluation is a history and physical examination, including a detailed atherosclerotic risk-factor assessment. In the differential diagnosis of IC, clinicians should consider etiologies such as arthritis, spinal stenosis, radiculopathy, venous claudication, or inflammatory processes. In >80% of all patients, it is possible to locate the responsible arterial segment by combining the location and severity of pain with a pulse examination. Noninvasive diagnostic studies help determine the level of disease, may unmask a hemodynamically significant stenosis, and are useful in follow-up. Arteriography is reserved for patients in whom the decision for revascularization has been made. Knowing the anatomic detail of a lesion allows the clinician to determine whether and what type of intervention is feasible. Standard therapy for all patients should be directed at both peripheral and systemic atherosclerosis, beginning with risk-factor modification in the form of smoking cessation, optimal diabetes control, and lipid normalization. The benefits of supervised exercise rehabilitation include significantly increased walking distance and enhanced quality of life. Platelet inhibition has been shown to reduce the risk of ischemic stroke, myocardial infarction, and vascular death and should be prescribed for all but those in whom it is medically contraindicated. Symptom-specific pharmacotherapy with a broad range of medications has yielded disappointing results in the past. However, recent studies have demonstrated that patients receiving the novel agent cilostazol experienced increases in walking distance and improvements in quality of life.
 ...
PMID:Intermittent claudication: magnitude of the problem, patient evaluation, and therapeutic strategies. 1143 94

Both infections and injuries activate the immunity system, leading to a series of metabolic changes which place the organism at a disadvantage and contribute to its elimination, thus facilitating the repair of the injured tissue. The study of the actions of tumour necrosing factor alpha (TNF-alpha) and interleukin-6 (IL-6), classically implicated in inflammatory processes and in fighting infection, has revealed numerous metabolic effects. Some gene polymorphisms of TNF-alpha and IL-6 (associated with a different TNF-alpha or IL-6 transcription rate) and the plasma concentrations of the soluble TNF-alpha receptor are found to be simultaneously associated with resistance to insulin, the proportion of body fat and with the mortality linked with different chronic infections. Therefore, it seems that the immune system is designed to fight infections effectively and to provide certain survival advantages during periods of intermittent fasting so frequent in the past. By inducing a resistance to insulin in the muscles, the energy substrates would thus be reserved for neuronal metabolism. In the presence of an insulin-resistance genotype and a westernization of the environment (carbohydrate-rich diet, an increase in saturated fat, low fibre and sedentary lifestyle), a genotype with a high cytokine response will contribute to a worsening of the resistance to insulin and, finally, to type 2 diabetes mellitus and atherosclerosis. The advantages for our ancestors of a large cytokine response (eradication of the lesion) or moderate resistance to insulin (protection against food shortage) have led in the present day to the development of atherosclerosis now that the characteristics of the environment have changed. It is contended that these changes constitute examples of good adaptation to the environment or poor concordance between our current lifestyle and our genome.
 ...
PMID:[Insulin resistance and evolution]. 1192 38

The radial approach to coronary angiography is intuitively attractive for fully anticoagulated patients (INR > 2) but no data exist concerning efficacy or safety of this procedure. The consensus view is that the femoral approach is contraindicated in fully anticoagulated patients, and though some operators undertake femoral catheterization in such patients and use closure devices, there are no data to suggest that it is safe to do so. At our institution, the radial approach for coronary angiography is reserved for patients in whom there is a relative contraindication to the femoral route. We have undertaken over 600 radial coronary angiograms in such patients since 1996, 66 of whom underwent transradial catheterization specifically because of anticoagulation status (INR > 2). Thirty-eight patients (58%) were male, average age 67 +/- 11 years. All 66 patients had an INR > 2 but < 4.5. The approach was left radial in 26 (39%), right radial in the remainder; sheath size was 4 Fr in 4 (6%), 5 Fr in 13 (20%), and 6 Fr in 49 (74%). Seven operators in total were involved, though two operators undertook the majority of cases (47; 71%). Success rate was 97%, with no failure of access, and only one minor postprocedural hemorrhage. Failures were due to radial artery atherosclerosis (1) and subclavian tortuosity (1). The radial approach to coronary angiography is safe and to be recommended in the fully anticoagulated patient.
 ...
PMID:Coronary angiography in the fully anticoagulated patient: the transradial route is successful and safe. 1250 89

The aim of this study was to examine the use of risperidone in routine clinical care for very aggressive young children. This is a retrospective medical chart review of patients age less than 6 years 11 months who were treated with risperidone for 1 to 10 months during the 1-year study period. Treatment response, side effects, and Clinical Global Impression (CGI) scores were identified. One hundred and five such young children were identified; 8 had been treated with risperidone (6 boys, 2 girls: mean age 4.9 +/- 0.8 years). Risperidone was used in combination with other psychotropic medications in 7 of the 8 children. The mean daily dose of risperidone was 1.25 +/- 0.27 mg. Seventy-five percent of the children were on concomitant lithium, valproate, or carbamazepine; 63% were on stimulants or alpha adrenergics. This was a highly comorbid group, with 7 children presenting with attention deficit hyperactivity disorder and 5 children with bipolar disorder not otherwise specified. The average baseline CGI severity was 5.5 (SD = 0.5), and at last visit it was 3.5 (SD = 0.5), p < 0.0001. Mean CGI improvement score was 1.9 (SD = 0.6). Adverse effects included significant weight gain (mean 5.5 +/- 4.9 kg, p < 0.05) in 6 patients. One child had hyperprolactinemia. Given the potential development of atherosclerosis in obesity and endocrine response in hyperprolactinemia, risperidone should be reserved for those children with severe aggressive behavior who failed multiple trials with other agents. Further controlled trials are needed.
 ...
PMID:A case series of eight aggressive young children treated with risperidone. 1262 94

Enhanced activity of tyrosine kinase receptors (RTKs) has been implicated as a contributing factor in the development of malignant and nonmalignant proliferative diseases such as cancer and atherosclerosis. Several growth factors traducing mitogenic signals through RTKs are implicated in the development of tumor and cardiovascular diseases. Therefore, in recent years many efforts have been made to develop RTK small molecule inhibitors for the treatment of tumor and cardiovascular diseases. Recently, catechins, the main compounds of green tea leafs, have been identified as potent natural inhibitors of several RTKs. Furthermore, there is increasing evidence that catechins possess antiangiogenic properties. In summary, several animal and cell culture studies suggest that catechins are potential candidates for the clinical therapy of cancer and cardiovascular diseases. (c) 2002 Prous Science. All rights reserved.
 ...
PMID:Are Catechins Natural Tyrosine Kinase Inhibitors? 1267 78

Endothelial dysfunction is the early and crucial state of atherosclerosis that is associated with a poor prognosis. Mechanistically, endothelial dysfunction is caused by reduced nitric oxide bioactivity. HMG-CoA reductase inhibitors (statins) effectively lower cholesterol plasma levels and profoundly decrease the cardiovascular risk of hypercholesterolemic patients. It is well established that statins improve endothelial dysfunction in those patients. The underlying mechanisms are less clear. It is thought that pleiotrophic, cholesterol-independent effects of statins such as increase of nitric oxide bioactivity and reduction of oxidative stress may contribute to the vasoprotective effects of statins. Therefore, it is speculated that statins, at least in part, improve endothelial function independent of plasma cholesterol concentrations and may thereby exert beneficial clinical effects. This notion of statins as general atheroprotective drugs has been underlined by in vitro experiments, animal studies and small clinical trials. However, large-scale clinical intervention studies are needed to confirm a positive influence of statins on endothelial dysfunction and cardiac event rates in normochlesterolemic patients. (c) 2002 Prous Science. All rights reserved.
 ...
PMID:Improvement of Endothelial Function by HMG-CoA Reductase Inhibitors. 1267 13

A major challenge in medical research is to break the traditional compartmentalization that frequently separates different fields. Unexpected linkages between different areas of medicine are often of particular interest. An unsuspected "bridge" across clinical cardiology and basic immunology, as presented in this review, is a good example of such a linkage. Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a role in glucose homeostasis and adipocyte differentiation and has been implicated in diabetes mellitus, a metabolic disorder predisposing to atherosclerosis. In addition, PPARgamma ligands of the antidiabetic thiazolidinediones group exert beneficial effects on atherosclerosis. Expression of major histocompatibility complex class II (MHC class II), a key molecule in the immune response, has recently been observed in atherosclerotic plaques. In recent years, important effects of PPARgamma ligands on MHC class II expression, activated T lymphocytes and macrophage activation have been described. Using atherosclerosis as a model of an immune-mediated disease, we summarize in this review the recent exciting observations that link PPARgamma to the immune response. (c) 2002 Prous Science. All rights reserved.
 ...
PMID:The Role of PPARgamma Ligands as Regulators of the Immune Response. 1267 28

Low density lipoprotein has been shown to induce vascular smooth muscle cell proliferation and, therefore, to directly contribute to the development of atherosclerosis. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors involved in various cellular processes, such as cell cycle regulation and carcinogenesis. PPARgamma, the best characterized of the PPARs, plays a crucial role in the regulation of cell proliferation, adipocyte differentiation, insulin sensitivity, energy expenditure, development of atherosclerosis and carcinogenesis. In the present review we discuss recent findings showing that a new class of antidiabetic drugs, the PPARgamma ligands thiazolidinediones, might have potential antiatherosclerotic effects. (c) 2002 Prous Science. All rights reserved.
 ...
PMID:Inhibition of the Low Density Lipoprotein-Induced Vascular Smooth Muscle Cell Growth by PPARgamma Ligands. 1267 38

Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality in western societies. Although cholesterol is a major cardiovascular disease risk factor, therapeutic interventions to lower plasma cholesterol levels have had limited success in reducing coronary events, underscoring the need for other treatment strategies. A promising therapeutic target is an ATP binding cassette transporter called ABCA1, a cell membrane protein that is the gatekeeper for secretion of excess cholesterol from macrophages into the high-density lipoprotein (HDL) metabolic pathway. Mutations in ABCA1 cause Tangier disease, a severe HDL-deficiency syndrome characterized by accumulation of cholesterol in tissue macrophages and prevalent atherosclerosis. Thus, ABCA1-activating drugs have the potential to mobilize cholesterol from macrophages of atherosclerotic lesions, making them powerful agents for preventing and reversing cardiovascular disease. (c) 2002 Prous Science. All rights reserved.
 ...
PMID:ABCA1 as a New Therapeutic Target for Treating Cardiovascular Disease. 1267 41

Atherosclerosis preferentially occurs in areas of turbulent flow and low fluid shear stress, while laminar flow and high shear stress are atheroprotective. Well characterized atheroprotective mechanisms include inhibition of thrombosis (increased tissue-type plasminogen activator and decreased plasminogen activator inhibitor-1), inhibition of endothelial cell apoptosis, limitation of permeability (uptake of low-density lipoprotein), prevention of white blood cell binding and transmigration (no expression of adhesion molecules such as intercellular adhesion molecule-1 [ICAM-1] and vascular cell adhesion molecule-1 [VCAM-1] and no release of monocyte chemotactic protein-1) and increased bioavailability of nitric oxide (because of increased expression of endothelial nitric oxide synthase and manganese superoxide dismutase). Our lab has investigated flow-mediated inhibition of inflammatory cytokine action. In particular, we have shown that flow prevents tumor necrosis factor-alpha (TNF-alpha) mediated signal transduction. TNF regulates inflammatory gene expression (e.g., ICAM-1 and VCAM-1) in endothelial cells, in part, by stimulating mitogen activated protein (MAP) kinases that phosphorylate transcription factors. We hypothesized that fluid shear stress inhibits TNF inflammatory effects on endothelial cells by inhibiting TNF mediated activation of the c-Jun N-terminal kinase. To test this hypothesis, we determined the effects of steady laminar flow on TNF-stimulated activity of c-Jun N-terminal kinase. The results show that flow inhibits c-Jun N-terminal kinase activation through multiple mechanisms, including stimulation of counter-regulatory MAP kinases (extracellular signal regulated kinases [ERK]1/2 and ERK5) and inhibition of apoptosis signal-regulated kinase. In summary, the atheroprotective effects of steady laminar flow on the endothelium involve multiple synergistic mechanisms. These multiple mechanisms offer attractive targets for new drug therapies aimed at limiting atherosclerosis development and progression. (c) 2002 Prous Science. All rights reserved.
 ...
PMID:Atheroprotective Mechanisms Activated by Fluid Shear Stress in Endothelial Cells. 1267 55


<< Previous 1 2 3 4 5 6 7 8 Next >>