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

Bezafibrate is a lipid-lowering drug, chemically related to clofibrate. At its recommended dosage of 200 mg 3 times daily, or alternatively 400 mg once daily as a sustained-release preparation, it produces substantial reductions in plasma triglyceride and cholesterol concentrations in patients with hypertriglyceridaemia and hypercholesterolaemia, respectively. Preliminary investigations indicate that a single daily dose of 400 mg in a sustained-release preparation is as effective as 200 mg 3 times daily. In patients with any type of hyperlipoproteinaemia bezafibrate also increases the plasma HDL-cholesterol concentration. These effects are equivalent in patients with primary hyperlipoproteinaemia or hyperlipoproteinaemia secondary to diabetes or renal disease, although dosage adjustment is important in the latter group. During long term therapy (2 to 4 years) the influence of bezafibrate on the lipid profile is sustained. The lipid-lowering effects of bezafibrate are at least equivalent to those of clofibrate, fenofibrate, colestipol, probucol or sustained release etofibrate. In addition, the increase in HDL-cholesterol tends to be at least as great as with all alternative treatments studied. Bezafibrate is rapidly eliminated, and thus does not accumulate during prolonged administration in patients with normal renal function. Experimental studies have shown bezafibrate to have a complex range of effects on lipoproteins and on the enzymes and receptors involved in lipid metabolism. However, its exact mechanism of lipid-lowering action is unclear. Bezafibrate enhances anticoagulation in hyperlipoproteinaemic patients requiring anticoagulant therapy, and preliminary investigations indicate that it reduces the plasma fibrinogen concentration, especially in patients with hyperfibrinogenaemia. These properties of bezafibrate could contribute to an antiatherogenic effect of the drug, but further investigation is required to establish the drug's potential as chronic therapy in patients with hyperfibrinogenaemic atherosclerosis. Adverse reactions to bezafibrate have largely been restricted to gastrointestinal disturbances, with some cutaneous reactions and central nervous system effects. The incidence of side effects has been no greater than with comparative lipid-lowering drugs. In patients with renal disease, a few cases of marked elevation of serum creatine phosphokinase and myoglobin, and associated muscle cramps, have been reported (diagnosed as rhabdomyolysis). Hepatic enzyme induction by bezafibrate in rats results in hepatomegaly, but there has been no case of significant hepatotoxicity in man.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Bezafibrate. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hyperlipidaemia. 330 1

In North America, diuretics remain the most common first-line drug therapy for essential hypertension based on efficacy, safety and cost. The promotion of step-care programmes has firmly established their dominant use on this continent whereas in Europe, particularly in Scandinavia and Great Britain, beta-adrenoceptor blocking agents are more frequently chosen as first-line therapy. On both continents, combined therapy with a diuretic and a beta-blocker is probably the most common second step for patients with blood pressures uncontrolled on a single agent alone and diuretics remain useful, if not essential, to prevent sodium retention commonly observed with other antihypertensive agents. Although the forced loss of sodium and water may be responsible for their initial antihypertensive effect, the mechanism underlying their long-term effect is unknown but probably involves some alteration of vascular smooth muscle reactivity. More recently, concern has been expressed about their long-term safety as larger populations are being exposed to diuretic agents for a significant proportion of their life-span. These concerns include haemodynamic and biochemical consequences of diuretic therapy - excessive tachycardia at rest and with minimal exercise, postural hypotension, hypokalaemia and arrhythmias, muscle cramps or fatigue, glucose intolerance, hyperuricaemia and altered circulating lipids as markers or promotors of atherosclerosis and its complications. At present, there is insufficient evidence to alter the present recommendation of diuretic agents as first-line drug therapy in the treatment of hypertension.
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PMID:Diuretic treatment in essential hypertension. 661 41

In Japan, acetate-free biofiltration (AFBF) became commercially available in the year 2000, and these products have been reported to be clinically effective for controlling the decrease of blood pressure during dialysis or various types of dialysis intolerance. And more, acetate-free dialysis fluid was made clinically available in 2007, acetate-free hemodialysis (AFHD) is expected to inhibit the malnutrition-inflammation-atherosclerosis syndrome, improve anemia and the nutritional status of patients, stabilize hemodynamics, and reduce inflammation and oxidative stress. In a broad sense, AFBF can be classified as hemodiafiltration (HDF), and its clinical effects seem to be associated with multiple factors, including use of acetate-free dialysis fluid, massive removal of low molecular weight proteins by convection, and the sodium concentration of the replacement fluid. Therefore, the clinical significance of acetate-free dialysis fluid could be demonstrated more clearly by comparing AFHD with conventional hemodialysis (conv. HD) using dialysis fluid containing about 10 mEq/l acetate. Since 2005, we have been investigating the efficacy of various modalities of blood purification therapy by continuously monitoring changes of tissue blood flow in the lower limbs and earlobes (head) using non-invasive continuous monitoring method (NICOMM). In this report, we assess the clinical effectiveness of AFHD on the basis of clinical findings and head stability index (head SI) obtained by NICOMM, particularly with respect to the influence on autonomic regulation. After switching to AFHD from conv. HD, anemia, stored iron utilization, and the frequency of treatments for dialysis hypotension and of muscle cramps were significantly improved. Further, the head SI was also significantly smaller with AFHD than conv. HD. This finding suggests that AFHD improved the maintenance of homeostasis by the autonomic nervous regulation system. In addition, we could not find clinical features of excessive alkalosis during an observation period of about 1 year, even if online HDF using acetate-free dialysis fluid as the substitution fluid. Our conclusion is that the advent of acetate-free dialysis fluid has led to investigations into new clinical effectiveness of AFHD or online HDF/HF using ultrapurified acetate-free dialysis fluid as the substitution fluid.
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PMID:Improvement of autonomic nervous regulation by blood purification therapy using acetate-free dialysis fluid - clinical evaluation by laser Doppler flowmetry. 2093 41

Percutaneous transluminal angioplasty with stent implantation is used to dilate arteries narrowed by atherosclerotic plaques and to revascularize coronary arteries occluded by atherothrombosis in myocardial infarction. Commonly applied drug-eluting stents release antiproliferative or anti-inflammatory agents to reduce the incidence of in-stent stenosis. However, these stents may still lead to in-stent stenosis; they also show increased rates of late stent thrombosis, an obstacle to optimal revascularization possibly related to endothelial recovery. Here, we examined the contribution of neutrophils and neutrophilic granule proteins to arterial healing after injury. We found that neutrophil-borne cathelicidin (mouse CRAMP, human LL-37) promoted reendothelization and thereby limited neointima formation after stent implantation. We then translated these findings to an animal model using a neutrophil-instructing, biofunctionalized, miniaturized Nitinol stent coated with LL-37. This stent reduced in-stent stenosis in a mouse model of atherosclerosis, suggesting that LL-37 may promote vascular healing after interventional therapy.
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PMID:Neutrophil-derived cathelicidin protects from neointimal hyperplasia. 2212 87

After the advent of Statins in 1960's, they are being extensively used as Antiathrogenic drug for Primary Hyperlipidemia, Angina, Ischemic Heart Disease (Medical or Post Surgical), Atherosclerosis, Diabetes mellitus and Hypertension. Rarely, these drugs have been observed to cause hypocholesterolemia. We present a case of forty years old male who was started on Atorvastatin after his angioplasty following anterior myocardial infarction. Six weeks after the start of antilipid drug patient developed symptoms of phobias, nightmares, insomnia, forgetfulness, body aches, muscle cramps, cognitive, sexual and psychomotor disturbances. On investigation he was found to have hypocholesterolemia. Atorvastatin was stopped and dietary restrictrictions were lifted. Over five month patients symptoms resolved as the serum cholesterol levels became normal. Because of similarities of symptoms of hypocholesterolemia secondary to antilipid therapy and the disease itself, hypocholesterolemia was overlooked initially by physicians. Patients on antilipids must be evaluated for any fall in serum cholerterol if they develop unusual symptoms and patients on long-term antilipids must have regularly lipid profile checked.
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PMID:Hypocholesterolemia secondary to atrovastatin therapy. 2233 62

Vascular dysregulation refers to the regulation of blood flow that is not adapted to the needs of the respective tissue. We distinguish primary vascular dysregulation (PVD, formerly called vasospastic syndrome) and secondary vascular dysregulation (SVD). Subjects with PVD tend to have cold extremities, low blood pressure, reduced feeling of thirst, altered drug sensitivity, increased pain sensitivity, prolonged sleep onset time, altered gene expression in the lymphocytes, signs of oxidative stress, slightly increased endothelin-1 plasma level, low body mass index and often diffuse and fluctuating visual field defects. Coldness, emotional or mechanical stress and starving can provoke symptoms. Virtually all organs, particularly the eye, can be involved. In subjects with PVD, retinal vessels are stiffer and more irregular, and both neurovascular coupling and autoregulation capacity are reduced while retinal venous pressure is often increased. Subjects with PVD have increased risk for normal-tension glaucoma, optic nerve compartment syndrome, central serous choroidopathy, Susac syndrome, retinal artery and vein occlusions and anterior ischaemic neuropathy without atherosclerosis. Further characteristics are their weaker blood-brain and blood-retinal barriers and the higher prevalence of optic disc haemorrhages and activated astrocytes. Subjects with PVD tend to suffer more often from tinnitus, muscle cramps, migraine with aura and silent myocardial ischaemic and are at greater risk for altitude sickness. While the main cause of vascular dysregulation is vascular endotheliopathy, dysfunction of the autonomic nervous system is also involved. In contrast, SVD occurs in the context of other diseases such as multiple sclerosis, retrobulbar neuritis, rheumatoid arthritis, fibromyalgia and giant cell arteritis. Taking into consideration the high prevalence of PVD in the population and potentially linked pathologies, in the current article, the authors provide recommendations on how to effectively promote the field in order to create innovative diagnostic tools to predict the pathology and develop more efficient treatment approaches tailored to the person.
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PMID:The primary vascular dysregulation syndrome: implications for eye diseases. 2374 77

Atherosclerosis is a chronic inflammatory disease of arterial wall. Mitochondrial DNA (mtDNA) and human antimicrobial peptide LL-37 (Cramp in mice) are involved in atherosclerosis. Recently, mtDNA has been found to escape from autophagy and cause inflammation. Normally, mtDNA as an inflammatogenic factor cannot escape from autophagy and degradation by DNase II. In this study, we found elevated amounts of LL37-mtDNA complex in atherosclerotic plasma and plaques. The complex was resistant to DNase II degradation and escaped from autophagic recognition, leading to activation of Toll-like receptor 9 (TLR9)-mediated inflammatory responses. Mouse model studies indicated that Cramp-mtDNA complex aggravated atherosclerotic lesion formation in apolipoprotein E-deficient mice and antibody treatment against the complex alleviated the lesion. These findings suggest that the LL-37-mtDNA complex acts as a key mediator of atherosclerosis formation, and thus represents a promising therapeutic target.
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PMID:Mitochondrial DNA-LL-37 Complex Promotes Atherosclerosis by Escaping from Autophagic Recognition. 2668 Feb 6

Chronic kidney disease (CKD) predisposes one to either deficiency or toxic excess of different micronutrients. The knowledge on micronutrients-specifically water-soluble vitamins and trace elements-in CKD is very limited. Consequently, current guidelines and recommendations are mostly based on expert opinions or poor-quality evidence. Abnormalities of micronutrient resources in CKD develop for several reasons. Dietary restrictions and anorexia lead to an insufficient micronutrient intake, while diuretics use and renal replacement therapy lead to their excessive losses. Absorption is unpredictable, and metabolism impaired. Better understanding of the micronutrient needs of CKD patients could have an impact on many complications linked to vitamin and trace element disorders, including high mortality, increased risk of atherosclerosis, inflammation, oxidative stress, anemia, polyneuropathy, encephalopathy, weakness and fragility, muscle cramps, bone disease, depression, or insomnia. Here, we summarize the up-to-date knowledge on micronutrient resources in different stages of CKD, and share our experience with the assessment of micronutrient status.
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PMID:Vitamins and Microelement Bioavailability in Different Stages of Chronic Kidney Disease. 2829 76

Auto-immunity is believed to contribute to inflammation in atherosclerosis. The antimicrobial peptide LL-37, a fragment of the cathelicidin protein precursor hCAP18, was previously identified as an autoantigen in psoriasis. Given the reported link between psoriasis and coronary artery disease, the biological relevance of the autoantigen to atherosclerosis was tested in vitro using a truncated (t) form of the mouse homolog of hCAP18, CRAMP, on splenocytes from athero-prone ApoE(-/-) mice. Stimulation with tCRAMP resulted in increased CD8+ T cells with Central Memory and Effector Memory phenotypes in ApoE(-/-) mice, differentially activated by feeding with normal chow or high fat diet. Immunization of ApoE(-/-) with different doses of the shortened peptide (Cramp) resulted in differential outcomes with a lower dose reducing atherosclerosis whereas a higher dose exacerbating the disease with increased neutrophil infiltration of the atherosclerotic plaques. Low dose Cramp immunization also resulted in increased splenic CD8+ T cell degranulation and reduced CD11b+CD11c+ conventional dendritic cells (cDCs), whereas high dose increased CD11b+CD11c+ cDCs. Our results identified CRAMP, the mouse homolog of hCAP-18, as a potential self-antigen involved in the immune response to atherosclerosis in the ApoE(-/-) mouse model.
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PMID:The cathelicidin protein CRAMP is a potential atherosclerosis self-antigen in ApoE(-/-) mice. 2909 29