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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xenotransplantation will certainly solve the problem of the allogeneic organ shortage if long-term organ function can be achieved. Acceptance or rejection of the grafts depend not only on immunological mechanism but, as already recognized in chronic rejection (i.e. transplant atherosclerosis), on many other biochemical, physiological, and even morphological characteristics including inflammatory events originating from infections. The way in which signals in the form of hormones, neurotransmitters, enzymes and growth factors are translated in xenogeneic systems has not received adequate attention, if any at all. Central questions still to be answered are, how many xenogeneic hormonal and enzymatical interactions are possible? Are they able to maintain the metabolism in a foreign organ or body and for how long? In addition, transport molecules, the most important of which is albumin, must be considered when trying to achieve long-term survival using organs from a widely divergent species. Large quantities of foreign proteins, mediators and enzymes are released into the circulation when, for example, xenogeneic livers or other organs suffer from hyperacute rejection. The function of the liberated enzymes, hormones and inhibitors is far from being understood or even investigated. The amount of potassium released from a deteriorating xenogeneic liver is able to mimic a sometimes lethal cardioplegic solution. The first data coming from intravital microscopy herald that adhesion molecules, the newest but not last in the line of troubleshooters, interact with interleukins and eicosanoids and play a major role in the regulation of microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1994
PMID:Xenotransplantation--is it just around the corner? 770 54

Accumulation and distribution of cell cholesterol in plasma lipoproteins of incubated blood was examined in 36 patients with chronic renal failure including 13 who were dialysis-independent, 12 on haemodialysis, and 11 on continuous ambulatory peritoneal dialysis (CAPD), 17 renal transplant recipients, and 8 healthy controls. In addition, transport of cholesterol between red blood cells and high-density lipoprotein subfraction 3 (HDL3) isolated from a subgroup of patients with chronic renal failure was determined. Significantly less cell cholesterol appeared in plasma (P < 0.002) and HDL (P = 0.03), the main recipient of cell cholesterol, in patients with chronic renal failure compared with healthy subjects. Corresponding values in blood from renal transplant recipients were similar to controls. In patients with chronic renal failure, plasma HDL3 cholesterol levels (P < 0.02), HDL3 phospholipid content (P < 0.001) and net transport of red cell cholesterol to isolated HDL3 (P < 0.001) were significantly lower compared with controls. The data suggest that in patients with chronic renal failure, low levels of plasma HDL3 of abnormal composition may restrict the incorporation of cell cholesterol into the antiatherogenic HDL fraction potentially leading to inefficient transport of cholesterol from peripheral tissues and the development of atherosclerosis. These abnormalities appear to be reversed by renal transplantation.
Nephrol Dial Transplant 1995
PMID:Cell cholesterol transport to plasma in blood from patients with renal failure or a kidney transplant. 779 31

In summary, the decreased concentration of heparan sulphate within the extracellular matrix of patients with insulin-dependent diabetes mellitus is caused by a combination of genetic factors and poor metabolic control. Decreased concentrations of heparan sulphate are seen in patients with diabetes mellitus and proteinuria and this might be the explanation for the proteinuria as well as the expansion of the mesangium and the intimal dysfunction, including increased permeability of the vessel wall to macromolecules, which is present in such patients. Thus, the effective remodelling of extracellular matrix might explain coincidence of proteinuria, decline in renal function and premature atherosclerosis in patients with diabetes mellitus.
Nephrol Dial Transplant 1994
PMID:Nephropathy and coronary death--the fatal twins in diabetes mellitus. 780 Feb 2

Transplantation is the preferred method of renal replacement therapy in end-stage renal failure. Short- and medium-term graft survival is good but, in the longer term, grafts are lost due to vascular obliteration, i.e. chronic vascular rejection. The pathogenesis of these changes is unclear. We carried out a histopathological and immunocytochemical study of 31 vessels from 20 graft nephrectomies. Four patterns of arterial pathology were identified: (1) subendothelial inflammation ('endothelialitis') with little intimal thickening; (2) 'Endothelialitis' with thickening; (3) Intimal thickening without 'endothelialitis'; and (4) Intimal thickening with calcification and cholesterol clefts ('natural atherosclerosis'). We suggest that the lesions of chronic vascular rejection evolve, at varying rates, from an early 'endothelialitis' to a later stage with pronounced intimal thickening but no subendothelial inflammation. These changes probably reflect a delayed type hypersensitivity response involving activated macrophages and T lymphocytes and smooth muscle cell proliferation.
Nephrol Dial Transplant 1994
PMID:Arterial endothelialitis in chronic renal allograft rejection: a histopathological and immunocytochemical study. 787 Mar 72

It has been shown that hyperhomocysteinemia is a risk factor for atherosclerotic vascular disease. In this study, we measured total plasma homocysteine in continuous ambulatory peritoneal dialysis (CAPD) patients and evaluated its correlation with atherosclerosis. Subjects consisted of healthy volunteers, and hemodialysis (HD) and CAPD patients. Fluoro-HPLC was employed to estimate plasma levels of total homocysteine (Hcy). Plasma levels of total Hcy were significantly higher in the CAPD patients compared with the HD patients and controls. Atherosclerotic score (ASS) was calculated, and the correspondence with plasma levels of total Hcy was analyzed. There was a significant correlation between plasma levels of total Hcy and ASS in CAPD patients. However, plasma levels of total Hcy did not correlate with age, plasma vitamin B6 level, residual renal function, protein catabolic rate (PCR), or KT/V. Our present study suggests that elevated concentrations of total plasma Hcy might play a role in the development of atherosclerosis in CAPD patients.
Adv Perit Dial 1994
PMID:Hyperhomocysteinemia as a possible role for atherosclerosis in CAPD patients. 799 46

Cardiac events are a major cause of death in dialysed patients. This is due, at least in part, to the high prevalence of atherosclerotic coronary heart disease. To a large extent, however, coronary lesions are acquired in the predialytic phase of chronic renal failure. The susceptibility of the heart to ischaemia is modulated by a number of factors, e.g. microvascular abnormalities, increased cardiac pulsatile workload, disturbed cardiac glucose metabolism, imbalanced autonomic innervation. The paradoxical result of there being no relationship of cardiac death in dialysis patients to blood pressure may be explained by confounding factors. Intradialytic hypotension appears to be an independent risk factor. The dialysis patient is exposed to hypertension and dyslipidaemia, two potent risk factors of atherosclerosis. Although no definite information is available, it is conceivable that factors related to dialysis procedures may also influence early or late events in atherogenesis. Such potential factors include oxidative modification of lipids, modulation of insulin resistance or glucose metabolism by non-insulin-dependent pathways, expression of adhesion molecules and activation of potential effector cells in atherogenesis, particularly monocytes and platelets, changes of synthesis and/or response to endothelin and nitroxide (EDRF), and possibly also accelerated formation of advanced plaques by hyperphosphataemia and/or hyperparathyroidism. Such proatherogenic mechanisms must be balanced against factors potentially protecting against atherogenesis; these comprise altered arachidonic acid metabolism (increased prostacyclin and decreased thromboxane synthesis), impaired platelet aggregation, antiatherosclerotic effects of heparin, and diminished concentrations of 1,25(OH)2D3, i.e. of a proatherogenic compound.
Nephrol Dial Transplant 1994
PMID:Atherogenesis and cardiac death: are they related to dialysis procedure and biocompatibility? 806 10

Glomerulosclerosis and atherosclerosis share common pathobiological mechanisms. Experiments carried out in vitro over the past decade using cells thought to be involved in the atherosclerotic process such as endothelial cells, smooth muscle cells, and monocyte/macrophages have shown that postsecretory modifications such as oxidation increase the atherogenicity of LDL. Animal experiments employing antioxidant therapy have also been shown to slow the progression of atherosclerotic lesions. We set out to investigate the interactions between oxidized LDL (oxLDL) and rat mesangial cells (RMC) that might be of importance in the glomerulosclerotic process. Our results show that RMC have the ability to oxidize LDL, that oxLDL binding was 2-3-fold greater than native LDL (nLDL), and that oxLDL was more cytotoxic to these cells than nLDL. We speculate that cell-mediated oxidation of LDL in vivo may play a role in the progression of the glomerulosclerotic process.
Nephrol Dial Transplant 1993
PMID:Oxidation of low-density lipoproteins by rat mesangial cells and the interaction of oxidized low-density lipoproteins with rat mesangial cells in vitro. 839 31

Hyperlipidaemia is common after renal transplantation, and because of its association with atherosclerosis, interest has increased in the use of lipid-lowering drugs in transplant patients. Dietary approaches have not been consistently successful, and multiple pharmacotherapy and drug interactions have led to difficulties in establishing lipid-lowering drug regimes. The statins reduce plasma cholesterol by inhibiting the rate-limiting step in cholesterol synthesis, and although some side-effects have been reported in their use after transplantation, the efficacy and safety of low doses has not been formally established. A randomized single-blind placebo crossover study designed to determine the safety and effectiveness of simvastatin in a single daily 5-mg evening dose was therefore conducted in 26 stable renal transplant patients, 14 of whom were receiving cyclosporin A. The results demonstrated no difference between total cholesterol levels in the baseline simvastatin and placebo periods: 7.97 +/- 1.2 and 7.59 +/- 1.5 mmol/l respectively. After 8 weeks of simvastatin, the total cholesterol declined significantly to 6.72 +/- 0.87 mmol/l (P < 0.001). A significant difference was found when the placebo and simvastatin cholesterol levels were compared at 4 and 8 weeks (P < 0.01). LDL cholesterol decreased from 4.74 +/- 0.87 to 3.78 +/- 0.78 mmol/l after 8 weeks on simvastatin (P < 0.001), and apo B fell from 142 +/- 31 to 112 +/- 22 mg/dl (P < 0.001). The difference in LDL cholesterol and apo B after 8 weeks of simvastatin when compared with the corresponding values on placebo was also significant (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1993
PMID:Low-dose simvastatin is safe in hyperlipidaemic renal transplant patients. 839 49

Hypercholesterolemia has been recognized as a significant risk factor for atherosclerosis and coronary artery disease. The aim of this study was to evaluate the prevalence of hypercholesterolemia and the role, if any, of type of dialysis. In 19 hemodialysis (HD) and 20 continuous ambulatory peritoneal dialysis (CAPD) subjects, body weight, body mass index (BMI), arm muscle area (AMA), total cholesterol (C), HDL and LDL fractions, triglycerides, C/HDL ratio, glycosylated hemoglobin, and apolipoproteins AI, AII, B, CII, CIII, and E were evaluated. Hypercholesterolemia was defined as cholesterol greater than 220 mg/dL and LDL greater than 150 mg/dL. Body weight, body mass index, and arm muscle area were higher (p < 0.05) in CAPD as compared with HD; so were total cholesterol, LDL, C/HDL ratio, and glycosylated hemoglobin (Hbalc). Hypercholesterolemia prevalence was 3/19 in HD and 11/20 in CAPD (p < 0.05). A relationship between Hbalc and C/HDL ratio was found in the CAPD group (r = 0.48; p < 0.05). We are greatly concerned about these metabolic effects of CAPD; therefore, we should carefully select patients to be treated by CAPD. Aggressive nutritional and pharmacological treatment for glucose intolerance and hypercholesterolemia in CAPD patients must be performed in order to reduce the incidence of coronary artery disease (CAD).
Perit Dial Int 1993
PMID:Does continuous ambulatory peritoneal dialysis induce hypercholesterolemia? 839 29

Atherosclerosis and thrombosis, two major causes of morbidity and mortality in renal transplant recipients, share the same clinical risk factors including decreased fibrinolysis and lipid disturbances. In a cross-sectional study we have determined parameters of fibrinolysis in control subjects (n = 23) and stable renal allograft recipients without cyclosporin (CsA) (n = 10) and with CsA (n = 87) in their immunosuppressive treatment. In CsA-treated patients, tissue-type plasminogen activator was moderately increased compared to patients without CsA (8.4+/-3.3 vs 5.5+/-2.8 ng/ml). The plasminogen activator inhibitor (PAI) activity in plasma was clearly increased in CsA-treated patients: 14.5+/-8.8 vs 7.2+/-3.2 in normal controls and 8.5+/-2.4 AU/ml in patients without CsA. Total cholesterol and LDL cholesterol levels were higher in CsA-treated patients (256+/-62 and 169+/-60 mg/dl) than in patients without CsA (209+/-45 and 136+/-44 mg/dl). The two groups did not differ in HDL cholesterol, triglycerides, and lipoprotein(a). Hypercholesterolaemia, obesity, and steroid-induced diabetes could be identified as risk factors for elevated plasma PAI activity in CsA-treated patients. Hypofibrinolysis induced by elevated PAI levels and increased LDL cholesterol may contribute to the increased thrombogenicity and accelerated atherosclerosis observed in cyclosporin-treated patients.
Nephrol Dial Transplant 1996 Feb
PMID:Elevated plasminogen activator inhibitor levels in cyclosporin-treated renal allograft recipients. 867 91


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