Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to identify the characteristics of coronary heart disease (CHD) in renal transplant recipients as well as to assess the impact of coronary angiography on allograft function. The 21 cases including 2 women and 19 men who underwent coronary angiography were retrospectively studied for age at transplantation and at diagnosis of coronary disease; risk factors; angio findings; serum creatinine and blood urea nitrogen (BUN) values before and after angio; and revascularization procedures. The mean ages at transplantation and at diagnosis were 40 +/- 7 years and 44 +/- 7 years, respectively. Eighteen patients (86%) had hypertension, 16 (76%) exhibited hyperlipidemia, and 5 (24%) diabetes mellitus. Coronary angiography revealed three-vessel disease in 10 patients, two-vessel disease in 3 patients, one-vessel disease in 4 patients, ectatic vessels in 2 patients, and normal coronary arteries in 2 patients. The mean serum creatinine and BUN levels after angio were not significantly different from the baseline values (pre creatinine and BUN 1.7 +/- 0.5 mg/dL and 33.8 +/- 8.6 mg/dL versus post 1.8 +/- 0.6 mg/dL and 32.8 +/- 10.0 mg/dL, respectively). Ten patients with three-vessel disease underwent coronary artery bypass surgery; 4 patients, coronary angioplasty. The other patients received medical therapy. The study showed an increased likelihood of three-vessel disease among recipients compared with the general population and confirmed that coronary artery bypass surgery may be performed successfully in these patients. In conclusion coronary angiography is a safe diagnostic procedure with respect to allograft function.
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PMID:Characteristics of coronary heart disease in renal transplant recipients. 1501 30

Large-scale clinical trials have shown that the oral adsorbent AST-120 improves renal function and delays the initiation of dialysis in chronic renal failure (CRF) secondary to chronic glomerulonephritis. If renal failure progresses via common mechanisms, then the same effects can be expected in diabetic nephropathy. However, no study on diabetic nephropathy has been reported. Thus, we enrolled patients with statistically significant progression of CRF secondary to diabetic nephropathy, and analyzed the changes in renal function after AST-120 therapy, and the clinical factors associated with response to therapy. We enrolled 276 patients with diabetic nephropathy, whose serum creatinine (Scr) had increased from 3.4 to 4.5 mg/dL during the 4.5 +/- 3.7 months prior to the study. These patients took AST-120 at a dose of 5.0 +/- 1.4 g/day for 6 months. The clinical data were analyzed by dividing the patients into three groups based on the changes in Scr after AST-120 therapy, with responders showing a decrease (N = 82), partial responders showing <1.5-fold increase (N = 144), and non-responders showing >/=1.5-fold increase (N = 50). AST-120 significantly lowered the slope of 1/Scr-time line, suggesting that AST-120 suppressed the progression of renal impairment. No responders required dialysis, whereas 24.3% of the partial responders and 36.0% of the non-responders started dialysis therapy. In responders, the 1/Scr-time slope showed a negative-to-positive shift and serum urea nitrogen decreased significantly, whereas the improvement was moderate in partial responders and minimal in non-responders. Among responders, AST-120 therapy significantly improved renal function despite the presence of hypoproteinemia, hyperlipidemia, anemia or hypertension in many patients. The beneficial effect of AST-120 was significantly more marked in patients with blood pressure controlled within the normal ranges and hematocrit maintained at 30% or above. AST-120 reversed renal dysfunction or delayed the initiation of dialysis therapy in patients with progressive aggravation of CRF secondary to diabetic nephropathy, independent of hypoproteinemia, hyperlipidemia, anemia and hypertension. Active use of AST-120 may be recommended in patients with good control of blood pressure and hematocrit above 30%.
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PMID:Protective effect of an oral adsorbent on renal function in chronic renal failure: determinants of its efficacy in diabetic nephropathy. 1515 77

A 49-year-old women with arteriosclerosis obliterans (ASO) complicated with light chain deposition disease (LCDD) is described. Renal biopsy showed a diffuse mesangial nodular lesion and tubulointerstitial changes. Congo red and lambda light chain staining were negative; however, the kappa light chain was positive in both glomeruli and tubular basement membranes by immunostaining. Using electron microscopy, electron-dense materials were found within glomerular basement membrane, mesangium and tubular basement membrane. The patient had renal dysfunction and nephrotic syndrome with progressive skin ulcers in the left leg. The patient was diagnosed as ASO with LCDD. She received low-density lipoprotein (LDL) apheresis once weekly for 10 consecutive weeks. Serum total cholesterol and phospholipid levels were decreased, and serum creatinine and blood urea nitrogen levels also tended to decline after treatment. Urinary protein excretion was reduced markedly, and hypoalbuminemia was also improved. Ischemic symptoms including leg pain and leg coldness and numbness improved after apheresis. The walking distance increased on a treadmill. The skin temperature was increased from 33.8 degrees C to 35.5 degrees C after apheresis and the skin ulcers were also improved. Plasma nitric oxide (NO) levels were increased from 66.0 microM/l to 88.0 microM/l and plasma endothelin (ET)-1 levels were decreased from 14.5 pg/ml to 5.8 pg/ml after apheresis. LDL apheresis was effective in ameliorating hyperlipidemia, massive proteinuria, hypoalbuminemia and high serum creatinine levels in an LCDD patient with nephrotic syndrome. Furthermore, we showed beneficial effects of LDL apheresis on skin ulcers due to ischemia in an ASO patient complicated with LCDD.
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PMID:Low-density lipoprotein apheresis in a patient with arteriosclerosis obliterans and light chain deposition disease. 1522 7

Remedies for primary osteoporosis are increasing in brands but not always with concomitant improvements in efficacy and safety. Clinical studies suggest that nitrogen-containing bisphosphonates alone display sufficient practical effectiveness to survive as effective therapy. However, their less effectiveness in highly osteopenic patients due to their lack of genuine bone anabolic effect waits improvements. Pinpointing statins as the inducer of BMP-2 provoked a rush of clinical and laboratory studies to identify bone anabolic properties. Clinical studies, even if only through observational, suggest that under conventional dosing conditions for hyperlipemia, the liver-targeted statins now in use display insufficient bone anabolic effect, although laboratory studies seem to be clarifying the mechanisms underlying intrinsic bone anabolic properties. While incomplete, these studies indicate the possibility that, if bioavailability to bone could be improved by simply changing dosing methods and/or deliberate derivatization, the genuine anabolic properties of statins on bone could be extracted and put into therapeutic use.
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PMID:Osteoporosis requires bone-specific statins. 1532 Jul 48

Reactive oxygen species (ROS), including superoxide (*O2-), hydrogen peroxide (H2O2), and hydroxyl anion (OH-), and reactive nitrogen species, such as nitric oxide (NO) and peroxynitrite (ONOO-), are biologically important O2 derivatives that are increasingly recognized to be important in vascular biology through their oxidation/reduction (redox) potential. All vascular cell types (endothelial cells, vascular smooth muscle cells, and adventitial fibroblasts) produce ROS, primarily via cell membrane-associated NAD(P)H oxidase. Reactive oxygen species regulate vascular function by modulating cell growth, apoptosis/anoikis, migration, inflammation, secretion, and extracellular matrix protein production. An imbalance in redox state where pro-oxidants overwhelm anti-oxidant capacity results in oxidative stress. Oxidative stress and associated oxidative damage are mediators of vascular injury and inflammation in many cardiovascular diseases, including hypertension, hyperlipidemia, and diabetes. Increased generation of ROS has been demonstrated in experimental and human hypertension. Anti-oxidants and agents that interrupt NAD(P)H oxidase-driven *O2- production regress vascular remodeling, improve endothelial function, reduce inflammation, and decrease blood pressure in hypertensive models. This experimental evidence has evoked considerable interest because of the possibilities that therapies targeted against reactive oxygen intermediates, by decreasing generation of ROS and/or by increasing availability of antioxidants, may be useful in minimizing vascular injury and hypertensive end organ damage. The present chapter focuses on the importance of ROS in vascular biology and discusses the role of oxidative stress in vascular damage in hypertension.
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PMID:Reactive oxygen species in vascular biology: implications in hypertension. 1533 29

Regucalcin plays an important role as a regulatory protein in intracellular signaling pathway in many cells. Regucalcin transgenic (TG) rats have been shown to induce a remarkable increase in serum triglyceride and HDL-cholesterol concentrations at the age of 36 weeks (35). Furthermore, this was investigated in regucalcin TG rats with increasing age (14, 25, 36 or 50 weeks). Serum triglyceride or HDL-cholesterol concentration was markedly increased in regucalcin TG male and female rats at 14, 25, 36 or 50 weeks of age. Serum-free fatty acid concentration was significantly elevated in regucalcin TG male and female rats at 25, 36 or 50 weeks. In the TG female rats, a significant increase in serum free fatty acid concentration was also observed at 14 weeks of age, while it was not seen in the TG male rats. Serum-free cholesterol concentration was significantly increased in regucalcin TG female rats at 14, 25, 36 or 50 weeks. Such an increase was not induced in the TG male rats. Moreover, serum calcium concentration was significantly raised in regucalcin TG male and female rats at 50 weeks of age. Also, serum albumin concentration was significantly elevated in regucalcin TG female rats at 25, 36, or 50 weeks of age. Such an increase was not observed in the TG male rats. Serum zinc, glucose or urea nitrogen concentration was not significantly altered in TG male and female rats. This study demonstrates that hyperlipidemia is uniquely induced in regucalcin TG rats with increasing age.
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PMID:Hyperlipidemia is induced in regucalcin transgenic rats with increasing age. 1537 96

Hyperlipemia in horses is a disorder of lipid metabolism peculiar to ponies. This study reports changes of blood biochemical values from the acute to the postconvalescent phases in 3 Shetland ponies with hyperlipemia in Japan. Diseased ponies (all 7 to 9 years old, in late pregnancy, and obese) were fed in the same farm. The periods of their hospitalizations ranged from 30 to 45 days. Twelve well-conditioned ponies (3 to 13 years old) around parturition were used to establish baseline values for blood test results. Main clinical findings in the affected ponies were depression, dysphagia, anorexia, ventral edema and milky-appearing plasma. Hypertriglyceridemia (40- to 70-fold rise of controls) was found in the acute phase of the disease in the affected ponies, and was derived from increased very-low density lipoproteins. Aspartate transaminase and gamma-glutamyl transpeptidase activities, blood urea nitrogen, and creatinin concentrations were increased in acute ponies compared to controls, suggesting impairment of liver and kidney functions. However, these values gradually recovered until the end of postconvalescent phase. Hyperinsulinemia was observed in the acute phase of the hyperlipemia of all affected ponies. And an exaggerated insulin response to intravenous glucose was observed in the 2 ponies given intravenous glucose tolerance tests. These findings suggest decreased insulin sensitivity in hyperlipemic ponies.
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PMID:Changes of blood biochemical values in ponies recovering from hyperlipemia in Japan. 1667 26

The metabolic syndrome has recently been recognized as a risk factor for kidney disease, but the mechanisms mediating this risk remain unclear. High fructose consumption by animals produces a model of the metabolic syndrome with hypertension, hyperlipidemia, and insulin resistance. The present study was conducted to test the hypothesis that consumption of a high-fructose diet could accelerate the progression of chronic kidney disease. Three groups of 14 male Sprague-Dawley rats were pair fed a specialized diet containing 60% fructose (FRU) or 60% dextrose (DEX) or standard rat chow (CON). After the animals were fed their assigned diet for 6 wk, five-sixths nephrectomy was performed, and the assigned diet was continued for 11 wk. Proteinuria was significantly increased and creatinine clearance was decreased in the FRU group compared with the CON and DEX groups, and blood urea nitrogen was higher in the FRU group than in the CON and DEX groups. Kidneys from the FRU group were markedly larger than kidneys from the CON and DEX groups. Glomerular sclerosis, tubular atrophy, tubular dilatation, and cellular infiltration appeared markedly worse in kidneys from the FRU group than in kidneys from the DEX and CON groups. Monocyte chemoattractant protein-1 (MCP-1) was measured in renal tissue homogenate and found to be increased in the FRU group. In vitro studies were conducted to determine the mechanism for increased renal MCP-1, and fructose stimulation of proximal tubular cells resulted in production of MCP-1. In conclusion, consumption of a high-fructose diet greatly accelerates progression of chronic kidney disease in the rat remnant kidney model.
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PMID:Fructose, but not dextrose, accelerates the progression of chronic kidney disease. 1767 Sep 4

The most common form of diabetes, type 2 diabetes (T2D) is a major Public Health issue which is receiving a great deal of attention both in industrial and public research, in order to develop new and more effective drugs. The hyperglycaemia of T2D is the result of two interdependent defects : decreased biological efficacy of insulin in target tissues (insulin resistance), and a decreased capacity for beta cells to secrete insulin in response to glucose. Furthermore, hyperglycaemia evolves with time and even with rigorous treatment there is a progressive deterioration of glucose homeostasis. Seventy five percent of DT2 patients are obese and show a perturbed lipid profile. beta-cell plasticity is a unique property of these cells to adapt their number and volume (beta-cell mass) and their function to the increased secretory demand linked to insulin resistance. This is well documented in physiological (pregnancy) as well in pathophysiological conditions (obesity, acromegaly). Although the lack of reliable techniques makes it very difficult to document it in humans, this property is likely altered in DT2, mainly as a consequence of the prolonged exposure of islet cells to high plasma levels of glucose and free fatty acids (gluco-lipotoxicity). The mechanisms by which hyperglycaemia and hyperlipidemia exert their deleterious effects on the beta-cell include the generation of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) and Advanced Glycosylation End Products (AGE). Altogether the prevailing clinical and experimental data urge us to consider that the pathophysiology of DT2 lies, at least in part, the inability of beta-cells to adapt their functional mass to the prevailing insulin demand. This re-evaluation of the pathophysiology of DT2 stimulates the research of new therapeutic approaches aimed at maintaining and/or restoring the functional beta-cell mass by targeting the mechanisms responsible for its decrease.
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PMID:[Anatomical and functional plasticity of pancreatic beta-cells and type 2 diabetes]. 1793 2

Therapeutic strategies to protect the ischemic myocardium have been studied extensively. Reperfusion is the definitive treatment for acute coronary syndromes, especially acute myocardial infarction; however, reperfusion has the potential to exacerbate lethal tissue injury, a process termed "reperfusion injury." Ischemia/reperfusion injury may lead to myocardial infarction, cardiac arrhythmias, and contractile dysfunction. Ischemic preconditioning of myocardium is a well described adaptive response in which brief exposure to ischemia/reperfusion before sustained ischemia markedly enhances the ability of the heart to withstand a subsequent ischemic insult. Additionally, the application of brief repetitive episodes of ischemia/reperfusion at the immediate onset of reperfusion, which has been termed "postconditioning," reduces the extent of reperfusion injury. Ischemic pre- and postconditioning share some but not all parts of the proposed signal transduction cascade, including the activation of survival protein kinase pathways. Most experimental studies on cardioprotection have been undertaken in animal models, in which ischemia/reperfusion is imposed in the absence of other disease processes. However, ischemic heart disease in humans is a complex disorder caused by or associated with known cardiovascular risk factors including hypertension, hyperlipidemia, diabetes, insulin resistance, atherosclerosis, and heart failure; additionally, aging is an important modifying condition. In these diseases and aging, the pathological processes are associated with fundamental molecular alterations that can potentially affect the development of ischemia/reperfusion injury per se and responses to cardioprotective interventions. Among many other possible mechanisms, for example, in hyperlipidemia and diabetes, the pathological increase in reactive oxygen and nitrogen species and the use of the ATP-sensitive potassium channel inhibitor insulin secretagogue antidiabetic drugs and, in aging, the reduced expression of connexin-43 and signal transducer and activator of transcription 3 may disrupt major cytoprotective signaling pathways thereby significantly interfering with the cardioprotective effect of pre- and postconditioning. The aim of this review is to show the potential for developing cardioprotective drugs on the basis of endogenous cardioprotection by pre- and postconditioning (i.e., drug applied as trigger or to activate signaling pathways associated with endogenous cardioprotection) and to review the evidence that comorbidities and aging accompanying coronary disease modify responses to ischemia/reperfusion and the cardioprotection conferred by preconditioning and postconditioning. We emphasize the critical need for more detailed and mechanistic preclinical studies that examine car-dioprotection specifically in relation to complicating disease states. These are now essential to maximize the likelihood of successful development of rational approaches to therapeutic protection for the majority of patients with ischemic heart disease who are aged and/or have modifying comorbid conditions.
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PMID:Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning. 1804 61


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