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

Diffuse atherosclerosis entails a 15-30% risk of plaques on renal arteries (ARAS), with a correlation with coronary atherosclerosis. Ischemia induces generation of angiotensin II (Ang II) that maintains sufficient hydrostatic pressure within the tuft to preserve the GFR. Ang II inhibition suppresses this protective mechanism. In fact, any antihypertensive drug may lead to reaching a "critical perfusion pressure". ARAS should be suspected in case of renal asymmetry. It should also be envisaged in case of "flash pulmonary edemas". Ultrasonography and renal tomography show aortic calcifications and often the outline of an abdominal aortic aneurysm. Tomodensitometry may detect large aorto-renal plaques. Spiral scanner tomography represents a progress, in terms of renal artery imaging and of renal cortical atrophy. Magnetic resonance imaging is less accurate but avoids iodine toxicity. The best noninvasive method is pulsed echo-doppler. It is particularly useful for evaluating stenoses progression. Some stenoses progress to renal atrophy and renal artery thrombosis, whereas others follow a stable course. Pulsed Doppler helps predict whether revascularization will improve renal function, according to the resistance index. Renal arteriography entails a high risk of cholesterol crystal embolism. However, it is the obligatory first step for angioplasty and stent positioning, indicated when the kidney is not atrophic. The indication for revascularization essentially depends on evaluation of the benefits vs risks of angioplasty or surgery. Some publications underscore the frequent stability of renal function and the fact that, revascularized or not, most patients will shortly die of myocardial infarction. Renal cholesterol crystal embolism (CCE) is a severe condition, which occurs when large arteries undergo surgery, aortography or interventional radiology. Anticoagulants are a frequent cause of CCE. CCE may also occur spontaneously, resulting in slowly progressive renal insufficiency. Migration of crystals in small caliber intrarenal arteries induces obstruction, followed by an inflammatory reaction. The clinical picture resembles angiitis, with laboratory evidence of inflammation along with high eosinophil counts and hypocomplementemia. Diagnosis rests on: 1) a iatrogenic event in a patient with an atherosclerotic background; 2) examination of the skin disclosing purple toes, small necrotic lesions and livedo of the lower limbs. Crystals may also be found by funduscopy. Skin or muscle biopsy are contributive in showing crystals and help avoid renal biopsy; 3) other localizations involve the mesenteric circulation and the central nervous system. Until recently, the prognosis was considered disastrous. However, a recently published treatment schedule proved efficient in reducing mortality. A last issue regarding the relationships between atherosclerosis and the kidney deserves mention. In an autopsy-based study it was shown that atherosclerosis per se is accompanied by an increase in the glomerular surface area along with a greater proportion of obsolescent glomeruli by comparison with matched controls. Finally, it should be recalled that atherogenic hyperlipidemia usually aggravates the course of any renal disease, including ARAS. Treatment with statins is indicated in all forms of atherosclerotic renal disease.
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PMID:[Atherosclerosis and the kidney]. 1689 85

Given the elevated risk of cardiovascular events and the higher prevalence of silent coronary artery disease (CAD) in diabetic versus non-diabetic patients, screening asymptomatic diabetic patients for CAD is an appealing concept. However, many factors argue against implementing a broad-based screening program at the present time. Foremost is the lack of any published data demonstrating that a prospectively applied screening program improves outcome in asymptomatic diabetic patients. The true prevalence of CAD, and in particular prognostically important CAD, in this population is uncertain. Consensus documents recommend more aggressive treatment of hypertension and hyperlipidemia solely on the basis of diabetes status, without differentiation based on the presence or absence of identifiable CAD. There is no evidence that use of anti-ischemic medication can alter the natural history of CAD in these patients. Retrospectively performed studies using stress single-photon emission computed tomography (SPECT) imaging have reported that approximately 50% and 20% of patients have abnormal and high-risk images, respectively. However, the only prospectively designed study, the DIAD (Detection of Ischemia in Asymptomatic Diabetics) study, reported a much lower percentage of abnormal SPECT images (16%) and images with a very large (>/=10% of the left ventricle) defect (1%). The financial implications of screening all asymptomatic diabetic patients determined to be at intermediate and high risk by clinical scoring systems is enormous. Clearly more data are needed to address this issue. Future studies should consider possible methods to enrich the patient subset that might benefit from screening and should include carefully performed cost-effective analyses.
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PMID:Screening asymptomatic diabetic patients for coronary artery disease: why not? 1690 46

Chronic Allograft Nephropathy (CAN) is one of the most common cause of kidney transplant loss. CAN may be caused by immunologic as well as nonimmunologic factors which may interfere and increase response. Immunologic factors include acute rejection, degree of HLA mismatch, inadequate immunosuppression. Nonimmunologic factors contain delayed graft function, ischemia-reperfusion injury, nephrotoxicity of calcineurin inhibitors, hyperfiltration, hypertension and hyperlipidemia. The histopatological description of CAN may indicate two phases of injury. An initial phase by one year include tubulointerstitial infiltration in the late phase of CAN arteriolar hyalinosis and glomerulosclerosis were revealed. Modification of the immunosuppressive treatment with reduction or withdrawal of calcineurin inhibitors may prevent graft loss, while addition of nonnephrotoxic agents such as mycophenolate mofetil or sirolimus should be considered by the risk of acute rejection. Additionally effective management by hypertension and hyperlipidemia is essential.
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PMID:Chronic allograft nephropathy--immunologic and nonimmunologic factors. 1702 23

The predictors for coronary artery disease (CAD) in patients with delayed systolic blood pressure (SBP) recovery after graded exercise are unclear. We studied 672 patients with preceding positive symptom-limited exercise treadmill testing (ETT) and underwent their first coronary angiography within 90 days to determine the high-risk profiles for angiographic CAD in patients with paradoxical SBP elevation (the SBP at 3-min of recovery was equal to or higher than that at 1-min of recovery). Among them, 356 patients were diagnosed as CAD, of which 173 were severe CAD. Among 208 patients with paradoxical SBP elevation, 158 (76%) were CAD, and 101 (48.6%) were severe CAD. Multivariate logistic regression analyses identified male gender and hyperlipidemia as positive predictors and maximal heart rate and exercise time as negative predictors for CAD or severe CAD. In conclusion, patients with both positive ETT for ischemia and paradoxical SBP elevation during recovery have a high prevalence of CAD and severe CAD. The high-risk patients for the presence of CAD or severe CAD were those of male, with hyperlipidemia, low achievable maximal heart rate, and short exercise time after graded exercise.
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PMID:Predictors for coronary artery disease in patients with paradoxical systolic blood pressure elevation during recovery after graded exercise. 1705 13

Hyperlipidemia is a well-known risk factor for atherosclerosis. Several trials have demonstrated the importance of lowering low-density lipoprotein cholesterol (LDL-C) levels to reduce all-cause mortality, coronary ischemia, and cerebrovascular accidents. Although the optimal goal for LDL-C levels in patients with known coronary heart disease has been less than 100 mg/dL, more recent findings support achieving even lower LDL-C levels for very high-risk patients. As the target levels for LDL-C trend towards lower values, it is important to evaluate the status for optimal management with statin therapy. In this review article, we discuss the role of percent LDL-C reduction versus attained LDL-C levels as targets for statin therapy in order to maximize the preventive care provided to high-risk patients.
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PMID:Statin therapy: is the percent reduction or the attained low-density lipoprotein cholesterol level more important? 1716 41

Flexibility in substrate selection is essential for the heart to maintain production of energy and contractile function, and is managed through multiple mechanisms including PPAR-alpha and AMP-activated protein kinase (AMPK). Rats injected with 55 mg/kg STZ (D55) were kept for 4 days (acute diabetes; D55-A) prior to termination. Fatty acid (FA) oxidation increased in D55-A hearts, with no significant change in gene expression of PPAR-alpha, or its downstream targets. However, both AMPK and ACC phosphorylation were significantly higher in these hearts, effects that were reversed by insulin. Unexpectedly, when the duration of diabetes in D55 rats was extended to 6 weeks (chronic diabetes; D55-C), AMPK and ACC phosphorylation were comparable in control and D55-C hearts. In D55-C rat hearts, lack of AMPK activation was closely associated to an overload of plasma and cardiac lipids. To validate the relationship between lipids and cardiac AMPK activation, we either induced more severe diabetes (100 mg/kg STZ to provoke both hyperglycemia and hyperlipidemia acutely; D100-A) or infused intralipid (IL) to enlarge circulating lipids. There was no difference in cardiac AMPK and ACC phosphorylation in D100-A rats compared to control. Measurement of AMPK and ACC phosphorylation in control and D55-A hearts revealed that their phosphorylation was inhibited by acute intralipid infusion. Our data suggest that activation of AMPK is an adaptation that would ensure adequate cardiac energy production when glucose utilization is compromised. However, in severe diabetes, with the addition of augmented plasma and heart lipids, AMPK activation is prevented, and control of FA oxidation is likely through alternate mechanisms. Given that AMPK plays an important role in preventing cardiac ischemic/reperfusion damage, it is possible that in these diabetic hearts, the accelerated damage observed during exposure to ischemia/reperfusion could be a likely outcome of a compromised activation of AMPK.
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PMID:AMPK control of myocardial fatty acid metabolism fluctuates with the intensity of insulin-deficient diabetes. 1718 7

The aim of this study is to identify the risk factors for development of chronic critical limb ischemia (CLI) in diabetic and nondiabetic patients with peripheral arterial disease (PAD). 127 patients (pts) with PAD (63 with type 2 diabetes and 64 nondiabetic) were randomly included in a cross sectional study. Out of them 17 were with CLI. Population was investigated for age, height, weight, sex, duration of PAD and diabetes, arterial hypertension, hyperlipidemia, smoking, obesity, systolic blood pressure, value of ankle-brachial index, previous claudicating distance and peripheral intervention, amputation, medical treatment with prostanoids, insulin and antiplatelet drugs and histories of cerebrovascular disease, coronary artery disease and other concomitant diseases. After adjudging linear correlation between mentioned variables and presence of CLI, logistic regression model was built. There were no significant differences in demographic data between both populations. Hyperlipidemia was more frequent in nondiabetic population. Multiple regression model show ankle-brachial index < 0,5, measured in previous 1-3 years (OR 3.39 CI 95% 0.28-40.78), microvascular complication retinopathy (OR 12.98 CI 95% 1.76-95.58), heart failure (OR 1.91 CI 95% 0.29-2.72) and previous prostanoids treatment (OR 15.92 CI 95% 0.53-476.58) as predictors of development of CLI in diabetic population with PAD. After heart failure exclusion of model of nondiabetic pts, previous surgery (OR 3.14 CI 95% 0.61-16.09) and smoking (OR 0.35 CI 95% 0.78-1.62) were presented as prognostic factors for CLI's onset. Our results indicate differences between predictors of CLI's onset in diabetic and nondiabetic population with PAD. Presence of retinopathy, previous measured ankle-brachial index and prostanoids treatment are predictors of development of CLI in diabetic population. Previous surgery is independent predictor for CLI'onset in nondiabetics. Treating concomitant heart failure for both populations and modifying risk factor smoking in nondiabetic population, have an important clinical usefulness in risk assessment approach of peripheral arterial disease patients.
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PMID:Risk factors for development of critical limb ischemia -- a survey of diabetic vs. nondiabetic population. 1721 Dec 94

Calcineurin inhibitors (CNIs) are routinely used in immunosuppressive therapy and both Cyclosporine (CsA) and Tacrolimus (FK506) show similar efficacies to prevent rejection and death within the first year after organ transplantation. However, their use is limited by side effects such as kidney damage, hypertension, onset of diabetes and hyperlipidemia. It is a consensus that compared with CsA, FK506 causes less changes in blood pressures, serum lipids and renal function. Nevertheless, FK506 use is associated with a higher incidence of post-transplant diabetes mellitus (PTDM). FTY720 is a new compound that has shown a protective effect in animal models with respect to rejection in transplantation, ischemia-reperfusion injury, autoimmune diseases and tumor development. FTY720 acts by altering lymphocytes homing from blood to peripheral lymphoid organs. In mice, FTY720 administered in combination with CsA during 21 days has prolonged skin allograft survival without causing significant renal changes. In a model of CsA-induced chronic nephropathy in rats, FTY720 administration prevented renal injury suggesting benefit from using a combination of these drugs. In a canine kidney allograft model, FTY720 in combination with low doses of CsA or FK506 showed an addictive anti-rejection effect without causing critical adverse effects. We therefore, investigated whether 21 days of FTY720 administration in association with FK506 could prevent renal damage and development of diabetes in mice. Mice receiving FK506 alone or FTY720 + FK506 during 21 days showed changes in kidney function and structure besides an increase in blood glucose and lymphopenia. The FTY720 + FK506 combination requires further investigation with an aim toward understanding the mechanisms involved with respect to side effects.
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PMID:Tacrolimus in combination with FTY720--an analysis of renal and blood parameters. 1721 91

The present study was designed to observe the influence of cerebral ischemia/reperfusion injury on learning and memory in hyperlipidemic rats and estimate the changes of activity of autonomic nervous system. Twenty-three male Wistar rats were randomly divided into three groups, named control group (C group, n=10), hyperlipidemia group (H group, n=6) and hyperlipidemia-ischemia group (HI group, n=7), respectively. The rats in H and HI group were fed a high-fat diet for 2 weeks and the rats in all groups were examined through Morris water maze (MWM) task. The rats in HI group underwent ischemia/reperfusion by 2-vessel occlusion (2-VO) method, and had electrocardiogram (ECG) recording simultaneously. The MWM task and ECG recording were taken again after 7 d of recuperation. The following results were obtained: (1) In the second place navigation performance and probe trial performance, the frequency of memory in quadrant of hidden-platform and memory score decreased significantly in HI group compared to that in C and H groups. (2) The heart rate in HI group decreased slowly after ischemia; the power at high frequency band (HF) reduced gradually, meanwhile the power at middle frequency band (MF) and the ratio of power at MF and HF decreased clearly compared to baseline value. (3) After 7 d of ischemia/reperfusion, the heart rate in HI group was significantly higher than that in H group (P<0.05). While there was no statistical change in the power at MF, the power at HF decreased and the ratio of MF/HF increased significantly (P<0.05). The data demonstrated that ischemia/reperfusion decreased the activity of autonomic nervous system, and the reduction of sympathetic nerve activity was much more than that of vagus nerve activity. The results suggest that the hippocampus neuron injury caused by ischemia induces cognitive disorder and imbalance of vago-sympathetic nerve activity accompanied by vagus nerve suppression.
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PMID:[Changes of heart rate variability and impairment of learning and memory induced by cerebral ischemia/reperfusion in rats]. 1729 40

The pharmacologic treatment of the cardiovascular comorbidities in patients with peripheral arterial disease (PAD) can have a profound effect on the outcomes of these patients. Guidelines for the treatment of hypertension, hyperlipidemia, diabetes, and tobacco use have been published by the American Heart Association and American College of Cardiology (AHA/ACC). Patients with PAD are often under-treated for these conditions. We sought to evaluate the adherence to these established guidelines in all new patients presenting with PAD to a vascular surgery clinic and delineate the opportunity for vascular surgeon involvement in these treatments. Consecutive new patients with symptomatic, objectively proven PAD (ankle-brachial index < 0.9) were evaluated in a vascular surgery clinic by a staff vascular surgeon. PAD risk factors, pre-visit medications, and prior cardiovascular interventions were recorded. Patients were stratified whether they were receiving appropriate preventive pharmacotherapy and whether they were meeting AHA/ACC goals. In patients without prior cardiovascular history, screening for these conditions was performed. One hundred sixty-seven new patients were evaluated over a 1-year period. Objectively diagnosed PAD included intermittent claudication in 115 (69%) and critical limb ischemia in 52 (31%) patients. Average age was 67.8 years, and 73 patients (44%) were current smokers. At initial evaluation, only 115 (69%) patients reported antiplatelet use. Patients with a recorded diagnosis of hypertension met clinical guidelines in 39 instances (71%). Eighteen patients (20%) with diabetes mellitus had poor glycemic control (Hgb-A1C > 7.0%). Seventeen (19%) of 88 patients with a history of hyperlipidemia were not adequately treated. Vascular surgeon medical interventions resulted in 31% of patients being started on antiplatelet therapy, 29% of hypertension therapies were modified, 19% of established lipid therapy was modified, and lipid therapy was initiated in 20%. A new diagnosis of hypertension was made in 10 cases (6%) and hyperlipidemia in 13 cases (7%). Despite clear guidelines for the medical community regarding cardiovascular prevention, a large percentage of patients with symptomatic PAD presenting to the vascular surgery clinic are not receiving appropriate therapy for their comorbidities or are not meeting the established goals. Vascular surgeons have an important role in promoting vascular health through the systemic prevention of ischemic events.
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PMID:Pharmacologic risk factor treatment of peripheral arterial disease is lacking and requires vascular surgeon participation. 1734 57


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