Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inflammatory myopathies encompass a group of heterogenous muscle diseases which have in common an acquired myopathy with histological signs of endomysial inflammation. We present evidence based on recently emerged clinical, histologic, immunopathologic, demographic and therapeutic observations that these myopathies comprise three major and distinct groups: polymyositis (PM), dermatomyositis (DM), and inclusion-body myositis (IBM). Immune-mediated mechanisms characteristic for each group appear to play a primary role in the pathogenesis of these diseases. In DM there is an intramuscular microangiopathy mediated by the C5b-9 membranolytic attack complex, leading sequentially to loss of capillaries, muscle ischemia, muscle fiber necrosis and perifascicular atrophy. In contrast, in PM and IBM the muscle fiber injury is initiated by sensitized CD8+ cytotoxic T cells that recognize MHC-I restricted muscle antigens, leading to phagocytosis and fiber necrosis. Among the viruses implicated in the cause of inflammatory myopathies, only the retroviruses, HIV, HTLV-1 and simian retroviruses, have been convincingly associated with PM. Retroviruses, therefore, appear to be the leading group of viruses capable of triggering these diseases. The treatment of inflammatory myopathies has been largely empirical. A detailed therapeutic plan based on our experience with a large number of patients is presented. Patients with bona fide PM or DM respond to steroids to some degree and for some period of time. In contrast, patients with IBM do not respond to any therapy and the disease should be suspected when a patient with presumed PM has failed treatment. Methotrexate and cyclophosphamide are disappointing. Cyclosporine and Azathioprine are commonly used but they are of uncertain benefit. Plasmapheresis is ineffective. High-dose intravenous immunoglobulin is a promising new therapeutic modality.
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PMID:Clinical, immunopathologic, and therapeutic considerations of inflammatory myopathies. 142 35

We investigated the protective effect of Cyclosporin A (CsA) against ischemia-reperfusion injury in the brain using a transient focal ischemia model in rats. In CsA-treated rats, ischemic brain edema formation 1 day after reperfusion in the cerebral cortex perfused by the middle cerebral artery (MCA) and infarct size were decreased compared with those in olive oil treated control rats. These results suggest that CsA is beneficial in reducing ischemia-reperfusion injury, possibly by the suppression of immunological reactions.
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PMID:Cyclosporin A protects against ischemia-reperfusion injury in the brain. 146 51

Cyclosporine has been shown to reduce renal perfusion and to decrease glomerular filtration rate. Experimental studies suggest that nifedipine might reverse this renal vasoconstrictive effect of cyclosporine. We studied renal hemodynamics of 5 cyclosporine-treated renal transplant recipients before and after 2 weeks of therapy with high-dose nifedipine (up to 120 mg/day). Pretreatment GFR and renal plasma flow (RPF) were decreased. Following administration of nifedipine, RPF increased by 18% (P less than 0.01), while GFR did not change. Filtration fraction decreased by 10.5% (P less than 0.01). Mean arterial pressure declined from 111 +/- 5 to 96 +/- 3 mmHg (P less than 0.01). Renal vascular resistance dropped by 25% (P less than 0.01). Calculated postglomerular plasma flow increased by 20.5% (P less than 0.01). Urinary albumin excretion rate was unaffected. Cyclosporine whole blood levels were unchanged. The increase in RPF and in postglomerular plasma flow suggests that high-dose nifedipine might lessen cyclosporine-induced glomerular and interstitial ischemia in renal allograft recipients.
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PMID:The effect of high-dose nifedipine on renal hemodynamics of cyclosporine-treated renal allograft recipients. 156 41

Giant mitochondria in kidneys have increasingly been observed since the introduction of Cyclosporin A (CSA) as immunosuppressant in kidney transplants and in patients with autoimmune disorders. In animals treated with CSA, giant mitochondria were also described. In a study of "zero-hour" biopsies taken immediately before or after reperfusion of the renal transplant, giant mitochondria were often unexpectedly found. Retrospective analysis revealed that a significant increase in the number of giant mitochondria is more often associated with CSA therapy than ischemia. Giant mitochondria with sparse cristae seem to prevail in ischemia, whereas those with dense matrix and crystalloid structures predominate in CSA therapy.
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PMID:Giant mitochondria in "zero-hour" transplant biopsies. 158 95

The discovery of cyclosporine has had a significant impact on preventing the rejection of transplanted organs in humans. In this study, we present another positive aspect of cyclosporine. Rats were pretreated with cyclosporine (10 mg/kg, i.v.), or untreated. After 2-hr ischemia or 1 hr of reperfusion following 2-hr ischemia, livers were isolated and liver adenine nucleotide concentrations were determined. Liver mitochondria were prepared and their function was estimated polarographically. Leakage of AST, ALT, LDH, and adenine nucleotides into the hepatic vein just after reperfusion was also measured. Cyclosporine treatment did not affect ischemia-induced mitochondrial dysfunction, nor did it prevent the associated decrease in adenosine triphosphate concentration. However, treatment with cyclosporine accelerated the recovery of mitochondrial function and of tissue adenosine triphosphate concentrations. Cyclosporine treatment also mitigated leakage of AST, ALT, LDH, and adenine nucleotides after reperfusion. These results indicate that cyclosporine shows a potent protective effect on ischemia-reperfusion-related liver injury.
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PMID:Beneficial effects of cyclosporine on postischemic liver injury in rats. 173 23

Acute tubular necrosis (ATN) after renal transplantation is related to the duration of warm and cold ischemia and leads to temporary or permanent impairment of graft function. An increased incidence of ATN has been reported since the introduction of cyclosporin A. Kidney damage resulting from hypothermic storage is generated in part during reperfusion rather than during ischemia itself. Potential mediators of the reperfusion injury are oxygen-derived free radicals. Therefore, the influence of two oxygen radical antagonists, allopurinol and superoxide dismutase, was evaluated in syngeneic rat kidney transplantation with and without concurrent administration of cyclosporin A. At 15 h cold ischemia, 28-day survival increased from 8% (no treatment) to 22% (superoxide dismutase), 33% (superoxide dismutase and allopurinol), and 73% (allopurinol). Cyclosporin A cotreatment (10 mg/kg over 14 days) resulted in survival rates of 0%, 25%, 17%, and 50% for the respective treatment groups. The results of serum creatinine values and morphological evaluation of biopsies paralleled the survival rates. Cyclosporin A nephrotoxicity was evidenced by significant serum creatinine elevations throughout the 28-day period of observation. In conclusion, allopurinol significantly protects syngeneic rat kidney transplants against a critical duration of cold ischemia. Under the conditions of this experiment, allopurinol was clearly superior to superoxide dismutase treatment. Cyclosporin A nephrotoxicity was, however, not ablated by the oxygen radical antagonists employed.
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PMID:Protective effect of allopurinol and superoxide dismutase in renal isografts in cyclosporin A-treated rats. 178 Apr 91

The outcome of renal transplantation in CAPD patients is still controversial since age and clinical differences often make comparison with hemodialysis patients difficult. The aim of this study was to analyse two homogeneous groups of patients, on CAPD and on hemodialysis. 18 CAPD (Group A) and 18 hemodialysis patients (Group B) were selected for a case-control analysis, matched for age, presence of acute tubular necrosis and Cyclosporine A regimen. Group A and B were not different for male/female ratio, donor age, HLA-Dr mismatches, arterial pressure, cold ischemia, or follow-up. Patient, graft survival and number of rejection episodes did not differ significantly at 1 year; serum creatinine at 6 and 12 months and CyA doses at 1 and 6 months were not different; hospitalization rates for first and subsequent admissions did not differ. Infection-free patients were 9/18 in Group A and 15/18 in Group B, with 12 episodes in Group A and 3 in Group B. Post transplant cholesterol levels showed a trend to increase in both groups and triglycerides levels to a decrease; differences in pre and post transplant in body weight were not significant at 12 months. In conclusion, the outcome of transplantation in CAPD patients is not significantly different from that in hemodialysis patients with similar clinical characteristics.
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PMID:Comparison between two dialytic populations undergoing renal transplantation. 198 44

A retrospective study was performed on our series of 240 primary cadaveric renal transplant recipients to dissect the influence of vascular anastomosis time, warm ischemia time and cold ischemia time on ultimate graft survival. 177 patients received conventional immunosuppression with Azatioprine and steroids, and 63 patients received Cyclosporine A therapy. The data was analyzed for sub-groups of ischemia time and comparisons were performed using the method of Tarone-Ware. The present study fails to demonstrate a detrimental effect of ischemic insults on graft survival. The use of Cyclosporine A in the pre and post-transplant, monitoring periodically serum cyclosporine levels and the use of renal allograft biopsy, allows the use of this agent without a high incidence of nefrotoxicity.
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PMID:[Effect of time of vascular anastomosis and of hot and cold ischemia, on survival of cadaver renal graft]. 205 39

We examined whether ultrastructural changes in renal mitochondria associated with Cyclosporine A treatment might reflect underlying alterations in mitochondrial molecular structure. A nonrejected renal transplant removed from a patient treated with Cyclosporine A showed a decreased level of beta subunit antigen of mitochondrial F1-ATPase compared to controls. This decrease was more marked in the medulla than in the cortex (56% vs. 70% of pooled controls). Spontaneously hypertensive rats treated with a high dose of Cyclosporine A showed a similar decrease of beta-subunit antigen in the renal medulla and decreased levels of two subunit antigens of cytochrome c oxidase, but had increased medullary levels of the alpha subunit antigen of the F1-ATPase. Such changes were not detected in a normotensive strain of rats. Our data indicate that Cyclosporine A administration is associated with structural alterations in renal mitochondria at the molecular level, predominantly in the medulla, and that additional renal damage due to ischemia or hypertension may predispose to this cyclosporine effect.
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PMID:Alterations in molecular structure of renal mitochondria associated with cyclosporine A treatment. 301 38

The present analysis of risk factors in human cardiac transplantation is based on a review of 682 endomyocardial biopsies from 52 grafts in 51 recipients. Acute rejection was diagnosed in 149 biopsies (21.8%). The cumulative 1-year graft survival was 91.5 4%. Four out of seven patients died of irreversible rejection. An univariate analysis using the linearized rate of total rejection showed significantly higher frequency of acute rejection when donor and recipient differed for two HLA-DR antigens compared to zero or one HLA antigen disparity (p less than 0.01), as well as in patients treated with low dose steroids, Cyclosporine (CyA) and Azathioprine (p less than 0.01), compared to treatment with CyA high dose steroids. Other risk factors were graft ischemia extending 60 minutes (p less than 0.05) and patient age exceeding 40 years (p less than 0.05). A multivariate analysis using the competing risk hazard model for irreversible (= lethal) rejection was performed. The presence of two HLA-DR mismatches between donor and recipient was found to be an independent risk factor (relative risk = 8.9), and immunosuppression with CyA and high dose steroids without Azathioprine another (relative risk = 15.3). Potential risk factors such as donor and recipient sex, donor age, prior surgery and time on extracorporeal circulation were not of significant prognostic value neither in regard to rejection nor irreversible rejection.
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PMID:Human heart transplantation. Rejection risk factors. 305 17


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