Flavonoids are a diverse group of compounds originating from several natural plant sources. Various biological effects of flavonoids have been reported, including antimicrobial and antifungal activities. In this study, we showed the possibility of using commercial flavonoids, i.
View Article and Find Full Text PDFJ Chromatogr B Analyt Technol Biomed Life Sci
June 2003
A precise and accurate HPLC assay for polymyxin E(1) in rat and dog plasma has been validated. Samples and standards are extracted from plasma with a 96-well C(8) extraction disk plate. Sample extracts are derivatized with dansyl chloride, and polymyxin E(1) derivative is quantitated on a C(8) column by HPLC with fluorescence detection.
View Article and Find Full Text PDFRecent U.S. Phase III trials of the aerosolized delivery of tobramycin to cystic fibrosis (CF) patients demonstrated a significant improvement in pulmonary function and in sputum bacterial density.
View Article and Find Full Text PDFAddition of phospholipase A2 (PLA2) to isolated proximal tubular segments (PTS) has previously been shown to decrease hypoxic cell death without altering ATP concentrations. The study presented here was undertaken to identify determinant(s) of this protection, and to define the spectrum of injuries against which it can operate. PTS were extracted from mouse kidneys and subjected to diverse forms of injury (hypoxia/reoxygenation, antimycin A, Ca2+ ionophore, amphotericin B, FeSO4, and myohemoglobin).
View Article and Find Full Text PDFUnlabelled: This study assessed the impacts of iron, heme oxygenase (HO), hydroxyl radical (.OH), and glutathione (GSH) on the initiation phase of myohemoglobinuric proximal tubular injury using a novel model system. Rhabdomyolysis was induced in rats by glycerol injection and four hours later proximal tubular segments (PTS) were isolated.
View Article and Find Full Text PDFBackground: The severity of "reperfusion injury" is dependent on the extent to which the involved pathways are activated and on the degree of tissue susceptibility to them. This study was undertaken to ascertain whether preexistent ischemic proximal tubular damage (ischemic "pre-conditioning") significantly alters the expression of two purported mediators of reperfusion damage: oxidant stress and cytosolic Ca2+ loading.
Experimental Design: Male Sprague-Dawley rats underwent 35 minutes of bilateral renal arterial occlusion.
Proc Natl Acad Sci U S A
September 1993
During hypoxic or ischemic renal tubular injury, phospholipase A2 (PLA2) induces membrane deacylation, causing fatty acid accumulation and phospholipid breakdown. Because these changes can compromise cellular integrity, PLA2 activity has been widely proposed as a critical mediator of hypoxic renal tubular injury and, hence, of ischemic acute renal failure. To explore this hypothesis, isolated rat proximal tubules were subjected to continuous oxygenation or to hypoxic injury with or without exogenous PLA2 addition (porcine or bovine pancreatic PLA2; bee or snake venom PLA2).
View Article and Find Full Text PDFAfter O2 deprivation, tissue acidosis rapidly self-corrects. This study assessed the effect of this pH correction on the induction, and pathways, of posthypoxic proximal tubular injury. In addition, ways to prevent the resultant injury were explored.
View Article and Find Full Text PDFJ Clin Invest
February 1993
Iron-dependent free radical reactions and renal ischemia are believed to be critical mediators of myohemoglobinuric acute renal failure. Thus, this study assessed whether catalytic iron exacerbates O2 deprivation-induced proximal tubular injury, thereby providing an insight into this form of renal failure. Isolated rat proximal tubular segments (PTS) were subjected to either hypoxia/reoxygenation (H/R: 27:15 min), "chemical anoxia" (antimycin A; 7.
View Article and Find Full Text PDFWe investigated the correlation between trough cyclosporine concentration in plasma measured by polyclonal fluorescence polarization immunoassay (FPIA) and polyclonal radioimmunoassay (RIA) or in whole blood measured by high-performance liquid chromatography (HPLC) and the risk of renal dysfunction or acute graft-versus-host disease in 29 patients undergoing allogeneic bone marrow transplantation for leukemia. The FPIA and RIA values were highly correlated (r = 0.93) and on the average CsA concentrations measured by FPIA were 1.
View Article and Find Full Text PDFThe purpose of this study was to assess whether proximal renal tubules generate excess hydroxyl radical (.OH) during hypoxia/reoxygenation or ischemia/reperfusion injury, thereby supporting the hypothesis that reactive oxygen species contribute to the pathogenesis of postischemic acute renal failure. In the first phase of the study, rat isolated proximal tubular segments (PTS) were subjected to hypoxia (95% N2- 5% CO2) for 15, 30, or 45 min, followed by 15 to 30 min of reoxygenation in the presence of sodium salicylate, a stable .
View Article and Find Full Text PDFUnlabelled: Body temperature (T) profoundly alters the severity of ischemic acute renal failure. Therefore, the present study evaluated T effects on: (a) in vitro proximal tubular cell killing during hypoxia/reoxygenation to assess when it exacerbates injury; (b) renal ATP losses and metabolic rate (O2 consumption) during hemorrhagic shock (55-60 mm Hg); and (c) membrane deacylation (assessed by free fatty acid, FFA, release) to determine if T modifies this pathway of ischemic renal damage. Hypoxic cell kill (45 minutes) was 20 +/- 1% 47 +/- 4%, and 61 +/- 2% at 32 degrees C, 37 degrees C, and 40 degrees C respectively (by lactate dehydrogenase release; p less than 0.
View Article and Find Full Text PDFUnlabelled: Renal cortex (C) has predominantly aerobic metabolism, whereas inner medulla (IM) has both aerobic and anaerobic capacities. This study was undertaken (1) to assess how well rat IM anaerobic metabolism maintains this region's ATP content during ischemia; and (2) to determine whether regional variations in adenylate pool/catabolite responses to ischemia exist, obscuring interpretation of cellular energetics in rat studies of acute renal failure (ARF). Adenine nucleotides/catabolites were measured in rat C, IM and outer medulla (OM) after 15 and 45 min of ischemia.
View Article and Find Full Text PDFDrug Metab Dispos
June 1990
A novel metabolite of cyclosporin A was observed in human blood and urine. An analytical sample of this metabolite was isolated from human urine and the structure was determined to be (8-hydroxy-6,7-dihydro-MeBMT1) cyclosporin based on the 1H-NMR, 13C-NMR, FAB-MS, and HPLC characteristics of the biological sample as well as by comparison with a synthetically derived authentic sample. The significance of this metabolite in terms of the pathway by which cyclosporin A is metabolized is discussed.
View Article and Find Full Text PDFAm J Physiol
December 1989
To assess the effects of xanthine oxidase (XO) inhibition on ischemic injury, rats were pretreated with oxypurinol (OXY, 5 mg/kg) and subjected to 30 min of bilateral renal artery occlusion. OXY's effect on adenine nucleotide-nucleoside-purine base concentrations was determined at 10 and 30 min of ischemia and during reperfusion (5 and 30 min). To assess whether XO-mediated oxidant stress influences the severity of ischemic acute renal failure (IARF), the effects of 1) OXY pretreatment and 2) hypoxanthine infusion were assessed.
View Article and Find Full Text PDFThe purpose of this study was to assess the degree, time sequence, and biochemical correlates of hypothermic protection against ischemic acute renal failure. Rats subjected to 40 minutes of bilateral renal artery occlusion (RAO) were made mildly hypothermic (32 degrees-33 degrees C, by cold saline peritoneal lavage) during the following time periods: 1) RAO only, 2) reperfusion only (beginning at 0, 15, 30, or 60 minutes after RAO and maintained for 45 minutes), or 3) during and after (0-45 minutes) RAO. Continuously normothermic (37 degrees C) RAO rats served as controls.
View Article and Find Full Text PDFGeburtshilfe Frauenheilkd
November 1989
This is a case report on a nulliparous women, who developed the HELLP syndrome following intravenous tocolysis. Contrary to our expectations, neither schistocytes nor signs of intravasal coagulation were apparent; however, we found Fenoterol-associated anti-erythrocyte antibodies. However, the low titre of these antibodies does not explain the massive haemolysis.
View Article and Find Full Text PDFBlood cyclosporine pharmacokinetics were studied in 85 patients aged 1-52 (median: 22) years undergoing allogeneic bone marrow transplantation for the treatment of hematologic disease. Pharmacokinetic studies were carried out during the first two weeks posttransplant after an intravenous dose of 2.1-4.
View Article and Find Full Text PDFCyclosporine (CSA) is biotransformed to many metabolites which may contribute to its immunosuppressive and nephrotoxic activity. We report a rapid and sensitive, automated column-switching high-performance liquid chromatographic (HPLC) method for measuring CSA-M17 in whole blood; the method also separates CSA-M1. CSA metabolite standards were isolated by a preparative-scale HPLC method.
View Article and Find Full Text PDFBone Marrow Transplant
February 1987
Renal dysfunction is the major dose-limiting toxicity associated with cyclosporin therapy. We have previously shown in patients undergoing allogeneic bone marrow transplantation that serum cyclosporin concentrations, as measured by radioimmunoassay (RIA), correlate significantly with the development of renal dysfunction. However, since the RIA measures both parent drug and metabolites, the relative role of each in the development of nephrotoxicity could not be determined.
View Article and Find Full Text PDFClin Pharmacol Ther
October 1986
We evaluated the effect of age on cyclosporine pharmacokinetics in 69 nonobese patients aged 10 months to 56 years (median 22 years) undergoing allogeneic bone marrow transplantation for treatment of aplastic anemia or hematologic malignancy. Cyclosporine pharmacokinetics were studied during the first 2 posttransplant weeks after an intravenous dose of 2.6 to 3.
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