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 aim of our work was to study the changes in activity, abundance and distribution of sodium, potassium-adenosine triphosphatase (Na+,K+-ATPase) in membranes of cortical tubular cells in an in vivo model of ischemic injury without reperfusion. Na+,K+-ATPase, alkaline phosphatase (AP) activities and their distribution in membranes isolated from renal cortex using a Percoll gradient were studied after different ischemic periods. Na+,K+-ATPase alpha-subunit protein abundance was analysed by Western-blot. Plasma urea and cortical adenosine 5' triphosphate (ATP) were also measured. In cortical homogenates 5 min of ischemia promoted a diminution in ATP content. Na+,K+-ATPase activity diminished after 40 min and AP after 100 min of ischemia. Na+,K+-ATPase activity in the Percoll gradient fractions after 5 min peaked at a higher density and was significantly decreased after 40 min. AP activity was decreased in typically enriched apical membranes after both times of ischemia. At each time studied Na+,K+-ATPase abundance was increased in cortical homogenates and membranes. Our results showed opposite effects of ischemia on Na+,K+-ATPase activity and abundance. Increased levels of Na+,K+-ATPase protein were observed. The enzyme would be rapidly delivered to membrane domains and become inactivated as ischemia persists.
Nephron 2001 Sep
PMID:Cortical Na+,K+-ATPase activity, abundance and distribution after in vivo renal ischemia without reperfusion in rats. 1152 37

Potential of sanguiin H-6, a component of Sanguisorbae Radix, to protect against oxidative damage in renal mitochondria and apoptosis mediated by peroxynitrite (ONOO(-)) was examined using a model in which rats were injected with lipopolysaccharide (LPS) and then subjected to renal ischemia followed reperfusion (LPS plus ischemia-reperfusion). Ischemia-reperfusion was achieved by occluding bilateral renal artery for 60 min and then releasing for 350 min. At 50 min after ischemia started, LPS was injected intravenously. LPS plus ischemia-reperfusion induced a large amount of 3-nitrotyrosine, an oxidative product of protein that is produced via ONOO(-) nitration, which was not detectable in normal group. Oxidative damage of mitochondria was indicated by an accumulated thiobarbituric acid (TBA)-reactive substance, glutathione (GSH) depletion and glutathione peroxidase (GSH-Px) inactivation in the mitochondria. Treatment of rats with sanguiin H-6 (10 mg/kg body weight/day) for 30 days prior to LPS plus ischemia-reperfusion attenuated the oxidative damage in the mitochondria. The amount of TBA-reactive substance was decreased and the GSH levels significantly increased as compared with that in control group. However, its effect on GSH-Px activity was much weaker. Apoptosis induced by LPS plus ischemia-reperfusion was detected by fluorescence staining, TdT-mediated dUTP-biotin nick end labeling and electrophoretic analysis. Sanguiin H-6 appeared to inhibit apoptosis, and this was associated with the suppression of caspase-3 activity. These beneficial effects of sanguiin H-6 against oxidative damage in mitochondria and apoptosis contributed to the improvement in renal function by reversing the elevated levels of blood urea nitrogen and creatinine caused by ONOO(-).
Nephron 2002 Sep
PMID:Potential of sanguiin H-6 against oxidative damage in renal mitochondria and apoptosis mediated by peroxynitrite in vivo. 1218 96

Heme oxygenase-1 (HO-1) is an antioxidant enzyme and is believed to protect against oxidative stress-induced tissue injury. Renal ischemia-reperfusion (IR) injury seems at least in part to be caused by the oxidative stress. The aim of this study was to improve the renal IR injury by clinically available means. When littermate hemolysate was intravenously administered into rats, HO-1 was markedly induced in the kidneys. To investigate whether prior induction of HO-1 by the hemolysate injection ameliorates the subsequent renal IR injury, we assessed the levels of blood urea nitrogen (BUN) and serum creatinine (SCr), markers for renal injury, in rats with 45 min of ischemia followed by 18 h of reperfusion. To avoid the nephrotoxicity induced by hemolysate, small but effective amounts of hemolysate was injected into rats at 48 h prior to the ischemia. The levels of BUN and SCr values were significantly improved as compared to the rats with renal IR injury alone. Administration of HO inhibitor abolished the efficacy of hemolysate pretreatment. Our findings indicated that the prior induction of HO-1 by treatment of littermate hemolysate ameliorated the subsequent renal IR injury. Prior injection of self-hemolysate would be clinically useful for the protection against the renal IR injury induced by kidney transplantation and kidney surgery without immunological and infectious problems.
Nephron 2002 Oct
PMID:Hemolysate pretreatment ameliorates ischemic acute renal injury in rats. 1221 21

Given the important effects of ischemic preconditioning (IPC) in minimizing tissue damage induced by sustained ischemia in several tissues, this study evaluated the effect of IPC in preserving renal function and identified up-regulated genes after 30 min of preconditioning. IPC induced by 2, 3 and 4 min of ischemia, intercalated by 5 min of reperfusion, induced a measurable protection of renal function and morphology. The improved functional and histological parameters occurred in parallel with up-regulation of 39 genes, as evaluated by subtractive hybridization; for 13 of them we could show, by RNAse protection assay, a significant increase in mRNA levels. These genes code for chaperones/chaperonins and cytoskeleton proteins that could be involved in preservation of protein folding and cellular structures after sustained ischemia; proteins related to oxidative metabolism that might be relevant for cellular use of alternate sources of energy or for faster recovery of ATP levels in this condition, and proteins that are putative scavengers of oxidant products. Summarizing, ischemic preconditioning induced up-regulation of genes that code proteins whose functional roles suggest their involvement in the tolerance of the preconditioned tissue to sustained ischemia.
Nephron Exp Nephrol 2003
PMID:Ischemic preconditioning of renal tissue: identification of early up-regulated genes. 1266 Apr 13

As an experimental model for the different forms of muscle degeneration, injury caused by 2 hours' ischemia has been studied from 20 minutes to 16 hours after release of the tourniquet. Discoid degeneration developed in stretched fibers by dissolution of the I bands (Z substances and actin). The discs represented the Q bands (A-H-A). In fibers which passively maintained contraction lengths during degeneration, the Z substances were dissolved, but the continuity of the fibrils was preserved, since the filaments are continuous over all sarcomeres under these conditions. Mitochondria and the tubules of the endoplasmic reticulum swelled, ruptured, and disintegrated. Granular degeneration developed in fibers where mitochondria were abundant. Unstretched degenerating fibers with few mitochondria gave a homogeneous or hyaline appearance. The different forms of degeneration therefore were dependent on the status of stretch and the fiber type. The extent of degeneration was not a function of time after ischemia, there being both nearly normal and severely damaged fibers at 20 minutes and 16 hours after the release of tourniquets. When degeneration occurred, however, the basic alterations were the same in all fibers; there was mitochondrial and reticular swelling, dissolution of the Z substances, and finally disintegration of the contractile material. Some damage developed in the sarcolemmas and capillaries. The mitochondrial disintegration was not linked with inactivation of the succinic dehydrogenase system.
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PMID:Electron microscopic and histochemical observations of muscle degeneration after tourniquet. 1339 42

Poly(ADP-ribose) polymerase (PARP) activation after free-radical-induced DNA damage depletes cellular energy stores and participates in ischemia-reflow injury. We studied the potential protective effect of the water-soluble PARP inhibitor 3-aminobenzamide (3-AB) in a rat model of acute renal failure (ARF) from combined administration of radiocontrast, indomethacin and N(omega)-nitro-L-arginine methyl ester. Kidney function at 24 h was better preserved in rats treated with 3-AB as compared to control animals. However, the extent of tubular hypoxic damage was not significantly mitigated. It is concluded that PARP inhibition may attenuate renal dysfunction in this model of ARF with medullary hypoxic tubular injury even while the extent of tubular necrosis is not significantly altered. Further studies of this dyssynchrony of structure and function may provide important insights into the sequence of events that promotes renal failure after medullary injury.
Nephron Physiol 2003
PMID:Effect of poly(ADP-ribose) polymerase inhibition on outer medullary hypoxic damage. 1452 6

Reperfusion injuries after organ transplantation affect graft function and influence long-term graft survival. As hypothermic storage, which minimizes the extent of unspecific tissue injury after ischemia and reperfusion, is significantly influenced by the composition of preservation solutions, strategies to optimize the different components may lead to longer graft survival. In the present study the effects of the preservation solution B2 on early renal function and histopathological changes were compared to histidine-tryptophan-ketoglutarate solution (HTK, Bretschneider) in a model of isolated blood-perfused porcine kidneys. B2-preserved kidneys displayed a lower renal resistance and significantly better creatinine clearance as compared to HTK. Mean differences were also found for filtration fraction and sodium fraction reabsorption. The functional data were also related to histopathological changes. Together, these data indicate that the recently developed preservation solution B2 offers new principles of preservation and is a useful preservation solution for experimental isolated perfused kidney models. B2 may also be an interesting model for optimizing preservation within other organ perfusion models.
Nephron Physiol 2004
PMID:Protective effects of B2 preservation solution in comparison to a standard solution (histidine-tryptophan-ketoglutarate/Bretschneider) in a model of isolated autologous hemoperfused porcine kidney. 1498 62

Radical nephrectomy is the gold standard curative operation for patients with localized renal cell carcinoma (RCC). Since its introduction in 1990, laparoscopic radical nephrectomy is being increasingly done at numerous institutions worldwide. In the hands of experienced laparoscopic urological surgeons and with adherence to established principles of open radical nephrectomy, laparoscopic radical nephrectomy is now a standard of care for patients with T1-3a N0 M0 RCC. Intermediate-term outcome data indicate equivalent cancer-free survival to open radical nephrectomy in such cases. Nephron-sparing surgery (NSS) is now an established approach for patients with localized RCC when there is a clinically relevant need to preserve renal function. NSS is also indicated in patients with a single, small, unilateral, localized RCC when the opposite kidney is completely normal. The technical success rate with NSS for RCC is excellent, and long-term patient survival free of cancer is comparable with that obtained after radical nephrectomy. We recently reviewed the results of NSS in 107 patients with localized sporadic RCC treated at the Cleveland Clinic before 1988 who were followed up for a minimum of 10 years. Long-term preservation of renal function was achieved in 93% of patients, and the 10-year cancer specific survival rate was 73%. Although open surgical partial nephrectomy remains the gold standard for nephron-sparing treatment of RCC, laparoscopic partial nephrectomy is now available in selected cases. The optimal indications for laparoscopic NSS are in patients with a relatively small and peripheral renal tumor. In such cases, laparoscopic NSS is proving to be an effective, minimally invasive therapeutic approach with respect to renal functional outcome, with additional advantages of reduced postoperative narcotic use, earlier hospital discharge, and a faster convalescence. The laparoscopic approach is associated with longer warm renal ischemia time, more major intraoperative complications, and more postoperative urological complications. Continued efforts are required to develop laparoscopic renal hypothermia techniques and to facilitate intrarenal suturing while minimizing the warm ischemia time.
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PMID:Laparoscopic and partial nephrectomy. 1544 25

Acute renal failure (ARF) induced by sepsis has a high mortality but lacks effective treatments. To develop novel therapies we must diagnose renal injury early and accurately in septic patients and identify any additional insults such as nephrotoxic drugs and ischemia. In this short review we describe our experience using MRI with dendrimer-based contrast agents in mouse models of ARF. This technique can diagnose early renal injury before serum creatinine is elevated, distinguish different ARF etiologies, track drug therapy and predict outcome. As an ARF biomarker, MRI with dendrimer-based contrast is a promising technique deserving further development.
Nephron Clin Pract 2006
PMID:Imaging acute renal failure with polyamine dendrimer-based MRI contrast agents. 1654 55

The importance of analyzing the kinetics of reactive oxygen species or related substances in vivo is increasing. Electron paramagnetic resonance (EPR) is currently a powerful method for in vivo, non-invasive analysis of oxidative stress. We have applied EPR imaging for murine renal ischemia-reperfusion injury, as a model of acute renal damage, and NF-E2-related factor 2 (Nrf2)-deficient mice, a model for chronic progressive renal disease. In the ischemia-reperfusion model, EPR imaging revealed that the renal radical-reducing activity showed only partial recovery when serum creatinine and BUN have recovered. In the Nrf2-deficient mice, we have revealed that the impaired antioxidant activity is brought by both Nrf2 deficiency and the aging process and may play a key role in the onset of autoimmune nephritis in this model. In addition, EPR imaging is recently being applied to the redox analysis of several nephrosis models, hypertensive rats and streptozotocin-induced diabetic rats. This article summarizes the nephrological application of EPR imaging and in vivo EPR.
Nephron Clin Pract 2006
PMID:Electron paramagnetic resonance imaging of oxidative stress in renal disease. 1654 59


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