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 morphological factors contributing to the reduction GFR in an early phase of NE-induced ARF (0.75 microgram/kg/min) were evaluated by comparing renal morphology at the end of NE infusion with that 2 hr later in unilaterally nephrectomized dogs. GFR 2 hr after NE infusion was reduced to 50% of the preinfusion level in a 30 min infusion group (N = 6), to 13% in a 60 min infusion group (N = 7), and to 2% in a 120 min infusin group (N = 5). On the other hand, simultaneous RBF was not significantly reduced in any group. Dilated PT lumina filled with eosinophilic granular materials in paraffin sections fixed in Zenker-Formol or with impacted swollen blebs in Epon sections fixed in diluted Karnovsky's solution and osmium were found diffusely immediately following 60 and 120 min NE infusion, but patchily after 30 min infusion. Similar changes were found 2 hr after the infusion, except that some PTs came to have dilated but transparent lumina in the 60 and 120 min NE infusion groups. Electron microscopic studies revealed that a part of the membrane-bounded cytoplasm of PT cells extruded into the tubular lumen and became impacted swollen blebs during NE-induced ischemia. There was no prominent foot process fusion in any group. It is concluded that the tubular obstruction by impacted swollen blebs generated in PT during ischemia is a major factor responsible for the reduction in GFR in the early phase of NE-induced ARF.
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PMID:Morphological changes in an early phase of norepinephrine-induced acute renal failure in unilaterally nephrectomized dogs. 741 55

Multiple organ failure is the most common cause of death in critically ill patients in the United States. Acute respiratory failure is the most important single component of this clinical scenario, with a mortality risk > 50%. Key pathophysiologic events occur in the pulmonary microvasculature at the interface between circulating elements and the external environment. In particular, the response of the alveolar capillary endothelial cell is of fundamental importance in this injury process. A variety of clinical stimuli initiate a systemic inflammatory response that contributes to acute microvascular lung injury. Sepsis, trauma, thermal injury, acute pancreatitis, and ischemia-reperfusion injury are among these stimuli. The particular emphasis of this review is on events associated with intestinal ischemia-reperfusion, a common and important clinical event. The pathogenic mechanisms that lead to acute lung injury in this setting are not completely understood, although it is clear that neutrophil-endothelial interactions regulated by both humoral and local mediators are crucial. Oxygen-derived free radicals, proteases, cytokines, eicosanoids, endotoxin, complement activation products, and probably platelet activating factor and nitric oxide are involved as either signalling or effector molecules. The key cellular participants during the acute phase of injury are the polymorphonuclear neutrophil (PMN) and the microvascular endothelial cell. Each of these participants is considered with regard to phlogistic behavior and the potential for therapeutic intervention. Adherence of the neutrophil to the endothelium creates a microenvironment in which PMN-derived oxidants, proteases, and cationic proteins are discharged under conditions that lead to cellular injury. Loss of microvascular integrity results and pulmonary dysfunction follows. At present, we offer only nonspecific supportive care for patients with this problem. However, investigations into relevant molecular and cellular regulatory events offer important opportunities for directed therapy. We are now approaching the threshold for utilization of several new and specific approaches. While no single pharmacologic therapy is likely to be curative for this complex problem, it is probable that certain approaches will be of clinical benefit in the near future. This review is designed to provide a basis for understanding this evolution.
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PMID:Pulmonary microvascular injury following intestinal reperfusion. 780 96

Acute renal failure induced by the administration of gentamicin (GM) was studied enzymochemically in comparison with that in rats with tubular disorder resulting from postischemic reperfusion. Renal ischemia was caused by clamping the renal artery for 30 minutes to create complete ischemia and reflow. The activities of renal tissue glutathione peroxidase (GSH-Px) and the values to the renal contents of glutathione (GSH) and malondialdehyde (MDA) were measured in each sample. In order to confirm whether GSH plays an important role in the intrinsic anti-oxidant system in this model, buthionine sulfoximine (BSO), which is a gamma-glutamylcysteine synthetase inhibitor, was administered intraperitoneally to decrease the renal GSH content before the procedure in renal ischemia. On the other hand, the GM-induced ARF model was made by injection with GM 100 mg/kg during a period of 5 days. In the GM group, a significant increase in MDA and a reduction in the sphigomyelin (SPH)/phosphatidylcholine (PC) ratio and inactivation of PLA2 were observed. In the kidney tissue obtained 15 min. after reperfusion, the renal content of MDA was elevated markedly in the BSO-preadministered group. A reduction of SPH/PC ratio was also observed in the reperfusion model. PAL2 hydrolyzes the acyl group at the 2-position containing much of the highly unsaturated fatty acids that are easily oxidized. Further, PLA2 is considered to act directly on one of PC or phosphatidylinositol. Phospholipidosis thesauruses, noted in acute renal failure induced by GM, is considered to be caused by reduced liberation of lysosomal intramembranous phospholipid into the cytoplasm and accelerated peroxidation of intramembranous lipid.
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PMID:[Lipid peroxidation and tubular disorder in experimental acute renal failure-enzymochemical study in the rat kidney]. 807 17

The aim of this study was to gain further insight into the greater susceptibility to acute ischemic renal failure (ARF, 30 min of renal arteries clamping) of old rats (O, 18 months) as against young rats (Y, 3 months). All the rats ate a hypoproteic diet (14% of casein) to avoid age-related glomerulosclerosis in O. Basal renal dynamics was similar in O and Y (Groups CON). One day after ARF, the decrease in GFR was more severe in O than in Y (-82% and -57% vs. respective CON, P < 0.05), due to a greater rise of RVR in O (+258%) than in Y (+104%). The histological renal damage after ischemia was comparable in the two groups with ARF. Five days after ARF, the recovery of renal function was characterized by a slower rise of GFR in O than in Y. In two further groups, two different scavengers of oxygen-free radicals, dimethylthiourea (DMTU) and superoxide dismutase (SOD), were administered at the time of arterial occlusion. DMTU had protective effects in Y but not in O (delta GFR was -28% and -72%, respectively); in contrast, SOD was more effective in O (delta GFR = -58%) than in Y rats (delta GFR = -40%). To test the hypothesis that such a difference was related to the capacity of SOD to increase the levels of nitric oxide (NO), four more groups of Y and O rats were pretreated with L-arginine (ARG), precursor of NO, in tap water (1.5%). No difference in renal dynamics was detected in basal conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional versus structural changes in the pathophysiology of acute ischemic renal failure in aging rats. 807 48

Previous experimental and human data suggests a detrimental effect on the course of acute renal failure related to exposure of blood to artificial dialysis membranes of poor biocompatibility. We performed a 2.5-year prospective randomized trial to compare the clinical course of acute renal failure (post-operative ischemic acute tubular necrosis, ATN) in patients receiving a cadaveric renal transplant requiring supportive hemodialysis in the immediate post-transplant setting. Patients were randomized to either a cuprophane or polymethylmethacrylate (PMMA) conventional hollow fiber dialyzer. All patients received a standard immunosuppressive regimen which included induction therapy with either horse anti-thymocyte gamma globulin (ATGAM) or the murine anti-CD3 monoclonal antibody (OKT3). Of 53 patients randomized, 17 were excluded (2 for intervening biopsy-proven rejection prior to recovery from ATN, 10 for primary graft nonfunction and 5 for other reasons), leaving 36 evaluable cases of uncomplicated ATN, 18 in each group. There was no difference by age, race, gender, cause of ESRD, immunosuppressive regimen, cold or warm ischemia time, use of pre-transplant dialysis, percent oliguria or the incidence of intra-dialytic hypotension between the 2 groups. There was no difference in the mean time to recovery from ATN posttransplant (8.9 days in the cuprophane group vs 9.5 days in the PMMA group, p = NS) or in the average number of hemodialysis treatments required (3.6 in both groups, p = NS). There was also no difference in long term allograft outcome in terms of the nadir serum creatinine, the number of episodes of subsequent acute rejection or in the development of chronic rejection. An intent-to-treat analysis of all 53 originally randomized patients similarly yielded no significant differences. A subsequent, non-randomized study using a membrane of intermediate biocompatibility (Hemophan) also showed no difference in recovery time from ATN. Bioincompatible membranes do not seem to have a significant clinical impact on the course of recovery of this form of acute renal failure. The striking benefits of biocompatibility in the course of ARF seen in other human trials may relate more to the non-renal systemic toxic effects of bioincompatibility.
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PMID:Biocompatible dialysis membranes and acute renal failure: a study in post-operative acute tubular necrosis in cadaveric renal transplant recipients. 898 57

Sternothyroid muscle biopsy specimens, obtained during tracheostomies from 15 patients with acute stroke and respiratory failure, were examined immunohistochemically to immunoreactivity to myoglobin (Mb). A marked decrease or lack of Mb immunoreactivity in association with hyaline degeneration was observed in 0.8 to 44.4% of the muscle fibers on both the paretic and non-paretic sides of all patients. The percentages of negative staining for Mb were less than 3.1% in 5 patients with acute respiratory failure due to causes other than stroke. The pattern and incidence of attenuated Mb immunoreactivity in the muscle fibers was found to be distinctively different in the two patients groups. In one group of 5 patients, a large number of muscle fibers (24.8 +/- 15.6%) had no Mb staining and were clearly bordered and grouped. In another 10-patient group, only a limited number of muscle fibers (3.3 +/- 2.5%) had no staining for Mb and these fibers were scattered. Four patients in the former group had catastrophic outcomes, while all the patients in the latter group survived. Ischemia, produced by an increase in catecholamines, and the consequent vasoconstriction, rather than hypoxemia seemed to be the cause of the negative immunoreactivity for Mb in the group pattern. In contrast, hypoxemia may have caused the scattered pattern of negative Mb immunoreactivity. It was concluded that negative immunostaining for Mb in muscle fibers represents a common and characteristic complication in acute stroke patients.
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PMID:Lack of immunoreactivity for myoglobin in skeletal muscle of acute stroke patients. 902 93

Partial liquid ventilation (PLV) using perfluorooctylbromide (PFOB) was studied for use in treating experimental animal models in which acute respiratory failure was caused by hypoxia, oleic acid lung injury, or saline lung lavage. Clinical trials are currently being conducted in the United States. We studied the effectiveness of PLV with PFOB in treating acute respiratory failure after ischemia reperfusion pulmonary injury in a rabbit model; left lung ischemia was induced with a hilar clamp. Ninety minute later, the clamp was removed for reperfusion. Fifteen Japanese white rabbits weighing from 2.5 to 3.2 kg were divided into three groups-conventional mechanical ventilation (CMV) after reperfusion, PLV after reperfusion and controls (conventional mechanical ventilation without ischemia reperfusion injury). In the PLV group, a dose of 7 ml/kg PFOB was administered through an endotracheal tube. In the CMV group, PaO2 value decreased to 79 +/- 13 mmHg 120 min after reperfusion, significantly lower than in the PLV group 404 +/- 70- or controls -494 +/- 61-. PaCO2 was significantly higher in the CMV group-61.9 +/- 14.4 mmHg- than in the PLV group-45.7 +/- 6.1- or controls-32.1 +/- 2.2. Peak airway pressure was slightly higher in the CMV group-19.0 +/- 4.9-than in the PLV group-18.2 +/- 5.4- or controls-16.2 +/- 1.8. mPAP/mSAP did not differ significantly among groups. The heart rate decreased in the CMV and PLV groups, but was unchanged in controls. Microscopic studies revealed markedly reduced alveolar hemorrhage, lung fluid accumulation, and inflammatory infiltration in the PLV group, compared to the CMV group. PLV thus is effective in improving gas exchange and preventing pulmonary injury in acute respiratory failure after ischemia reperfusion injury in a rabbit model.
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PMID:[Experimental study in partial liquid ventilation for acute respiratory failure after ischemia reperfusion pulmonary injury in a rabbit model]. 951 27

Fluorocarbons are characterized by exceptional chemical and biological inertness, extreme hydrophobicity, lipophobicity, high gas-dissolving capacities, low surface tensions, high fluidity and spreading coefficients, high density, absence of protons, and magnetic susceptibilities comparable to that of water. These unique properties are the foundation for a range of biomedical applications. An injectable fluorocarbon-in-water emulsion is in advanced clinical trials as a temporary oxygen carrier (blood substitute) to prevent tissue hypoxia or ischemia in the surgical and critical care patient. A liquid fluorocarbon is in Phase II/III clinical trials for treatment of acute respiratory failure through liquid ventilation. Several fluorocarbon-based contrast agents for ultra-sound imaging are in various stages of clinical investigation. Multiple families of well-defined pure fluorinated surfactants have recently been synthesized. These surfactants have a modular structure which allows stepwise adjustment of their physicochemical characteristics. Their polar head group derives from polyols, sugars, aminoacids, amides, amine oxides, phosphocholine, phosphatidylcholine, etc. Fluorinated surfactants are significantly more surface-active than their hydrocarbon analogs and they display a greater tendency to self-assemble, thus forming well-ordered, stable supramolecular assemblies such as vesicles, tubules, fibers, ribbons, etc. Fluorinated amphiphiles also allowed the obtaining of a variety of stable reverse and multiple emulsions and gels. These systems are being investigated as drug delivery devices.
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PMID:Fluorinated materials for in vivo oxygen transport (blood substitutes), diagnosis and drug delivery. 979 31

Without a doubt PEG-SOD has been the enzyme most studied in PEGylation. One can say that it represents the preferred model to assess chemistries for PEG activation, analytical procedures suitable for conjugate characterization, the influence of PEG size in conjugate removal from circulation and elimination of immunogenicity and antigenicity, and the effect of route of administration. The effect of PEG conjugation was studied in vitro and in vivo models in comparison with the free enzyme and the following conclusions may be drawn: (1) At the blood vessel level, PEG-SOD has been shown to provide a greater resistance to oxidant stress, to improve endothelium relaxation and inhibit lipid oxidation. (2) In the heart, PEG-SOD proved to be at least as effective as native SOD in treatment of reperfusion-induced arrhythmias and myocardial ischemia. (3) In the lung, PEG-SOD appeared to be able to reduce oxygen toxicity and E. coli-induced lung injury, but not in the treatment of lung physiopathology associated with endotoxin-induced acute respiratory failure and in the reduction of asbestos-induced cell damage. (4) On cerebral ischemia/reperfusion injuries the effect of PEG-SOD was uncertain, also due to the difficulty of cerebral cell penetration. (5) In kidney and liver ischemia both enzyme forms were found to ameliorate reperfusion damage. In view of so much positive research on PEG-SOD, it is surprising that no approved application in human therapy has been established and approved.
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PMID:Polyethylene glycol-superoxide dismutase, a conjugate in search of exploitation. 1205 16

The outcome of ischemic acute renal failure (IARF) is better in young than adult rats. Insulin-like growth factor I (IGF-I) treatment may increase mortality of adult rats with IARF, probably because of an exaggerated inflammatory response. We report the response to IGF-I therapy in young rats with IARF. Male rats, aged 28+/-1 days, with IARF were given subcutaneous IGF-I, 50 microg/100 g at 0, 8, and 16 h after reperfusion (IGF) or were untreated (ARF). Sham-operated rats were used as controls. At 2 and 7 days after ischemia, serum urea nitrogen and histological damage score, cell proliferation, apoptosis, neutrophil infiltration, and IGF-I receptor mRNA in kidneys were analyzed. The degree of renal failure, mortality rate, histological damage, cell proliferation, and neutrophil infiltration were not different between IGF-I and ARF rats. Hence, short-term IGF-I treatment did not modify the course of IARF in young rats.
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PMID:Insulin-like growth factor I administration in young rats with acute renal failure. 1247 49


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