Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the role of copper as a potential mediator of postischemic reperfusion injury in the isolated, perfused rat heart. Hearts were equilibrated with Krebs-Henseleit buffer for 10 minutes and then loaded with copper by way of perfusion with buffer containing 20 microM copper(II)-bis-histidial for 30 minutes. Control hearts were perfused with Krebs-Henseleit buffer alone during the loading period. Hearts than were washed with buffer for 10 minutes and subjected to 20 minutes of normothermic global ischemia followed by 30 minutes of reperfusion. Atomic absorption spectroscopy revealed a 67% increase in total copper content in loaded hearts by the end of the wash. By the end of the 30-minute period of reperfusion, control hearts demonstrated a 50-60% recovery of myocardial function as determined by peak systolic pressure, contractility, and heart rate. In contrast, copper-loaded hearts exhibited virtually no functional recovery within the 30-minute time period. Using salicylate as a probe, we determined that peak and duration of .OH formation appears to be increased in copper-loaded hearts during reperfusion. Furthermore, efflux of lactic dehydrogenase was significantly increased in copper-loaded hearts. Our results clearly demonstrate that increasing cardiac content of copper results in enhanced postischemic reperfusion injury associated with increased formation of .OH, thus suggesting an important catalytic role for this transition metal.
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PMID:Copper loading of hearts increases postischemic reperfusion injury. 187 80

Recent studies of interventional therapy by way of the coronary venous system have demonstrated that it can protect acutely ischemic myocardium. To evaluate the efficacy of coronary venous retroinfusion compared with systemic intravenous administration of recombinant tissue-type plasminogen activator (rt-PA), 14 dogs were studied with a copper coil-induced thrombus in the left anterior descending coronary artery. The rt-PA (24,000 fluorescence units/kg) was administered continuously, either intravenously (n = 8) or retrogradely (n = 6), for 30 min beginning 60 min after coronary occlusion. Thrombolysis was determined by repetitive coronary angiography. All dogs were killed 3 h after termination of rt-PA infusion and infarct size was measured by the triphenyltetrazolium chloride staining technique. Complete thrombolysis occurred in five of the six dogs in the retroinfusion group and four of the eight dogs in the systemic intravenous infusion group. Partial lysis was achieved in two dogs treated by intravenous infusion. Lysis did not occur in one dog treated with retroinfusion and in two dogs treated with intravenous infusion. Time to thrombolysis was 13.4 +/- 2.3 min in the retroinfusion group versus 27.8 +/- 4.8 min in the intravenous group (p less than 0.001). Myocardial functional recovery in the ischemic zone measured by two-dimensional echocardiography 60 min after reperfusion was significant only in the retroinfusion group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Retrograde coronary venous administration of recombinant tissue-type plasminogen activator: a unique and effective approach to coronary artery thrombolysis. 190 6

The efficacy of coronary venous retroinfusion vs intravenous administration of streptokinase was compared in 20 closed chest dogs with copper coil induced thrombosis of the left anterior descending coronary artery. Streptokinase was continuously infused for 60 min (100 IU kg-1 min-1) starting 60 min after coronary artery occlusion. Time to clot lysis was determined by coronary angiography performed at 5 min intervals. Complete lysis occurred in eight out of 10 dogs receiving intravenous streptokinase and in all 10 dogs in the coronary venous group. Time to thrombolysis was significantly shorter with coronary venous retroinfusion (23 +/- 8 min) than after systemic infusion (62 +/- 26 min; P less than 0.001). Recovery of ischaemic zone left ventricular systolic function, studied by two-dimensional echocardiography, was significantly better in the animals that received retrograde streptokinase than in the group that received intravenous streptokinase (17 +/- 12% vs -2 +/- 16%; P less than 0.05). Myocardial necrosis expressed as a percentage of the risk area was 8 +/- 12% after retroinfusion of streptokinase compared with 32 +/- 25% (P less than 0.005) after intravenous administration. In conclusion, coronary venous administration of streptokinase was more effective than intravenous therapy as determined by more rapid clot lysis which resulted in improved functional recovery of the ischaemic myocardium and a significant reduction in myocardial necrosis.
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PMID:More rapid thrombolysis with coronary venous retroinfusion of streptokinase compared with intravenous administration. An experimental study in canines. 226 44

On the basis of experiments with 42 rats, quantitative statements are made regarding the influence of surface area and dwelling time of intravitreal copper particles on the electroretinogram. The influence of these factors on the extent of recovery of function after extraction of the foreign body is demonstrated. The rate of mental intoxication (metallosis retinae) is indicated separately from the mechanical damage. Ophthalmoscopic findings are also described. The practical relevance of these results to the clinical situation is discussed in detail in connection with earlier reports.
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PMID:[Regeneration capacity in retina and vitreous body changes following extraction of intravitreal copper particles]. 353 94

The use of salicylate as a chemical trap for .OH represents a simple and convenient alternative to the use of spin trapping techniques to study oxidative injury in isolated perfused organs. In these systems, salicylate is included in the perfusion buffer at concentrations ranging from 0.1 to 2 mM depending on the detection apparatus employed. In our studies, we have used a coulometric detector, which has a theoretical efficiency of 100% as compared to 1-5% for the standard glassy carbon electrode. We have been able to generate reproducible results by inclusion of only 100 microM salicylate, a concentration demonstrated not to affect pre- or post-ischemic cardiac function. In initial studies, we observed an increase in perfusate 2,5-dihydroxybenzoic acid consistent with an early post-ischemic burst of .OH, not unlike that reported using spin trapping techniques. Since then we and others have used this technique to examine possible relationships between .OH formation and treatments that alter post-ischemic cardiac functional recovery. For example, preischemic loading of hearts with copper results in increases in post-ischemic dysfunction and LDH release that were associated with an increase in 2,5-dihydroxybenzoate and by inference, .OH formation. Alternatively, we have reported that the nitroxide spin label, TEMPO, reputed to be a superoxide dismutase mimetic, decreased post-ischemic arrhythmias and 2,5-dihydroxybenzoate formation. Most recently, we have observed that preischemic loading of hearts with zinc-bis-histidinate results in improved post-ischemic cardiac function and decreased LDH release; changes that were associated with decreased 2,5-dihydroxybenzoate formation. These studies indicate that under certain conditions, salicylate is a valuable alternative to spin trapping techniques to probe the role of .OH in cardiac oxidative injury, particularly when applied to the isolated perfused heart preparation.
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PMID:Salicylate trapping of .OH as a tool for studying post-ischemic oxidative injury in the isolated rat heart. 783 50

Dietary copper deficiency affects a number of enzymes, the function of which may influence the outcome of myocardial ischemia-reperfusion injury. Male weanling rats were fed diets that were adequate (> 5 mg/kg) or deficient (< 1 mg/kg) in copper. After 4 wk, the rats' hearts were isolated and used to study the effects of ischemia-reperfusion on intraventricular developed pressure (DevP), positive and negative rates of intraventricular pressure change (+dp/dt and -dp/dt) and release of lactate dehydrogenase and creatine kinase from the heart. The ischemia-perfusion protocol included a 15-min equilibration period, 30 min of warm, total ischemia and reperfusion for 30 min. Preischemic hearts from copper-deficient rats produced lower DevP than hearts from copper-adequate rats at all levels of preload. However, postischemic recovery of DevP was significantly greater in the hearts of the copper-deficient group. Furthermore, the postischemic patterns of lactate dehydrogenase and creatine kinase release in the two groups were significantly different. These findings indicate that, although dietary copper deficiency adversely affects a number of enzymatic systems, the functional recovery of hearts subjected to ischemia-reperfusion injury is improved when the diet is restricted in copper.
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PMID:Isolated hearts from copper-deficient rats exhibit improved postischemic contractile performance. 822 93

The relationships between bacterial community diversity and stability were investigated by perturbing soils, with naturally differing levels of diversity, to equivalent toxicity using copper sulfate and benzene. Benzene amendment led to large decreases in total bacterial numbers and biomass in both soils. Benzene amendment of an organo-mineral/improved pasture soil altered total soil bacterial community structure but, unlike amendment of the mineral/arable soil, maintained genetic diversity, based on polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis targeting DNA and RNA, until week 9 of the perturbation experiment. Assuming equivalent toxicity, the genetic diversity of the naturally more diverse soil was more resistant to benzene perturbation than the less diverse soil. The broad scale function (mineralization of 14C-labelled wheat shoot) of both benzene- and copper-treated soil communities was unaffected. However, narrow niche function (mineralization of 14C-labelled 2,4-dichlorophenol) was impaired for both benzene-polluted soils. The organo-mineral soil recovered this function by the end of the experiment but the mineral soil did not, suggesting greater resilience in the more diverse soil. Despite a large reduction in bacterial numbers and biomass in the copper-treated soils, only small differences in bacterial community diversity were observed by week 9 in the copper-polluted soils. The overall community structure was little altered and functionality, measured by mineralization rates, remained unchanged. This suggested a non-selective pressure and a degree of genetic and functional resistance to copper perturbation, despite a significant reduction in bacterial numbers and biomass. However, initial shifts in physiological profiles of both copper-polluted soils were observed but rapidly returned to those of the controls. This apparent functional recovery, accompanied by an increase in culturability, possibly reflects adaptation by the surviving communities to perturbation. The findings indicate that, although soil communities may be robust, relationships between diversity and stability need to be considered in developing a predictive understanding of response to environmental perturbations.
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PMID:Bacterial diversity promotes community stability and functional resilience after perturbation. 1568 91

Peripheral nerve injury (PNI) produces functional changes in lesioned neurons in which oxidative stress is considered to be the main cause of neuronal damage. As superoxide dismutase (SOD) is an important antioxidative enzyme involved in redox regulation of oxidative stress, the present study determined whether melatonin would exert its beneficial effects by preserving the SOD reactivity following PNI. Adult rats subjected to hypoglossal nerve transection were intraperitoneally injected with melatonin at ones for 3, 7, 14, 30 and 60 days successively. The potential neuroprotective effects of melatonin were quantitatively demonstrated by neuronal nitric oxide synthase (nNOS), mitochondrial manganese SOD (Mn-SOD), and cytosolic copper-zinc SOD (Cu/Zn-SOD) immunohistochemistry. The functional recovery of the lesioned neurons was evaluated by choline acetyltransferase (ChAT) immunohistochemistry along with the electromyographic (EMG) recordings of denervation-induced fibrillation activity. The results indicate that following PNI, the nNOS immunoreactivity was significantly increased in lesioned neurons peaking at 14 days. The up-regulation of nNOS temporally coincided with the reduction of ChAT and SOD in which the Cu/Zn-SOD showed a greater diminution than Mn-SOD. However, following melatonin administration, the nNOS augmentation was successfully suppressed and the activities of Mn-SOD, Cu/Zn-SOD, and ChAT were effectively preserved at all postaxotomy periods. EMG data also showed a decreased fibrillation in melatonin-treated groups, suggesting a potential effect of melatonin in promoting functional recovery. In association with its significant capacity in preserving SOD reactivity, melatonin is suggested to serve as a powerful therapeutic agent for treating PNI-relevant oxidative damage.
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PMID:Melatonin preserves superoxide dismutase activity in hypoglossal motoneurons of adult rats following peripheral nerve injury. 1828 69

Multiple sclerosis is a neurodegenerative disease characterized by episodes of autoimmune attack of oligodendrocytes leading to demyelination and progressive functional deficits. Because many patients exhibit functional recovery in between demyelinating episodes, understanding mechanisms responsible for repair of damaged myelin is critical for developing therapies that promote remyelination and prevent disease progression. The chemokine CXCL12 is a developmental molecule known to orchestrate the migration, proliferation, and differentiation of neuronal precursor cells within the developing CNS. Although studies suggest a role for CXCL12 in oligodendroglia ontogeny in vitro, no studies have investigated the role of CXCL12 in remyelination in vivo in the adult CNS. Using an experimental murine model of demyelination mediated by the copper chelator cuprizone, we evaluated the expression of CXCL12 and its receptor, CXCR4, within the demyelinating and remyelinating corpus callosum (CC). CXCL12 was significantly up-regulated within activated astrocytes and microglia in the CC during demyelination, as were numbers of CXCR4+NG2+ oligodendrocyte precursor cells (OPCs). Loss of CXCR4 signaling via either pharmacological blockade or in vivo RNA silencing led to decreased OPCs maturation and failure to remyelinate. These data indicate that CXCR4 activation, by promoting the differentiation of OPCs into oligodendrocytes, is critical for remyelination of the injured adult CNS.
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PMID:CXCR4 promotes differentiation of oligodendrocyte progenitors and remyelination. 2067 29

The present study aimed at assessing the recovery of phototrophic and heterotrophic biofilm communities after a decrease in copper exposure. An original experiment was designed to evaluate the possible influence of non-exposed (i.e. pristine) communities (e.g. via immigration processes) in recovery dynamics. Laboratory channels were used to study the structural and functional changes in microbial communities after a 4-week Cu exposure period in the presence and absence of pristine biofilms. When pristine biofilms were present, phototrophic communities recovered within 6 weeks, both in terms of biomass, structure and photosynthetic activity. Recovery processes were also detected using the PICT approach. In contrast, in the absence of pristine communities, all of the Cu-induced changes recorded in the phototrophic communities remained throughout the recovery period. Regardless of the presence or absence of pristine biofilms, the decrease in Cu exposure did not abolish Cu-induced changes in bacterial community structure, whereas functional recovery (based on beta-glucosidase activity) was complete in both recovery contexts. These results revealed that microbial community response to a decrease in Cu exposure differs between phototrophic and heterotrophic communities. The presence of pristine communities greatly influences the structural and functional recovery of phototrophic communities, suggesting an important role of microbial immigration processes, but have far less influence on the recovery trajectory of heterotrophic communities.
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PMID:Structural and functional recovery of microbial biofilms after a decrease in copper exposure: influence of the presence of pristine communities. 2221 May


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