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

The bronchosecretolytic agent ambroxol added to histidine-tryptophan-ketoglutarate (HTK) solution has recently been shown to protect cold stored rat hepatocytes. The aim of the present study was to confirm these observations in a rat liver transplantation model. Before orthotopic liver transplantation, donor livers from 30 syngeneic Wistar rats were assigned to three groups (n = 10): (A) in situ flush (ISF) and 1/2-h cold storage (CS) with HTK solution, (B) ISF and 3-h CS with HTK, and (C) ISF and 3-h CS with HTK + 10(-3) mol/L ambroxol. The efficacy of the drug was evaluated by postoperative survival (> 14 days) and liver enzyme release (ALT), bile flow, histomorphological injury, and malondialdehyde (MDA) level in the grafts 15 min after reperfusion. After 1/2-h CS with HTK solution (A), 90% of the transplanted rats survived. In comparison with donor conditions, bile flow in the reperfused grafts decreased to 87 +/- 5.3%, whereas postoperative ALT levels slightly increased. After 3-h HTK preservation (B), the survival rate decreased to 60%, while ALT values markedly increased and bile flow after reperfusion declined to 82 +/- 6.6%. Ambroxol added to HTK solution (C) enhanced bile flow to 106 +/- 3.4%(p < .05), and reduced ALT and MDA levels and histomorphological injury of the transplanted livers, so that its beneficial effect in organ preservation has been confirmed in the transplant model. However, survival rate was not improved by the agent, probably because of the low cold ischemia tolerance of the Wistar rat livers used.
 ...
PMID:Protective effects of ambroxol in hypothermic liver preservation: a transplant study. 1099 99

Oxidative stress is a recognized factor of ischemia reperfusion injury. It shares damage of lipids (LPO) and proteins (PPO), and consequently might cause changes in activity of transport systems. Global 15 min ischemia followed by 2, 24 and 48 hour reperfusion was induced by four-vessel occlusion in Wistar rats of both sexes. Levels of TBARS and conjugated dienes as parameters of LPO were analyzed in forebrain homogenates. Concentrations of total free sulfhydryl (SH) groups and emission spectra of tryptophan were measured to quantify PPO. Our results indicate that lipid peroxidation and protein oxidation occurs mainly during the period of reperfusion. However, significant increase in the level of conjugated dienes can be detected already after 15 min ischemia. Attack of proteins by free radicals leads to modification in structure of proteins seen as a decrease of free SH groups and tryptophan fluorescence. Ischemia/reperfusion induces formation of lipid peroxidation products as well as protein modifications.
 ...
PMID:Ischemia/Reperfusion-induced oxidative stress causes structural changes of brain membrane proteins and lipids. 1198 52

Many neurodegenerative disorders and syndromes are associated with an excessive generation of reactive oxygen species (ROS) and oxidative stress. The pathways to nerve cell death induced by diverse potential neurotoxins such as peptides, excitatory amino acids, cytokines or synthetic drugs commonly share oxidative downstream processes, which can cause either an acute oxidative destruction or activate secondary events leading to apoptosis. The pathophysiological role of ROS has been intensively studied in in vitro and in vivo models of chronic neurodegenerative diseases such as Alzheimer's disease (AD) and of syndromes associated with rapid nerve cell loss as occuring in stroke. In AD, oxidative neuronal cell dysfunction and cell death caused by protofibrils and aggregates of the AD-associated amyloid beta protein (Abeta) may causally contribute to pathogenesis and progression. ROS and reactive nitrogen species also take part in the complex cascade of events and the detrimental effects occuring during ischemia and reperfusion in stroke. Direct antioxidants such as chain-breaking free radical scavengers can prevent oxidative nerve cell death. Although there is ample experimental evidence demonstrating neuroprotective activities of direct antioxidants in vitro, the clinical evidence for antioxidant compounds to act as protective drugs is relatively scarce. Here, the neuroprotective potential of antioxidant phenolic structures including alpha-tocopherol (vitamin E) and 17beta-estradiol (estrogen) in vitro is summarized. In addition, the antioxidant and cytoprotective activities of lipophilic tyrosine- and tryptophan-containing structures are discussed. Finally, an outlook is given on the neuroprotective potential of aromatic amines and imines, which may comprise novel lead structures for antioxidant drug design.
 ...
PMID:Oxidative nerve cell death in Alzheimer's disease and stroke: antioxidants as neuroprotective compounds. 1203 40

Mitochondrial respiratory function was studied in permeabilized pig liver biopsies. The cell membrane was permeabilized mechanically in tissue samples of 2-7 mg, for application of a standardized substrate/inhibitor titration protocol in high-resolution respirometry. Specific respirometric tests demonstrated complete plasma membrane permeabilization and accessibility of substrates to intact mitochondria. High respiratory adenylate control ratios and cytochrome c conservation in the tissue preparation were comparable or even better than in isolated mitochondria. Citrate synthase and cytochrome c oxidase activities remained at 85% of controls after up to 98 h storage of liver tissue at 0 degrees C in histidine-tryptophan-ketoglutarate solution. Multiple mitochondrial defects, however, were indicated after 48 h cold storage by the decline in respiratory capacity, which was lowered to a larger extent with complex I substrates compared to respiration with substrates for complex II or IV, measured in the absence of cytochrome c. After prolonged ischemia, the adenylate control ratio was significantly reduced, and cytochrome c depletion was detected by the stimulatory effect of cytochrome c. High-resolution respirometry allows the assessment of mitochondrial function in a few milligrams of permeabilized liver tissue, without isolation of mitochondria. This provides a basis for the analysis of mitochondrial function in human liver biopsies.
 ...
PMID:Evaluation of mitochondrial respiratory function in small biopsies of liver. 1205 47

Reduction of cerebral edema, an early symptom of ischemia, is one of the most important remedies for reducing subsequent chronic neural damage in stroke. Melatonin, a metabolite of tryptophan released from the pineal gland, has been found to be effective against neurotoxicity in vitro. The present study was aimed to demonstrate the effectiveness of melatonin in vivo in reducing ischemia-induced edema using magnetic resonance imaging (MRI). Rats were subjected to middle cerebral artery (MCA) occlusion/reperfusion surgery. Melatonin was administered twice (6.0 mg/kg, p.o.): just prior to 1 h MCA occlusion and 1 day after the surgery. T2-weighted multislice spin-echo images were acquired 1 day after the surgery. Increases in T2-weighted signals in ischemic sites of the brain were clearly observed after MCA occlusion. The signal increase was found mainly in the striatum and in the cerebral cortex in saline-treated control rats. In the melatonin-treated group, the total volume of cerebral edema was reduced by 45.3% compared to control group (P < 0.01). The protective effect of melatonin against cerebral edema was more clearly observed in the cerebral cortex (reduced by 56.1%, P < 0.01), while the reduction of edema volume in the striatum was weak (reduced by 23.0%). The present MRI study clearly demonstrated that melatonin is effective in reducing edema formation in ischemic animals in vivo, especially in the cerebral cortex. Melatonin may be highly useful in preventing cortical dysfunctions such as motor, sensory, memory, and psychological impairments.
 ...
PMID:Melatonin reduces cerebral edema formation caused by transient forebrain ischemia in rats. 1246 99

Melatonin, a pineal secretory product, synthesized from l-tryptophan, has received increased attention because of its antioxidative and immunomodulatory properties. It has been detected in the gut and shown to protect the gastric mucosa, and liver from acute damage, but the role of melatonin in the protection of the pancreas against acute inflammation is not clear. The aim of this study was to investigate the effects of melatonin and its precursor, l-tryptophan, on caerulein-induced pancreatitis (CIP) and on ischemia/reperfusion (I/R)-provoked pancreatitis in rats. CIP was induced by subcutaneous infusion of caerulein to the rats (25 microg/kg). I/R was induced by clamping of the inferior splenic artery for 30 min followed by 2 hr of reperfusion. Melatonin (10, 25 or 50 mg/hr) or l-tryptophan (50, 100 or 250 mg/kg) was given as a bolus intraperitoneal (i.p.) injection 30 min prior to the onset of pancreatitis. CIP and I/R were confirmed by histologic examination and manifested by typical pancreatic edema, by an increase of plasma levels of amylase (by 500% in CIP and by 40% in I/R) and the pro-inflammatory tumor necrosis factor alpha (TNFalpha) (by 500%). Lipid peroxidation products such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), were increased several fold in the pancreas CIP and I/R, whereas pancreatic blood flow (PBF) was significantly reduced in these animals. Pretreatment of rats subjected to CIP or to I/R with melatonin (25 or 50 mg/kg i.p.) or l-tryptophan (100 or 250 mg/kg i.p.) significantly reduced pancreatic edema, plasma levels of amylase and TNFalpha and diminished pancreatic MDA + 4-HNE contents, while enhancing PBF, pancreatic integrity and plasma levels of the anti-inflammatory interleukin 10 (IL-10). This was accompanied by a marked and dose-dependent rise of plasma melatonin immunoreactivity. Gene expression of N-acetyl transferase, an enzyme involved in melatonin biosynthesis, was detected in the pancreas of normal rats and was significantly enhanced in the rats with CIP. We conclude that exogenous melatonin, and that produced from l-tryptophan, attenuates pancreatic damage induced by CIP or by I/R and this effect may be attributable to the reduction in lipid peroxidation and TNFalpha release combined with an increase of plasma anti-inflammatory IL-10 in rats with acute pancreatitis.
 ...
PMID:Protective effect of melatonin and its precursor L-tryptophan on acute pancreatitis induced by caerulein overstimulation or ischemia/reperfusion. 1248 71

Celsior, a new preservation solution in thoracic organ transplantation was evaluated for efficacy in cold preservation of human hepatocytes and compared with University of Wisconsin solution (UW) and histidine-tryptophan-ketoglutarate solution (HTK, Custodiol). Human hepatocyte cultures were preserved at 4 degrees C in Celsior, UW and HTK for 2, 6, 12, 24 and 48 h with 6 h of reperfusion. Levels of lactate dehydrogenase (LDH; cell necrosis), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT; mitochondrial function), and adenosine 5'-triphosphate (ATP; loss of intracellular energy) were measured. Cell necrosis, mitochondrial dysfunction, and loss of ATP were significantly ( P<0.001, P<0.001, P<0.002, respectively) lower in Celsior than in HTK. The amount of cell necrosis and mitochondrial dysfunction in Celsior solution (CS) and UW was equal ( P=n.s.) up to 24 h and significantly lower in UW after 48 h ( P<0.001). Additionally, the intracellular level of ATP was significantly higher after ischemia ( P<0.001) and reperfusion from long-term ischemia (24, 48 h) ( P<0.002). We can conclude that Celsior was superior to HTK and equal to UW in the protection of human hepatocytes against cold preservation injury from ischemia and reperfusion. Furthermore, Celsior was effective in long-term preservation of human hepatocytes.
 ...
PMID:Celsior solution compared with University of Wisconsin solution (UW) and histidine-tryptophan-ketoglutarate solution (HTK) in the protection of human hepatocytes against ischemia-reperfusion injury. 1269 41

Melatonin, a pineal secretory product synthesized from tryptophan, has been found to be effective against neurotoxicity. The present study was aimed at demonstrating the effectiveness of melatonin in vivo in reducing ischemia-induced cerebral edema using magnetic resonance imaging (MRI). Rats were subjected to middle cerebral artery (MCA) occlusion/reperfusion surgery. Melatonin was administered twice (6.0 mg/kg, p.o.) just prior to 1 hr of MCA occlusion and 1 day after the surgery. T2-weighted multislice spin-echo images were acquired 1 day after the surgery. In the saline-treated control rats, increases in T2-weighted signals (water content) were clearly observed in the striatum and in the cerebral cortex. In the melatonin-treated group, total volume of edema was reduced by 51.6% compared with control group (P < 0.01). The protective effect of melatonin against edema was more clearly observed in the cerebral cortex (reduced by 59.8%, P < 0.01) than in the striatum (reduced by 34.2%, P < 0.05). Edema volume in a coronal slice was the greatest at the level of the bregma. Suppression of cerebral edema by melatonin was more effective posterior than anterior to the bregma. Melatonin appeared to reduce the volume of the edematous sites rather than to shift the signal intensity distribution. The present MRI study clearly demonstrates the effectiveness of melatonin against cerebral edema formation in ischemic animals in vivo, especially in the cerebral cortex. Melatonin may be highly useful in preventing cortical dysfunctions such as motor, sensory, memory, and psychological impairments associated with ischemic stroke.
 ...
PMID:Melatonin suppresses cerebral edema caused by middle cerebral artery occlusion/reperfusion in rats assessed by magnetic resonance imaging. 1467 26

Adenosine 5'-triphosphate (ATP) depletion is a major cause of cellular injury during ischemia and reperfusion in organ transplantation. Therefore, histidine-tryptophan-ketoglutarate solution (HTK; alpha-ketoglutarate) and University of Wisconsin solution (UW; adenosine) were supplied with energy substrates to achieve graft viability. Nevertheless, their efficacy for maintaining the ATP level, particularly in human liver endothelial cells, was uncertain. Furthermore, it is of interest whether a high ATP level is beneficial in human liver endothelial cell viability. We used human liver endothelial cells between the 3rd and 6th passages in a cell culture model. Human liver endothelial cells were exposed to hypothermic preservation (4 degrees C) in HTK and UW for 2, 6, 12, 24 and 48 h with subsequent reperfusion of 6 h. ATP and lactate dehydrogenase (LDH) were measured after each interval. In comparison to HTK, UW demonstrates a statistically significantly higher level of ATP after each interval of ischemia (p < 0.001) and reperfusion (p < 0.002). Additionally, UW-preserved human liver endothelial cells exceed the ATP level of the warm control during all intervals of ischemia. The loss of cell viability (LDH) was statistically significantly higher after ischemia (p < 0.01) and reperfusion (p < 0.01) in HTK than in UW except after the interval of 48 h. In conclusion, adenosine was more effective than alpha-ketoglutarate in maintaining a high ATP level in human liver endothelial cells after ischemia and reperfusion. Different pathways of energy substrate utilization were a contributing factor. The beneficial effect of the higher ATP level caused by adenosine to human liver endothelial cell viability was limited to 24 h of ischemia. Beyond this ischemia time we could not prove a favorable impact of adenosine on human liver endothelial cells.
 ...
PMID:Value of energy substrates in HTK and UW to protect human liver endothelial cells against ischemia and reperfusion injury. 1473 Feb 20

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.
 ...
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


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>