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)

Inflammatory reactions induce the production of reactive oxygen species (ROS): the reverse sequence of these events is also true. Moreover, many components of these reactions interact with a synergistic effect. In this short comprehensive review we analyze some of these interactions which may have pathological effects. Inflammatory reactions are triggered off by exogenous or endogenous aggressions and are characterized by cellular and vascular events. The activated leucocytes leave the circulating blood and reach the site of the aggression where they release a large amount of ROS as well as the content of their granules. The granular content is made in a large part by molecules with killing and degradative activities such as myeloperoxidase, defensins, elastase, collagenase, cathepsins and lysozyme. The inflammatory reaction is beneficial for humans when its effects are limited to the pathogens. The insufficiency of a component of the inflammatory reaction such as the production of ROS which is seen, for example in chronic granulomatous disease, leads to severe and recurrent bacterial infections. In other situations inflammatory reactions are deleterious because they are directed against normal tissues instead or in addition to pathogens. In some cases the behaviour of the phagocytes is modified because they have been primed by inflammatory molecules such tumor necrosis factor, LPS, interleukins or interferons. Priming often leads to a decreased speed of locomotion of the leucocytes with an increased susceptibility to their stimuli. The combination of these effects leads to a premature release by the phagocytes of their killing and degradative factors. Production of ROS such as that seen during irradiation, drug metabolism, or ischemia followed by reperfusion for example, induces inflammatory reactions with a secondary amplification of ROS production. Acute ROS production can also lead to thrombosis, whereas chronic ROS production can induce a chronic inflammatory reaction of the endothelium with atherosclerosis as a possible consequence. Some examples are also given to show that ROS might control positively or negatively the activity of inflammatory molecules. The multiplicity of the cross reactions between ROS and inflammation allows to suggest that drugs that disconnect these two events might be therapeutically used.
 ...
PMID:[Reactive oxygen species and inflammation]. 801 8

In vivo administration of nonlethal doses of lipopolysaccharide (LPS) to rodents can result in protection from subsequent lethal doses of endotoxin or LPS. We have previously demonstrated that hepatic ischemia/reperfusion (I/R) results in a TNF-dependent lung and liver injury and we postulated that pretreatment with sublethal concentrations of LPS prior to hepatic I/R could be protective from this injury. To test this hypothesis, five groups of rats were studied. LPS-I/R received 25 micrograms of LPS i.v. 24 hr prior to I/R, VEH-I/R received an equivalent volume of vehicle iv 24 hr prior to I/R, LPS-LPS received 25 micrograms of LPS i.v. 24 hr prior to sham laparotomy at which time an additional 25 micrograms of LPS was given i.v., VEH-LPS received an equivalent volume of vehicle 24 hr prior to sham laparotomy and 25 micrograms of LPS i.v. immediately prior to sham laparotomy, and SHAM consisted of sham-operated control animals. Peak plasma tumor necrosis factor-alpha (TNF) levels occurred between 30 and 150 min of reperfusion: LPS-I/R = 778 +/- 150 pg/ml (n = 5), VEH-I/R = 145 +/- 46 pg/ml (n = 5), LPS-LPS = 970 +/- 716 pg/ml (n = 4), VEH-LPS = 15,949 +/- 10,937 (n = 5), and SHAM = 3 +/- 1 (n = 5). As previously demonstrated by other investigators, pretreatment with LPS decreases TNF release in response to a second dose of LPS; however, TNF release was increased following hepatic I/R in those animals pretreated with LPS (LPS-I/R vs VEH-I/R, P = 0.014).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:LPS pretreatment protects from hepatic ischemia/reperfusion. 807 80

Monoclonal antibody to tumor necrosis factor-alpha (TNFa-MAb), z8, was used to explore protective effect on multiple organ dysfunction caused by intestinal ischemia and reperfusion in rats. Systemic plasma TNF level rose rapidly after release of the clamp, on superior mesenteric artery, and reached peak level 2 hours later. Endotoxemia and bacteremia were associated with systemic TNF level, and portal endotoxin concentration increased significantly before elevation of TNF activity. Pretreatment with anti-TNFa antibody markedly attenuated the increase of TNF level and provided protection from the development of hypotension, vital organ dysfunction, and metabolic acidosis. As a result the survival rate in treatment group increased by 35.7%. Our results demonstrated that TNF might play an important role in mediating the pathophysiologic changes in the pathogenesis of multiple organ damage in this intestinal ischemia-reperfusion injury model, and monoclonal antibody to TNF offered significant protection against multiple organ dysfunction or failure after severe trauma.
 ...
PMID:[Protective effect of monoclonal antibody of tumor necrosis factor-alpha for vital organs in a model suffering from intestinal ischemia and reperfusion injury]. 811 80

The role of complement as potential activator for tissue macrophages and neutrophils was investigated in an experimental model of endotoxin-induced liver injury in male Fischer rats. Injection of Salmonella enteritidis endotoxin (1 mg/kg) into Corynebacterium parvum-pretreated animals (7 mg/kg; single dose 6 days before endotoxin) resulted in severe oxidant stress, as indicated by a 37-fold increase of plasma levels of glutathione disulfide (basal concentration, 0.36 +/- 14 mumol/L), accumulation of neutrophils in the liver (600 +/- 31 neutrophils/50 high-power fields) and liver injury (plasma ALT, 1184 +/- 185 U/l; necrosis; 19% +/- 3%) 10 hr after endotoxin. The oxidant stress induced by 1 mg/kg endotoxin in the C. parvum-treated animals was always significantly higher than that in control animals receiving the same dose of endotoxin. Inhibition of complement activation with the soluble complement receptor type 1 attenuated the oxidant stress and liver injury by 50% to 65% but had no effect on hepatic neutrophil accumulation or plasma tumor necrosis factor-alpha levels. Treatment with a monoclonal antibody directed against the alpha-chain of CD11b/CD18 adhesion proteins (clone 17), which was highly effective in attenuating ischemia-reperfusion injury in the liver by reducing the number of neutrophils and functionally inactivating these cells, neither protected against parenchymal cell injury nor affected hepatic neutrophil infiltration in the C. parvum model. We conclude that reactive oxygen derived from complement-stimulated macrophages is critical for the development of liver injury in the C. parvum/endotoxin model.
 ...
PMID:Contribution of complement-stimulated hepatic macrophages and neutrophils to endotoxin-induced liver injury in rats. 813 72

To reduce ischemia-reperfusion injury, a number of clinical lung transplant programs employ prostaglandin E1 (PGE1) or prostacyclin (PGI2) before donor lung flush and harvest. The effect of prostaglandins on the reperfusion component of this ischemia-reperfusion complex is unknown. We investigated the effect of PGE1 given only during the period of reperfusion, on ischemic lung injury in an in situ rabbit model. To examine the mechanisms involved, we measured pulmonary hemodynamics as well as myeloperoxidase, circulating platelet, and tumor necrosis factor (TNF) values. Two hours of warm ischemia of the left lung was produced in anesthetized New Zealand white rabbits. The animals were randomly allocated into four groups based on treatment received only during reperfusion: PGE1, PGI2, nitroprusside (NP), or no treatment (controls). After 2 h of reperfusion, PaO2 in the PGE1 group was significantly higher (423 +/- 52.7 mm Hg) than in all other groups (PGI2, 239 +/- 43.4, p < 0.05; NP, 146 +/- 14.2 p < 0.01; controls, 74 +/- 19.1 mm Hg, p < 0.01), despite similar pulmonary vascular resistance in the PGE1 and NP groups. Although lower than in the PGE1 group, PaO2 in the PGI2 group was still significantly higher than that in controls. Wet/dry lung weight ratios were significantly lower in the PGE1 and PGI2 groups (6.5 +/- 0.2 [p < 0.01] and 6.9 +/- 0.6 [p < 0.05], respectively, versus 8.2 +/- 0.1 in controls). There were no significant differences in plasma TNF levels, platelet sequestration across the lungs, or lung myeloperoxidase activity in the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Amelioration of post-ischemic lung reperfusion injury by prostaglandin E1. 821 43

Mechanisms of Mn-superoxide dismutase (Mn-SOD) expression in human umbilical endothelial cells were investigated by Northern blot analysis, enzyme-linked immunosorbent assay, and immunoelectron microscopy. The Mn-SOD in human endothelial cells was markedly induced by the cytokines tumor necrosis factor (TNF), interleukin-1, and lipopolysaccharide as well as by phorbol esters [12-O-tetradecanoylphorbol 13-acetate (TPA)]. The induction was partially blocked by dexamethasone and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, a potent inhibitor of protein kinase C (PKC). In endothelial cells in which PKC had been desensitized to TPA by pretreatment for 24 h, addition of TNF caused overexpression of Mn-SOD. These facts suggested that at least two separate signal-transducing pathways are involved in expression of the Mn-SOD gene. Immunoelectron-microscopic studies showed that Mn-SOD was localized to the mitochondrial matrix of the capillary vascular endothelial cells of cardiac tissues and cultured endothelial cells. Mn-SOD, which is normally abundant in endothelial cells relative to other cell types, may play an important protective role against stresses such as ischemia and inflammation.
 ...
PMID:Manganese-superoxide dismutase in endothelial cells: localization and mechanism of induction. 823 2

Effect of hepatic ischemia and reperfusion on hepatic regeneration after 70% partial hepatectomy was evaluated in rats. Total hepatic ischemia by portal triad cross clamping (15 minutes) and reperfusion (15 minutes) was repeated two times during partial hepatectomy in the PS, non-PS, and G groups. In the C group, partial hepatectomy was made as a control without ischemia and reperfusion. In order to evaluate the effect of portal pooling, portal systemic shunt (PS shunt) was made by splenic transposition to subcutaneous space in the PS group, and compared with the non-PS group. Gadolinium chloride (GdCl3), the selective blocker of Kupffer (K) cell, was intravenously administered to the rat in the G group. Hepatic regeneration rates, labelling index of liver cells, rates of bacterial infection of mesenteric lymph nodes (MLN), blood levels of endotoxin (Ex) and tumor necrosis factor-alpha (TNF) were compared. Hepatic regeneration at 28 days was suppressed by total hepatic ischemia in the non-PS group. Increased positive rates of MLN culture and blood levels of Ex showed bacterial translocation induced by the portal pooling during portal triad clamping. PS shunt reduced both bacterial translocation and the suppression of hepatic regeneration occurred in the PS group. Hepatic regeneration was not suppressed and blood TNF level did not increased in the G group by the inhibition of K cell function. In conclusion, repeated total hepatic ischemia and reperfusion induced portal pooling, bacterial translocation, and activated K cell, then inhibited hepatic regeneration after partial hepatectomy.
 ...
PMID:[Inhibitory effect of portal pooling, bacterial translocation, and Kupffer cell activation on hepatic regeneration after partial hepatectomy by repeated portal triad cross clamping in rats]. 828 11

The influences of body temperature (T), seasonal variation, antiserum of tumor necrosis factor (TNF), exogenous and endogenous antioxidants on the extent of renal injury in a rodent model were examined. Renal injury was induced by 15-45 min of renal vascular (arterial and venous) occlusion followed by 1-3 days of reperfusion in right-nephrectomized male rats. Plasma creatinine concentration (PC, a reflection of renal injury) was independent of T when T was within 35-40 degrees C (n = 8), but directly related to T when T was within 31-35 degrees C (n = 10). PCs in rats with renal insults performed during October, November and December were similar (600 mcM, n = 10-24), but were higher than that during April (380 mcM, n = 16). Neither TNF antiserum nor exogenous antioxidants (Trolox, ascorbic acid, phytic acid, U-78517F) reduce PC (n = 5-7). However, PC was lower in normal rats than vitamin E deficient rats when subjected to 45 min (329.1 +/- 93.6 mcM vs. 695.9 +/- 37.7 mcM, n = 5-6), but not to 15-30 min of ischemia. In conclusion, renal injury induced by ischemia/reperfusion was T- and season-dependent. An excess of exogenous antioxidants did not reduce, whereas a reduction in endogenous antioxidant vitamin E level enhanced, renal injury.
 ...
PMID:Rodent model of renal ischemia and reperfusion injury: influence of body temperature, seasonal variation, tumor necrosis factor, endogenous and exogenous antioxidants. 833 31

The role of tumor necrosis factor (TNF-alpha) was investigated in an anaesthetized rat model of coronary artery ligation (60 min) followed by reperfusion (60 min; MI/R). Sham operated rats were used as controls (Sham MI/R). Myocardial necrosis, myocardial myeloperoxidase activity (MPO; investigated as an index of leukocyte adhesion and accumulation), serum creatinphosphokinase (CPK) activity and serum and macrophage TNF-alpha were studied. Ischemia and reperfusion produced a marked myocardial injury, with enhancement of serum CPK levels and myocardial MPO activity in the area at risk and in the necrotic area. Furthermore, serum TNF-alpha was undetectable during the occlusion period, but increased significantly after release of the coronary artery. At the end of reperfusion, macrophage TNF-alpha was also enhanced. A passive immunization with a hyperimmune serum containing antibodies against murine TNF-alpha or administration of an inhibitor of TNF-alpha synthesis, such as cloricromene, significantly lowered myocardial necrosis, reduced the increase in serum CPK and decreased MPO activity in the area at risk and in the necrotic area. Finally, the administration of the specific anti-TNF-alpha antibodies neutralized the serum levels of TNF-alpha and the injection of cloricromene reduced both serum and macrophage TNF-alpha. These data are consistent with an involvement of TNF-alpha in myocardial ischemia-reperfusion injury and suggest that drugs capable of reducing TNF-alpha might represent a novel therapeutic approach to the treatment of myocardial reperfusion injury.
 ...
PMID:[Tumor necrosis factor in myocardial ischemia and reperfusion]. 838 76

The role of tumor necrosis factor-alpha was investigated in an anaesthetized rat model of coronary artery ligation (60 min) and reperfusion (MI/R). Sham-occluded rats (sham MI/R) were used as controls. Survival rate, myocardial necrosis, myocardial myeloperoxidase activity, serum creatinine kinase activity and serum and macrophage tumor necrosis factor-alpha were studied. Ischaemia-reperfusion injury significantly reduced survival rate (45%), produced marked myocardial injury, increased serum creatinine kinase activity and increased myocardial myeloperoxidase activity in the area-at-risk and in the necrotic area. Serum tumor necrosis factor-alpha was undetectable during the occlusion period, but increased significantly upon release of the coronary artery. At the end of reperfusion, macrophage tumor necrosis factor-alpha was also increased. Passive immunization with a hyperimmune serum containing antibodies against murine tumor necrosis factor-alpha significantly increased survival rate (80%), lowered myocardial necrosis, reduced the increase in serum creatinine kinase activity and decreased myeloperoxidase activity in the area-at-risk and in the necrotic area. These data are consistent with an involvement of tumor necrosis factor-alpha in myocardial ischaemia-reperfusion injury.
 ...
PMID:Tumor necrosis factor involvement in myocardial ischaemia-reperfusion injury. 839 37


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