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 beneficial effect of beta-blockade has been reported in acute myocardial ischemia as well as in the postinfarction period. Recent interest focused on the special effect of beta-blocking agents regarding the changes of lipid metabolism, free radical mediated reactions and arachidonic acid cascade. In previous experiments on dogs we have shown that ultrashort-acting beta-blocker (Brevibloc) could modify production of prostacyclin and thromboxane in ischemic heart tissue. The purpose of this study was to investigate the effect of Brevibloc on the function of isolated neutrophils and platelets during myocardial ischemia and reperfusion. In mongrel dogs the left descending coronary artery (LAD) was ligated for 1 or 2 hours followed by one hour reperfusion. Animals were divided into two groups: Group I control dogs (n = 21) no drugs were given; in Group II. (n = 20) short half-life beta-blocker esmolol HCl (Brevibloc) was administered intravenously. Polymorphonuclear leukocytes (PMN) were isolated from venous blood before and after LAD ligature and following reperfusion. Spontaneous and phorbol myrystate acetate (PMA) stimulated superoxide radical generation of isolated PMN was measured. Platelets were separated at the same periods and maximal aggregation was determined in platelet rich plasma (PRP) after stimulation with collagen, adrenaline and ADP. There was no spontaneous radical production of PMN neither in the control, nor in the Brevibloc treated animals. Neutrophil superoxide production after activation in Group I was 9.54 +/- 0.3 O2-/min/1.5 x 10(6) before LAD ligature, and significant elevation was present following one hour reperfusion (14.8 +/- 0.8 O2-/min/1.5 x 10(6)). Increased production of neutrophils was inhibited by beta-blocker therapy (9.32 +/- 1.05, 8.25 +/- 0.82 respectively). Collagen and ADP stimulated platelet aggregation increased more than 20% during ischemia in Group I, which elevated further after reperfusion. Administration of Brevibloc diminished maximal aggregation in both cases, after 1-2 hours of LAD ligature and after reperfusion, compared to the initial value. Our findings suggested that ultrashort-acting beta-blocker has in vivo inhibitory action on neutrophil superoxide generation and platelet aggregation influencing the pathological cellular interactions.
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PMID:Influence of the beta-blocker therapy on neutrophil superoxide generation and platelet aggregation in experimental myocardial ischemia and reflow. 858 3

Despite a relatively low incidence of serious side effects, fluoroquinolones and the fluoroquinolone pefloxacin have been reported to occasionally promote tendinopathy that might result in the complication of spontaneous rupture of tendons. In the present study, we investigated in rodents the intrinsic deleterious effect of pefloxacin (400 mg/kg of body weight) on Achilles tendon proteoglycans and collagen. Proteoglycan synthesis was determined by measurement of in vivo and ex vivo radiosulfate incorporation in mice. Collagen oxidative modifications were measured by carbonyl derivative detection by Western blotting. An experimental model of tendinous ischemia (2 h) and reperfusion (3 days) was achieved in rats. Biphasic changes in proteoglycan synthesis were observed after a single administration of pefloxacin, consisting of an early inhibition followed by a repair-like phase. The depletion phase was accompanied by a marked decrease in the endogenous serum sulfate level and a concomitant increase in the level of sulfate excretion in urine. Studies of ex vivo proteoglycan synthesis confirmed the in vivo results that were obtained. The decrease in proteoglycan anabolism seemed to be a direct effect of pefloxacin on tissue metabolism rather than a consequence of the low concentration of sulfate. Pefloxacin treatment for several days induced oxidative damage of type I collagen, with the alterations being identical to those observed in the experimental tendinous ischemia and reperfusion model. Oxidative damage was prevented by coadministration of N-acetylcysteine (150 mg/kg) to the mice. These results provide the first experimental evidence of a pefloxacin-induced oxidative stress in the Achilles tendon that altered proteoglycan anabolism and oxidized collagen.
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PMID:Pefloxacin-induced achilles tendon toxicity in rodents: biochemical changes in proteoglycan synthesis and oxidative damage to collagen. 1072 83

The loss of microvascular basal lamina antigen is known to be a consequence of cerebral ischemia, but little information is available on its role in traumatic brain injury (TBI). The aim of our study was (1) to test the hypothesis that there is damage to the basal lamina of brain microvasculature after TBI, (2) to localize microvascular damage, and (3) to compare this loss with that in ischemia. Rats (n=14) were either sham operated (n=5) or subjected to fluid percussion injury (n=9; TBI=1.5 atm) and killed after 0 (n=5, sham), 12 (n=4), or 24 h (n=5). Collagen-type-IV immunoreactivity and a digital image-processing system were used to localize and quantify the number of stained vascular elements and the total collagen stained area. Western blot was used to compare collagen-type-IV content on the traumatic and nontraumatic brain side. The cortex of animals subjected to TBI and killed after 24 h showed a reduction in the area of stained collagen amounting to 19+/-4% (p<0.009) and a reduction in the total number of microvessels identified by collagen stain (29+/-6%; p<0.02). The Western blot revealed a 31+/-6% (p<0.03) reduction of collagen, compared to the mirror cortical area after 24 h. No significant reduction was found in the group that survived 12 h or in basal ganglia in both groups. TBI causes microvascular basal lamina damage. Whereas TBI affected only cortical areas, cerebral ischemia also induced microvascular basal lamina damage in the basal ganglia. After 24 h, the extent of severe basal lamina damage due to TBI was less severe than in ischemia.
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PMID:Microvascular basal lamina antigen loss after traumatic brain injury in the rat. 1296 53

Kidney-targeted gene therapy could be an ideal treatment for renal diseases since the therapeutic molecule is limited in the kidney and the systemic effect may be minimized. The technical development of the gene delivery to kidney and the identification of the responsive gene for a particular disease encourage the challenge to hereditary diseases. Collagen type IV reassembling was reported to be succeeded in Alport syndrome model by introduction of exogenous COL4A5 gene. Many gene therapies are evaluated in various glomerulonephritis models and unilateral ureteral obstruction (UUO) model, and favorable results are accumulated. Transplant kidney is an ideal target for gene therapy, by which ischemia reperfusion, acute rejection and chronic allograft nephropathy can be treated. The importation of the novel technology, for example hybrid stem cell-gene therapy could promote the gene therapy of renal diseases toward clinical application.
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PMID:Gene therapy in renal diseases. 1508 90

We evaluated the antiplatelet effects of two classes of ATP-sensitive potassium channel openers (K(ATP) openers) on washed human platelets, and the study's emphasis was on the role of mitochondrial K(ATP) in platelet aggregation. Collagen-induced platelet aggregation was inhibited in a dose dependent manner by lemakalim and SKP-450, which are potent cardio-nonselective K(ATP) openers, and also by cardioselective BMS-180448 and BMS-191095 (IC50: 1,130, >1,500, 305.3 and 63.9 microM, respectively), but a significantly greater potency was noted for the cardioselective K(ATP) openers. The latter two K(ATP) openers also inhibited platelet aggregation induced by thrombin, another important blood-borne platelet activator, with similar rank order of potency (IC50: 498.0 and 104.8 microM for BMS-180448 and BMS-191095, respectively). The inhibitory effects of BMS-191095 on collagen-induced platelet aggregation were significantly blocked by a 30-min pretreatment of platelets with glyburide (1 microM) or sodium 5-hydroxydecanoate (5-HD, 100 microM), a nonselective and selective mitochondrial K(ATP) antagonist, respectively, at similar magnitudes; this indicates the role of mitochondrial K(ATP) in the antiplatelet activity of BMS-191095. However, glyburide and 5-HD had no effect when they were added to the platelet cuvette immediately prior to the addition of BMS-191095. These findings indicate that cardioselective mitochondrial K(ATP) openers like BMS-191095 are able to exert cardioprotective effects in cardiac ischemia/reperfusion injury via dual mechanisms directed at the inhibition of platelet aggregation and the protection of cardiomyocytes, and both these mechanisms are mediated by mitochondrial K(ATP).
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PMID:BMS-191095, a cardioselective mitochondrial K(ATP) opener, inhibits human platelet aggregation by opening mitochondrial K(ATP) channels. 1574 10

Extracellular matrix (ECM) metabolism and homeostasis is sensitive to changes in oxygen tension manifest in ischemia. We hypothesize that in chronically ischemic limbs, abnormalities in uninjured skin, secondary to hypoxia, predispose to dermal breakdown. Paired biopsies of uninjured distal ischemic and proximal non-ischemic skin were harvested at below knee amputation from 14 patients with peripheral vascular disease following quantification of ischemia. Age- and site-matched controls were taken at total knee replacement (TKR) and varicose vein (VV) operations. Matrix metalloproteinase (MMP)-2 and -9 expression was determined using gelatin zymography, MMP-1 by western blotting and ELISA and tissue inhibitor of MMP (TIMP) by reverse zymography. Collagen content was measured by determining hydroxyproline levels, and collagen type I synthesis by ELISA. Collagen type I synthesis was upregulated in ischemic tissue compared with non-ischemic matched pairs (p<0.001) and both TKR and VV controls, however, there was no increase in collagen deposition. Levels of MMP-2 (p<0.0005) and TIMP-2 (p<0.01), were elevated in ischemic samples. MMP-9 was unaltered, signifying no inflammatory changes. Tissue ischemia was linked to elevated ECM turnover, associated with matrix failure when compounded with problems of matrix stabilization, likely in ischemia. This represents a potential mechanism for ulcer formation.
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PMID:Abnormal extracellular matrix metabolism in chronically ischemic skin: a mechanism for dermal failure in leg ulcers. 1609 24

Oxygen free radicals are important components involved in pathophysiological tissue alteration observed during ischemia/reperfusion (I/R). This study was designed to determine the possible protective effect of aqueous garlic extract (AGE) on renal I/R injury. Wistar albino rats were unilaterally nephrectomized and subjected to 45 minutes of renal pedicle occlusion followed by 6 hours of reperfusion. AGE (1 mL/kg, i.p., corresponding to 500 mg/kg) or vehicle was administered twice: 15 minutes prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion period, rats were killed by decapitation. Kidney samples were taken for histological examination or determination of levels of free radicals; renal malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration. Renal tissue collagen content, as a fibrosis marker, was also determined. Creatinine and urea concentrations in blood were measured for the evaluation of renal function. The results revealed that I/R-induced nephrotoxicity, as evidenced by increases in blood urea and creatinine levels, was reversed by AGE treatment. The levels of free radicals, as assessed by the nitro blue tetrazolium test, were increased. Moreover, the decrease in GSH levels and the increases in MDA levels and MPO activity induced by I/R indicated that renal injury involves free radical formation. Treatment of rats with AGE (1 mL/kg) restored the reduced GSH levels, while it decreased free levels of radicals and MDA as well as MPO activity. Collagen contents of the kidney tissues increased by I/R were reversed back to the control levels with AGE. Since AGE administration reversed these oxidant responses and improved renal function and damage at the microscopic level, it seems likely that AGE protects kidney tissue against I/R-induced oxidative damage.
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PMID:Protective effect of aqueous garlic extract against renal ischemia/reperfusion injury in rats. 1617 41

Estrogen's prothrombotic effects are of increasing concern, particularly in stroke risk and recovery. Using an ischemic rodent model, the authors sought to determine (a) if estrogen replacement increases postischemic platelet reactivity, (b) if changes in estrogen status alter intraplatelet endothelial nitric oxide synthase (eNOS) synthesis, and (c) if estrogen-mediated effects on platelets alter cerebral blood flow during reperfusion. Intact (I), ovariectomized (OVX), and OVX + 17 beta-estradiol (E50) rats were subjected to 30 min of forebrain ischemia and 60 min of reperfusion. Using the platelet activation marker P-selectin, postischemic platelet reactivity was quantified by flow cytometry. In a separate cohort (I, OVX, E50), the authors quantified platelet eNOS by Western blot. Another cohort (OVX, E50) was subjected to ischemia/reperfusion, and cerebral blood flow was determined using the iodoantipyrine technique. Collagen-stimulated platelet P-selectin expression was increased in the OVX rats at 60 min of reperfusion, and this effect was reversed by estrogen treatment. No differences in platelet eNOS expression were detected among groups. Cerebral blood flow at 60 min reperfusion was comparable between the OVX and the E50 rats. The authors conclude that during reper-fusion, estrogen deficiency increases postischemic platelet sensitivity to stimuli in estrogen-deficient rats. Estrogen treatment mitigates effects of estrogen loss on platelets, but this early effect is apparently not caused by intraplatelet eNOS depression. Neither estrogen deficiency nor estrogen treatment changes early postischemic regional brain blood flow. In this rodent global cerebral ischemic model, physiologic doses of estrogen are not deleterious to platelet reactivity and may initially reduce postischemic platelet reactivity.
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PMID:Effects of estrogen on platelet reactivity after transient forebrain ischemia in rats. 1626 75

Efficient islet isolation depends on the use of collagenase to digest the extracellular matrix within the islet-exocrine interface, the molecular structure of which is poorly understood. Recently it has been reported that transplantable yields of islets can be isolated from the tail segment of the pancreas alone. This study aimed to quantify and compare the amount of collagenase-resistant collagen VI within the islet-exocrine interface of the head, body, and tail of the human pancreas. Human adult pancreata (n = 5) were retrieved from heart-beating donors (age range, 40-62 years; cold ischemia times <10 hours). Tissue blocks from the head, body, and tail region of each pancreas were fixed in formalin and processed for immuno-labelling of collagen VI, which was quantified in the islet-exocrine interface using a Zeiss KS-400 image analysis system. Data were expressed as area of collagen at the interface relative to the islet area. Statistical analysis was done using paired t test. The mean islet areas in the head, body, and tail regions were not significantly different. Collagen VI was uniformly present within the islet-exocrine interface of all regions of the pancreas and was 0.326 +/- 0.064, 0.324 +/- 0.060, and 0.334 +/- 0.052 microm(2)/islet area (P = .441) in the head, body, and tail, respectively. The content of collagen VI within the islet-exocrine interface was uniform throughout all parts of the adult pancreas. Targeting this collagen subtype with novel collagenase blends may result in consistently improved islet yields and enable a wider number of available donor pancreata to be used.
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PMID:Comparison of the collagen VI content within the islet-exocrine interface of the head, body, and tail regions of the human pancreas. 1629 23

Transient ischemia has been shown to damage the basal lamina of the cerebral microvasculature. Other studies proved statins to be beneficial to non-cerebral microvessels. The aim of this study was to determine whether pravastatin pretreatment ameliorates microvascular basal lamina damage following transient ischemia. Using the suture model, we subjected 15 rats to focal ischemia (3 h) and reperfusion (24 h). Rats received pravastatin (20 mg/kg/day) or saline for 4 weeks prior to the experiment. The outcome was determined by a behavior test and the infarct size. Collagen type IV, a marker for an intact basal lamina, and hemoglobin extravasation were measured by Western blot analysis. A ratio (in percentage) between ischemic and contralateral hemispheres was calculated. Pravastatin pretreatment resulted in a significantly better neurological outcome and reduced infarct size (15 +/- 0.5 and 59 +/- 10 mm(3), respectively) compared with controls (12.25 +/- 0.4 and 167 +/- 13 mm(3), respectively, P < 0.01 for both). In controls, loss of collagen type IV was seen in the basal ganglia and in the cortex (43 +/- 4 and 64 +/- 5%, respectively). Pravastatin prevented significant collagen loss (basal ganglia: 106 +/- 17%; cortex: 112 +/- 14%, P < 0.01 for both) and significantly reduced the hemoglobin extravasation compared with controls in the basal ganglia (198 +/- 49 vs. 553 +/- 47%, P < 0.01). Pravastatin pretreatment resulted in a reduction of microvascular basal lamina damage and hemoglobin extravasation following transient ischemia. Pravastatin seems to protect the cerebral microvascular system.
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PMID:Pravastatin reduces microvascular basal lamina damage following focal cerebral ischemia and reperfusion. 1683 38


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