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)

Ischemia of the intestines damages the permeability of the intestinal wall, allowing lipopolysaccharide (LPS) (endotoxin) to leak from the gut lumen into the blood circulation, causing shock and death. We measured LPS levels associated with corticosteroid treatment vs. no treatment in cats whose superior mesenteric artery had been occluded for 60 min. In untreated cats, the preocclusion mean plasma LPS concentration remained stable at 0.069 +/- 0.015 ng/ml. Toward the end of the occlusion period, mean plasma LPS rose to 0.239 +/- 0.032 ng/ml (p less than .01). Release of the clamp and reperfusion with oxygenated blood was followed within 20 min by a large rise in plasma LPS concentration to 0.825 +/- 0.11 ng/ml (p less than .01), which had returned to preocclusion levels about 80 min later. Methylprednisolone (30 mg/kg) was infused into a second group of cats 1.5 h before SMA occlusion. In these cats there was a complete inhibition of the LPS rise both during and after occlusion. These data suggest that the reported beneficial effect of corticosteroids in the treatment of septic shock may be mediated, in part, by reducing LPS leakage from the gut.
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PMID:Effect of corticosteroid prophylaxis on lipopolysaccharide levels associated with intestinal ischemia in cats. 375 30

The ability of a single large intravenous dose of methylprednisolone sodium succinate (MPSS: 15, 30, or 60 mg/kg) to modify the evolution of lumbar spinal cord ischemia in cats undergoing a contusion injury of 500 gm-cm is examined. Repeated measurements of spinal cord blood flow (SCBF) in the dorsolateral funiculus were made via the hydrogen clearance technique before and for 4 to 5 hours after injury. The mean preinjury SCBF for all animals was 12.29 +/- 0.77 ml/100 gm/min. Following injury, SCBF began to decrease progressively in vehicle-treated animals to a level of 7.71 ml/100 gm/min, a fall of 37.3%. In contrast, cats that received a 30-mg/kg intravenous dose of MPSS at 30 minutes after injury maintained SCBF within normal limits (p less than 0.05 at 3 and 4 hours after contusion). A 15-mg/kg MPSS dose was less effective at preventing posttraumatic white matter ischemia, and a 60-mg/kg dose was essentially ineffective. It was determined that the 30-mg/kg MPSS dose was optimal for supporting SCBF when the drug was given at 30 minutes after spinal trauma, and a second series of experiments was carried out to examine the ability of this dose, when given at longer latencies, to improve decreased flow. Methylprednisolone given at 1 1/2 hours after injury in four cats produced a slight (12.7%) but transient improvement in SCBF, and when administered at 4 1/2 hours in another three animals was totally ineffective. These results show that MPSS in a 30-mg/kg dose can prevent posttraumatic spinal cord ischemia. However, it would appear that the ability of the steroid to reverse the ischemia once it has developed is limited, and probably lost, within a few hours of onset. This further suggests that the ischemic process is irreversible and underscores the need for early treatment with a large MPSS dose in order to prevent full development of ischemia and to promote neurological recovery.
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PMID:Effects of a single large dose of methylprednisolone sodium succinate on experimental posttraumatic spinal cord ischemia. Dose-response and time-action analysis. 637 68

An experimental model of acute mesenteric ischemia following 85 minutes of superior mesenteric artery (SMA) occlusion in male Wistar rats was used in this investigation. Untreated control animals had a 48-hour survival rate of 38% (n = 26), whereas sham laparotomy resulted in a 100% 48-hour survival rate (n = 10). Study groups received intravenous infusions of normal saline solution (16.6 ml/kg/hr; n = 26) or similar volumes of normal saline solution with the addition of glucagon (1.6 micrograms/kg/min; n = 26), dopamine (3.2 micrograms/kg/min; n = 26), or prostacyclin (PGI2) (10.7 ng/kg/min; n = 26). Infusions were begun 15 minutes after initiating 85 minutes of SMA occlusion and were continued for a total of 90 minutes. Glucagon increased the 48-hour survival rate to 85%, significantly greater than both control survival (p less than 0.001) and normal saline solution group survival rates (p less than 0.025). Neither normal saline solution alone nor dopamine significantly increased the 48-hour survival rate, which was 54% in both groups. The PGI2 group survival rate, 65% at 48 hours, was significantly greater than the control rate (p less than 0.05), was not statistically different from the normal saline solution group survival rate, and was 20% less than the glucagon group survival rate, the latter difference approaching statistical significance (p = 0.10). Methylprednisolone (40 mg/kg; n = 26) administered as an intravenous bolus 15 minutes after initiating SMA occlusion significantly increased the 48-hour survival rate to 73% (p less than 0.01), whereas neither intravenous heparin (150 U/kg; n = 26) nor superoxide dismutase (11,900 U/kg; n = 26) were beneficial. Glucagon, methylprednisolone, and PGI2 improved the survival rate in this model of acute mesenteric ischemia.
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PMID:Pharmacologic interventions in acute mesenteric ischemia: improved survival with intravenous glucagon, methylprednisolone, and prostacyclin. 638 66

Decreasing progressive dermal ischemia after burning could theoretically limit the amount of skin necrosis to the zone of coagulation. Methylprednisolone, aspirin, indomethacin, imidazole, dipyridamole, and methimazole have been shown to prevent dermal ischemia, suggesting that prostaglandins and/or thromboxanes may play a role in its pathogenesis. Specific antiprostaglandin antibodies (anti-PgE2, PgF2 alpha, PgI2, and TxA2) were reacted with tissue biopsies of burned guinea pig skin at various time intervals postburn. An immunoperoxidase technique with goat anti-rabbit immunoglobulin and horseradish peroxidase demonstrated the presence of the specific arachidonic acid metabolites. The burned tissue showed high levels of PgE2 and TxA2. The effects of three thromboxane inhibitors, imidazole, methimazole, and dipyridamole, on dermal ischemia were studied. Xenon133 washout studies were performed in burned and unburned areas. Tissue half-life of Xenon was prolonged in burned, untreated areas but this rapidly decreased in antithromboxane-treated burns. Repeated antiprostaglandin and antithromboxane antibody-immunoperoxidase studies on tissue from the thromboxane inhibitor-treated animals showed that PgE2, PgF2 alpha, and PgI2 were at the same levels as in untreated animals, but thromboxane (TxA2) was essentially absent, suggesting that thromboxane may be responsible for the progressive dermal ischemia after burning and that decreasing its production can increase dermal perfusion.
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PMID:Increasing dermal perfusion after burning by decreasing thromboxane production. 699 4

The effect of methylprednisolone on the distribution of myocardial flow during ischemia and after reperfusion was determined in 10 treated and 11 control dogs. Methylprednisolone, 30 mg/kg, was administered iv after occlusion. Transmural blood flow and the endo/epicardial ratio in the normal and ischemic zones was measured by injecting 141Ce- and 85Sr-labelled microspheres after 90 min of ischemia and 30 min after reperfusion, respectively. During ischemia, transmural blood flow (ml g-1 min-1) in the ischemic zone was higher in treated animals than in controls (0.25 +/- 0.04 vs 0.15 +/- 0.03; P less than 0.05) but not different in the normal zone for both groups (1.36 +/- 0.14 vs 1.15 +/- 0.10; P greater than 0.05). The endo/epicardial ratio of the ischemic zone was low but similar for both groups during ischemia (0.43 +/- 0.07 vs 0.40 +/- 0.09; P greater than 0.05). After reperfusion, transmural blood flow increased significantly in treated (0.25 +/- 0.13 vs 1.36 +/- 0.13; P less than 0.0005) as well as in control animals (0.15 +/- 0.03 vs 1.63 +/- 0.14; P greater than 0.0005), reaching similar values (1.36 +/- 0.13 vs 1.63 +/- 0.14; P greater than 0.05). The endo/epicardial ratio also increased during reperfusion in both treated (0.43 +/- 0.07 vs 1.12 +/- 0.12; P less than 0.0005) and control animals (0.40 +/- 0.90 vs 1.03 +/- 0.19; P less than 0.025). These data show that although methylprednisolone-treated dogs had higher myocardial blood flow during ischemia, after reperfusion the increase in flow in the ischemic zone of treated and control dogs was of the same magnitude.
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PMID:Experimental myocardial infarction: effect of methylprednisolone on myocardial blood flow after reperfusion. 718 24

Rejection crises after kidney transplantation could be associated with individual variability of pharmacokinetic parameters of steroids. We therefore investigated the individual pharmacokinetics of methylprednisolone on day 2 (60 mg intravenously) and day 4 (60 mg per os) in 40 patients after kidney transplantation. Methylprednisolone was determined in serum by HPLC. Within 6 months, all rejection episodes were recorded and confirmed by kidney transplant biopsy. Values are given as nonparametric medians with the 95% confidence interval (0.95 CI). The 7 patients with a rejection within the first 10 days had a methylprednisolone clearance of 437 ml/min (162-756) that was significantly higher than the 220 ml/min (121-604) in the 22 patients without a rejection episode (P = 0.04). In the complete group of 18 patients having a transplant rejection episode within 6 months, the methylprednisolone elimination half-life after oral dosage was 2.5 hr (1.6-3.9) and significantly shorter than 2.9 hr (1.7-4.0) in 22 patients without rejections (P = 0.03). No differences were seen for body weight, number of mismatches, cold ischemia time, immunosuppressive regimens, and other pharmacokinetic parameters of methylprednisolone (e.g. bioavailability, distribution volume, trough levels). We conclude that pharmacokinetic variability may contribute to the lack of immunosuppressive efficacy in patients with a short halflife of steroids. Therefore, a twice daily dose fraction might be useful for low-dose steroid regimens in kidney transplantation.
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PMID:Pharmacokinetics of methylprednisolone and rejection episodes in kidney transplant patients. 765 60

Only limited therapeutic measures are currently available for the treatment of spinal cord injury. This review describes the pathologic mechanisms of trauma-induced spinal cord injury in rats, which will contribute to new understanding of the pathologic process leading to spinal cord injury and to further development of new therapeutic strategies. Spinal cord injury induced by trauma is a consequence of an initial physical insult and a subsequent progressive injury process that involves various pathochemical events leading to tissue destruction; the latter process should therefore be a target of pharmacological treatment. Recently, activated neutrophils have been shown to be implicated in the latter process of the spinal cord injury in rats. Activated neutrophils damage the endothelial cells by releasing inflammatory mediators such as neutrophil elastase and oxygen free radicals. Adhesion of activated neutrophils to the endothelial cell could also play a role in endothelial cell injury. This endothelial cell injury could in turn induce microcirculatory disturbances leading to spinal cord ischemia. We have found that some therapeutic agents that inhibit neutrophil activation alleviate the motor disturbances observed in the rat model of spinal cord injury. Methylprednisolone (MPS) and GM1 ganglioside, which are the only two pharmacological agents currently clinically available for treatment of acute spinal cord injury, do not inhibit neutrophil activation in this rat model. Taken together, these observations raise a possibility that other pharmacological agents that inhibit neutrophil activation used in conjunction with MPS or GM1 ganglioside may have a synergistic effect in the treatment of traumatic spinal cord injury in humans.
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PMID:Spinal cord injury in the rat. 977 Feb 43

To study the efficacy of methylprednisolone/vitamin E in reducing cerebral edema and improving the ultimate neuropathological outcome in perinatal cerebral hypoxia-ischemia, 40 seven-day postnatal rats were subjected to right common carotid artery ligation followed by exposure to 8% oxygen at 37 degrees C for 3 h. The animals were divided into groups. Twenty rat pups received an intraperitoneal injection of 30 mg/kg body weight methylprednisolone and vitamin E (100 U/kg) immediately following cerebral hypoxia-ischemia. Control animals received either no therapy (n = 10) or an equivalent volume of normal saline (n = 10). After 72 h of recovery from hypoxia-ischemia, the animals were killed and their brains were examined to measure the water contents in the right and left hemispheres (29 rat pups), whereas the others were killed at 21 days for neuropathological examination. Methylprednisolone/vitamin E-treated rats had significantly less water content in the right hemisphere (87.08 +/- 0.28%, mean +/- S.E.M.) than saline-treated animals (89.07 +/- 0.37%, mean +/- S.E.M., P < 0.0001). Methylprednisolone/vitamin E significantly reduced water content in the right hemisphere of the brain. Neuropathological study was performed on nine rat pups. The brains of four methylprednisolone/vitamin E- and five saline-treated pups were examined at the end of the 21-day recovery period. Two groups of the right cerebral cortex included thinning of the cortex. Significantly less damage was seen in the methylprednisolone/vitamin E-treated pups. Our study suggests that trials of methylprednisolone/vitamin E might be effective if they are given to the mother at risk of fetal hypoxia during labor or to the hypoxic infant right after delivery in preventing hypoxic brain damage.
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PMID:Methylprednisolone and vitamin E therapy in perinatal hypoxic-ischemic brain damage in rats. 1040 17

A 30-year-old healthy woman was involved in a road traffic accident. She sustained a fracture dislocation of T11/12 with a complete Frankel A paraplegia below T11. She had no associated injuries. High Dose Methylprednisolone was administered according to the NASCIS III protocol (48 h) together with low molecular weight Heparin and gastroprotected medication. Complete transection of the spinal cord and an anterior haematoma from T11 to T12 were confirmed on X rays, CT's and MRI scans. Posterior surgical stabilisation was performed using Isola instrumentation, starting 8 h post injury. Her post surgical period was uneventful except for some episodes of low blood pressure (85/60 mmHg) from which she had no symptoms. On the 12th post operative day, while in the physiotherapy department, she complained of right scapular pain. This occurred every time she was sat up and was associated with paraesthesia of both upper limbs. Two days later she deteriorated neurologically and her level ascended initially to T8 and then to T3. MRI of the spine with and without gadolinium showed spinal cord oedema between C3 and T1. There was no evidence of haemorrhage or syringomyelia. The authors discussed this case making different hypotheses. They are mainly the following: (1) Gradually ascending ischaemia due to a vascular disorder; (2) Double spinal trauma; (3) Ischaemia related to repeated hypotensive episodes; (4) Low grade intramedullary tumour; and (5) Thrombus of the Radicularis Magna artery. The case has been recognised as being very rare and interesting. In the conclusions, the presenting author stresses the importance of adopting MRI-compatible instrumentation for the surgical stabilisation of the spine, and careful monitoring of blood pressure during the acute phase of spinal cord injury. Dr Aito agrees with Mr El Masry about the opportunity of forming a group of clinicians in order to discuss protocols to cope with this devastating complication.
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PMID:Ascending myelopathy in the early stage of spinal cord injury. 1049 Aug 52

While experimental and clinical evidence indicates that in brain injury blood glucose increases with injury severity and hyperglycemia worsens neurological outcome, the role of blood glucose in secondary mechanisms of neuronal damage after acute spinal cord injury has not yet been investigated. Data from spinal cord ischemia models suggests a deleterious effect of hyperglycemia, likely due to enhanced lactic acidosis, which is primarily dependent on the amount of glucose available to be metabolized. The purpose of this study is to summarize preliminary experimental and clinical observations on the role of blood glucose in acute spinal cord injury. Between 1995 and 1996 we used the New York University (NYU) rat spinal cord injury model to test the following hypotheses: 1) Blood glucose levels increase with injury severity. 2) Fasting protects from hyperglycemia and prevents secondary damage to the spinal cord. 3) Postinjury-induced hyperglycemia (dextrose 5% 2 gm/Kg) enhances spinal lesion volume. From a clinical perspective, we reviewed blood glucose records of 47 patients admitted to the Department of Neurosrgery in Verona, between 1991 and 1995, within 24 hours of acute spinal cord injury in order to determine: a) the incidence of hyperglycemia (> 140 mg/dl); b) the correlation between blood glucose and injury severity; and c) the role of methylprednisolone in affecting blood glucose. Results indicate that in a graded spinal cord injury model: 1) Early after injury, more severe contusions support significantly higher blood glucose levels. 2) Fasting overnight does not directly affect spinal cord lesion volume but influences blood gases, and we observed that a slightly systemic acidosis plays a minor neuroprotective role. Fasting also ensures more consistent normoglycemic baseline blood glucose values. 3) Postinjury-induced moderate hyperglycemia (160-190 mg/dl) does not significantly affect spinal cord injury. In the clinical study, we observed that during the first 24 hours after spinal cord injury: a) Glycemia ranges between 90 and 243 mg/dl (mean value 143 mg/dl), and close to 50% of the patients present blood glucose values higher than normal. b) Methylprednisolone administration is not associated to significantly higher blood glucose levels. c) There is a trend for larger glucose rises with more severe injury.
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PMID:Role of glycemia in acute spinal cord injury. Data from a rat experimental model and clinical experience. 1066 21


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