Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of intravenous infusions of Escherichia coli endotoxin on white blood cell counts, hemodynamics, gas exchange, body temperature, and lung lymph flow were studied in chronically instrumented unanesthetized sheep. Six sheep received endotoxin (0.5 micrograms/kg) in the presence and absence of methylprednisolone treatment. Six sheep received the same dose of endotoxin with and without meclofenamate and methylprednisolone infusion. Endotoxemia caused an early increase in pulmonary artery pressure from 15.5 +/- 1.3 (mean +/- SEM) to 52.7 +/- 2.1 cmH2O (p less than 0.05), an initial phase of high flow of protein-poor lung lymph, an elevation in core body temperature, severe leukopenia, and an early increase in the alveolar to arterial oxygen difference (AaPO2) from 7.4 +/- 2.5 mmHg to 35.9 +/- 2.5 mmHg (p less than 0.05). From 2 to 5 h after endotoxin infusion, lung lymph flow averaged 4.8 times that of the baseline measurement, although lymph protein concentration relative to plasma was not different from the baseline measurement. Peripheral leukopenia and significantly increased AaPO2 (28.8 +/- 4.5 mmHg) persisted at 2 to 5 h. Methylprednisolone attenuated the early pulmonary artery hypertension (43.0 +/- 3.4 cmH2O), but did not inhibit the initial febrile response, severe leukopenia, or the early increase in AaPO2 (29.2 +/- 1.6 mmHg) in response to endotoxemia. Methylprednisolone did prevent the late phase increase in lung lymph flow, significantly attenuated the late phase leukopenia and hypoxemia (AaPO2, 13.3 +/- 5.9 mmHg), and attenuated accumulation of granulocytes in peripheral lung tissue throughout the endotoxin reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Modification of pulmonary responses to endotoxemia in awake sheep by steroidal and nonsteroidal anti-inflammatory agents. 639 8

In this double-blind randomized study, 19 patients with acute transmural myocardial infarction were treated with methylprednisolone administered 4.4 +/- 0.7 hours (+/- SEM) after the onset of chest pain, and were compared with 21 patients who received placebo 4.5 +/- 0.4 hours after the start of clinical symptoms. The two groups were comparable in reference to sex, prevalence of risk factors, clinical status on admission, location of myocardial infarction and magnitude of ischemic injury as assessed by standard ECGs and precordial ST-segment and QRS maps. The treated patients, however, were older than the patients who received placebo. Methylprednisolone in an i.v. dose of 2.0 g was administered on admission and a similar dose was infused 3 hours later. Placebo administration followed an identical schedule. Mortality, cardiac rupture, incidence of ventricular arrhythmias, blocks, extension of myocardial infarction, pericarditis, postinfarction chest pain, persistent ST-segment elevation at discharge, and change in Killip class during hospitalization were the same in both groups. Peak enzyme values, and changes in ECG variables pertaining to resolution of ST-segment elevation or development of QRS evolutionary alterations were similar in both groups. Follow-up for 6 months did not reveal any differences in the clinical course of the two groups. Methylprednisolone infused in a total dose of 4.0 g within 12 hours after the onset of chest pain in patients with acute transmural myocardial infarction does not result in any demonstrable beneficial or harmful effects.
 ...
PMID:Effects of methylprednisolone on the ischemic damage in patients with acute myocardial infarction. 704 10

Inflammatory islet damage mediated by cytokines and oxygen radicals may limit the success of clinical islet transplantation for treatment of insulin-dependent diabetes mellitus. In this study, we investigated whether drugs such as currently used in islet-transplanted patients inhibit the release of IL-1beta, TNFalpha, and superoxide from mononuclear blood cells in vitro. Methylprednisolone (10 microg/ml) inhibited the release of IL-1beta and TNFalpha, but had no effect on superoxide generation. Both pentoxifylline (66 microg/ml) and cyclosporin A (300 ng/ml) slightly inhibited TNFalpha release without affecting IL-1beta or superoxide generation. Nicotinamide (0.25 mM) did not interfere with the generation TNFalpha or superoxide and only slightly inhibited IL-1beta production. A combination of methylprednisolone, pentoxifylline, cyclosporin A, and nicotinamide (concentrations for each substance as described above) inhibited TNFalpha generation by 74+/-6% (mean value+/-SEM, mononuclear blood cells from seven diabetic patients) without affecting IL-1beta or superoxide generation. These data show that standard immunosuppressive therapy in islet transplanted patients may partially inhibit cytokine release but does not affect the generation of potentially islet-toxic superoxide from mononuclear cells.
 ...
PMID:Oxygen radical production in human mononuclear blood cells is not suppressed by drugs used in clinical islet transplantation. 993 Sep 44

We wished to evaluate whether inhibition of the systemic inflammatory response by a single pre-operative dose of methylprednisolone reduced markers of early endothelial damage after fast-track total knee arthroplasty. We randomly allocated 70 patients undergoing elective unilateral total knee arthroplasty (1:1) to receive either pre-operative intravenous methylprednisolone 125 mg (methylprednisolone group) or isotonic saline (control group). All procedures were performed under spinal anaesthesia without a tourniquet, using a standardised multimodal analgesic regime. The outcomes included changes in Syndecan-1 concentrations, a marker of glycocalyx degradation, markers of endothelial cell damage and activation (plasma soluble thrombomodulin and sE-Selectin), and permeability by vascular endothelial growth factor, as well as C-reactive protein concentrations. Blood samples were collected at baseline and 2 h, 6 h and 24 h after surgery, with complete sampling from 63 patients for analyses. Methylprednisolone significantly reduced markers of endothelial damage at 24 h following surgery compared with saline (methylprednisolone group vs. control group, adjusted means (SEM)) expressed by circulating Syndecan-1: 11.6 (1.0) ng.ml-1 vs. 13.4 (1.1) ng.ml-1 p = 0.046; soluble thrombomodulin: 5.1 (0.1) ng.ml-1 vs. 5.7 (0.2) ng.ml-1 , p = 0.009; sE-Selectin: 64.8 (1.8) ng.ml-1 vs. 75.7 (1.9) ng.ml-1 , p = 0.001, and vascular endothelial growth factor: 35.3 (2.7) ng.ml-1 vs. 58.5 (2.8) ng.ml-1 , p < 0.001. The effect of the intervention increased with time for soluble thrombomodulin, sE-Selectin and vascular endothelial growth factor, and was more pronounced in patients with high baseline values. Finally, methylprednisolone reduced the C-reactive protein response 24 h postoperatively; 31.1 (1.1) mg.l-1 vs. 68.4 (1.1) mg.l-1 , p < 0.001. Pre-operative administration of methylprednisolone 125 mg reduced circulating markers of endothelial activation and damage, as well as the systemic inflammatory response (C-reactive protein) early after fast-track total knee arthroplasty. These findings may have a positive effect on surgical outcome, but require studies in major surgery.
 ...
PMID:The effect of pre-operative methylprednisolone on early endothelial damage after total knee arthroplasty: a randomised, double-blind, placebo-controlled trial. 2874 57

Continuous monitoring of the intracranial pressure (ICP) detects impending intracranial hypertension resulting from the impaired intracranial volume homeostasis, when expanding volume generates pressure increase. In this study, cellular brain edema (CE) was induced in rats by water intoxication (WI). Methylprednisolone (MP) was administered intraperitoneally (i.p.) before the start of CE induction, during the induction and after the induction. ICP was monitored for 60 min within 20 h after the completion of the CE induction by fibreoptic pressure transmitter. In rats with induced CE, ICP was increased (Mean+/-SEM: 14.25+/-2.12) as well as in rats with MP administration before the start of CE induction (10.55+/-1.27). In control rats without CE induction (4.62+/-0.24) as well as in rats with MP applied during CE induction (5.52+/-1.32) and in rats with MP applied after the end of CE induction (6.23+/-0.73) ICP was normal. In the last two groups of rats, though the CE was induced, intracranial volume homeostasis was not impaired, intracranial volume as well as ICP were not increased. It is possible to conclude that methylprednisolone significantly influenced intracranial homeostasis and thus also the ICP values in the model of cellular brain edema.
 ...
PMID:Methylprednisolone modulates intracranial pressure in the brain cellular edema induced by water intoxication. 2935 78