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)

Experiments with two models of intestinal ischemia were performed in order to examine the protective effect of dimethyl sulfoxide (DMSO). Segmental ischemia of the small intestine for 150 minutes caused necrosis of the affected bowel in 90% of the animals. Intravenous administration of DMSO or impregnation of the peritoneum with this substance prevented the development of gangrene in 28 of 29 rats. 30 or 60 minutes of complete ischemia of the small intestine, produced by clamping of the superior mesenteric artery, resulted in partial or complete necrosis of bowel segments with a high incidence of perforation and peritonitis and a high mortality rate within the first 24 hours. Intravenous DMSO, given upon declamping of the artery, effectively protected the bowel from the ischemic damage. There were no deaths among DMSO-treated animals and at 24 h there was no evidence of ischemic damage to the intestine. Though the exact mechanism of action of DMSO is unknown, the results of these and other experiments may warrant clinical trials especially in cases of mesenteric thrombosis.
 ...
PMID:The protective effect of dimethyl sulfoxide in experimental ischemia of the intestine. 657 85

Hyaluronidase has been shown clinically and experimentally to reduce the effects of tissue ischemia in myocardial infarction and hemorrhagic shock. Dimethyl sulfoxide (DMSO) has been shown to reverse the effects of cerebral ischemia in the primate model. A caudally based dorsal skin flap in the rat was used to study the effects of these two drugs in physiological doses on skin flaps, and to investigate their mechanisms of action. This study demonstrates that both hyaluronidase and DMSO, which are nontoxic in physiological doses, can increase the surviving length of an experimental skin flap. It is hypothesized that these substances exert their effect by decreasing tissue edema and by aiding in the transport of nutritive substances to the flap during its acute phase.
 ...
PMID:The effect of hyaluronidase and dimethyl sulfoxide (DMSO) on experimental skin flap survival. 663 21

"Synergistic denaturant therapy" is defined as the acute disruption of tumor cell structure by concurrent application of "denaturant" modalities such as hyperthermia, tumor-specific acidification, hypoenergia, ischemia, sulphydryl blockade, free-radical generation, detergents, and chemical denaturants (e.g. DMSO). Possible techniques for effective and tumor-specific clinical application of these modalities are discussed, and experimental investigations of their use in cancer therapy, alone or in synergistic combinations, are cited. Various of these modalities may also be used to potentiate the efficacy and specificity of traditional anti-mitotic therapies. Numerous therapeutic advantages are offered by a "synergistic denaturant" approach.
 ...
PMID:Synergistic denaturant therapy--a general strategy for treatment of solid malignancies. 700 Nov 91

The object of this investigation was to study the effects of dimethyl sulfoxide (DMSO) upon the evolution of cerebral infarction. Twenty adult cats anesthetized lightly with ketamine hydrochloride underwent right middle cerebral artery occlusion for 6 hours. Ten cats were not treated and 10 cats received DMSO (2.5 g/kg i.v.) immediately after occlusion. Regional cerebral blood flow (rCBF) changes in the right sylvian region were similar in the untreated and treated groups. The mean rCBF before occlusion was 46 +/- 10 ml/100 g/minute in the untreated group and 45 +/- 10 ml/100 g/minute in the treated group. Eight cats in both groups had rCBF measurements consistently below 18 ml/100 g/minute during the 6-hour period after occlusion. An index of erythrocyte flow was determined by measuring the transit of technetium-99 (99Tc)-labeled erythrocytes in the right sylvian region. The period of erythrocyte transit before occlusion was 10 +/- 1 seconds in the untreated group and 10 +/- 2 seconds in the treated group. After 6 hours of occlusion, the erythrocyte transit time was 18 +/- 3 seconds in the untreated group and 19 +/- 3 seconds in the treated group. Increasing delay in erythrocyte transit during the 6-hour occlusion period was seen in 5 untreated cats and 6 treated cats and was thought to represent a progressive increase in microvascular resistance. The complete washout of erythrocytes indicated the absence of microcirculatory obstruction. Electroencephalography (EEG) showed a reduced amplitude of activity in the right cerebral hemisphere after occlusion in cats with an rCBF consistently below 18 ml/100 g/minute. No significant EEG differences were found between the untreated and treated groups. Treatment with DMSO failed to modify the developing ischemia edema, neuronal alterations, or the changes in blood-brain barrier permeability to Evans blue dye and fluorescein. In this study DMSO was ineffective in preventing ischemic damage or acted when irreversible injury had already taken place.
 ...
PMID:Treatment of acute focal cerebral ischemia with dimethyl sulfoxide. 727 70

Dimethylsulfoxide (DMSO) has been advocated as a central nervous system (CNS) protectant against ischemia and trauma. The present study was performed to evaluate acute cardiovascular effects of DMSO which might complicate the clinical treatment of CNS compromised patients. Intravenously administered DMSO in doses which reportedly provide CNS protection, 2 g/kg, were infused in 6 dogs; hemodynamic variables were measured and compared to infusion of equal volumes of 0.9% sodium chloride. Immediately after infusion, DMSO caused increases in cardiac index, heart rate, pulmonary capillary wedge pressures (WP), and pulmonary arterial (systolic, mean, and diastolic) pressures which were significantly greater than changes induced by saline. DMSO decreased systematic diastolic pressure and systemic vascular resistance at the end of infusion. Most DMSO induced changes returned toward pre-infusion values 10 min after the end of infusion. These results suggest transient DMSO effects different from equal volumes of saline, possibly due to hyperosmotic expansion of plasma volume. A decrease in systemic vascular resistances was also observed. Although neither CNS production, intracranial pressure or blood flow were studied, these data suggest that DMSO used for CNS protection would not have adverse acute hemodynamic consequences. This may be particularly relevant in traumatized, hypovolemic patients.
 ...
PMID:Acute cardiovascular effects of dimethylsulfoxide. 731 58

Tissue injury that occurs as a result of ischemia and subsequent reperfusion is characterized by endothelial cell injury, edema formation, and the influx of inflammatory leukocytes. Two macrophage-derived proinflammatory cytokines which may play a critical role in cellular injury and leukocyte recruitment/activation that occurs in the setting of ischemia-reperfusion injury are tumor necrosis factor alpha (TNF) and macrophage inflammatory protein-1 alpha (MIP-1 alpha). To determine if modulation of ambient oxygen tensions in vitro alters the expression of proinflammatory cytokines from activated macrophages, murine alveolar macrophages (AMO) were cultured in various combinations of ambient oxygen concentrations, then the supernatant fluid and cell pellet assayed for the presence of TNF and MIP-1 alpha messenger RNA (mRNA) and protein. We demonstrated that conditions of anoxia (95% nitrogen/5% CO2) or hyperoxia (95% oxygen/5% CO2) independently resulted in the increased expression of both TNF and MIP-1 alpha mRNA and protein from lipopolysaccharide (LPS)-stimulated AMO, as compared with cells cultured in room air. The specific culture condition of anoxia (x 6 h) followed by hyperoxia (x 18 h) produced the greatest increases in both TNF and MIP-1 alpha, suggesting that when following a period of anoxic priming, oxygen stress results in exaggerated cytokine production. A period of at least 4.5 to 6 h of anoxia prior to hyperoxic exposure was found to be the minimal time required for anoxic priming. Furthermore, the coincubation of LPS-treated AMO with dimethyl sulfoxide (DMSO) attenuated the anoxia-hyperoxia-induced increases in TNF and MIP-1 alpha mRNA by 23% and 34%, respectively. These findings suggested that alterations in ambient oxygen tension can regulate the expression of TNF and MIP-1 alpha from activated AMO, and that oxidant-related cytokine production may represent an important mechanism by which inflammation occurs in the clinical settings of ischemia-reperfusion injury and hyperoxia.
 ...
PMID:Alterations of ambient oxygen tension modulate the expression of tumor necrosis factor and macrophage inflammatory protein-1 alpha from murine alveolar macrophages. 754 69

The antiarrhythmic effects of vehicle (0.1% dimethyl sulfoxide: DMSO) or capsaicin were evaluated in isolated perfused rat and guinea pig heart preparations. In the rat, capsaicin reduced ischemic ventricular tachycardia from 100% in control to 0%, and ischemic ventricular fibrillation from 60% in control to 0% at 30 microM, and diltiazem reduced the incidence of ischemic ventricular tachycardia and ventricular fibrillation to 55% and 0%, respectively. Reperfusion ventricular fibrillation was reduced from 90% to 20% and 33% for capsaicin and diltiazem, respectively, at these concentrations. In isolated perfused globally ischemic rat hearts, antiischemic efficacy was assessed as a significant extension (36% and 50%) in time to contracture with 30 microM capsaicin and 1 microM diltiazem, respectively. Capsaicin reduced left ventricular developed pressure by 35% in non-ischemic rat hearts, and increased coronary flow by 40%. The increased time to contracture for either compound was not blocked by glyburide (0.1 microM) suggesting a lack of any involvement of ATP-sensitive K+ channels. In isolated guinea pig hearts subjected to global ischemia, capsaicin and diltiazem reduced reperfusion ventricular fibrillation from 100% to 10% and 0% at 30 and 3 microM, respectively. Electrophysiologic evaluation in guinea pig papillary muscles using standard microelectrode techniques demonstrated significant (P < 0.05) action potential durations at 90% repolarization shortening at 1 Hz by 9%, 28% and 39%, and 23%, 37% and 51% at 10, 30, and 100 microM of capsaicin or diltiazem, respectively. Unlike diltiazem, no changes in action potential duration were observed with capsaicin (up to 100 microM) at faster stimulation rates (5 Hz). In conclusion, capsaicin displays both antiarrhythmic and antiischemic efficacy. These data suggest that the effects of capsaicin are mediated primarily through block of Ca2+ channels in these preparations.
 ...
PMID:In vitro effects of capsaicin: antiarrhythmic and antiischemic activity. 771 71

The regenerative repair response to folic acid and ischemia-reperfusion injury is characterized by different patterns of renal tubular cell proliferation. The purpose of this study was to examine the time course of the expression of two early growth response genes, c-jun and c-fos, and of the stress response gene hsp70 after such renal injuries and to determine the role played by reactive oxygen species generated during reperfusion, on gene induction. Ischemic injury caused an almost immediate increase of c-jun, c-fos and hsp70 mRNA expression, that reached a maximum at 1 h of reperfusion. Folic acid treatment increased c-fos and hsp70 mRNAs at 2 h, while c-jun accumulated at 1 h, although to a lesser extent. The intravenous administration of two antioxidant drugs, allopurinol or dimethyl sulfoxide (DMSO), 20 min before ischemia, to prevent the generation of oxygen free radicals during reperfusion, did not cause any change in gene expression. In contrast, the combined administration of allopurinol and DMSO reduced c-jun and c-fos mRNA expression as well as tubular cell damage at 1 h of reperfusion, although not at earlier times while hsp70 mRNA expression remained almost unchanged. Taken together, the results suggest that these scavengers, by reducing reactive oxygen species and renal damage during reperfusion, may affect the expression and/or persistence of transcripts involved in the control of epithelial cell proliferation.
 ...
PMID:Differential expression of c-jun, c-fos and hsp 70 mRNAs after folic acid and ischemia-reperfusion injury: effect of antioxidant treatment. 792 67

To assess the development of oxidative stress in cardiac ischemia/reperfusion, the resulting depletion of plasma ascorbate was monitored by electron spin resonance spectroscopic detection of ascorbyl free radical (AFR) in a homogeneous group of 12 patients undergoing aortic valve replacement. Dimethyl sulfoxide (DMSO) was used as an enhancer and stabilizer for AFR in plasma separated from blood samples collected 15 min before incision, 10 min before aortic declamping, and sequentially during the initial 30 min of reperfusion. Plasma DMSO/AFR levels of patients were found to be significantly lower than in healthy subjects (-25%), further decreased upon ischemia (-35%), dropped to their lowest values within the first 10 min of reperfusion (-46%), and did not recover their initial values within 30 min following reflow. Cardiac index measurements revealed a still depressed heart function 4 h postdeclamping and a more delayed tissue injury was evidenced by cardiac myosin and myoglobin release in plasma. DMSO/AFR levels at early reperfusion were slightly (+ 12%) higher in plasma obtained from coronary sinus samples than in plasma from peripheral blood, suggesting an extra ascorbate release from the injured heart tissue. The close analogy between these results and the reported measurements of other plasma markers of oxidative stress, including ascorbate, indicates that the present method could be of great value in clinical practice.
 ...
PMID:Ascorbyl free radical: a noninvasive marker of oxidative stress in human open-heart surgery. 800 38

The 21-aminosteroids are potent inhibitors of iron-dependent lipid peroxidation and more protective than methylprednisolone in models of trauma and reperfusion, but without glucocorticosteroid side effects. Histologically, animals treated with 21-aminosteroids have decreased neutrophil (PMN) infiltrates and diminished tissue destruction associated with trauma or reperfusion. Since PMN contribute to organ failure following ischemia-reperfusion, we assessed the effect of U-74389F (U7), on normal PMN function. Neutrophils from normal volunteers were incubated for 90 min with either vehicle, 15 microM U7 or 80 microM methylprednisolone (MP), in DMSO. Lactoferrin released and generation of leukotrienes to calcium ionophore A23187, also oxygen consumed to PMA and leukotriene B4 (LTB4) and chemotaxis to FMLP and LTB4, were determined for each group of PMN. Lactoferrin released to A23187 was significantly decreased in both steroid groups (7.29 +/- 0.82 micrograms vs 3.06 +/- 0.57 micrograms U7 and 2.88 +/- 0.62 micrograms MP, P < 0.01). PMN incubated with U7 or MP generated significantly less LTB4 (60.6 +/- 4.3 ng vs 47.7 +/- 2.4 ng U7 and 43.3 +/- 5.6 ng MP, P < 0.05). There were no differences noted in the ability of PMN incubated with either compound to consume oxygen or to respond to chemotactic stimuli. We conclude that the proven protective action of the 21-aminosteroids in models of ischemia-reperfusion is related to the ability of "steroids" to inhibit leukotriene generation and degranulation and may be related to the prevention of tissue lipid peroxidation by scavenging oxygen radicals.
 ...
PMID:Inhibition of neutrophil leukotriene generation by the 21-aminosteroid, U-74389F. 802 30


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