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)

Recent studies are reviewed on the etiology of primary dysmenorrhea as well as on proper treatment, based on physiology, of this disorder. These studies suggested that increased endometrial prostaglandin production and release may cause dysmenorrhea. Since prostaglandins cause myometrial contractility, then if production and release of prostaglandins are excessive, uterine ischemia and pain result. Studies of therapeutic value of prostaglandin synthetase inhibitors show good results; agents such as indomethacin and the fenamates inhibit the synthesis of prostaglandin through the synthetase system as well as antagonize prostaglandins' conventional action at the cell receptor level. Other more conventional forms of therapy for dysmenorrhea have also garnered good results, these include ingestion of oral contraceptives and dilatation of the cervix, and their effectiveness can be explained partly on the basis of a reduced level of prostaglandins in the menstrual fluid. The need for further evaluation of antiprostaglandin compounds is promoted.
 ...
PMID:New concepts in dysmenorrhea. 2 21

Compression ischemia of the central nervous system (CNS) in heparinized dogs caused areas of diminished cerebral blood flow measured by 14C-antipyrine autoradiography. Intravenous infusion of indomethacin (1.5 or 4.0 mg/kg) approximately 1 hour before ischemia eliminated the circulatory defects. Prophylactic inhibition of prostaglandin synthetase may promote postischemic perfusion of the CNS by preventing vasoconstriction and by anti-hemostatic effects on blood.
 ...
PMID:Indomethacin prevents impaired perfusion of the dogs's brain after global ischemia. 74 93

The effect of meclofenamate and indomethacin on renal blood flow and renal vascular resistance was determined under basal experimental conditions and during renal ischemia in pentobarbital-anesthetized dogs. Renal blood flow was measured with an electromagnetic flowmeter and renal arterial pressure was recorded from a catheter in the renal artery. Intra-arterial infusion of indomethacin or meclofenamate in concentrations of 4 and 4 to 8 mu-g/ml, respectively, did not cause any significant change in renal blood flow or renal vascular resistance under basal conditions. During the period of ischemia (50% reduction in renal blood flow), 4 mu-g/ml of either prostaglandin synthetase inhibitor caused a marked increase in renal vascular resistance. Prostaglandin E in the renal venous blood was decreased at the time renal vascular resistance was increased by meclofenamate. The renal vasoconstrictor response to angiotensin II injected intravenously was potentiated by both inhibitors under basal as well as ischemic conditions, which also suggested that prostaglandin synthesis was inhibited. The angiotensin antagonist 1-sar-8-ala-angiotensin II was infused intra-arterially in concentrations of 20 and 40 mmu-g/ml during renal ischemia. Subsequent administration of meclofenamate increased renal vascular resistance only slightly. The results of these experiments indicated that renal prostaglandins have more influence on renal blood flow during renal ischemia than under basal conditions, and that the renin-angiotensin system may be involved in activating synthesis and release of prostaglandins during ischemia.
 ...
PMID:Influence of the renin-angiotensin system on the effect of prostaglandin synthesis inhibitors in the renal vasculature. 80 74

We report the case of a six-day-old male infant exposed in utero to a prostaglandin synthetase inhibitor, who presented pulmonary arterial hypertension, tricuspid insufficiency, and electrocardiographic signs of diffuse myocardial ischemia. The necropsy showed organizing infarction of the anterior and posterior right papillary muscles (probably occurred in utero) with complete rupture of the former, besides abnormal muscularization of the intraacinar pulmonary arterioles (persistent fetal circulation of the newborn). The authors suggest a possible relation between the myocardial ischemic and pulmonary hypertensive lesions since the prostaglandin synthetase inhibitor can induce precocious pulmonary arteriolar muscularization and constriction of the arterial duct, leading to right ventricular overload, thus facilitating the occurrence of papillary and subendocardial ischemia.
 ...
PMID:Post-ischemic rupture of the anterior papillary muscle of the right ventricle associated with persistent pulmonary hypertension of the newborn: a case report. 162 31

Several feasible mechanisms have been proposed as sources of neuronal damage from ischemia and subsequent reperfusion. Included among these are oxidative damage caused by free radical production and lipid peroxidation and products derived from phospholipid breakdown. A series of 4-thiazolidinone compounds represented by LY178002 (5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene-4-thiazolidinon e) have been described as inhibitors of multiple enzymes in the arachidonic acid cascade, including fatty acid cyclooxygenase, 5-lipoxygenase, and phospholipase A2. Accordingly, we evaluated LY178002 in a four-vessel occlusion model of global forebrain ischemia with reperfusion. A 2-hour pretreatment of 11 male Wistar rats with 150 mg/kg LY178002 significantly protected against striatal (p = 0.0007) and hippocampal CA1 (p = 0.006) damage after 30 minutes of global ischemia. Similar protection was observed for the striatum (p = 0.005) and hippocampal CA1 layer (p = 0.025) after pretreatment of 13 rats with 50 mg/kg LY178002. We further evaluated LY178002 as a possible inhibitor of lipid peroxidation because part of its chemical structure incorporates the aromatic backbone of the known antioxidant butylated hydroxytoluene. We found LY178002 to be a potent inhibitor of iron-dependent lipid peroxidation. Few substances possessing a single pharmacological activity have been found to be of significant therapeutic benefit in global ischemia of 30 minutes' duration because the mechanisms that lead to cell death in response to ischemia are likely to be multifactorial. Thus, the efficacy of LY178002 in this model may be due to its ability to inhibit multiple sources of damage.
 ...
PMID:LY178002 reduces rat brain damage after transient global forebrain ischemia. 186 52

Excessive stimulation of excitatory amino acid (EAA) receptors and abnormal production of oxygen-derived free radicals have repeatedly been implicated in the series of events linking brain hypoxia or ischemia to neuronal death. We report here that in rat hippocampal slices the KCl-stimulated output of labeled D-3H aspartate or of endogenous aspartate and glutamate significantly increased under in vitro simulated hypoxic, hypoglycemic, or ischemic conditions. In particular, when the slices were incubated for 10 min at 32 degrees C under "ischemic" conditions (namely, lack of oxygen and glucose), endogenous aspartate and glutamate in the supernatant increased by 10 and 20 times, respectively. Since radical scavengers (D-mannitol), drugs reducing free radical formation (indomethacin, corticosteroid), or enzymes able to metabolize them (catalase and superoxide dismutase) significantly reduced this output, it was supposed that free radicals caused EAA release. A direct demonstration of this concept was obtained by showing a significant release of EAA after incubation of hippocampal slices with enzymes and substrates known to cause the formation of free radicals, such as xanthine plus xanthine oxidase or arachidonic acid plus prostaglandin synthase. Neither ischemia nor the enzymatic reactions leading to free radical production increased the activity of the cytoplasmic enzyme lactate dehydrogenase in the incubation medium, thus ruling out a nonspecific cellular lysis. It appears therefore that during ischemic states, brain production of reactive molecules (free radicals) causes an increased output of EAA. This may trigger a series of events which could help to explain the delayed loss of neurons after a transient ischemic period.
 ...
PMID:Excitatory amino acid release and free radical formation may cooperate in the genesis of ischemia-induced neuronal damage. 196 65

The lung is especially sensitive to a variety of vastly different agents and conditions including hyperoxia, certain drugs and xenobiotics, particulate debris, and ischemia/reperfusion. There is a growing body of experimental data to suggest that most, if not all, of these agents or conditions mediate pulmonary injury by forming reactive O2 metabolites such as O2-., H2O2.OH, HOCl, and RNHCl. The presence mechanisms by which these different agents converge to produce free radical-mediated pulmonary injury is not entirely clear. The lung does contain several metabolic pathways that will produce large amounts of reactive O2 metabolites. For example, hyperoxia-induced pulmonary injury may be mediated by oxidants produced by both mitochondrial and microsomal electron transport. Certain drugs and xenobiotics may be metabolized by nonspecific flavoproteins found in the mitochondrial electron transport chain and associated with microsomal mixed function oxidase system to yield a variety of free radicals and oxidants. Inhalation of particulate debris will activate resident phagocytic leukocytes to produce large quantities of cytotoxic oxidants. Ischemia and reperfusion appear to produce substantial amounts of xanthine oxidase-derived oxy-radicals that recruit and activate inflammatory phagocytes to produce cytotoxic HOCl and N-chlorinated oxidants. Finally, inappropriate metabolism of arachidonate by prostaglandin synthetase in the presence of NADH (NADPH) produces a burst of O2-. The fact that the lung contains so many different metabolic avenues for oxidant and free radical production suggests that this particular organ may be the most sensitive to oxidative insult.
 ...
PMID:Metabolic sources of reactive oxygen metabolites during oxidant stress and ischemia with reperfusion. 265 Sep 65

Following the demonstration that increased prostaglandin F2 alpha production causes pain similar to dysmenorrhea, and the finding that prostaglandin synthetase inhibitors are capable of relieving menstrual pain, the early theory of uterine ischemia has once again gained support as the most likely explanation for this condition. In a double-blind, placebo-controlled, crossover study, 30 of 43 women with moderate to severe dysmenorrhea who completed the trial preferred flurbiprofen (Ansaid, Upjohn), a potent new analgesic/anti-inflammatory agent (50 mg four times daily), to aspirin (650 mg four times daily) and placebo. Flurbiprofen was also rated superior to aspirin and placebo in the degree of pain relief. An algorithm for the diagnosis and treatment of 90 percent of women with primary dysmenorrhea is presented.
 ...
PMID:Flurbiprofen for the treatment of primary dysmenorrhea. 345 24

Primary dysmenorrhea may affect as many as 40 percent of all adult women, temporarily disabling one-tenth of them. The etiology of this condition may be related to excess production of prostaglandins by the endometrium following decline in progesterone levels consequent to corpus luteum regression. It is proposed that increased prostaglandin levels produce increased myometrial contractility and uterine ischemia and sensitization of pain fibers, resulting in pelvic pain. Administration of nonsteroidal anti-inflammatory agents which block the cyclooxygenase enzyme of the arachidonic acid cascade is an effective treatment for primary dysmenorrhea, as is oral contraceptive therapy. Criteria for an ideal prostaglandin synthetase inhibitor are described.
 ...
PMID:Current concepts in the etiology and treatment of primary dysmenorrhea. 354 8

The incubation of adult mouse skin pieces in a buffered salts medium at 37 degrees C led to a rapid accumulation of cyclic adenosine 3'5-monophosphate (cyclic AMP) in the tissue. In mouse skin maximum accumulation occurred after 2 min incubation; levels reverted to near control levels after a further 7 min incubation. the increase in cyclic AMP contents of the skin pieces was probably not due to the release of materials which activate adenylate cyclase after binding to cellular receptors. Thus, cyclic AMP accumulation was unaffected by the inclusion of alpha- or beta-adrenergic antagonists, or by the pretreatment of adult mouse skin with indomethacin (an inhibitor of prostaglandin synthetase). Furthermore, adenosine, a known activator of epidermal adenylate cyclase, could not be detected in the incubation medium. The functional integrity of epidermal adenylate cyclase was maintained during the cyclic AMP accumulation in response to ischemia. Thus, adenosine, histamine, isoproterenol and prostaglandin E2 (PGE2) augmented the cyclic AMP response. Cyclic AMP accumulation at 37 degrees C was not observed in newborn mouse skin; this lack of cyclic AMP accumulation was probably not due to increased activity of low affinity cyclic AMP phosphodiesterase in newborn mouse skin.
 ...
PMID:The effect of ischemia on cyclic adenosine 3',5'monophosphate accumulation in mouse skin. 627 64


1 2 Next >>