Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two patients are presented in whom cerebral angiography was complicated by bioccipital infarcts resulting in cortical blindness with persisting severe restriction of the visual field (case 1) and persisting cortical blindness (case 2). One patient (case 1) demonstrated a compensated, protracted disseminated intravascular coagulation (Table 1), which disappeared after treatment with phenprocoumon (Marcoumar). The other patient (case 2) demonstrated increasee spontaneous platelet aggregability (Table 2), which was treated sucessfully with acetylsalicylic acid (Magnyl) and dipyridamole (Persantine). We presume that the coagulation disturbances demonstrated after the angiography may be pathogenetic to the complications. We propose that patients with transient cerebral ischemia and apoplexy who are undergoing cerebral angiography should be studied with regard to coagulation before and after the cerebral angiography so that coagulation disturbances demonstrated may be treated before, or corrected after the angiography.
 ...
PMID:Possible increased tendency to thrombosis after cerebral angiography. 45 38

Aspirin is of proven value as an antithrombotic drug. In unstable angina it reduces the risk of death and myocardial infarction by half. After a myocardial infarction it reduces the risk of death by about 10% and of coronary incidence (coronary death or definite myocardial infarction) by about 25%. These effects appear to be additive with those of beta-blocking drugs. Aspirin also reduces the risk of occlusion of aortocoronary saphenous vein grafts by about half. In transient cerebral ischaemia, aspirin may reduce the risk of stroke and death by 50%. In most clinical trials to date the daily dose of aspirin ranges from 325 mg to 1400 mg. Interest in very low doses of aspirin (less than 60 mg daily) is considerable but has yet to be translated into proven clinical benefit. Dipyridamole has not been shown to be effective as an antithrombotic when used alone. Its antiplatelet action ex vivo may be enhanced by combination with aspirin but clinical trials have shown relatively little advantage of the combination over aspirin alone. Sulphinpyrazone has not become established as a first line antithrombotic drug. Epoprostenol is useful in extracorporeal circulations to prevent platelet consumption and possibly in severe inoperable peripheral vascular disease.
 ...
PMID:Aspirin and other antiplatelet drugs in the prophylaxis of thrombosis. 333 89

Stroke is the third leading cause of death in the United States. Efforts directed at reversing acute cerebral ischemia are promising but are hampered by multiple logistic and physiologic barriers. Prevention of stroke, therefore, remains of critical importance. Primary prevention is accomplished through reduction of risk factors and the appropriate use of warfarin or aspirin in patients with cardiac sources of emboli such as atrial fibrillation. Secondary prevention is designed to reduce the risk of stroke in patients with known stroke precursors, including transient ischemia, reversible ischemic deficits, and completed stroke. Aspirin and ticlopidine are two antiplatelet agents with an established role in secondary stroke prevention. In a major North American clinical trial, ticlopidine demonstrated superior efficacy to aspirin for the prevention of recurrent stroke, particularly in the first year following a stroke. Dipyridamole has not been shown to be useful for stroke prevention. The role of warfarin in the prevention of recurrent noncardiogenic stroke remains controversial and is currently under investigation. Stroke prevention remains an important challenge, and therapy should be individualized to achieve optimal results.
 ...
PMID:Stroke prevention therapies and management of patient subgroups. 788 86

Preliminary evidence suggests adenosine, a neuromodulator, has neuroprotective properties during cerebral ischemia. It is unclear, however, if adenosine has glioprotective effects. We studied the effect of adenosine on cellular injury in astroglial cultures subjected to combined glucose-oxygen deprivation. Adenosine (100-1,000 microM)dramatically reduced astroglial injury, whereas the adenosine agonists 2-chloroadenosine (10 nM-100 microM), N6-cyclopentyladenosine (1 nM-10 microM), 5'-N-ethylcarboxamidoadenosine (10 nM-100 microM), and N6-2-(4-aminophenyl)ethyladenosine (10 nM-100 microM) had no effect. Furthermore, the adenosine antagonists 8-cyclopentyl-1,3-dipropylxanthine (1 nM-1 microM), xanthine amine congener (10 nM-10 microM), and 8-(p-sulfophenyl)-theophylline (10-300 microM) failed to reverse the protective effect of 200 microM adenosine. Next, adenosine degradation products were studied. Inosine proved to be glioprotective at concentrations nearly identical to those of adenosine, but hypoxanthine and ribose had no effect. The protective effect of 200 microM inosine was not reversed by 8-(p-sulfophenyl)theophylline (10-300 microM). Adenosine deaminase (1 unit/ml) had no effect on protection produced by adenosine, whereas erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride (10 microM) reversed the protective effect of adenosine. Dipyridamole (4 microM) inhibited the protective effect of both adenosine and inosine. We conclude that adenosine dramatically decreases astroglial injury during combined glucose-oxygen deprivation and that this protective effect appears to be mediated by inosine.
 ...
PMID:Inosine mediates the protective effect of adenosine in rat astrocyte cultures subjected to combined glucose-oxygen deprivation. 886 13

Loss of inhibitory GABAergic modulation may induce hyperexcitability of neuronal elements and potentiate their vulnerability to excitotoxic injury. It has been also found that the adenosine system interacts with the GABAergic system during ischemia and anoxia where the adenosine receptors as well as the GABAergic receptors may conscript the same intracellular pathway to increase tolerance to ischemia. Therefore, it was aimed to study whether dipyridamole (CAS 58-32-2), an adenosine uptake inhibitor, or adenosine (CAS 58-61-7) could affect the rat brain gamma-aminobutyric acid (GABA, CAS 56-12-2) level after induction of cerebral ischemia, and to test their effect on the lactate dehydrogenase (LDH) activity of the ischemic rat brain. Ischemia was induced by bilateral clamping of the common carotid arteries for 60 min followed by reperfusion for other 60 min. Dipyridamole was administered alone and in combination with adenosine and the effect of the drugs on the brain GABA level as well as on LDH activity was determined. The results show that dipyridamole could protect the brain of rats against the ischemic insult, while adenosine when administered separately failed to influence the selected parameters. Protection of the rat brain by dipyridamole might be related to the elevated level of GABA.
 ...
PMID:Influence of inhibition of adenosine uptake on the gamma-aminobutyric acid level of the ischemic rat brain. 1208 19

New therapies are urgently needed for hematologic malignancies, especially in patients with relapsed acute myelogenous leukemia (AML) and multiple myeloma. We and others have previously shown that FDA-approved statins, which are used to control hypercholesterolemia and target the mevalonate pathway (MVA), can trigger tumor-selective apoptosis. Our goal was to identify other FDA-approved drugs that synergize with statins to further enhance the anticancer activity of statins in vivo. Using a screen composed of other FDA approved drugs, we identified dipyridamole, used for the prevention of cerebral ischemia, as a potentiator of statin anticancer activity. The statin-dipyridamole combination was synergistic and induced apoptosis in multiple myeloma and AML cell lines and primary patient samples, whereas normal peripheral blood mononuclear cells were not affected. This novel combination also decreased tumor growth in vivo. Statins block HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the MVA pathway. Dipyridamole blunted the feedback response, which upregulates HMGCR and HMG-CoA synthase 1 (HMGCS1) following statin treatment. We further show that dipyridamole inhibited the cleavage of the transcription factor required for this feedback regulation, sterol regulatory element-binding transcription factor 2 (SREBF2, SREBP2). Simultaneously targeting the MVA pathway and its restorative feedback loop is preclinically effective against hematologic malignancies. This work provides strong evidence for the immediate evaluation of this novel combination of FDA-approved drugs in clinical trials.
 ...
PMID:Immediate utility of two approved agents to target both the metabolic mevalonate pathway and its restorative feedback loop. 2499 12