Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stroke occurs due to haemorrhage or occlusive injury and results in ischaemia and reperfusion injury. A variety of destructive mechanisms are involved including oxygen radical generation, calcium overload, cytotoxicity and apoptosis as well as the generation of inflammatory mediators. Ebselen, 2-phenyl-1, 2-benzisoselenazol-3(2H)-one (PZ 51, DR3305), is a mimic of GSH peroxidase which also reacts with peroxynitrite and can inhibit enzymes such as lipoxygenases, NO synthases, NADPH oxidase, protein kinase C and H(+)/K(+)-ATPase. Ebselen is in a late stage of development for the treatment of stroke. The molecular actions of ebselen contribute to its anti-inflammatory and anti-oxidant properties, which have been demonstrated in a variety of in vivo models. Numerous in vitro experiments using isolated LDL, liposomes, microsomes, isolated cells and organs have established that ebselen protects against oxidative challenge. Unlike many inorganic and aliphatic selenium compounds, ebselen has low toxicity as metabolism of the compound does not liberate the selenium moiety, which remains within the ring structure. Subsequent metabolism involves methylation, glucuronidation and hydroxylation. Experimental studies in rats and dogs have revealed that ebselen is able to inhibit both vasospasm and tissue damage in stroke models, which correlates with its inhibitory effects on oxidative processes. Results from randomised, placebo-controlled, double-blind clinical studies on the neurological consequences of acute ischaemic stroke, subarachnoid haemorrhage and acute middle cerebral artery occlusion, have revealed that ebselen significantly enhances outcome in patients who have experienced occlusive cerebral ischaemia of limited duration. The benefit achieved with ebselen is closely related to the rapidity with which the treatment is initiated, following the onset of the stroke attack. Safety and tolerability are good and no adverse effects have become apparent. Ebselen is currently at the pre-registration stage for subarachnoid haemorrhage and stroke in Japan.
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PMID:Ebselen: prospective therapy for cerebral ischaemia. 1106 Jun 99

Low-dose aspirin (< 330 mg/d) is recommended for the prevention of myocardial infarction or ischemic stroke. Six to 12% of the general population is exposed to low-dose aspirin. The most frequently studied digestive complications are bleeding peptic ulcers, whose risk is increased twofold by low-dose aspirin treatment, and non-complicated peptic ulcers. History of bleeding or non-complicated peptic ulcer, alcohol intake, concomitant treatment with NSAID or calcic inhibitors are demonstrated risk factors of bleeding ulcer associated with low-dose aspirin. The role of enteric coating, of low-dose aspirin dose, of delay since low-dose aspirin treatment onset, and of Helicobacter pylori infection, remains controversial. Antisecretory drugs (H2 inhibitors, proton pump inhibitors), and nitroglycerin are associated with a decreased risk of bleeding ulcer. The protective effect of COX-2 inhibitors on the risk of bleeding ulcer is suppressed by concomitant treatment with low-dose aspirin. The risk of no- complicated peptic ulcer was increased by low-dose aspirin intake by a factor 2.9 in one study. Low-dose aspirin dose, infection by Helicobacter pylori, NSAID intake, and absence of enteric coating, are possible risk factors for non-complicated peptic ulcer. No association was retrieved with alcohol intake and peptic ulcer history.
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PMID:[Epidemiology of digestive complications associated with use of low-dose aspirin]. 1536 73

Dysphagia affects a large and growing number of individuals in the United States, particularly the elderly and those who are neurologically impaired. Swallowing difficulties may be due to age-related changes in oropharyngeal and esophageal functioning as well as central nervous system diseases such as stroke, Parkinson disease, and dementia. Among institutionalized individuals, dysphagia is associated with increased morbidity and mortality. An appreciation of the physiology of swallowing and the pathophysiology of dysphagia is necessary for proper patient management. Careful history, physical examination, and evaluation of radiologic and endoscopic studies should differentiate oropharyngeal and esophageal etiologies of dysphagia and distinguish mechanical (anatomic) disorders from functional (motor) disorders. A significant percentage of patients with dysphagia have concomitant acid-related disorders that are managed best with proton pump inhibitor (PPI) therapy. Three of the currently available PPIs are manufactured as capsules containing enteric-coated granules that may be mixed with soft foods or fruit juices before oral administration to those with swallowing difficulties. In addition, omeprazole and lansoprazole may be administered via gastrostomy or nasogastric feeding tubes as suspensions in sodium bicarbonate. Novel dosage formulations of lansoprazole that may be appropriate for patients with dysphagia include the commercially manufactured lansoprazole strawberry-flavored enteric-coated granules for suspension and lansoprazole orally disintegrating tablets.
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PMID:Management of acid-related disorders in patients with dysphagia. 1547 52

Aspirin is a very useful medication for the prevention of cardiovascular thrombotic events in patients with or those at risk for cardiovascular disease (CVD). Aspirin, however, carries an increased risk for gastrointestinal (GI) injury (e.g., ulceration) and its complications (e.g., hemorrhage), which may be caused by its antiplatelet and gastric mucosal effects. In those with established CVD, aspirin use has been documented to decrease the risk of a first myocardial infarction (MI). Its effects on stroke and vascular death are less conclusive. The use of aspirin in these individuals is recommended only for those whose risk for cardiovascular events (based on coronary risk assessment tools) is sufficiently high that it outweighs the risk for GI complications. Secondary prevention refers to the use of aspirin to prevent cardiovascular events in patients with established CVD such as an MI, stroke, or angina. The use of aspirin in these individuals is recommended based on a documented decrease in future cardiovascular events and mortality. The risk for GI events with aspirin is at least additive to the risk for these events in those who also are receiving therapy with a nonsteroidal anti-inflammatory drug. Patients being treated with aspirin, even at 81 mg/day for cardioprotection, should be assessed for factors that increase the risk for GI injury. Studies have confirmed that co-therapy with a proton pump inhibitor (PPI) or misoprostol decreases the risk for GI injury and complications. Although both classes of such gastroprotective agents are effective, treatment with a PPI is tolerated better, with fewer patients discontinuing the drug because of side effects such as diarrhea.
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PMID:Cardioprotective effects and gastrointestinal risks of aspirin: maintaining the delicate balance. 1547 56

Chronic pain in the elderly is frequently a result of arthritic disorders, particularly osteoarthritis. The cyclo-oxygenase (COX)-2 inhibitors are as effective as standard NSAIDs for the relief of pain and for improving function in elderly patients with osteoarthritis and rheumatoid arthritis. COX-2 inhibitors increase the risk of serious gastroduodenal adverse reactions but there is evidence that they carry a lower risk for these adverse effects than standard NSAIDs, except when there is concurrent aspirin use. Since gastroduodenal disorders are the most frequently reported serious adverse effects of NSAIDs and these disorders occur more frequently in the elderly, COX-2 inhibitors offer an alternative to standard NSAIDs in this age group. However, they are not appropriate for many patients with cardiovascular and renal disease. The adverse reaction profile of the COX-2 inhibitors has confirmed the role of the COX-2 enzyme in renal function, salt and water homeostasis and the vascular endothelium. Thus, like standard NSAIDs, COX-2 inhibitors can cause renal failure, hypertension and exacerbation of cardiac failure. Of note is that these disorders are dose related. Thus, there are good reasons to avoid high doses of COX-2 inhibitors in the elderly. Clinical trials indicate that daily doses of rofecoxib 12.5 mg, celecoxib 100-200 mg, valdecoxib 10mg and etoricoxib 60 mg are the minimum effective doses of these agents. Data from the New Zealand Intensive Medicines Monitoring Programme indicate that celecoxib 200 mg/day and rofecoxib 25 mg/day are/were the most commonly prescribed doses and that 6% of patients had taken rofecoxib 50 mg/day for longer than recommended. Recent research indicates that COX-2 inhibitors have a thrombotic potential, especially in high doses and when use is prolonged, and this further limits the extent to which they can be used in the elderly. Important interactions with COX-2 inhibitors in the elderly include those with warfarin, which can result in loss of control of anticoagulation, and those with ACE inhibitors, angiotensin II type 1 receptor antagonists and diuretics, which can result in loss of control of blood pressure and cardiac failure and, in hypovolaemic conditions, renal failure. The clinical significance of an interaction between celecoxib and aspirin to reduce the antiplatelet effect of the latter drug is unknown. Preliminary information from spontaneous reporting systems indicates that there may be differences in the risk of cardiac failure and hypertension between standard NSAIDs and COX-2 inhibitors and between rofecoxib and celecoxib. More formal studies using equivalent doses are needed to test this observation. Use of COX-2 inhibitors may be considered in the elderly to reduce the risk of gastroduodenal complications associated with standard NSAIDs but only when consideration has first been given to use of less toxic medicines as alternatives or supplements, the appropriate dose of the COX-2 inhibitor or standard NSAID, the presence and possible impact of co-morbidities, and the implications of taking COX-2 inhibitors with any concomitant medications. Equally important is regular monitoring of the patient taking a COX-2 inhibitor for efficacy and adverse effects, and ensuring that the patient has a continuing need to keep taking the drug. Close attention also needs to be paid to intercurrent illnesses and new prescriptions that may reduce the safety of the COX-2 inhibitor. A standard NSAID plus a proton pump inhibitor may be equally effective as a COX-2 inhibitor in reducing the risk of gastroduodenal toxicity and if used the same prescribing advice applies. Current knowledge concerning the thrombotic potential of COX-2 inhibitors suggests that this combination, if tolerated, may be preferable to a COX-2 inhibitor, particularly where prolonged use is required. This knowledge also indicates that for patients with or at high risk of ischaemic heart disease or stroke, COX-2 inhibitors are contraindicated.
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PMID:Cyclo-oxygenase-2 inhibitors: when should they be used in the elderly? 1581 52

Although low-dose aspirin is commonly used as the antiplatelet agent to prevent ischaemic events such as myocardial infarction and stroke, clopidogrel is probably superior at preventing ischaemic events. For patients who cannot tolerate aspirin, adding a proton pump inhibitor or substituting clopidogrel are options. Patients with endoscopy-confirmed ulcer healing were assigned to clopidogrel 75 mg/day or aspirin 80 mg/day and esomeprazole 20 mg b.i.d. for 12 months. There were 14 confirmed cases of recurrent ulcer bleeding, with 13 being from the 161 patients taking clopidogrel and 1 from the 159 patients taking aspirin plus esomeprazole. This trial has clearly shown that the combination of aspirin and esomeprazole is superior to clopidogrel in preventing recurrent ulcer bleeding. A more interesting study may have been to compare the effects of aspirin and clopidogrel in the presence of esomeprazole in patients with a history of ulcers.
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PMID:Aspirin and esomeprazole are superior to clopidogrel in preventing recurrent ulcer bleeding. 1595 77

Selective cyclooxygenase-2 inhibitors have been marketed as alternatives of conventional, non-steroidal anti-inflammatory drugs with the purpose of reducing/eliminating the risk of ulcer complications. Unexpectedly, randomized-controlled trials revealed that long-term use of coxibs, such as rofecoxib, significantly increased the risk of myocardial infarction and stroke, while the use of valdecoxib was associated with potentially life-threatening skin reactions. Subsequently, rofecoxib and valdecoxib were withdrawn from the market. Although more strict precautions for other coxibs, such as celecoxib, etoricoxib, lumiracoxib and parecoxib, may be accepted/recommended by regulatory agencies, a critical review of published data suggests that their use may not be justified - even in high-risk patients - taking benefits, costs and risks into consideration. Clinicians should, therefore, never prescribe coxibs to patients with cardiovascular risk factors, and should only reluctantly prescribe coxibs to patients with a history of ulcer disease or dyspepsia to overcome persistent pain due to, e.g. rheumatoid arthritis or osteoarthritis. Instead, they should consider using conventional non-steroidal anti-inflammatory drugs in combination with a proton pump inhibitor or a prostaglandin analogue, especially for patients with increased cardiovascular risks, i.e. established ischaemic heart disease, cerebrovascular disease and/or peripheral arterial disease, or alternatively acetaminophen. An evidence-based algorithm for treatment of a chronic arthritis patient with one or more gastrointestinal risk factors is presented.
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PMID:Systematic review: coxibs, non-steroidal anti-inflammatory drugs or no cyclooxygenase inhibitors in gastroenterological high-risk patients? 1639 77

The year 2005 was rich in new information. Many articles were published on antithrombotic therapy, the key stone in the management of several cardiovascular diseases which are the cardiologists' "daily bread". Antithrombotic treatment is essential in the treatment of patients undergoing interventional coronary procedures. The loading dose of 300 mg clopidogrel has been questioned. The ARMYDA-2 trial showed that a loading dose of 600 mg of clopidogrel administered 4 to 8 hours before coronary angioplasty significantly reduced the number of peri-procedural myocardial infarctions without increasing the risk of bleeding complications. Other molecules such as prasugrel could provide an alternative to treatment with clopidogrel. The results of a phase 2 trial (JUMBO-TIMI 26) comparing clopidogrel and prasugrel have opened the way for a large scale phase 3 trial which is currently under way. In myocardial infarction, the CLARITY-TIMI 28 trial showed that patients under 75 years of age with acute myocardial infarction of less than 12 hours duration treated with aspirin and thrombolytic therapy had better results with respect to the combined criteria of patency of the culprit artery and ischaemic complications with the addition of clopidogrel. In the CREATE trial, patients with acute myocardial infarction had a lower mortality and recurrence of infarction without significantly increasing the risk of stroke with reviparin. The development of ximelagatran has been held up by a potentially serious hepato-toxicity. Two large-scale trials were published this year, one in atrial fibrillation and the other in venous thrombosis. In the former, the hypothesis of non-inferiority compared with well conducted oral anticoagulation with coumadine was supported and, in the latter, the hypothesis of non-inferiority compared with treatment with enoxaparin followed by warfarin was also confirmed despite a higher number of coronary events in the xinelagatran group. Another study which merits a citation showed that in patients with a previous history of aspirin-induced bleeding ulcers, the association of low dose aspirin and a proton pump inhibitor was superior to the prescription of clopidogrel in the prevention of recurrent bleeding. A study of the pharmacogenetics of coumadine and the variability of its dosage was also a valuable contribution. In the field of management of bleeding, a study demonstrated the potential benefits of treatment with VIIa recombinant factor.
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PMID:[The best of thrombosis in 2005]. 1647 60

A relationship is described between H. pylori infection and diseases localized beyond the gastrointestinal tract, for example: atherosclerosis, stenocardia, cerebral stroke, chronic urticaria, rosacea, hemicrania and in, children with height deficit or anaemia, caused by iron deficiency. Two cases of sideropenic anaemia in children resistant to oral iron are presented. Gastrointestinal tract symptoms were not observed and most probably the reason for anaemia was H. pylori infection. The first 14 years old patient with normal menstrual periods had been treated for four months by oral iron, without any effect (Hgb 10.2 g%, Fe 36.8%, ferritin < 10.8 mg%). On endoscopy of upper gastrointestinal tract there were macroscopic typical changes of H. pylori infection in antrum part of the stomach. On histological examination of biopsy segments inflammation of stomach mucosa in average intensification and H. pylori infection was confirmed. Recovery caused normalization of iron in the organism and of erythrocyte morphology. There was no recurrence of anaemia in long-term observation of the girl. A 14 years old boy treated without success for severe sideropenic anaemia (Hgb 7.1 g%), with positive family history (father has gastric ulcer). In spite of lack of gastrointestinal tract symptoms, on endoscopy there were features of chronic active hemorrhagic inflammation of stomach mucosa with H. pylori infection. Oral iron and effective eradication (proton pump inhibitor, amoxycillin, clarithromycin), achieved normalization of morphological changes. Recurrence of anaemia has not been observed.
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PMID:[Helicobacter pylori infection as a cause of sideropenic anaemia resistant to treatment - own observation]. 1682 22

Proton translocation in the catalytic cycle of cytochrome c oxidase (CcO) proceeds sequentially in a four-stroke manner. Every electron donated by cytochrome c drives the enzyme from one of four relatively stable intermediates to another, and each of these transitions is coupled to proton translocation across the membrane, and to uptake of another proton for production of water in the catalytic site. Using cytochrome c oxidase from Paracoccus denitrificans we have studied the kinetics of electron transfer and electric potential generation during several such transitions, two of which are reported here. The extent of electric potential generation during initial electron equilibration between CuA and heme a confirms that this reaction is not kinetically linked to vectorial proton transfer, whereas oxidation of heme a is kinetically coupled to the main proton translocation events during functioning of the proton pump. We find that the rates and amplitudes in multiphase heme a oxidation are different in the OH-->EH and PM-->F steps of the catalytic cycle, and that this is reflected in the kinetics of electric potential generation. We discuss this difference in terms of different driving forces and relate our results, and data from the literature, to proposed mechanisms of proton pumping in cytochrome c oxidase.
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PMID:Elementary steps of proton translocation in the catalytic cycle of cytochrome oxidase. 1682 27


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