SEARCH · PubMed Health

Results for “SULFINPYRAZONE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources

PubMed1982

High uric acid and urea clearance in cirrhosis secondary to increased "effective vascular volume".

Since urea and uric acid clearance are affected by the effective intravascular volume, we measured the fractional urea and uric acid excretion in cirrhosis. High urea and uric acid clearances were observed in 30 and 55 percent, respectively, of 20 consecutive cirrhotic patients with normal renal function. In seven patients with a high fractional uric acid excretion, 5 mg of isosorbide dinitrate every four hours for 24 hours induced a significant increase in the serum uric acid level (from 3.7 +/- 0.8 mg/dl to 4.4 +/- 0.8 mg/dl; less than 0.001) with a concomitant decrease in the fractional uric acid excretion (from 14.0 +/- 3.2 percent to 8.8 +/- 3.1 percent; less than 0.02). During the same test, the blood urea level increased from 3.3 +/- 1.1 mmol/liter to 4.1 +/- 1.2 mmol/liter (p less than 0.005) with a decrease in fractional excretion from 51 +/- 4.5 percent to 39 +/- 5 percent (p less than 0.001). The oral intake of sulfinpyrazone in six of these patients induced a normal uricosuric response. In two cirrhotic patients with ascites, 40 mg of furosemide associated with a 24-hour severe water restriction was also shown to normalize the high fractional excretion of both urea and uric acid. In nine patients with ascites, we observed a significant increase in blood urea and uric acid concentration despite the absence of change in creatinine clearance once ascites was removed by diuretics. On the basis of these findings, we believe that the high fractional excretion of both urea and uric acid frequently observed in cirrhosis is related to an increase in the effective vascular volume.

Blood Volume↗

PubMed1980

Platelet malondialdehyde in cardiovascular disease: effect of prosthetic heart valves and cardioactive drugs on production.

Malondialdehyde (MDA), a product of platelet lipid peroxidation, was measured in human platelet-rich plasma. Levels of 3.19 n moles/10(9) platelets /+- 0.40 S.E. in 11 patients with prosthetic heart valves were elevated (p < 0.25) compared to 17 normal subjects (2.09 /+- 0.13 n moles/10(9) platelets). Reduced production (1.44 /+- 0.28 n moles/10(9) platelets, p < 0.5) was found in 10 patients with unstable angina. Normal levels were found in patients with mitral stenosis, cardiomyopathy or hypertension. Usual serum levels of drugs used in cardiac treatment reduced MDA levels as follows: acetaminophen, 47% (p < .01); aspirin, 58% (p < .05); furosemide, 32.6% (p < .005), and sulfinpyrazone, 41% (p < .05). Digoxin, dipyridamole, heparin, hydrochlorothiazide, lidocaine, nitroglycerin, procainamide, propranolol, quinidine, or warfarin had no significant effect at therapeutic concentrations. None of the drugs explained the enhanced production in patients with prosthetic valves while enhanced production in patients with prosthetic valves while analgesic therapy could explain the decreased levels in other cardiacs. The half-time of platelet survival, measured by suppression of malondialdehyde production, was 3.2 /+- 0.24 days in 9 normal subjects but could not be measured reliably in most patients because of multiple drug therapies. We conclude that the blood platelets of patients with prosthetic heart valves differ from those of normal subjects in their capacity to release malondialdehyde after stimulation with n-ethylmaleimide. Additionally, we find that inhibition of malondialdehyde production by several pharmacologic agents limits the usefulness of this method for the measurement of platelet survival in cardiac patients.

Blood Platelets↗

PubMed1994

Antiplatelet therapy in the prevention of ischaemic stroke.

Prevention of stroke is a crucial health care issue, as stroke is the third cause of death and the first cause of major disability in developed countries. The established role of platelet aggregation in TIA or minor and major ischaemic stroke has provided the rationale for many randomized trials of antiplatelet agents (aspirin, sulfinpyrazone, dipyridamole alone or in combination with aspirin, suloctidil, ticlopidine). The recent Antiplatelet Trialists' Collaboration (APT) meta-analysis (1994) based on 142 trials involving 100,000 vascular patients confirmed the data of the previous overview (1988). Aspirin, the only drug evaluated for primary prevention of ischaemic events, is not indicated for safety reasons in subjects at low risk of occlusive disease. Compared to control, antiplatelet therapy, notably aspirin which is by far the most widely used agent in trials, provides a 27% risk reduction of stroke, myocardial infarction or vascular death in patients suffering from ischaemic vascular events and a 22% risk reduction of these outcomes in patients having experienced a prior TIA/stroke. Aspirin (around 325 mg/day) and ticlopidine (500 mg/day) are currently the reference drugs for secondary prevention in cerebrovascular patients. The long term efficacy of ticlopidine, a specific antiaggregating agent, has been evaluated in two North American trials involving more than 4,000 patients. TASS showed ticlopidine to be significantly more effective in reducing the incidence of fatal or nonfatal stroke and death than aspirin in patients with TIA or minor stroke. The relative risk reductions over aspirin, the first year of greatest risk, were 41% for stroke and death and 46% for fatal or nonfatal stroke. CATS showed that ticlopidine compared with placebo induces a significant 30% relative risk reduction of stroke, myocardial infarction and vascular death over three years in patients who had suffered a recent thromboembolic stroke. The above results elicit two important issues: the optimal dose of aspirin and its tolerability compared to ticlopidine. The three controlled trials (UK-TIA, SALT, Dutch TIA) which have compared high (> or = 1 g/day) and low dose aspirin (< or = 300 mg/day) or various low doses of aspirin did not give a definite answer on the efficacy of low or very low (30 or 75 mg/day) doses of aspirin for reducing the risk of vascular outcomes in patients with stroke precursors. Even with low doses of aspirin there was still a risk of severe gastrointestinal bleeding, although minor side effects were less frequent.(ABSTRACT TRUNCATED AT 400 WORDS)

Aspirin↗

PubMedDate not supplied

Effect of antirheumatic drugs on cathepsin B1 from bovine spleen.

The inhibitory effect on cathepsin B1 of 39 antirheumatic and other agents has been studied. The enzyme was purified from bovine spleen (specific activity 2.8 units/ml/E280 unit) and the effect of the drugs measured by determining the decrease of enzyme activity towards BANA as substrate. Analgesics, antimalarials, cytostatic agents, steroids as well as d-penicillamine, colchicine, allopurinol, chlorzoxazone and chlorpromazine either had no effect on cathepsin B1 or inhibited it to a very small extent. Typical anti-inflammatory and antirheumatic agents like gold and pyrazolone derivatives (with the exception of sulfinpyrazone) suppressed the activity of the enzyme at a concentration of 10(-6) M. Two others, indomethacin and diclofenac, suppressed it at a concentration of 10(-5) M. Two sulfonated polysaccharides, arteparon and pentosan polysulfate (SP54), were also potent inhibitors. Salicylates, however, inhibited cathepsin B1 only at much higher concentrations (10(-2) M. Higher concentrations of cysteine (2 mM) decreased the inhibitory effect of some otherwise effective drugs. Inhibition of cathepsin B1 may be one way in which some of the drugs tested exercise their therapeutic effect in rheumatic diseases.

Animals↗

PubMed1977

Uptake of uric acid by separated renal tubules of the rabbit. II. Effects of drugs.

The effect of various drugs on the rate of uptake of uric acid by separated renal tubules of the rabbit was investigated. Determinations were made of 150 values and slopes of the inhibition curves. The most potent inhibitor of uric acid uptake was sulfinpyrazone, with an 150 of 0.02 mM. Calcium ipodate and benzbromarone were also potent inhibitors. Uricosuric drugs, with the exception of benzbromarone, had shallow inhibition slopes. Diuretic drugs had steep inhibition slopes. More than one mechanism of action is probably involved in the inhibition of uric acid uptake in separated renal tubules by drugs.

Animals↗

PubMed1997

Rat liver cytochrome P450 metabolism of N-acetylbenzidine and N,N'-diacetylbenzidine.

To provide the information necessary for assessing risk and preventing tumorigenesis, the metabolism of N-acetylbenzidine and N,N'-diacetylbenzidine was assessed with rat liver microsomes from control and beta-naphthoflavone-treated rats. The oxidation of [3H]N-acetylbenzidine to [3H]N'-hydroxy-N-acetylbenzidine (N'HA), [3H]N-hydroxy-N-acetylbenzidine (NHA), and 3H-ring oxidation products was assessed. For [3H]N,N'-diacetylbenzidine, the formation of [3H]N-hydroxy-N,N'-diacetylbenzidine (NHDA) and the 3H-ring oxidation product was assessed. With beta-naphthoflavone-treated microsomes, the rate of NHA formation was 8-fold more than observed with control. Although significant formation of ring-oxidation products was demonstrated, the formation of N'HA was at the limit of detection. With control microsomes, N'HA was a major metabolite with more N'HA (49 +/- 6 pmol/mg protein/min) produced than NHA (38 +/- 5). Whereas the oxidation of N,N'-diacetylbenzidine was not observed with control microsomes, significant formation of NHDA (421 +/- 49 pmol/mg protein/min) and ring-oxidation (182 +/- 28) product was observed with beta-naphthoflavone-treated microsomes. Metabolism of [3H]N-acetylbenzidine and [3H]N,N'-diacetylbenzidine by beta-naphthoflavone-treated microsomes was completely inhibited by the specific cytochrome P4501A1/1A2 inhibitors alpha-naphthoflavone and ellipticine at 10 microM. Except for the < 30% inhibition observed with the cytochrome P4502E1 inhibitor (disulfiram), inhibitors of cytochrome P4503A1/3A2 (troleandomycin) and P4502C6 (sulfinpyrazone) were not effective at 10 microM. N'HA formation by control microsomes was not prevented by any of these inhibitors. Conditions that inhibit flavin-dependent monooxygenase metabolism, methimazole (1 mM), and heat treatment (37 degrees C for 60 min) were also ineffective in preventing N'HA formation. The nonspecific cytochrome P450 inhibitor SKF-525A (10 microM) exhibited a partial dose-response inhibition (maximum 41% of complete reaction mixture) of N'HA formation, but did not alter NHA formation. In contrast, the nonspecific cytochrome P450 inhibitor, 2,4-dichloro-6-phenylphenoxyethylamine prevented formation of both N'HA and NHA. beta-Naphthoflavone treatment increased [3H]N-acetylbenzidine binding to DNA, but not [3H]N,N'-diacetylbenzidine. Binding of both compounds to DNA was inhibited by ellipticine. N'-(3'-monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine was detected by 32P-postlabeling in microsomal incubations with N-acetylbenzidine, but not N,N'-diacetylbenzidine. More adduct was detected with control than beta-naphthoflavone-treated microsomes. Results are consistent with cytochrome P4501A1/1A2 playing the major role in N-acetylbenzidine and N,N'-diacetylbenzidine metabolism by liver microsomes from control and beta-naphthoflavone-treated rats. The formation of N'HA by control, but not by beta-naphthoflavone-treated, rats and its insensitivity to inhibition by cytochrome P4501A1/1A2 inhibitors were unexpected.

Animals↗

PubMed1997

A controlled letter intervention to change prescribing behavior: results of a dual-targeted approach.

OBJECTIVE: To determine the effectiveness of a drug utilization review (DUR) letter intervention sent only to physicians, sent only to pharmacists, or sent to both physicians and pharmacists in changing physician prescribing behavior for dipyridamole. DATA SOURCES/STUDY SETTING: A Wisconsin Medicaid prescription drug database for data from March 1991 through May 1992 related to both long-term care and ambulatory patient settings. STUDY DESIGN: The effects of a DUR letter intervention were tested using a field study, pre-post, nonequivalent control group, quasi-experimental design. The effects of the letter intervention in terms of dipyridamole expenditures (dollars reimbursed to pharmacies by Medicaid), expenditures for related drugs (aspirin, ticlopidine, sulfinpyrazone) and numbers of patients for whom dipyridamole was discontinued were examined across three experimental groups and a control group. DATA COLLECTION/EXTRACTION METHODS: Dipyridamole expenditures for each study patient during a six-month preintervention and six-month postintervention period were collected from Medicaid prescription drug claims. Patients who had zero dipyridamole expenditures throughout the six-month postintervention period were classified as having had dipyridamole discontinued. PRINCIPAL FINDINGS: Letters sent to both physicians and pharmacists resulted in a greater percentage of patients discontinuing dipyridamole relative to controls and statistically significant differences in postintervention dipyridamole expenditures relative to controls in both the long-term care and ambulatory patient populations. CONCLUSIONS: Interventions that focus on another person in the drug use process in addition to the physician may have greater effects on a change in the prescribing of a targeted drug than letters to physicians alone.

Aged↗

PubMed1976

Platelet adhesion, release and aggregation in flowing blood: effects of surface properties and platelet function.

Platelet adhesion to natural and artificial surfaces and adhesion-induced aggregation were investigated in vitro using an annular perfusion chamber. The surfaces were exposed to anticoagulated blood under identical flow conditions (approximately arterial shear rates). The initial attachment of platelets (contact) appeared less surface specific than spreading and release. Fibrillar collagen was the most powerful inducer of platelet degranulation whereas elastin, microfibrils and epon were virtually inactive. Fibrillar collagen caused release also in the absence of spreading. Surface coverage with platelets did not exceed 25% unless spreading occurred. Perfusion with platelet-free plasma or platelet-poor blood did not remove adhering platelets. However, platelets were translocated from mural thrombi to the surface by such perfusion. In addition, platelets which detached from mural thrombi adhered more readily to elastin or microfibrils than platelets from the circulating blood. The initial attachment of platelets to subendothelium was inhibited in von Willebrand's disease, the Bernard-Soulier syndrome and at high concentrations of dipyridamole; spreading was inhibited in storage pool disease of rats, at low temperature (20 degrees C), with EDTA (3 MM) and Prostaglandin E1 (1 muM); and adhesion-induced aggregation was inhibited in thrombasthenia, storage pool disease and after ingestion of sulfinpyrazone or Aspirin. It is concluded that the initial attachment (contact) of platelets, spreading and surface-induced release of platelet constituents are at least partially indendent phenomena, the latter two being highly surface specific. At flow conditions which cause the disappearance of platelet adhesion appears as an irreversible process.

Animals↗

PubMed1965