PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Meclofenamic Acid”

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 325 records · Page 18Linked to original sources
PubMed1984

Effect of enzymatically generated reactive oxygen metabolites on the cyclic nucleotide content in isolated rat glomeruli.

In the present study we examined the effect of reactive oxygen metabolites (generated by the xanthine-xanthine oxidase system), on adenosine-3',5'-cyclic monophosphate (cyclic AMP) and guanosine-3',5'-cyclic monophosphate (cyclic GMP) content in glomeruli and tubules that were isolated from rat renal cortex. Xanthine (0.1 mM)-xanthine oxidase (0.025 U/ml) significantly increased (P less than 0.001) the cyclic AMP content in glomeruli from 18 +/- 1 to 50 +/- 4 pmol/mg protein (n = 13). The response was dose dependent and was markedly inhibited (delta %-74 +/- 9, n = 3) by allopurinol (10(-3), a specific inhibitor of xanthine oxidase. Cyclic AMP content in the tubules, and the cyclic GMP content in glomeruli and tubules, were not altered by the xanthine-xanthine oxidase system. This lack of response was not due to lack of responsiveness of the tissues because parathyroid hormone caused a marked increase in the cyclic AMP content in tubules, and nitroprusside markedly increased the cyclic GMP content in glomeruli. The increase in cyclic AMP in glomeruli was due to generation of reactive oxygen metabolites rather than of other products (e.g. uric acid) of the xanthine-xanthine oxidase reaction--addition of uric acid to incubations had no effect; using another substrate for xanthine oxidase, acetaldehyde significantly increased (delta % 112 +/- 7, n = 4, P less than 0.001) the cyclic AMP content; and catalase that destroys hydrogen peroxide caused a marked inhibition (delta % -90 +/- 5, n = 4) of the response to xanthine-xanthine oxidase. The marked inhibition by catalase, and the lack of effect of superoxide dismutase (in a concentration that completely scavenged superoxide) suggested hydrogen peroxide as the responsible oxygen metabolite for the observed effect. Glucose-glucose oxidase (a system that directly generates hydrogen peroxide), and direct addition of hydrogen peroxide caused a dose-dependent increase in the cyclic AMP content in glomeruli, which further supports the role of hydrogen peroxide as the responsible species for the observed effect. Additional experiments that used prostaglandin synthesis inhibitors and antagonists of serotonin and histamine suggested that hydrogen peroxide increases cyclic AMP content in glomeruli by enhancing prostaglandin synthesis.

Allopurinol↗
PubMed2002

Molecular modelling of the differential interaction between several non-steroidal anti-inflammatory drugs and human prostaglandin endoperoxide H synthase-2 (h-PGHS-2).

The prostaglandin endoperoxide H synthase-1 (PGHS-1) and prostaglandin endoperoxide H synthase-2 (PGHS-2) are the targets of non-steroidal anti-inflammatory drugs (NSAIDs). The high degree of selectivity for inhibition of PGHS-2 shown by certain compounds appears to stem from two mechanisms (time-dependent, time-independent inhibition) by which they interact with each isoform. Molecular models of the complexes between indomethacin, fenamates, 2-phenylpropionic acids and the selective cyclooxygenase-2 (COX-2) inhibitors, with the cyclooxygenase active site of human PGHS-2 have been built by combining homology modelling, conformational searching and automated docking techniques. The stability of the resulting complexes has been assessed by molecular dynamics simulations combined with extended linear response calculations. The results allow us to identify regions of biological significance consistent with both X-ray crystallographic and kinetic results. The selective PGHS-2 inhibitors exploit the extra space of a side-pocket in the active site of PGHS-2 that is not found in PGHS-1. The results obtained point out a marked relationship between the experimental affinity and the electrostatic interaction energy alone for a series of NSAIDs. Analysis of the structural and the energetic data provides evidence supporting that network of hydrogen bonds between Tyr355, Glu524, Arg120 and Arg513 might be involved in mediating the binding of the time-dependent inhibitors of PGHS-2.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1983

Double-blind multicenter studies with meclofenamate sodium in the treatment of rheumatoid arthritis in the United States and Canada.

The therapeutic efficacy of N-(2,6-dichloro-m-tolyl)anthranilic acid, sodium salt (meclofenamate sodium, Meclomen) in the management of rheumatoid arthritis was clearly established in four large, double-blind, controlled multicenter studies in 757 patients. In one study, 200 mg/day of meclofenamate sodium was compared with 300 mg/day and placebo for six weeks. Another compared meclofenamate sodium, 300 mg/day, with acetylsalicylic acid (ASA), 3.6 g/day, for eight weeks. Two other long-term studies compared meclofenamate sodium and ASA, 300 mg/day and 3.6 g/day, respectively, for six months; in one, the patients were allowed to receive concomitant gold salts or steroids, while in the other, they were not. Both objective and subjective measures showed that meclofenamate sodium was as effective as ASA and superior to placebo. Gastrointestinal reactions, most commonly diarrhea, were seen more often with meclofenamate sodium than with ASA or placebo, but withdrawal for adverse reactions did not differ significantly between treatment groups. ASA-associated side effects such as tinnitus and deafness were not experienced by the patients receiving meclofenamate sodium. Meclofenamate sodium is a safe, effective agent for the treatment of rheumatoid arthritis.

Adolescent↗
PubMed1980

Prostaglandins activation of erythropoietin production and erythroid progenitor cells.

A model is presented postulating a role for prostaglandins E and prostacyclin in kidney generation of erythropoietin and the activation of the erythroid progenitor cell (CFU-E) compartment by erythropoietin (Ep). Several criteria have been met to prove that prostanoids mediate erythropoiesis: 1) several E-type prostaglandins (PGE2, 15-methyl prostaglandin E2, 16,16-dimethyl E2, 6-keto-E1 and PGE1) produced a significant increase in radioiron incorporation in red cells of exhypoxic polycythemic mice; 2) prostaglandin E2 increased kidney production of erythropoietin in the isolated perfused dog kidney; 3) arachidonic acid, a precursor for all bisenoic prostaglandins, increased kidney production of erythropoietin in the isolated perfused dog kidney which was blocked by pretreatment with the cyclo-oxygenase inhibitor drug indomethacin; 4) hypoxemic perfusion of the isolated perfused dog kidney increased kidney production of erythropoietin and produced an elevation in prostacyclin in the perfusates; 5) albuterol, a beta-2 adrenergic agonist, produced a significant increase in perfusate levels of erythropoietin and PGE in the isolated perfused dog kidney; 6) renal ischemia increased Ep and PGE levels in renal venous plasma which was blocked by pretreatment with indomethacin; 7) prostaglandin E2 and arachidonic acid produced a significant increase in erythroid colonies (CFU-E) in vitro in normal mouse bone marrow; 8) E-type prostaglandins (15-methyl E2) increased in vivo erythroid colony (CFU-E) formation in bone marrows of post-hypoxic polycythemic mice; and 9) injections of 15-methyl E2 daily for six weeks in normal and hypoxic mice produced a significant elevation in the total circulating red cell mass. These studies indicate that hypoxic stimulation of kidney production of erythropoietin may be related to the generation of prostacyclin (PGI2). On the other hand, albuterol and ischemic (reduction in renal blood flow) stimulation of kidney production of erythropoietin involves prostaglandins of the E type. In addition, E-type prostaglandins were found to enhance the effects of erythropoietin in activating erythroid progenitor cells (CFU-E) in the bone marrow. We postulate from our model that prostaglandins E and prostacyclins are involved in the mechanism of kidney production of erythropoietin as well as the activation of the Ep-responsive cell (ERC) compartment.

Albuterol↗
PubMed1989

Effect of a lipoxygenase inhibitor on vasoconstriction in dog lung.

The effects of lipoxygenase inhibition and cyclooxygenase plus lipoxygenase inhibition on the pressor responses to serotonin (5-HT), acetylcholine (ACh), and norepinephrine (NE) were studied in the isolated, blood-perfused dog lung. Bolus doses of 50-250 micrograms 5-HT, 1-5 mumol ACh, and 10-50 micrograms NE were given before and after the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), or the cyclooxygenase inhibitor, meclofenemate (Meclo), followed by NDGA. Lobar vascular resistance (LVR) was partitioned into upstream (Ra) and downstream (Rv) segments by venous occlusion. 50 microM NDGA did not change base-line LVR, Ra, or Rv; however, 100 microM NDGA increased base-line LVR (P less than 0.05) without increasing Ra or Rv (P greater than 0.05). Neither 50 or 100 microM NDGA affected the pressor response to 5-HT, ACh, or NE; however, the response to 50 micrograms 5-HT was slightly enhanced. Meclo increased base-line LVR (P less than 0.05) and subsequent addition of 50 microM NDGA did not change LVR (P greater than 0.05) from post-Meclo values. The LVR increase to both 5-HT and ACh was potentiated after Meclo (P less than 0.05) and 50 microM NDGA after Meclo did not change the LVR increase to either 5-HT or ACh. In contrast, Meclo did not enhance the pressor response to NE, and addition of 50 microM NDGA after Meclo diminished the increase to 20 and 50 micrograms NE (P less than 0.05). Our results suggest that unlike cyclooxygenase inhibition, lipoxygenase inhibition does not increase base-line LVR or the pressor response to either 5-HT or ACh.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1995

Nitric oxide-related vasoconstriction in lungs perfused with red cell lysate.

The present study in isolated rat lungs demonstrates that nitric oxide gas (.NO, 70 nM) added to the perfusate containing a small amount of hemolysate [175 microliters of lysed red blood cells (RBC) per 50 ml of Earle's balanced salt solution (EBSS)] triggered profound and sustained vasoconstriction. Vasoconstriction was not observed when .NO was added to lungs perfused with washed intact rat or human RBC or with oxyhemoglobin (Hgb 20 microM). The presence of hemolysate in the perfusate also caused vasoconstriction in response to n-acetylcysteine (50 microM), glutathione (10(-4) M), or ascorbic acid (10(-4) M) and potentiated greatly the vasoconstrictor response to 5 mM KCl. Not only .NO, but also nitroprusside (SNP) or L-arginine and paradoxically three .NO synthesis inhibitors, including N-monomethyl L-arginine, L-NAME, and nitroblue tetrazolium, which have different mechanisms of action, each caused in the presence of hemolysate large vasoconstrictive responses. Hemolysate itself enhanced O2 consumption by slices of lung; no effects of this dose of .NO on lung slice respiration were seen in the absence of hemolysate. Both Hgb and hemolysate lowered perfusate cGMP levels to the same degree suggesting that the vasoconstrictive response was not due to unique effects of hemolysate on guanylyl cyclase. Addition of superoxide dismutase (SOD) and catalase (CAT) to the hemolysate containing perfusate, or addition of a cyclooxygenase or 5-lipoxygenase inhibitor, virtually abolished the .NO induced vasoconstriction. The latter data are consistent with the concept that exposure of the vasculature to hemolysate may result in the formation of peroxynitrite. However, SOD and CAT did not abolish the pulmonary vasoconstriction induced by L-arginine or by NAC. Our data indicate that hemolysate has profound effects on lung vessel tone regulation and on lung tissue mitochondrial function, yet the precise molecular mechanisms responsible for the action of hemolysate are likely to be very complex.

Animals↗
PubMed1984

Selection of therapeutic agents for intraocular proliferative disease. Cell culture evaluation.

A variety of antimetabolites, steroids, and nonsteroidal anti-inflammatory agents were tested for their ability to inhibit rabbit dermal and conjunctival fibroblast proliferation in cell culture. Doxorubicin hydrochloride and fluorouracil produced notable inhibition in concentrations of less than 1 mg/L. Meclofenamate sodium and indomethacin produced notable inhibition at concentrations of 11 and 40 mg/L, respectively. Dexamethasone sodium phosphate and triamcinolone acetonide produced inhibition at 200 and 150 mg/L, respectively, but paradoxically increased proliferation almost two-fold at concentrations ranging from 1 to 30 mg/L under identical culture conditions. Methotrexate sodium demonstrated only limited effectiveness. This assay system may be a useful approach to drug selection in the treatment of a variety of ocular proliferative disorders. Fluorouracil may prove to be of significant value in the treatment of intraocular proliferative disorders.

Animals↗
PubMed1987

Meclofenamate sodium monohydrate inhibits chemotactic factor-induced human polymorphonuclear leukocyte function. A possible explanation for its antiinflammatory effect.

Meclofenamate sodium monohydrate (MSM), a potent nonsteroidal antiinflammatory agent, specifically inhibits chemotactic factor-induced human polymorphonuclear leukocyte functions: chemotaxis, degranulation, and generation of superoxide anion radicals. These effects of MSM were found to be dependent upon the concentrations of drug not bound to albumin (free drug), and were caused by its ability to interfere at both a receptor and post-receptor (i.e., a step distal to mobilization of polymorphonuclear leukocyte intracellular Ca2+) level. These unique actions of MSM may provide a partial explanation for its potent antiinflammatory effect.

Adult↗
PubMedDate not supplied

Analgesic efficacy of meclofenamate sodium in episiotomy pain.

Meclofenamate sodium was compared, double-blind, with codeine and placebo for the treatment of acute episiotomy pain. One hundred sixty-eight women with moderate or severe episiotomy pain after normal delivery were assigned randomly to one of four treatment groups: one received meclofenamate sodium 200 mg at dose 1 and 100 mg at doses 2 and 3; one received meclofenamate sodium 100 mg at dose 1 and 50 mg at doses 2 and 3; one received codeine 60 mg at all three doses; and one received placebo at all three doses. Efficacy measurements were evaluated periodically for 6 hours after medication. After the first administration, both doses of meclofenamate sodium were significantly superior to placebo and to codeine from 2-6 hours in pain intensity difference and pain relief. For second and third doses, data were available for too few patients to allow valid analysis and interpretation. Adverse effects occurred in 4 patients in each meclofenamate sodium group, and in 8 in the codeine group and in 6 in the placebo group. The study indicates that single 100- and 200-mg doses of meclofenamate sodium are as safe as, and significantly more effective than, codeine 60 mg or placebo for episiotomy pain.

Adolescent↗
PubMed1979

Blood flow and permeability changes in the immune lymphocyte transfer reaction.

Blood flow (133Xe clearance) and plasma exudation ([133I]HSA) have been measured in the immune lymphocyte transfer (ILT) reaction and skin grafts in rabbits. Injection of sensitised lymphocytes produced a dose-related increase in plasma exudation and blood flow at 48 hr, reached a maximum at day 3 and faded from day 5 to 8. There was an increased blood flow and plasma exudation on day 4 after grafting autografts and homografts, but the increase in plasma exudation was significantly higher in homografts. In the ILT reaction (48 hr) and the homografts (4 days) but not in autografts, prostaglandin synthetase inhibition caused a significant reduction in the increased blood flow, but did not abolish it nor did they affect the increased plasma exudation. It is concluded that the ILT reaction is a suitable model for the study of mediators of the vascular effects of the early phase of the skin graft reaction. The present experiments suggest that the vasodilatation is partly due to prostaglandin formation, but part of the vasodilatation and all the plasma exudation are mediated by substances other than prostaglandins.

Animals↗
PubMedDate not supplied

Vasodilatory effect of aerosol histamine during pulmonary vasoconstriction in unanesthetized sheep.

The effects of aerosol histamine on pulmonary vascular resistance during pulmonary vasoconstriction were studied in 12 unanesthetized sheep. Sheep were chronically instrumental with Silastic catheters in the pulmonary artery and left atrium, thermodilution Swan-Ganz catheter in the main pulmonary artery for measurement of cardiac output, and tracheostomy for delivery of hypoxic gas and/or aerosol histamine. Seven minutes of isocapnic hypoxia (FIO2 = 0.12) caused pulmonary artery pressure (PPA) to increase from 17.2 +/- 0.4 to 27.0 +/- 1.0 cm H2O (mean +/- SEM, P less than 0.05) and pulmonary vascular resistance (PVR) to increase from 3.94 +/- 0.33 to 4.71 +/- 0.38 cm H2O x L-1 x min (P less than 0.05). When sheep breathed a combination of aerosol histamine (5 mg/ml) and 12% O2, PPA rose only 21.3 +/- 1.11 cm H2O and PVR decreased to 3.51 +/- 0.31 cm H2O x L-1 x min. This was a significantly (P less than 0.05) smaller response compared to hypoxia alone. Aerosol histamine alone had to significant effect on PPA or PVR. Meclofenamate did not restore the histamine-induced loss of hypoxic vasoconstriction. Aerosol histamine significantly blunted the pulmonary vasoconstriction caused by intravenous serotonin (8 micrograms/kg/min) and intravenous prostaglandin H2-analog (0.74 microgram/kg/min). It was concluded that in the awake sheep aerosol histamine acted as a pulmonary vasodilator only in the presence of pulmonary vasoconstriction.

Aerosols↗
PubMed1991

The effect of intravascular complement activation and brief episodes of hypoxia on protein in bronchoalveolar lavage fluid in C5 sufficient and deficient mice.

Our earlier investigations indicated that systemic complement activation with iv cobra venom factor (CVF) or infused zymosan-activated rabbit plasma or rabbit C5a does not significantly increase bronchoalveolar lavage albumin in rabbits (Am Rev Respir Dis 1982; 125:335-340); but that complement activation due to CVF combined with a brief episode of hypoxia increases lavage albumin and is associated with the presence of neutrophils for its expression (J Clin Invest 1985; 75:902-910). In order to determine if intravenous CVF and hypoxia cause similar alterations in mice, and to investigate the time course of the response as well as the importance of C5 fragments to the process, we challenged the B10.D2/nSn strain of C5 sufficient mice (C5+) and the congenic B10.D2/oSn strain of C5 deficient mice (C5-) with intravenous CVF, 15 min of 12% oxygen, or CVF followed by hypoxia. Neither C5+ nor C5- mice had significant increases in lavage protein after either CVF or hypoxia. However, the combined insults significantly increased lavage protein in C5+ but not C5- mice; polyacrylamide gel electrophoresis showed increased amounts of proteins of low and high molecular weights in lavage fluid from the C5+ strain. While the time course of abnormalities in mice was different from that in rabbits, both meclofenamate pretreatment and neutrophil depletion attenuated the increases in lavage protein after the combined insults in both animal species. Infusion of prostaglandin E2 (PGE2) with CVF in the C5+ mice also led to significant increases in lavage protein. We conclude that in mice, intravenous complement activation, as an isolated event, does not cause a significant increase in lavage protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Nitrone spin-traps block calcium channels and induce pulmonary artery relaxation independent of free radicals.

Free radicals react with nitrones to form stable nitroxides which can be identified by ESR spectroscopy. Unfortunately, little is known regarding the pharmacological properties of these compounds. In this study, three commonly used nitrones, 5,5-dimethylpyrroline-N-oxide (DMPO), alpha-phenyl-tert-butylnitrone (PBN), and alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), were found to induce relaxation of preconstricted isolated rat pulmonary artery rings. Additional experiments with PBN indicated that vasorelaxation could not be attributed to production of endothelial derived factors, prostaglandins, or free radicals. Patch-clamp techniques revealed reversible calcium channel blockade with PBN at a concentration below that needed to detect free radicals. Calcium channel blockade probably accounts for the vasorelaxation observed in the isolated ring preparations described here, and should be considered when using nitrone spin-traps both in in vivo and clinical studies.

Animals↗
PubMed1990

Interactions between the brain renin-angiotensin system and brain prostanoids in the control of vasopressin secretion.

Experiments were carried out in conscious, unrestrained, male rats to evaluate possible interactions between brain prostanoids and the brain renin-angiotensin system in the control of vasopressin release and in cardiovascular regulation. The intracerebroventricular (icv) administration of prostaglandin D2 (PGD2) resulted in transient increases in the plasma vasopressin concentration (PAVP) and heart rate and a gradual increase in mean arterial blood pressure (MABP). Pretreatment icv with saralasin, an angiotensin II-receptor antagonist, moderately attenuated the vasopressin response to PGD2, but had no effect on the heart rate and blood pressure responses. Angiotensin II icv increased both PAVP and MABP. This vasopressin response was almost completely prevented by prior icv meclofenamate, a cyclooxygenase inhibitor, and the blood pressure response was attenuated. These observations, combined with previous studies of the role of central angiotensin II and central prostanoids in the physiological control of vasopressin release, suggest that there may be important interactions between brain prostanoids and the brain renin-angiotensin system in this control.

Angiotensin II↗
PubMed1995

Prostaglandins are involved in the stimulation of renin gene expression in 2 kidney-1 clip rats.

This study was done to obtain information about a possible involvement of prostaglandins in the renal baroreceptor mechanism regulating renin secretion and renin gene expression. To this end the effect of the cyclooxygenase inhibition was examined on renin secretion and on renal renin gene expression in 2 kidney-1 clip rats. The influences of the cyclooxygenase inhibitors indomethacin (2mg/kg twice a day) and meclofenamate (8 mg/kg twice a day) on renal renin m-RNA levels, on plasma renin activity (PRA) and on blood pressure were measured 2 days after clipping the left renal arteries of male Sprague-Dawley rats with 0.2 mm clips. In sham-clipped animals, indomethacin and meclofenamate had no significant effect on basal PRA and renin m-RNA levels. In vehicle-treated animals unilateral renal artery clipping increased blood pressure from 120 +/- 4.1 to 150 +/- 6.1 mmHg, increased PR6A from 7.4 +/- 1.6 to 27.6 +/- 3.8 as expressed in nanograms of angiotensin I per hour per millilitre, increased renin m-RNA levels of clipped kidneys from 105 +/- 5.9% of standard to 482.6 +/- 56% of standard and decreased renin m-RNA levels of contralateral kidneys from 116 +/- 9.7% of standard to 34 +/- 9.0% of standard. While blood pressure, PRA and renin m-RNA levels of the contralateral kidneys were virtually unchanged by the cyclooxygenase inhibitors indomethacin and meclofenamate, renin gene expression in the clipped kidney was markedly influenced by inhibition of prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗