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PubMed2002

Efficacy and safety of low-dose fluticasone propionate compared with montelukast for maintenance treatment of persistent asthma.

OBJECTIVE: To compare the long-term effects of an inhaled corticosteroid with those of a leukotriene modifier on measures of clinical efficacy, subject preference, and safety in patients with persistent asthma. PATIENTS AND METHODS: Between November 17, 1998, and May 26, 2000, we conducted a multicenter, randomized, double-blind, double-dummy, parallel-group study of patients aged 15 years or older with persistent asthma. The patients were symptomatic while taking short-acting beta2-agonists alone and were treated with fluticasone propionate (88 microg [2 puffs of 44 microg] twice daily) or montelukast (10 mg/d) for 24 weeks. Measures of pulmonary function, asthma symptoms, albuterol use, nighttime awakenings, physician assessments of efficacy, patient satisfaction, asthma-related quality of life, and safety were evaluated. RESULTS: A total of 522 patients were randomized to receive fluticasone or montelukast, and 395 patients completed the study. At end point, treatment with fluticasone significantly improved pulmonary function, asthma symptom scores, the percentage of symptom-free days, rescue albuterol use, and the number of nighttime awakenings due to asthma when compared with montelukast (P< or = .002, each comparison). Significantly more patients were satisfied with fluticasone therapy (83%) compared with montelukast therapy (66%) (P<.001), and fluticasone therapy was rated as effective by a significantly greater portion of physicians (67%) than was montelukast therapy (54%) (P<.001). Treatment with fluticasone significantly improved asthma-related quality-of-life measures compared with montelukast (P< or =.01). The incidence of asthma exacerbations was similar in the fluticasone (19 patients, 7%) and montelukast (21 patients, 8%) treatment groups, although slightly more patients in the montelukast group were withdrawn from the study because of asthma exacerbations (6% vs 4%, respectively). CONCLUSION: Long-term treatment with a low dose of inhaled fluticasone is more effective than oral montelukast as first-line maintenance therapy for the treatment of persistent asthma.

Acetates↗
PubMed1975

[Anti-inflammatory action of 2-(2-fluoro-4-biphenylyl) propionic acid (flubiprofen].

2-(2-fluoro-4-biphenylyl) propionic acid (flurbipofen, FP-70), a newly synthesized anti-inflammatory agent, was examined for its effects and then compared with the actions of other standard drugs. Inhibition of capillary permeability in mice: the activity of FP-70 was 7.8 times as potent as ibuprofen (IP), 61 times that of acetylsalicylic acid (AS), 5.7 times that of indomethacin (IM) and 25 times that of phenylbutazone (PB). Inhibition of carrageenin-induced edema in rat paw: the activity of FP-70 was 52 times as potent as IP, 250 times that of potent as AS, 14 times that of potent as IM and 110 times that of potent as PB. Inhibition of heat-induced coagulation of BSA: the activity of FP-70 showed the marked effects much the same as IP. In adrenalectomized rat, FP-70 was also effective. Inhibition of the ultra-violet erythema in guinea-pigs, the activity of FP-70 was 26 times as potent as IP, 790 times that of AS, 25 times that of IM and 68 times that of PB. Regarding the inhibition of CMC induced pouch in rats, the potency of FP-70 was to the same degree as that of predonisolone. In adjuvant induced arthritis in rats, FP-70 reduced and cured inflammatory syndromes and activity was the same or more effective than that of IM. From these results, FP-70 appears to be a most potent nonsteroidal anti-inflammatory agent.

Animals↗
PubMed1977

[Effects of methy-2[(chloro-4'-benzoyl)-4-phenoxy]-2 propionic acid on the respiratory activity of isolated rat liver mitochondria].

The effects of methyl-2 [(chloro-4' benzoyl)-4 phenoxy]-2 propionic acid (LF 153) on mitochondrial respiration and oxidative phosphorylation are studied in vitro. Its activity is related to that of 3,5,3'-triiodo-L-thyronine (LT3), 3,5,3'-triiodothyroacetic acid (TA3), and to that of clofibrate, LF 153 acts as an inhibitory uncoupler of oxidative phosphorylation. Its uncoupling action is however very intense.

Animals↗
PubMed2004

Propionic acidemia and zinc deficiency presenting as necrolytic migratory erythema.

Necrolytic migratory erythema was first described in 1942 in a patient with pancreatic islet cell carcinoma. The disease can, however, have other etiologies including nutritional dermatoses. Here, we describe the clinicopathological picture of a 7-year-old female patient who presented with necrolytic migratory erythema which we believe is secondary to a rare combination of zinc deficiency and propionic acidemia.

Acrodermatitis↗
PubMed1992

[Pathology and pathogenesis of propionic acidemia].

Described in this paper are pathomorphological alterations in a male newborn with propionic acidemia. Adequate cases from the international literature are evaluated, and the pathogenesis is discussed. The pathological findings are predominantly degenerative alterations in the brain and proteinaceous deposits in liver, kidney, skin and fatty tissue.

Adipose Tissue↗
PubMedDate not supplied

[Effect of propionate pathway metabolites on the oxidative activity of liver mitochondria under normal conditions and in vitamin B12 deficiency].

We performed a comparative investigation in vivo and in vitro of the propionate and methylmalonate effect on oxidative activity of liver mitochondria in control and vitamin B12-deficient rats and found that efficiency of the effects were less pronounced in vitamin B12-deficient rats. It is also shown that the rates of respiration and phosphorylation decreased in liver mitochondria of vitamin B12-deficient rats.

Animals↗
PubMed2005

Synthesis of some new 2-(2-fluoro-4-biphenylyl)propionic acid derivatives as potential anti-inflammatory agents.

The synthesis of a group of 1,3,4-oxadiazoles, 1,2,4-triazoles, 1,3,4-thiadiazoles and 1,2,4-triazine derived from 2-(2-fluoro-4-biphenylyl) propionic acid is described. The structures of new compounds are supported by IR, 1H NMR and MS data. These compounds were tested in vivo for their anti-inflammatory activity. The compounds which showed activity comparable to the standard drug flurbiprofen, were screened for their analgesic, ulcerogenic and lipid peroxidation activities. Five out of seventeen new compounds, showed very good anti-inflammatory activity in the carrageenan induced rat paw edema test with negligible ulcerogenic action. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde production (MDA), which is one of the byproducts of lipid peroxidation. The study showed that the compounds inhibit the induction of gastric mucosal lesions and it can be suggested from our results that their protective effects may be related to an inhibition of lipid peroxidation in the gastric mucosa.

Animals↗
PubMed1990

[Molecular basis of organic acidemia--propionic acidemia].

Propionic acidemia is an inborn error of organic acid metabolism caused by deficiency of propionyl-CoA carboxylase (PCC: E. C. 6. 4. 1. 3.). We have detected three types of mutation in the same exon of the coding sequence of beta-subunit of PCC (beta PCC) from two ethnic background (Caucasians and Japanese): an insertion/deletion which replaces 14 nucleotides with 12 unrelated nucleotides results in the elimination of an Msp I site; a 3-bp inframe deletion results in loss of one of two consecutive isoleucine codons immediately preceding the same Msp I site; the C----T transition results a in loss of the same Msp I site. The insertion/deletion and the C----T transition show high allele frequency in Caucasians (0.32) and in Japanese (0.3), respectively. These results reveal the possibility of the independent origin of the mutation in the two ethnic backgrounds and suggest a key role of this exon in the structure and catalytic function of the beta-subunit of PCC.

Acyl Coenzyme A↗
PubMed1989

3-(2-Imidazo[4,5-b]pyridine)propionic acid and some of its derivatives with suspected tuberculostatic activity.

The reactions of corresponding 2,3-diamino-pyridines with succinic anhydride were carried out. 3-(2-Imidazo[4,5-b]pyridine)propionic acid and its N-1 and N-3 methyl derivatives were isolated. The acids obtained were converted into the esters, amides, nitriles, thioamides, amidoximes and hydrazides. Some of the synthesized compounds were tested for tuberculostatic activity.

Antitubercular Agents↗
PubMedDate not supplied

Synthesis and pharmacological properties of diphenylimidazolidine acetic and propionic acids derivatives.

Several derivatives of diphenylimidazolidine-2,4-dione and diphenylimidazolidin-4-one acetic and propionic acids have been synthesized. Some of them were screened for their effect on the CNS in mice and rats. All the investigated compounds showed an analgesic activity. The most active one was 1-benzyl-5,5-diphenyl-3-imidazolidine-2,4-dione acetic acid. That compound exerted an inhibitory activity against the CNS, anxiety-relieving, anticonvulsant and antidepressive effects.

Acetates↗
PubMed1989

[The evaluation of hormone and metabolite profiles after the infusion of glucose, propionate and butyrate in cattle].

Lactational performance in high-yielding dairy cows has its limits in metabolic processes. Energy metabolism is maintained by mobilization of body reserves via hormonal regulation, resulting in lipolysis and sometimes ketoacidosis. For characterization of such conditions the intraruminal and intravascular application of glucose and volatile fatty acids was used in ruminant physiology. On the other hand the results of such experiments were correlated to actual and potential milk yield. For this investigation pairs of monozygous Holstein Friesian twins were tested as heifers and as cows by intravenous infusion of glucose, propionate and butyrate after 18 hours of feed withdrawal. Insulin, growth hormone, glucose, free fatty acids and beta-hydroxybutyrate were measured before, during and up to 4 hours after infusion of substrates. Each substrate caused a transient change in plasma concentrations of metabolites and hormones. Differences between heifers and cows are discussed with the time series of the mean concentrations. The reaction profile of each animal was characterized by different parameters. Analysis of these parameters revealed a close relation between hormones and metabolites even under the conditions of the load-test.

Animals↗
PubMed1986

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 2nd communication: inhibitory effects on acute inflammation and prostaglandin-related reactions.

Since a newly synthesized nonsteroidal antiinflammatory drug (NSAID) having weaker effects on gastrointestinal tract, 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid (CN-100), was found to markedly inhibit rat paw edema induced by carrageenin and other phlogists, the effects of the drug on other acute inflammatory reactions and prostaglandins (PGs)-related reactions were compared with those of known NSAID in this study. At even a large dose of CN-100, 20 mg/kg, the drug did not significantly inhibit the increased vascular permeability induced by histamine in rat skin, but CN-100 could dose-dependently inhibit the increased vascular permeability induced by acetic acid in mouse peritoneum. The inhibitory activity of CN-100 in the latter was equivalent to that of pranoprofen and indometacin. CN-100 exerted a potent inhibitory action on erythema induced by UV irradiation, which was equal to and 3 times stronger than pranoprofen and indometacin in activity, respectively. Since PGs participate in these acute inflammatory reactions, the effects of CN-100 on reactions relevant to PGs were examined. The drug at dose levels lower than antiinflammatory doses could prevent acute death and diarrhea induced by i.v. injection of arachidonic acid in rabbits and endotoxin in mice, respectively, suggesting that the drug had a potent inhibitory action on biosynthesis of PGs. The adverse effects of CN-100 on gastric and small intestinal mucosa was very weak, the activity being about one-tenth of that of pranoprofen and indometacin.

Animals↗
PubMed1988

Studies on aziridine derivatives. III. Synthesis and immunopharmacological activity of aziridine derivatives of propionic acid.

Several new aziridine derivatives of propionic acid were synthesized (10-15, 19, 20). o-, m-, p-Chloroanilide of chloroacetic acid 1-3 and chloride of 3-/p-chlorobenzoyl/acrylic acid 16 were the substrates. The compounds 1-3 in reaction with nicotine aldehyde or p-chlorobenzaldehyde were transformed into appropriate anilides of 2,3-epoxypropionic acid 4-9. These, in turn reacted with ethylenimine giving the appropriate 3-aziridine derivatives 10-15. Acid chloride 16 in reaction with amines gave the appropriate amides 17 and 18 which formed 2-aziridine derivatives 19 and 20 when under the influence of ethylenimine. Pharmacological analysis revealed that the aziridine derivatives 12-15, 19 and 20 modulate some immunological reactions with the prevailing effect of the suppressive component (PFC, RFC, IgM level, cellular response to SRBC). The stimulatory effect was observed with some compounds on the level of circulating IgG and GvH reaction. The mechanism of these compounds consists in their interference with the activity of Ts cells and mediators of the immunological reactions.

Animals↗
PubMedDate not supplied

Enantiomer resolution and assay of propionic acid-derived herbicides in formulations by using chiral liquid chromatography and achiral gas chromatography.

Enantiomers of 6 propionic acid-derived herbicides in the form of their esters were resolved using liquid chromatography with a chiral column. Free acids are converted to methyl esters by means of a BF3-catalyzed reaction. Chromatographic resolutions for 6 of 8 herbicides investigated were in the range of 2 to 4. The method was applied for the simultaneous determination of mecoprop and 2,4-D content and individual mecoprop enantiomers in 2 formulations containing racemic and R-mecoprop in mixture with 2,4-D. Precision and accuracy of content determination was comparable to standard methods, and enantiomer contents were in good agreement with declared values. The enantiomers of dichlorprop and mecoprop were also resolved as diastereomeric menthyl esters by achiral high resolution gas chromatography (HRGC). HRGC data on enantiomer composition were in good agreement with those from the LC method and other data.

Chromatography, Gas↗
PubMed1986

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 1st communication: inhibitory effects of rat paw edema.

In the development process of a new nonsteroidal antiinflammatory drug (NSAID) with less toxicity and side-effects, 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepein-2-yl) propionic acid (CN-100) was chosen as the most excellent NSAID from synthetic tricyclic compounds after screening test. For the series of studies on antiinflammatory effects of this compound in detail, its effect on rat paw edema induced by various phlogists was first investigated. The inhibitory effect of CN-100 on carrageenin-induced edema was remarkable and nearly equal to that of indometacin. The effect was not affected by continuous administration for 2 weeks or adrenalectomy. Similarly to indometacin, CN-100 had no significant effect on yeast-induced edema mediated by 5-hydroxytryptamine and concanavalin-A-induced edema unrelated with prostaglandins. However, CN-100 displayed a weaker inhibitory effect on nystatin-induced edema than indometacin, suggesting that CN-100 has a low membrane stabilizing action and a strong blocking action on synthesis of prostaglandins. CN-100 inhibited the sustained edema induced by mustard, but the drug did not interfere with the increase in body weight of rats. Indometacin in the same dose caused decrease in body weight and death. The toxicity of CN-100 was definitely less than that of indometacin, although both drugs were similar in antiinflammatory activity and mode of action on rat paw edema. Results suggest that CN-100 is an effective drug on not only acute but also subacute and chronic inflammation.

Adrenalectomy↗
PubMed1986

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 3rd communication: inhibitory effects on leucocyte emigration and proliferation of granulation.

The effects of 2-(10,11-dihydro-10-oxodibenzo [b,f]thiepin-2-yl)propionic acid (CN-100), which has a significant inhibitory effect on acute inflammatory reactions, on leucocyte emigration and proliferation of granulation were examined in this study. The compound obviously inhibited the protein exudation and polymorph emigration 6 h after application of carboxymethylcellulose pouch method. It also definitely inhibited the monocyte emigration occurring 24 h after carrageenin pleurisy, and the inhibitory activity of the compound was nearly equal to that of pranoprofen and weaker than that of indometacin. CN-100 inhibited the proliferation of granulation in the test by paper disk method, i.e., the compound inhibited wound healing. The antigranulation activity of CN-100 was also nearly equal to that of pranoprofen and weaker than that of indometacin. These results proved that CN-100 should definitely inhibit the reactions of the second and third inflammatory phases of the whole reactions from the exudative phase throughout proliferative phase, suggesting that the compound is a useful antiinflammatory drug.

Animals↗
PubMed1986

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl]propionic acid. 4th communication: inhibitory effects on rat adjuvant arthritis.

The preventive and therapeutic effects of 2-(10,11-dihydro-10-oxodibenzo [b,f]thiepin-2-yl)propionic acid (CN-100) on local and systemic changes of rats with adjuvant arthritis being used frequently as experimental model of rheumatoid arthritis were investigated in comparison with those of reference drugs, indometacin and pranoprofen. Preventively and therapeutically CN-100 showed potent inhibitory effects on adjuvant primary inflammation and secondary lesion. CN-100 also exerted an evident preventive effect on destruction of foot bone, improved the changes in organ weight, and stimulated weight gain. These effects were dose-dependent, and the effects at 5.0 mg/kg were almost the same as those of indometacin and pranoprofen at 1.25 and 2.5 mg/kg, respectively. The mode of action of CN-100 resembled that of reference compounds. Although CN-100 improved the change in albumin/globulin ratio, which was a parameter of systemic inflammatory reactions, the effect was more remarkable in therapeutic administration than in preventive one. This suggests that CN-100 is suitable for clinical application.

Animals↗