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PubMed1978

[Ketotic hiperglycinemia: one case of possible propionic acidemia (author's transl)].

Authors present the first case to be observed in Spain of neonatal propionic acidemia. The subject is a newborn with symtoms free interval, family consanquinity and siblings who have died prematurely with a similar picture of hyperventilation "sine materiae", progressive metabolic acidosis without anionic discrepancy and terminal coma. The possibility that it might be a question of other metabolopathies is under discussion, but bio-chemical examination, with discovery of large quantities of propionic acid in urine (51 mcg./ml.) and concentrations of aminoacids in plasma, strongly suggest the diagnosis of a new case of neonatal propionic acidemia.

Amino Acids↗
PubMed1983

Propionic acidaemia. First case in the Finnish population.

Propionic acidaemia is a defect of propionyl-CoA-carboxylase activity characterized by urinary excretion of propionic acid, its metabolites and hyperglycinaemia. The clinical picture of this autosomally, recessively inherited disorder, which has been reported in the literature in 63 patients varies from overwhelming metabolic crisis in the neonate to an almost asymptomatic disease responding to protein restriction and biotin supplementation. The first Finnish patient with propionic acidaemia had a severe type of disease with neonatal onset simulating nonketotic hyperglycinaemia. In spite of protein restriction and biotin supplementation this infant developed progressive psychomotor retardation and died of intercurrent infection at the age of 8.5 months. The definite, correct diagnosis was not reached until a severe infection occurred, during which the pathognomonic organic aciduria manifested. This delay in the diagnosis illustrates the importance of performing the analysis of urinary excretion of organic acids during stress situations, such as infections, since the metabolic block may be undetectable under normal conditions.

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

The application of 13C-labelled short chain fatty acids to measure acetate and propionate production rates in the large intestines. Studies in a pig model.

The production rates of acetate and propionate were measured in the large intestine of pigs by applying the single injection technique of (1-13C)acetate and (1-13C)propionate. Both acids were injected individually through the caecal cannula and for both acids the experiments were performed during two diets with different crude fibre contents. For acetate the increase of dietary crude fibre from 5.1 to 18.3% of dry matter resulted in an increase of mean production rate from 27.4 to 56.2 mmol/h. The mean propionate production rate was raised from 3.6 to 7.0 mmol/h when the dietary crude fibre was increased from 4.4 to 24.3%. From both experimental series the contribution of hindgut fermentation to energy maintenance requirement were estimated to be in a range between 7 and 40% depending on the body weight of the animals and the percentage of dietary crude fibre.

Acetates↗
PubMed1977

Utilization of propionic acid by the L4 and adult stages of Cooperia punctata (Nematoda: Trichostrongylidae) grown in vitro.

Cultures of Cooperia punctata, a nematode parasitic in cattle, were studied in Ae medium at a pH of 7.2 to 7.3 under air. In fourth and fifth stages of development, they absorbed or otherwise took into their free pool and tissues, carbon derived from 14C-labeled sodium propionate and converted, by pathways not elucidated, a portion of this carbon into protein and lipid fractions. Thirty minutes postincubation in balanced slat solution was adequate to reduce the amount of isotope in the nematode gut to a constant level. Activity from specifically-labeled 14C-propionate was recovered (as glucose pentaacetate) from worm glucose and from CO2 evolved from cultures consisting of L4 and adult stages. Use of propionate by these worms, for whatever metabolic purpose, would result in depriving the ruminant host of some of its necessary glucogenic precursors, and could account for a specific pathogenic mechanism attendant to heavy infections with this parasite.

Animals↗
PubMedDate not supplied

Destruction of Salmonella enteritidis in poultry feed by combination of heat and propionic acid.

A factorial laboratory experiment was conducted to assess the effects of heating times of 0, 20, 40, and 80 sec at 160 F and propionic acid concentrations of 0, 0.1%, and 0.2% on reduction of Salmonella enteritidis in poultry feed with approximately 15% moisture. The results showed that after 80 sec heating time an approximately 10,000-fold reduction in living salmonella was obtained in the samples with 0.2% propionic acid. Survival in the 0.2% acid group was 2 log10 lower than in the 0.1% and control groups. This difference was statistically significant. Multivariate analysis with repeated measures showed there was no interaction between heating time and propionic acid concentration (P = 0.4113). There were overall significant effects for both acid concentration (P < 0.00001) and heating time (P < 0.0001).

Animal Feed↗
PubMed1996

Fluticasone propionate is associated with severe infection after endoscopic polypectomy.

OBJECTIVE: To test whether the use of fluticasone dipropionate nasal spray after endoscopic ethmoidectomy for multiple polyps is associated with a high incidence of infection. DESIGN. Randomized control study comparing the incidence of infection with the use of beclomethasone dipropionate or fluticasone propionate nasal spray after functional endoscopic sphenoethmoidectomy. Patients were followed up for 6 to 12 months. PATIENTS AND METHODS: Sixty patients with recurrent bilateral nasal polyps underwent functional endoscopic sphenoethmoidectomy and were then randomly allocated into 2 groups of 30 patients each. One group received beclomethasone dipropionate spray (100 micrograms in each nostril every 12 hours), and the other group received fluticasone propionate spray (100 micrograms/d in each nostril). RESULTS: In the fluticasone propionate group, 6 patients (20%) developed acute gram-positive pansinusitis requiring hospitalization and discontinuation of treatment. CONCLUSION: The use of fluticasone dipropionate aqueous nasal spray for the postoperative control of recurrent nasal polyps seems to be associated with a high incidence of acute pansinusitis.

Acute Disease↗
PubMed1997

AMPA receptor agonists: resolution, configurational assignment, and pharmacology of (+)-(S)- and (-)-(R)-2-amino-3-[3-hydroxy-5-(2-pyridyl)-isoxazol-4-yl]-propionic acid (2-Py-AMPA).

We have previously shown that whereas (RS)-2-amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propionic acid (APPA) shows the characteristics of a partial agonist at (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors, (S)-APPA is a full AMPA receptor agonist and (R)-APPA a weak competitive AMPA receptor antagonist. This observation led us to introduce the new pharmacological concept, functional partial agonism. Recently we have shown that the 2-pyridyl analogue of APPA, (RS)-2-amino-3-[3-hydroxy-5-(2-pyridyl)isoxazol-4-yl]propionic acid (2-Py-AMPA), is a potent and apparently full AMPA receptor agonist, and this compound has now been resolved into (+)- and (-)-2-Py-AMPA (ee > or = 99.0%) by chiral HPLC using a Chirobiotic T column. The absolute stereochemistry of the enantiomers of APPA has previously been established by X-ray analysis, and on the basis of comparative studies of the circular dichroism spectra of the enantiomers of APPA and 2-Py-AMPA, (+)- and (-)-2-Py-AMPA were assigned the (S)- and (R)-configuration, respectively. In a series of receptor binding studies, neither enantiomer of 2-Py-AMPA showed detectable affinity for kainic acid receptor sites or different sites at the N-methyl-D-aspartic acid (NMDA) receptor complex. (+)-(S)-2-Py-AMPA was an effective inhibitor of [3H]AMPA binding (IC50 = 0.19 +/- 0.06 microM) and a potent AMPA receptor agonist in the rat cortical wedge preparation (EC50 = 4.5 +/- 0.3 microM) comparable with AMPA (IC50 = 0.040 +/- 0.01 microM; EC50 = 3.5 +/- 0.2 microM), but much more potent than (+)-(S)-APPA (IC50 = 5.5 +/- 2.2 microM; EC50 = 230 +/- 12 microM). Like (-)-(R)-APPA (IC50 > 100 microM), (-)-(R)-2-Py-AMPA (IC50 > 100 microM) did not significantly affect [3H]AMPA binding, and both compounds were weak AMPA receptor antagonists (Ki = 270 +/- 50 and 290 +/- 20 microM, respectively).

Alanine↗
PubMed2001

Resolution, configurational assignment, and enantiopharmacology at glutamate receptors of 2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA) and demethyl-ACPA.

We have previously described (RS)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA) as a potent agonist at the (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor subtype of (S)-glutamic acid (Glu) receptors. We now report the chromatographic resolution of ACPA and (RS)-2-amino-3-(3-carboxy-4-isoxazolyl)propionic acid (demethyl-ACPA) using a Sumichiral OA-5000 column. The configuration of the enantiomers of both compounds have been assigned based on X-ray crystallographic analyses, supported by circular dichroism spectra and elution orders on chiral HPLC columns. Furthermore, the enantiopharmacology of ACPA and demethyl-ACPA was investigated using radioligand binding and cortical wedge electrophysiological assay systems and cloned metabotropic Glu receptors. (S)-ACPA showed high affinity in AMPA binding (IC(50) = 0.025 microM), low affinity in kainic acid binding (IC(50) = 3.6 microM), and potent AMPA receptor agonist activity on cortical neurons (EC(50) = 0.25 microM), whereas (R)-ACPA was essentially inactive. Like (S)-ACPA, (S)-demethyl-ACPA displayed high AMPA receptor affinity (IC(50) = 0.039 microM), but was found to be a relatively weak AMPA receptor agonist (EC(50) = 12 microM). The stereoselectivity observed for demethyl-ACPA was high when based on AMPA receptor affinity (eudismic ratio = 250), but low when based on electrophysiological activity (eudismic ratio = 10). (R)-Demethyl-ACPA also possessed a weak NMDA receptor antagonist activity (IC(50) = 220 microM). Among the enantiomers tested, only (S)-demethyl-ACPA showed activity at metabotropic receptors, being a weak antagonist at the mGlu(2) receptor subtype (K(B) = 148 microM).

Alanine↗
PubMed1976

Solubilities of testosterone propionate and related esters in organic solvents.

The solubility parameters of a range of saturated hydrocarbons were calculated from vapor pressures and heats of vaporization. Solubilities of testosterone propionate were determined in these solvents at 25 degrees and yielded solute solubility parameters which varied from solvent to solvent. The solubility parameter of testosterone propionate was determined by several other methods, and support was found for the previously published figure of 9.5 cal(1/2) cm(-3/2). The geometric mean coefficient (l(12)) in saturated hydrocarbons was found to be a rectilinear function of the branching ratio (r). The mean l(12) of androstanolone and testosterone propionates was used to calculate the solubilities of other esters, giving good agreement with experimental results. IR data, presented as the sum of the shifts of the 3-keto and 17-ester carbonyl stretching frequencies in polar solvents, correlated rectilinearly with the geometric mean coefficients and the plot extrapolated to the l(12) value of n-hexane, calculated from the branching ratio plot. Attempts to predict solubilities of other esters in polar solvents using l(12) values achieved only limited success.

Chemical Phenomena↗
PubMed2000

Structure-based development of pyridoxal propionate derivatives as specific inhibitors of cathepsin K in vitro and in vivo.

We found that pyridoxal phosphate shows considerable inhibition of cathepsins. CLIK-071, in which the phosphate ester of position 3 of pyridoxal phosphate was replaced by propionate, strongly inhibited cathepsin B. Three new types of synthetic pyridoxal propionate derivatives showing specific inhibition of cathepsin K were developed. New synthetic pyridoxal propionate derivatives, -162, -163, and -164, in which the methyl arm of position 6 of CLIK-071 was additionally modified, strongly inhibited cathepsin K and cathepsin S weakly, but other cathepsins were not inhibited. CLIK-166, in which the position 4 aldehyde of CLIK-071 is replaced by a vinyl radical and position 5 is additionally modified, showed cathepsin K-specific inhibition at 10(-5) M. Pit formation due to bone collagen degradation by cathepsin K of rat osteoclasts was specifically suppressed by administration of CLIK-164, but not by inhibitors of cathepsin L or B.

Animals↗
PubMed2002

Intranasal fluticasone propionate inhibits allergen induced bone marrow eosinophilia in mice.

Local corticosteroids are currently the most efficient safe anti-allergic treatment, which attenuate eosinophilic tissue inflammation through several mechanisms. We evaluated the effect of local airways corticosteroid on repeated allergen exposure-induced bone marrow activation and airway eosinophilia using the number of eosinophils in bone marrow, bronchoalveolar lavage fluid (BALf) and airways tissue as study end-points. Male BALB/c mice were sensitized by intraperitoneal injections of aluminum-precipitated ovalbumin (OVA) on two different days (5 days apart). Eight days after the second sensitization, the animals were challenged intranasally with OVA or phosphate-buffered saline (PBS) on 5 consecutive days. Concomitantly with challenges mice were treated with fluticasone propionate or respective vehicle. OVA exposures induced a significant increase in eosinophil numbers in bone marrow, BALf and airways tissue (P<0.005). Treatment with fluticasone propionate significantly reduced the increase of absolute number of mature bone marrow eosinophils (P=0.014) and showed a tendency towards decrease in the immature bone marrow eosinophil number (P=0.057) compared to controls. However, fluticasone propionate had no significant effect on BALf and airways tissue eosinophils (P=0.28 and 0.07, respectively). In this murine allergy model intranasal corticosteroid reduced number of bone marrow mature eosinophils, but did not significantly affect airways cell populations.

Allergens↗
PubMed2002

Impact of inhaled salmeterol/fluticasone propionate combination product versus budesonide on the health-related quality of life of patients with asthma.

OBJECTIVE AND DESIGN: Measurement of health-related quality of life (HR-QOL) may show benefits of asthma treatments not revealed by objective monitoring and can complement clinical and physiological assessments of treatment outcome. HR-QOL was measured in four countries in a multicenter, double-blind, randomized comparison of salmeterol/fluticasone propionate combination and budesonide in patients aged > or =12 years with moderate-to-severe asthma uncontrolled by inhaled corticosteroids. METHODS: Patients received, twice daily, either salmeterol/fluticasone propionate 50/250 microg (Seretide/ Advair) via Diskus inhaler (n = 55) or budesonide 800 microg (Pulmicort) via Turbuhaler (n = 58). Patients completed the Asthma Quality of Life Questionnaire (AQLQ) at baseline and after 12 weeks treatment (or early withdrawal). The analysis included 113 patients. RESULTS: Mean improvement in AQLQ scores achieved clinical importance in all four domains in the salmeterol/fluticasone group (AQLQ change > or =0.5), but in only two domains in the budesonide group. Although the mean overall improvement in AQLQ scores observed in the salmeterol/fluticasone group was significantly greater than that observed in the budesonide group (difference of 0.45; p = 0.002), the difference was less than the minimal important difference (0.5). Nevertheless, further analysis showed that the number-needed-to-treat was only 3.4. This indicates that only 3.4 patients need to be treated with the salmeterol/fluticasone combination for one patient to experience a meaningful improvement in HR-QOL, relative to monotherapy with an increased dose of budesonide. CONCLUSION: Treatment of moderate-to-severe asthma with salmeterol/fluticasone propionate resulted in superior gains in HR-QOL relative to increasing the dose of inhaled corticosteroids.

Administration, Inhalation↗
PubMed1996

Specific long-chain fatty acids promote optimal growth of Frankia: accumulation and intracellular distribution of palmitic and propionic acid

Frankia isolates from nodules of the genera Casuarina (BR, S21, Thr), Allocasuarina (Allo2), and Gymnostoma (G80) were found to grow exponentially with high biomass yield and minimal sporangia formation in stirred propionate mineral medium when supplemented either with 2.4 μM palmitic acid (C16:0), pentadecanoic (C15:0), heptadecanoic (C17:0), or linoleic (C18:2, cis 9, 12) fatty acids. Strains also grew with lauric (C12:0) or myristic (C14:0) acids, but gave lower biomass yield. Stearic acid (C18:0) produced a good biomass yield, but cultures slowly accumulated sporangia; oleic acid (C18:1, cis-9) was detrimental to growth. Caprylic (C8:0) or capric (C10:0) acids proved to be prejudicial for long-term storage of Frankia strains. In experiments using labeled 1,2-dipalmitoyl phosphatidylcholine and palmitic acid, radioactivity bound rapidly to the insoluble, but solvent-extractable fraction of Frankia cells. In contrast, label from propionic acid accumulated in the cytosolic fraction. Therefore, the beneficial effect of some specific phospatidylcholines or free fatty acids on Frankia growth appears to result from their utilization as building blocks for the membrane, suggesting that membrane biosynthesis may be the limiting step for Frankia growth in unamended propionate mineral medium.

Journal Article↗
PubMed2001

Treatment of rhinitis medicamentosa with fluticasone propionate--an experimental study.

The efficacy of fluticasone propionate aqueous nasal spray (0.05% w/w) in the treatment of rhinitis medicamentosa has been studied in an animal model (guinea pig). Rhinitis medicamentosa was induced through the instillation of 0.05% naphthazoline nitrate (Privine) for 8 weeks. Fluticasone propionate nasal spray was then administered to the animals for 2 weeks. The spray successfully cleared the interstitial edema which is the pathologic hallmark of rhinitis medicamentosa. The study suggests that fluticasone propionate nasal spray can be beneficial in the treatment of patients with rhinitis medicamentosa.

Administration, Intranasal↗
PubMed2003

Simultaneously evaluating the effects of one-week fluticasone propionate inhalation therapy on lung ventilation and permeability in children with asthma.

This study evaluated the effects of fluticasone propionate inhalation therapy on lung ventilation and alveolar permeability by quantitative Tc-99m DTPA radioaerosol inhalation lung scintigraphy in 15 children with asthma. Lung ventilation was evaluated as the distribution percentage (D%) of Tc-99m DTPA radioaerosols in the central, intermediate and peripheral regions of the right lung. Alveolar permeability was measured by the rate of Tc-99m DTPA radioaerosol clearance curve from the peripheral alveoli of the right lung and represented as slope. The D% and slopes were calculated before and after one-week inhalation therapy (100 microg fluticasone propionate two times daily for one-week) to evaluate the effects of inhalation therapy on lung ventilation and alveolar permeability. The preliminary results revealed statistically significantly improved lung ventilation but no significant change of alveolar permeability in the right lung after one-week fluticasone propionate inhalation therapy in children with asthma. We suggest that the widely available and noninvasive Tc-99m DTPA radioaerosol inhalation lung scintigraphy can simultaneously evaluate lung ventilation and alveolar permeability in one study and should contribute to any disorder involving both alveoli and airways.

Adolescent↗
PubMedDate not supplied

The efficacy and tolerability of clobetasol propionate foam 0.05% in the treatment of mild to moderate plaque-type psoriasis of nonscalp regions.

BACKGROUND: Clobetasol propionate foam 0.05% (Connetics Corporation, Palo Alto, CA) is approved by the United States Food and Drug Administration for the treatment of corticosteroid-responsive scalp dermatoses, but there is only limited data available for its efficacy and tolerability in treating dermatoses which affect nonscalp sites. OBJECTIVE: The efficacy and tolerability of clobetasol propionate foam (clobetasol foam) in treating psoriatic lesions at nonscalp sites was evaluated in a multicenter, randomized, double-blinded, placebo-controlled study of 279 patients with mild to moderate plaque-type psoriasis. METHODS: The patients applied clobetasol foam or placebo to the psoriatic lesions twice daily for two weeks. In addition to receiving clinical evaluations, the study patients completed a questionnaire evaluating various characteristics of the foam formulation, including their preference for its use and their projected likelihood to comply with similar therapy in a nonstudy environment. RESULTS: At Week 2 (or end of treatment), 68% (94/139) of patients who received clobetasol foam had a Physician's Static Global Assessment score of 0 (clear, except for minor residual discoloration) or 1 (majority of lesions have individual scores for plaque thickness, erythema, and scaling that averages 1). This was significantly more than the 21% (30/140) observed in the placebo group (P < 0.0001). Similar results were obtained for the Patient's Global Assessment score at Week 2 and in changes (from Baseline to Week 2) in the scores for the signs of psoriasis at a target lesion and for pruritus. Adverse effects were generally limited to mild and transient burning or other application site reactions in only a few patients in each treatment group. In the patient's poststudy questionnaire (completed at Week 2, or end of treatment) a majority of patients rated the characteristics of the foam formulation very highly. The patients ranked the foam formulation as superior to other topical formulations based on factors impacting their quality of life and indicated they would be more likely to comply with a recommended course of therapy with the foam formulation than with other topical formulations. CONCLUSION: Clobetasol propionate foam 0.05% is safe and effective for the treatment of plaque-type psoriasis on scalp and nonscalp areas, when applied twice daily for two weeks. As it is understood that patient dissatisfaction with select topical formulations affects their compliance with therapy, which necessarily affects the effectiveness of the therapy, the results of the patient's poststudy questionnaire suggest that there are multiple and integrated benefits for the use of clobetasol foam in the treatment of psoriasis of nonscalp sites.

Administration, Topical↗
PubMed1987

Intermale social aggression: reinstatement in castrated rats by implants of testosterone propionate in the medial hypothalamus.

Male hooded rats were castrated, subcutaneously implanted with testosterone-filled silastic tubes, and individually housed with an intact adult female rat. An unfamiliar male intruder was introduced into each colony on a weekly basis and the aggressive behavior of the resident male was recorded. When the intermale social aggressive behavior of the resident male toward the intruder reached a high level in terms of a composite aggression score, the subcutaneous testosterone tubes were removed. Weekly tests of aggression toward unfamiliar intruders continued until the aggression of the resident male dropped to a low level for two successive weeks in terms of our composite aggression score. Bilateral implants of pellets of testosterone propionate were then made into the medial hypothalamus or adjacent tissue. A control group was implanted with cholesterol pellets into the medial hypothalamus. During four weekly tests following the implant, rats with testosterone propionate implants in the medial hypothalamus showed increases in lateral attacks, lateral attack duration, bites, and piloerection. The increase in aggression was not consistently displayed by animals with testosterone propionate implants dorsal or anterior to the medial hypothalamus or by animals with cholesterol implants in the medial hypothalamus. These results suggest that the medial hypothalamus or closely adjacent tissue contains testosterone-sensitive neural circuitry modulating intermale social aggression.

Aggression↗
PubMed1981

Male sex behavior and testosterone concentrations in gilts administered testosterone propionate.

Two gilts were administered testosterone propionate and their subsequent plasma testosterone concentrations and male sex behavior were recorded. These were compared to testosterone concentrations and male sex behavior in boars. Testosterone propionate (75 mg) was administered to the gilts every other day for 20 days (induction scheme) and every 10 days there-after (maintenance scheme). Concentrations of testosterone in plasma were elevated to concentrations detected in the boars during the induction scheme. During the maintenance scheme, concentrations of testosterone appeared to be lower than in boars. At 20, 30 and 40 days following the first injection, sniffing, nosing and mating song behaviors were exhibited by the testosterone treated gilts similar in frequency to the boars. Mounting behavior was first detected 30 days following the first testosterone propionate injection, and by day 40, the frequency of mounting was greater than observed in boars.

Journal Article↗