SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Calves fed whole milk had 2,000-fold fewer (P less than 0.001) coliforms in the cranial part of the small intestine than did calves fed skim milk (fat removed). Calves fed milk with 32 mM added propionic acid had nearly 1,000-fold lower (P less than 0.001) counts of lactobacilli in the entire gastrointestinal tract than did calves fed milk without added propionic acid.
Biotin deficiency induced in the rat, with a biotin-deficient diet but with added avidin involves clinical symptoms of deficiency as well as an important drop (80%) in propionyl-CoA carboxylase activity in the liver, heart and kidneys. But major biochemical anomalies (ketoacidosis and increased urinary elimination of propionic acid), characteristic of propionic acidaemia due to propionyl-CoA carboxylase deficiency in man, are not observed in the rat. Nevertheless, abnormal urinary elimination of methylcitrate and tiglylglycine reflects an appreciable decrease in the metabolism of propionyl-CoA in these animals. The propionyl-CoA load caused by the administration of metabolic precursors of this substance, mainly L-isoleucine, does not induce important biochemical variations except for excretion of propionylglycine.
A simple and accurate method is presented for gas-liquid chromatographic (GLC) determination of propionic acid in bakery products. Propionic acid is extracted with a mixture of dichloromethane and formic acid to which isobutyric acid has been added as an internal standard. The extract is injected directly into the GLC system. A glass column packed with 5% SP-1000 is used. The simplicity and convenience of the method make it suitable for routine determination.
The reaction of 5'-amino-2',5'-dideoxyuridine and 5'-amino-5'-deoxy-2',3'-O-ethoxymethyliden-6- azauridine with 3-(3-indolyl)propionic or 1-nitroanthraquinon-2-carboxylic acids in THF in the presence of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) resulted in the corresponding amide derivatives. The reaction conditions of the standard procedure for the removal of the O-alkylidene protecting group turned out to be too severe for the 5'-N-acylamide derivatives of 6-azauridine. 5'-Deoxy-5'-[3-(3-indolyl)propionyl-amino]-6-azauridine was synthesized from 5'-amino-5'-deoxy-6-azauridine and 3-(3-indolyl)propionic acid in THF in the presence of EEDQ. A reaction between 5'-O-tosyl-2',3'-O-ethoxymethyliden-6-azauridine and 3-aminopropanol gave 3-(3-hydroxypropylamino)-2-(2',3'-O-ethoxymethylidene-beta- D-ribofuranosyl)-as-triazine-5(2H)-one, the structure of which was confirmed also by synthesis from O2,5'-anhydronucleoside and 3-aminopropanol followed by further chemical transformations. A reaction of 3-(3-hydroxypropylamino) derivative obtained with nicotinoyl chloride prepared in situ, or with 1-nirtoanthraquinon-2-carboxylic acid in the presence of DCC with subsequent deprotection, afforded 3-[(3-pyridin-3-ylcarboxy)propylamino]- or 3-[3-(1-nitroanthraquinon-2-carboxy)propylamino]-2-beta-D-ribof ura nosyl-as- triazine-5(2H)-one, respectively. Structures of the nucleosides prepared were examined by 1H NMR spectroscopy. 2',5'-Dideoxy-5'-[(1-nitroanthraquinon-2-carbonyl)amino]uridine at a 10(-4) M concentration was shown to inhibit thymidine incorporation into cell DNA (CE50 10(-5) M) by 72%.
Propionic Acidemia is an inherited disorder of organic acid metabolism characterized by a wide spectrum of clinical and biochemical findings. Many times is present in the neonatal period, when mortality is high and neurologic residua in survivors is severe. The present case concerns to a healthy male newborn who started with a picture of refusing to feed, lethargy and hypothermia at 49 hours of life. He developed a severe neurotoxicity state with metabolic acidosis. The laboratory evaluation showed high levels of 3-hidroxi-propionic, 2-metil-hidroxibutiric and metil-citric in urine, confirming the diagnosis of proprionic acidemia.
BACKGROUND: We compared the efficacy and tolerability of the intranasal corticosteroid fluticasone propionate with that of the antihistamine terfenadine in patients with seasonal allergic rhinitis. METHODS: Two hundred thirty-two adults and adolescents with seasonal allergic rhinitis received intranasal fluticasone propionate (200 micrograms once daily), terfenadine tablets (60 mg twice daily), or placebo for 2 weeks in a double-blind, randomized, parallel-group study. Main outcome measures were clinician- and patient-rated individual and total nasal symptom scores (based on ratings of nasal obstruction, sneezing, nasal itching, and rhinorrhea); clinician-rated overall response to therapy; changes in nasal inflammatory cell counts; adverse events; and morning plasma cortisol concentrations. RESULTS: Both clinician- and patient-rated total and individual nasal symptom scores were significantly lower in the fluticasone group than in either the terfenadine group or the placebo group at nearly every measured time point throughout the treatment period. After 2 weeks of therapy, clinician-rated total nasal symptom scores decreased by 49% in the fluticasone group compared with 27% in the terfenadine group and 19% in the placebo group. In general, therapy with terfenadine was not statistically distinguishable from that with placebo based on patient-rated total or individual nasal symptom scores. According to clinician ratings, 64% of fluticasone-treated patients compared with 49% and 44% of patients treated with terfenadine and placebo, respectively, experienced significant or moderate improvement. A greater percentage of fluticasone-treated patients compared with either terfenadine- or placebo-treated patients experienced reductions in intranasal eosinophil and basophil counts after 2 weeks of therapy. No unusual or serious drug-related adverse events were reported. Morning plasma cortisol concentrations after 2 weeks of therapy did not differ among groups. CONCLUSION: Fluticasone aqueous nasal spray, a well-tolerated corticosteroid preparation that can be administered once daily, is more effective than terfenadine tablets or placebo in controlling symptoms of seasonal allergic rhinitis.
Beneficial effects of treatment of viral croup with inhaled corticosteroids and administered with a jet-nebulizer have been reported in recent years. To facilitate such therapy at home and avoid hospitalization, the administration of inhaled corticosteroids with a metered dose inhaler (MDI) with a holding-chamber was studied as a potential alternative. In a hospital-based prospective, double-blind, randomized study, 17 children admitted with croup were treated with either fluticasone propionate MDI (2,000 microg with the Babyhaler spacer) or placebo. The primary outcome variable was the croup symptom score recorded from 0 up to 24 hours. Secondary outcome variables were the need for administration of nebulized corticosteroids with a nebulizer, the need for intubation, and the duration of hospitalization. The administration of the drug with an MDI and spacer was well tolerated in each child. In all children the clinical course was favorable, without any significant differences between the actively treated and placebo-treated group. One child needed additional use of inhaled corticosteroids with a jet nebulizer, despite treatment with fluticasone. Mean duration of hospitalization was 2.6 (1-4) and 2.4 (1-4) days for treatment with fluticasone and placebo, respectively. No undesirable side effects of treatment were reported. In conclusion, this study did not demonstrate therapeutic benefits of fluticasone propionate when administered with an MDI and a spacer compared with placebo. We hypothesize that the lack of effect is probably due to the inadequate deposition of adequate inhaled corticosteroids in the upper airways.
When treating bronchial hyperresponsiveness to so-called direct and indirect stimuli, distinct pathophysiological mechanisms might require differences in dose and duration of inhaled corticosteroid therapy. To test this hypothesis in children with asthma, we investigated the time- and dose-dependent effects of 2 doses of fluticasone propionate (FP, 100 or 250 microg bid.) in improving exercise- (EIB) and methacholine-induced bronchoconstriction during 6 months of treatment, using a placebo-controlled parallel group study design. Thirty-seven children with asthma (aged 6 to 14 years; forced expired volume in 1 sec (FEV(1)) >/=70% predicted; EIB >/=20% fall in FEV(1) from baseline; no inhaled steroids during the past 4 months) participated in a double-blind, placebo-controlled, 3-arm parallel study. Children receiving placebo were re-randomized to active treatment after 6 weeks. Standardized dry air treadmill exercise testing (EIB expressed as %fall in FEV(1) from baseline) and methacholine challenge using a dosimetric technique (expressed as PD(20)) were performed repeatedly during the study. During FP-treatment, the severity of EIB decreased significantly as compared to placebo within 3 weeks, the geometric mean % fall in FEV(1) being reduced from 34.1% to 9.9% for 100 microg FP bid, and from 35.9% to 7.6% for 250 microg FP bid (P < 0.05). These reductions in EIB did not differ between the 2 doses and were sustained throughout the treatment period. PD(20) methacholine improved significantly during the first 6 weeks as compared to placebo (P < 0.04) and steadily increased with time in both treatment limbs (P = 0.04), the difference in improvement between doses (100 microg FP bid, 1.6 dose steps; 250 microg FP bid, 3.3 dose steps) approaching significance after 24 weeks (P = 0.06). We conclude that in childhood asthma, the protection afforded by inhaled fluticasone propionate against methacholine-induced bronchoconstriction is time- and dose-dependent, whereas protection against EIB is not. This suggests different modes of action of inhaled steroids in protecting against these pharmacological and physiological stimuli. This has to be taken into account when monitoring asthma treatment.
The aim of this study was to compare the efficacy and safety in children of salmeterol (50 microg twice daily) plus fluticasone propionate (100 microg twice daily) when delivered together via a single Diskus inhaler (Seretide; combination therapy) or concurrently using two separate Diskus inhalers (concurrent therapy). In a multicenter, randomized, double-blind, double-dummy, parallel-group study, 257 children with reversible airways obstruction who remained symptomatic on inhaled corticosteroids (200-500 microg daily) alone were randomized to combination or concurrent therapy for 12 weeks. Efficacy was assessed by measuring daily peak expiratory flow (PEF), symptom scores, and rescue salbutamol use. In addition, lung function tests were performed at each clinic visit. Safety assessments included monitoring of adverse events and morning serum cortisol concentrations. The primary efficacy parameter (mean morning PEF) increased during treatment in both groups; adjusted mean changes were 33 and 28 L/min for the combination and concurrent therapies, respectively. The 90% confidence interval for the difference in mean morning PEF between treatment groups was within the +15 L/min criterion for clinical equivalence. Similarly, there were improvements in pulmonary function, symptom score, and rescue salbutamol use during treatment in both groups, with no significant differences between the combination and concurrent therapy groups for any of these secondary efficacy parameters. Both treatment regimens were well-tolerated and had comparable adverse event profiles. Mean morning serum cortisol levels increased similarly in both groups during the study. In conclusion, salmeterol and fluticasone propionate therapy given as a new combination product is as safe and effective in children with asthma as the same drugs given concurrently via separate inhalers.
We have previously shown that (RS)-2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol -4-yl] propionic acid (2-Me-Tet-AMPA) is a selective agonist at (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors, markedly more potent than AMPA itself, whereas the isomeric compound 1-Me-Tet-AMPA is essentially inactive. We here report the enantiopharmacology of 2-Me-Tet-AMPA in radioligand binding and cortical wedge electrophysiological assay systems, and using cloned AMPA (GluR1-4) and kainic acid (KA) (GluR5, 6, and KA2) receptor subtypes expressed in Xenopus oocytes. 2-Me-Tet-AMPA was resolved using preparative chiral HPLC. Zwitterion (-)-2-Me-Tet-AMPA was assigned the (R)-configuration based on an X-ray crystallographic analysis supported by the elution order of (-)- and (+)-2-Me-Tet-AMPA using four different chiral HPLC columns and by circular dichroism spectra. None of the compounds tested showed detectable affinity for N-methyl-D-aspartic acid (NMDA) receptor sites, and (R)-2-Me-Tet-AMPA was essentially inactive in all of the test systems used. Whereas (S)-2-Me-Tet-AMPA showed low affinity (IC(50) = 11 microM) in the [(3)H]KA binding assay, it was significantly more potent (IC(50) = 0.009 microM) than AMPA (IC(50) = 0.039 microM) in the [(3)H]AMPA binding assay, and in agreement with these findings, (S)-2-Me-Tet-AMPA (EC(50) = 0.11 microM) was markedly more potent than AMPA (EC(50) = 3.5 microM) in the electrophysiological cortical wedge model. In contrast to AMPA, which showed comparable potencies (EC(50) = 1.3-3.5 microM) at receptors formed by the AMPA receptor subunits (GluR1-4) in Xenopus oocytes, more potent effects and a substantially higher degree of subunit selectivity were observed for (S)-2-Me-Tet-AMPA: GluR1o (EC(50) = 0.16 microM), GluR1o/GluR2i (EC(50) = 0.12 microM), GluR3o (EC(50) = 0.014 microM) and GluR4o (EC(50) = 0.009 microM). At the KA-preferring receptors GluR5 and GluR6/KA2, (S)-2-Me-Tet-AMPA showed much weaker agonist effects (EC(50) = 8.7 and 15.3 microM, respectively). It is concluded that (S)-2-Me-Tet-AMPA is a subunit-selective and highly potent AMPA receptor agonist and a potentially useful tool for studies of physiological AMPA receptor subtypes.
The enantiodiscriminating potential of the weak anion exchange-type quinine-based chiral stationary phases (CSPs) for direct enantiomer separation of racemic 2-methoxy-2-(1-naphthyl)propionic acid (selectand, SA) was studied. The influence of structure variations of the selector (SO) in the carbamate functional group and/or in the C6' position of quinoline moiety on retention and enantioselectivity was investigated. Systematic chromatographic studies were made to gain more insight into the overall chiral recognition mechanism for a given mobile phase. In this context, the tert-butylcarbamoyl quinine and the corresponding diisopropylphenyl-derived selector provided the highest resolution and enantioselectivity under polar-organic conditions with the elution order of (R) before the (S) enantiomer. When the bulkiness of the substituents in the C6' position of the SO was increased, the selectivity was decreased in all cases. Alkylation of the nitrogen atom in the carbamate functionality of the SO resulted in the complete loss of enantiomer separation, confirming the crucial importance of the hydrogen-bond formation involved in the stereodiscriminating events. In addition, ten different mono-, bi-, or trivalent acids, necessary as competitor molecules (counter-ions) of the mobile phase, were screened to judge their influence on retention and overall enantioselectivity. Among them, acetic acid, formic acid, N-acetylglycine, and glycolic acid proved to be the most promising counter-ions with R(S) values of 6.35, 6.81, 8.19, and 7.34, respectively. On the basis of chromatographic data, a tentative molecular recognition model was proposed. Simultaneous ion-pairing and hydrogen bonding, in concert with pi-pi stacking and steric interactions, were expected to be responsible for chiral recognition mechanism. This was partially corroborated by structural and/or conformational analysis of the tert-butylcarbamoyl quinine-2-methoxy-2-(1-naphthyl)propionic acid (SO-SA) complex.
Coupled liquid chromatography and ion trap mass spectrometry (LC/MS) was used for the characterization of the semi-synthetic 16-membered ring macrolide josamycin propionate. On-line identification of impurities in this antibiotic complex was performed with an ion trap mass spectrometer without recourse to time-consuming isolation and purification procedures. Ion trap mass spectrometry is ideally suited to identification of impurities because it provides MSn capability, enabling multiple stages of mass spectrometry to obtain the maximum amount of structural information for a given molecule. The ion trap was used with an electrospray ionization source operated in the positive ion mode or with an atmospheric pressure chemical ionization source operated in the negative ion mode. The identity of the unknown compounds was deduced using the MS/MS and MSn collision-induced dissociation spectra of reference substances or structural analogs as interpretative templates, combined with knowledge about the nature of functional group fragmentation behavior. Given the importance attached to the identification of impurities of unknown identity in pharmaceutical substances, this study is useful for companies producing josamycin propionate. The knowledge of the fragmentation behavior is also of importance in further research on other 16-membered macrolides.
Solubilities of testosterone and testosterone propionate in binary solvents composed of the inert solvent, cyclohexane, combined with the active solvents, chloroform, octanol, ethyl oleate, and isopropyl myristate, were investigated with the extended Hildebrand solubility approach. Using multiple linear regression, it was possible to obtain fits of the experimental curves for testosterone and testosterone propionate in the various binary solvents and to express these in the form of regression equations. Certain parameters, mainly K and log alpha 2, were employed to define the regions of self-association, nonspecific solvation, specific solvation, and strong solvation or complexation.
The 2-(2,4-dichlorphenoxy)propionic acid (2,4-DP)-degrading bacterial strain MH was isolated after numerous subcultivations of a mixed culture obtained by soil-column enrichment and finally identified as Flavobacterium sp. Growth of this strain was supported by 2,4-DP (maximum specific growth rate 0.2 h-1) as well as by 2,4-dichlorophenoxyacetic acid (2,4-D), 4-(2,4-dichlorophenoxy)butyric acid (2,4-DB), and 2-(4-chloro-2-methylphenoxy)propionic acid (MCPP) as sole sources of carbon and energy under aerobic conditions. 2,4-DP-Grown cells (10(8] of strain MH degraded 2,4-dichlorophenoxyalkanoic acids, 2,4-dichlorophenol (2,4-DCP), and 4-chlorophenol at rates in the range of 30 nmol/h. Preliminary investigations indicate that cleavage of 2,4-DP results in 2,4-DCP, which is further mineralized via ortho-hydroxylation and ortho-cleavage of the resulting 3,5-dichlorocatechol.
The atrophogenic potential of medium-potent topical glucocorticoids is still controversial. In a double-blind controlled trial 24 healthy volunteers either applied 0.25% prednicarbate cream or the corresponding vehicle to one and 0.1% betamethasone-17-valerate cream or 0.05% clobetasol-17-propionate cream to the other forearm twice daily. Skin thickness was regularly assessed during the six week period of application and for further three weeks thereafter, using both the B- and A-mode of a 20 MHz ultrasound scanner. Both betamethasone-17-valerate and clobetasol-17-propionate cream significantly reduced skin thickness as compared to cream base while prednicarbate cream did not. Given that 0.1% betamethasone-17-valerate- and 0.25% prednicarbate cream are reported to be about equipotent in the treatment of atopic eczema the latter preparation shows an increased ratio between its desired anti-inflammatory and its unwanted atrophogenic effect.
As previously found, the glucocorticosteroid clobetasol-17-propionate inhibits cell proliferation during the early growth stage of normal baby foreskin fibroblasts and collagen synthesis in confluent cultures of these cells. The degree of inhibition of cell proliferation decreases with increasing cell density and, moreover, is transient. The anabolic steroids nandrolone and nandrolone-phenyl-propionate have similar effects on these cells. Likewise the magnitude of the inhibition is dose-dependent. When present together the two types of drug do not act in an additive manner. Even at low concentrations the anabolic steroids abolish the inhibitory effect of the glucocorticosteroid on cell proliferation. Furthermore, in this case only the inhibitory effect of the glucocorticosteroid on collagen synthesis is found and there is no further increase in this effect due to the presence of the anabolic steroids. Our results imply that the use of low concentrations of anabolic steroids combined with glucocorticosteroids in topical application to the skin may abolish some of the undesirable side effects of the glucocorticosteroids.
The effect of the anabolic hormone 19-nortestosterone propionate (Superanabolon Spofa) on the metabolism of chronically ischaemic striated muscle (anterior tibial m.) was studied in a described model in the rat. Metabolic changes were estimated in terms of the activities of a number of enzymes in muscle fibres. Enzyme activities (AcP, ATPase, CE, LDH, MDH) were determined both biochemically and histochemically excepting SDH, which was determined only by the histochemical way. Morphological changes were investigated by routine histology. Administration of 19-nortestosterone propionate prevented enzymatic changes which are typical for chronic ischaemia, primarily the decrease in the activities of dehydrogenases of Krebs' cycle tricarboxylic acides (MDH, SDH). In addition, the ratio of red to white muscle fibres increased. Administration of anabolic hormone has a similar favourable action on ischaemic muscle as training, studied previously.
Cationic amino acids, arginine and lysine partition differentially from water into aqueous micellar sodium dodecanoate. Conversely, partitioning of serine, glycine, aspartic acid, glutamic acid, threonine, alanine, proline, valine, leucine, phenylalanine and isoleucine do not vary appreciably. Partitioning from neat hexane into dodecylammonium propionate trapped water in hexane is, however, dependent upon both electrostatic and hydrophobic interactions. These results imply that the interior of dedecylammonium propionate aggregates is negatively charged and is capable of hydrogen bonding in addition to providing a hydrophobic enviroment. The solubilities of amino acids in neat hexane substantiate the previously derived amino acid hydrophobicity scale. Relevance of partitioning in these systems to the postulated selective amino acid compartmentalization is discussed.