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PubMed1999

Anaerobic conversion of carbon dioxide to methane, acetate and propionate on washed rice roots.

Washed excised roots of rice (Oryza sativa) produced H(2), CH(4), acetate, propionate and butyrate when incubated under anoxic conditions. Acetate production was most pronounced with a maximum rate (mean+/-standard error; four different root preparations) of 3.4+/-0.6 µmol h(-1) g-dry weight(-1) roots, compared to 0.45+/-0.13, 0.06+/-0.03, and 0.04+/-0.01 µmol h(-1) g-dw(-1) for propionate, butyrate and CH(4)1 kPa after one day of incubation. Then it decreased and reached more or less constant concentrations of about 50-80 Pa after about 7-8 days. Hydrogen partial pressures were always high enough to allow exergonic methanogenesis (DeltaG=-67 to -98 kJ mol(-1) CH(4)) and exergonic homoacetogenesis (DeltaG=-18 to -48 kJ mol(-1) acetate) from H(2) plus CO(2). Radioactive bicarbonate/CO(2) was incorporated into CH(4), acetate and propionate. The specific radioactivities of the products indicated that CH(4) was exclusively produced from H(2)/CO(2) confirming a previous study. The contribution of CO(2) to the production of acetate and propionate was 32-39% and 42-61%, respectively, assuming that each carbon atom was equally labeled. Propionate also became radioactively labeled, when the roots were incubated with either [1-(14)C]acetate or [2-(14)C]acetate accounting for 60-76% of total propionate production. Reductive formation of propionate was thermodynamically favorable both from H(2) plus acetate plus CO(2) (DeltaG=-15 to -38 kJ mol(-1) propionate) and from H(2) plus CO(2) (DeltaG=-34 to -85 kJ mol(-1) propionate). A substantial fraction of propionate was apparently reductively formed from acetate and/or CO(2). In conclusion, our results demonstrate an intensive anaerobic dark metabolism of CO(2) on washed rice roots with reduction of CO(2) contributing significantly to the production of acetate, propionate and CH(4). The CO(2) reduction seemed to be driven by decay and fermentation of root material.

Journal Article↗
PubMed1996

Comparative adrenal suppression with inhaled budesonide and fluticasone propionate in adult asthmatic patients.

BACKGROUND: A study was performed to compare the adrenal suppression caused by inhaled fluticasone propionate and budesonide on a microgram equivalent basis, each given by metered dose inhaler to asthmatic patients. METHODS: Twelve asthmatic patients of mean age 29.9 years, with a forced expiratory volume in one second (FEV1) 92.9% predicted and forced expiratory flow 25-75% (FEF25-75) 69.5% predicted, on less than or equal to 400 micrograms/day inhaled corticosteroid, were studied in a double blind placebo controlled crossover design comparing single doses of inhaled budesonide 400, 1000, 1600, 2000 micrograms and fluticasone propionate 500, 1000, 1500, 2000 micrograms. Doses were administered at 22.00 hours by metered dose inhaler with mouth rinsing and measurements were made in the laboratory 10 hours later. RESULTS: Serum cortisol levels compared with placebo (mean 325.2 nmol/l) were suppressed by fluticasone at doses of 1500 micrograms (211.6 nmol/l) and 2000 micrograms (112.3 nmol/l) and by budesonide at 2000 micrograms (243.4 nmol/l). Fluticasone propionate 2000 micrograms produced lower absolute serum cortisol levels than budesonide 2000 micrograms (95% CI for difference 42.9 to 219.2). The dose ratio (geometric mean) for the relative potency was 2.89 fold (95% CI 1.19 to 7.07). In terms of percentage suppression versus placebo, fluticasone propionate also produced greater effects (means and 95% CI for difference): budesonide 1600 micrograms (16.0) versus fluticasone propionate 1500 micrograms (40.9) (95% CI -0.6 to 50.6), budesonide 2000 micrograms (26.0) versus fluticasone 2000 micrograms (65.2) (95% CI 10.5 to 67.8). Individual serum cortisol levels at the two highest doses showed 15 of 24 patients below the normal limit of the reference range (150 nmol/l) for fluticasone and five of 24 for budesonide. Fluticasone propionate also caused greater ACTH suppression than budesonide (as % versus placebo): budesonide 1600 micrograms (12.0) versus fluticasone propionate 1500 micrograms (31.9) (95% CI 7.6 to 32.1), budesonide 2000 micrograms (13.5) versus fluticasone propionate 2000 micrograms (44.4) (95% CI 13.2 to 48.7). For overnight 10 hour urinary cortisol (nmol/10 hours) there was a difference between the lowest doses of the two drugs: budesonide 400 micrograms (37.2) versus fluticasone propionate 500 micrograms (19.9) (95% CI 6.9 to 27.8). CONCLUSIONS: Like budesonide the systemic bioactivity of fluticasone propionate is mainly due to lung vascular absorption. Fluticasone propionate exhibited at least twofold greater adrenal suppression than budesonide on a microgram equivalent basis in asthmatic patients.

Administration, Topical↗
PubMed2005

Comparison of acetate and propionate uptake by polyphosphate accumulating organisms and glycogen accumulating organisms.

Enhanced biological phosphorus removal (EBPR) performance is directly affected by the competition between polyphosphate accumulating organisms (PAOs) and glycogen accumulating organisms (GAOs). This study investigates the effects of carbon source on PAO and GAO metabolism. Enriched PAO and GAO cultures were tested with the two most commonly found volatile fatty acids (VFAs) in wastewater systems, acetate and propionate. Four sequencing batch reactors (SBRs) were operated under similar conditions and influent compositions with either acetate or propionate as the sole carbon source. The stimulus for selection of the PAO and GAO phenotypes was provided only through variation of the phosphorus concentration in the feed. The abundance of PAOs and GAOs was quantified using fluorescence in situ hybridisation (FISH). In the acetate fed PAO and GAO reactors, "Candidatus Accumulibacter phosphatis" (a known PAO) and "Candidatus Competibacter phosphatis" (a known GAO) were present in abundance. A novel GAO, likely belonging to the group of Alphaproteobacteria, was found to dominate the propionate fed GAO reactor. The results clearly show that there are some very distinctive differences between PAOs and GAOs in their ability to take up acetate and propionate. PAOs enriched with acetate as the sole carbon source were immediately able to take up propionate, likely at a similar rate as acetate. However, an enrichment of GAOs with acetate as the sole carbon source took up propionate at a much slower rate (only about 5% of the rate of acetate uptake on a COD basis) during a short-term switch in carbon source. A GAO enrichment with propionate as the sole carbon source took up acetate at a rate that was less than half of the propionate uptake rate on a COD basis. These results, along with literature reports showing that PAOs fed with propionate (also dominated by Accumulibacter) can immediately switch to acetate, suggesting that PAOs are more adaptable to changes in carbon source as compared to GAOs. This study suggests that the PAO and GAO competition could be influenced in favour of PAOs through the provision of propionate in the feed or even by regularly switching the dominant VFA species in the wastewater. Further study is necessary in order to provide greater support for these hypotheses.

Acetates↗
PubMed1998

Propionic acid stimulates superoxide generation in human neutrophils.

Short-chain carboxylic acids are the metabolic by-products of pathogenic anaerobic bacteria and are found at sites of infection in millimolar quantities. We previously reported that propionic acid, one of the short-chain carboxylic acids, induces an increase in intracellular Ca2+ ([Ca2+]i) in human neutrophils. Here we investigate the effect of propionic acid on superoxide generation in human neutrophils. Propionic acid (10 mm) induced inositol 1,4, 5-trisphosphate (IP3) formation and a rapidly transient increase in [Ca2+]i, but not superoxide generation, whereas 1 microm formylmethionyl-leucyl-phenylalanine (fMLP), a widely used neutrophil-stimulating bacterial peptide, stimulated not only IP3 formation and Ca2+ mobilization but also superoxide generation. The IP3 level induced by propionic acid was slightly lower than that induced by fMLP. The transient increase in [Ca2+]i induced by propionic acid immediately returned to the basal level, whereas a sustained increase in [Ca2+]i, which was higher than the basal level, following a transient increase in [Ca2+]i was induced by fMLP. The peak level induced by propionic acid was lower than that with fMLP. In the absence of extracellular Ca2+, thapsigargin, a potent inhibitor of endoplasmic reticulum Ca2+-ATPase, induced an increase in [Ca2+]i even after propionic acid stimulation, but not after fMLP. The Ca2+ ionophore A23187 and thapsigargin induced superoxide generation by themselves. Propionic acid enhanced the superoxide generating effect of A23187 and thapsigargin. These results suggest that Ca2+ mobilization induced by propionic acid is much weaker than that with fMLP, and propionic acid is able to generate superoxide in the presence of a Ca2+ ionophore and a Ca2+ influx activator.

Adult↗
PubMed1983

The effect of propionate on the regulation of the pyruvate dehydrogenase complex in the rat liver.

Propionate inhibited the metabolic flux through the pyruvate dehydrogenase reaction in the perfused rat liver when the perfusate concentration of propionate was below 10 mM and the perfusate pyruvate concentration was held within the physiological range. At higher propionate concentrations (e.g., 20 mM) the inhibition of pyruvate dehydrogenase was alleviated and the activation state of the pyruvate dehydrogenase complex was nearly doubled. In livers perfused with a high pyruvate concentration (e.g., 5 mM), propionate coinfusion at all concentrations inhibited the rate of pyruvate decarboxylation. Additional studies were performed in liver mitochondria maintained in State 3 where the ATP/ADP and the NADH/NAD+ ratios were held constant. Low propionate concentrations (e.g., 0.5 mM) inactivated the mitochondrial pyruvate dehydrogenase complex, whereas propionate levels in excess of 1 mM activated the enzyme complex. CoA distribution analyses of the mitochondrial incubations indicated that the presence of either 0.5 or 10 mM propionate caused a substantial accumulation of propionyl-CoA and methylmalonyl-CoA at the expense of free CoASH. Experiments were performed in which the ratios of various acyl-CoA derivatives to CoASH were varied by sequentially increasing the L-carnitine concentrations in the incubation. An inverse relationship between the propionyl-CoA/CoASH and methylmalonyl-CoA/CoASH ratios and the activity of the pyruvate dehydrogenase complex was observed. Experiments using freeze-thawed liver mitochondrial membranes indicated that propionate protected the pyruvate dehydrogenase complex from ATP-mediated inactivation by the pyruvate dehydrogenase kinase. It is our contention that the inactivation of pyruvate dehydrogenase complex at low propionate levels may be due to an increase in the mitochondrial acyl-CoA/CoASH ratios, whereas the activation of the enzyme complex demonstrated at high propionate levels is due to the inhibition of the pyruvate dehydrogenase kinase in a manner similar to that caused by pyruvate or dichloroacetic acid.

Animals↗
PubMedDate not supplied

Inhibition of hepatic propionyl-CoA synthetase activity by organic acids. Reversal of propionate inhibition of pyruvate metabolism.

Intracellular accumulation of propionyl-CoA is associated with impairment of important hepatic metabolic pathways. Since propionate absorbed from the intestine can be converted to propionyl-CoA in the liver, inhibition of propionyl-CoA synthesis from propionate and CoA may provide a strategy for decreasing toxicity from plasma propionate. Therefore, inhibition of propionyl-CoA formation by several organic acids was investigated. In isolated, solubilized mitochondria, octanoate, butyrate, salicylate and p-nitrobenzoate inhibited propionyl-CoA synthesis. Octanoate was the most potent inhibitor of propionyl-CoA synthetase activity and had a Ki of 58 microM. In isolated hepatocytes, octanoate inhibited propionate oxidation in a concentration-dependent manner. Consistent with previous studies, propionate (1.0 mM) inhibited the rates of 14CO2 formation from [1-14C]pyruvate (10 mM) to 55% of the control values in the hepatocyte system. Octanoate (0.8 mM) had no effect on [1-14C]pyruvate oxidation under control conditions, but increased 14CO2 formation from pyruvate to 88% of the control values in the presence of 1.0 mM propionate. Reversal of propionate inhibition of pyruvate oxidation by octanoate was associated with a 44% decrease in hepatocyte propionyl-CoA content. In contrast, while pyruvate oxidation rates were decreased to 53% of control rates in the presence of 10 mM propionylcarnitine, octanoate stimulated pyruvate oxidation under these conditions only to 67% of control levels. In conclusion, mitochondrial propionyl-CoA synthetase activity and hepatocyte propionyl-CoA accumulation can be inhibited by octanoate with consequent decreased propionate oxidation and toxicity in intact hepatocytes. The reversal by octanoate of propionate's inhibition of cellular metabolism may be useful in reducing tissue toxicity from circulating propionate.

Acyl Coenzyme A↗
PubMed2005

Effect of dietary calcium propionate on performance, hepatic enzyme activities and aflatoxin residues in broilers fed a diet containing low levels of aflatoxin B1.

This study was undertaken to the study toxic effects of aflatoxins and reducing toxic effects of calcium propionate on performance, hepatic enzyme activities and aflatoxin residues in broilers. Two hundred and seventy 1-day-old hybrid Arbor Acor broiler chickens were fed conventional feed for 3 days. Broilers were then randomly divided into nine groups of 30 birds each. The nine dietary treatments consisted of (1) conventional feed as a negative control diet, (2) 0.25% calcium propionate, (3) 0.5% calcium propionate, (4) 50 ppb aflatoxin B1, (5) 50 ppb aflatoxin B1 plus 0.25% calcium propionate, (6) 50 ppb aflatoxin B1 plus 0.5% calcium propionate, (7) 100 ppb aflatoxin B1, (8) 100 ppb aflatoxin B1 plus 0.25% calcium propionate, (9) 100 ppb aflatoxin B1 plus 0.5% calcium propionate. Test diets were offered for 6 weeks continuously and the birds were sacrificed. Decreased body weight gain, feed consumption and feed conversion ratio were observed in aflatoxin treated groups whereas aflatoxin B1-calcium propionate supplemented diet groups increased, in comparison to the control group. Significant difference was observed after 4 weeks of feeding. Serum samples were tested for gamma glutamyl transferase (gamma-GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Gamma-GGT, AST and ALT were significantly increased in aflatoxin treated groups, in comparison among the dietary treated groups. Muscle and liver tissues were analyzed for aflatoxin residues. The residual levels of aflatoxin B1 and aflatoxin M1 were significantly higher in liver than in muscle. The levels in the liver and the muscle were highest in the aflatoxin B1-supplemented groups and lower in the aflatoxin B1-calcium propionate supplemented groups. Results of this study indicate that addition of calcium propionate to diets containing aflatoxin B1 appears to be effective in reducing toxicity. Aflatoxin contamination in broiler feed may cause economic losses by lowering body weight gain. Therefore, lower levels of aflatoxin B1 in the chicken feeds should be required if all acceptable risk is to be avoided. Additionally, the risk of aflatoxins in broiler as a food appears to remain very low, although the levels of aflatoxins in human foods should be kept as low as possible to reduce the incidence of hepatic cancer.

Aflatoxin B1↗
PubMed1971

Interactions of acetate, propionate and butyrate in sheep liver mitochondria.

1. Interactions in the rates of consumption of acetate, propionate and butyrate in sheep liver mitochondria were examined in the presence and absence of l-malate and alpha-oxoglutarate. 2. Acetate was not consumed in absence of ancillary substrate but utilization of acetate (7.2nmol/min per mg of protein) occurred in the presence of alpha-oxoglutarate. This consumption was abolished by propionate or butyrate but the presence of acetate did not affect consumption of propionate or butyrate. 3. Propionate consumption (10.1nmol/min per mg of protein) was unaffected by malate but was stimulated by 63% by butyrate or by 180% by alpha-oxoglutarate. 4. Butyrate consumption (3.3nmol/min per mg of protein) was stimulated by 117% by malate, by 151% by propionate and by 310% by alpha-oxoglutarate. 5. In the absence of ancillary substrates the maximum rate of total volatile fatty acid utilization (24.7nmol/min per mg of protein) occurred with a mixture of propionate and butyrate. When both propionate and butyrate were present total consumption was not affected by malate but was stimulated by 24% by alpha-oxoglutarate. With alpha-oxoglutarate present, propionate and butyrate each decreased the other's consumption by about 26%, but the total utilization was the greatest observed. 6. The inhibition of acetate consumption by propionate or butyrate is unexplained, but the remaining effects are consistent with an interaction of propionate and butyrate through oxaloacetate together with a general limitation imposed by a need for GTP to rephosphorylate AMP formed during activation of the volatile fatty acids.

Acetates↗
PubMed1995

Effect of propionate on fatty acid and cholesterol synthesis and on acetate metabolism in isolated rat hepatocytes.

In the present study the actual role of propionic acid in the control of fatty acid and cholesterol synthesis was investigated in isolated liver cells from fed rats maintained in the presence of near-physiological concentrations of glucose, glutamine and acetate. Using 3H2O for lipid labelling, propionate appears as an effective inhibitor of fatty acid synthesis and to a lesser extent of cholesterol synthesis, even at the lowest concentration used (0.6 mmol/l). Butyrate is a potent activator of both synthetic pathways, and the activating effect was not counteracted by propionate. Using 1-[14C]acetate, it was observed that propionate at a moderate concentration, or 1 mmol oleate/l, are both very effective inhibitors of 14C incorporation into fatty acid and cholesterol. This incorporation was drastically inhibited when propionate and oleate were present together in the incubation medium. The net utilization of acetate by rat hepatocytes was impaired by propionate, in contrast to oleate. 1-[14C]butyrate was utilized at a high rate for fatty acid synthesis, but to a lesser extent for cholesterol synthesis; both processes were unaffected by propionate. Intracellular citrate concentration was not markedly depressed by propionate, whereas it was strongly elevated by butyrate. In conclusion, propionate may represent an effective inhibitor of lipid synthesis when acetate is a major source of acetyl-CoA, a situation which is encountered with diets rich in readily-fermentable fibres. The present findings also suggest that propionate may be effective at concentrations close to values measured in vivo in the portal vein.

Acetates↗
PubMed1988

Luminal propionate-induced secretory response in the rat distal colon in vitro.

1. The stimulatory action of propionate on colonic electrolyte transport and involvement of the enteric reflex in this was studied in vitro using an Ussing chamber in the rat. The short-circuit current (Isc) and bidirectional fluxes of Na+ and Cl- were measured. Mucosa-submucosa preparations, containing the submucosal nerve, from the distal colon were used in most cases. 2. Mucosal application of propionate caused transient increases in the transmural potential difference, with the mucosal side negative, Isc and conductance. Serosal application of the acid had no effect. 3. Adaptation of the Isc response occurred when the acid was applied to the bathing solution cumulatively without washing out the first dose. If tissues were washed and held more than 20 min before the next application, the response was almost completely restored. 4. The increase in Isc in response to propionate was concentration dependent, with a 50% effective concentration of approximately 7 x 10(-5) M. 5. Two other short-chain fatty acids (SCFAs), n-butyrate and n-valerate, but not acetate, increased Isc when added to the mucosal bathing solution. 6. Bumetanide (3 x 10(-5) M) and the serosal chloride-free condition, but not amiloride (10(-4) M), inhibited the responses of Isc to propionate. Propionate-stimulated Cl- secretion resulted mainly from an increase in unidirectional serosal-to-mucosal Cl- movement. Propionate did not affect the Na+ flux. 7. Tetrodotoxin (10(-7) M), somatostatin (10(-7) M) and hexamethonium (10(-4) M) inhibited the propionate-evoked increase in Isc by 40, 70 and 30%, respectively. 8. Atropine (10(-5) M) also inhibited the Isc-increase response to propionate more than 90%. 9. Pre-treatment (2 min) of the mucosal surface with procaine (5 x 10(-4) M) inhibited the propionate-evoked increase in Isc by 90%. 10. The results suggest that luminal propionate transiently stimulated the colonic chloride secretory response that is not due to direct action on colonocytes, but due in large part to release of acetylcholine at neuro-colonocyte junctions, probably via an enteric reflex involving a mucosal sensory mechanism, cholinergic motor nerves and submucosal ganglia.

Action Potentials↗
PubMed2001

Pathway of propionate oxidation by a syntrophic culture of Smithella propionica and Methanospirillum hungatei.

The pathway of propionate conversion in a syntrophic coculture of Smithella propionica and Methanospirillum hungatei JF1 was investigated by (13)C-NMR spectroscopy. Cocultures produced acetate and butyrate from propionate. [3-(13)C]propionate was converted to [2-(13)C]acetate, with no [1-(13)C]acetate formed. Butyrate from [3-(13)C]propionate was labeled at the C2 and C4 positions in a ratio of about 1:1.5. Double-labeled propionate (2,3-(13)C) yielded not only double-labeled acetate but also single-labeled acetate at the C1 or C2 position. Most butyrate formed from [2,3-(13)C]propionate was also double labeled in either the C1 and C2 atoms or the C3 and C4 atoms in a ratio of about 1:1.5. Smaller amounts of single-labeled butyrate and other combinations were also produced. 1-(13)C-labeled propionate yielded both [1-(13)C]acetate and [2-(13)C]acetate. When (13)C-labeled bicarbonate was present, label was not incorporated into acetate, propionate, or butyrate. In each of the incubations described above, (13)C was never recovered in bicarbonate or methane. These results indicate that S. propionica does not degrade propionate via the methyl-malonyl-coenzyme A (CoA) pathway or any other of the known pathways, such as the acryloyl-CoA pathway or the reductive carboxylation pathway. Our results strongly suggest that propionate is dismutated to acetate and butyrate via a six-carbon intermediate.

Bacteria, Anaerobic↗
PubMed1994

Effect of intraruminal propionic acid infusion on metabolism of mesenteric- and portal-drained viscera in growing steers fed a forage diet: I. Volatile fatty acids, glucose, and lactate.

This experiment investigated the effect of intraruminal infusion of propionic acid on ruminal VFA metabolism and the absorption of nutrients by the mesenteric- and portal-drained viscera of seven Friesian steers, average BW 127 kg, fed a dried grass-pellet diet. Each received by random allocation 0 (control), .5, or 1.0 mol of propionic acid/d for 7 d. Ruminal acetate and propionate irreversible loss rates and carbon exchange between VFA and CO2 were measured during continuous intraruminal infusions of 2-14C-acetic acid and 2-14C-propionic acid. Ruminal acetate irreversible loss rate was not affected by propionic acid infusion (overall mean 8.09, error mean square [EMS] 2.68 mol/d), whereas propionate irreversible loss increased incrementally with PA supply (3.22 vs 4.16, EMS .61 mol/d, for control and 1.0 mol of propionic acid/d, respectively, P = .09). Glucose irreversible loss rate was increased at the highest level of PA infusion (2.84, 2.83, and 3.22, EMS .06 mol/d, for control, .5, and 1.0 mol of propionic acid/d, respectively; P = .02 for control vs .5 + 1.0), although the proportion of glucose irreversible loss derived from propionate remained constant (.6). Net absorption into venous blood showed that propionate was extensively metabolized in the rumen wall and that the tissues of the small intestine utilized acetate. Utilization of glucose was reduced in portal tissues as a result of intraruminal infusion, and the data were used to derive a model of glucose and lactate interrelationships in gut tissues.

Absorption↗
PubMedDate not supplied

Effectiveness of fluticasone propionate in patients with moderate asthma: a dose-ranging study.

This study was undertaken to evaluate the efficacy and safety of fluticasone propionate, an inhaled corticosteroid, in adolescents and adults with moderate asthma who were previously taking inhaled corticosteroids. After a 2-week, open-label screening period, a double-masked, randomized, parallel-group, dose-ranging study was conducted over 12 weeks in 21 outpatient centers throughout the United States. Patients (N = 304) > or = 12 years of age with moderate asthma previously treated with inhaled corticosteroids and beta-sympathomimetic bronchodilators were enrolled. Patients were assigned to receive placebo or fluticasone propionate 100, 250, or 500 micrograms twice daily via a metered-dose inhaler without a spacer device. These doses refer to the amount of fluticasone propionate released from the valve of the metered-dose inhaler; the corresponding doses released from the activator of the metered-dose inhaler are 88 micrograms, 220 micrograms, and 440 micrograms, respectively. Between baseline and end point, mean values of forced expiratory volume in 1 second decreased 0.31 L in the placebo group and improved 0.39 L, 0.30 L, and 0.43 L in patients receiving 100-micrograms, 250-micrograms, and 500-micrograms fluticasone propionate, respectively. The differences between placebo and all treatment groups were statistically significant. More patients were withdrawn from placebo (72%) than from fluticasone propionate (13% to 16%) because of failure to meet predetermined asthma stability criteria. Differences in baseline-to-end point changes in morning peak expiratory flow rate, physician overall assessments and patient-rated assessment of symptoms, and albuterol use for symptom control also significantly favored each fluticasone propionate group over placebo. There were essentially no differences in efficacy among the three fluticasone propionate groups. Treatment-related adverse events occurred in 8% of placebo-treated patients and 13% to 15% of fluticasone propionate-treated patients; these events were mainly localized to the oropharynx/ larynx. A 12-week course of fluticasone propionate (100, 250, and 500 micrograms twice daily) was well tolerated and more effective than placebo based on maintenance of asthma stability, pulmonary function tests, physician and patient assessments, and rescue bronchodilator use. No dose-related effects were observed with the dosages of fluticasone propionate used in this study.

Adolescent↗
PubMed2002

Contribution of heme-propionate side chains to structure and function of myoglobin: chemical approach by artificially created prosthetic groups.

Horse heart myoglobin was reconstituted with mesohemin derivatives methylated at the 6- or 7-position to evaluate the role of the heme-6-propionate or heme-7-propionate side chain in the protein. The association and dissociation of the O(2) binding for the deoxymyoglobin with 6-methyl-7-propionate mesoheme are clearly accelerated. Furthermore, the myoglobin with 6-methyl-7-propionate mesoheme shows fast autoxidation from oxymyoglobin to metmyoglobin compared to the myoglobin with 6-propionate-7-methyl heme and the reference protein. These results indicate the 6-propionate plays an important physiological role in the stabilization of oxymyoglobin because of the formation of a salt-bridge with the Lys45. The acceleration of CO binding rate is observed for the myoglobin with 6-propionate-7-methyl mesoheme, suggesting that the replacement of the 7-propionate with a methyl group has an influence on the His93-heme iron coordination. The structural perturbation of His93 imidazole was also supported by 1H NMR spectra of cyanide and deoxy forms of the myoglobin with 6-propionate-7-methyl mesoheme. Thus, it is found that the 7-propionate regulates the hydrogen-bonding network and His93-heme iron coordination in the proximal site.

Animals↗
PubMed2005

Effect of fluticasone propionate-salmeterol therapy on seasonal changes in airway responsiveness and exhaled nitric oxide levels in patients with pollen-induced asthma.

BACKGROUND: There has been concern that in allergic asthmatic patients there might be an interactive effect on inflammation between regular salmeterol use and exposure to allergens, resulting in increased airway responsiveness. OBJECTIVE: To determine the effects of salmeterol on allergen-induced changes in airway responsiveness and exhaled nitric oxide (ENO) levels in allergic asthmatic patients concomitantly taking inhaled corticosteroids. METHODS: Forty-two asthmatic patients sensitized to pollen allergens were randomly allocated to treatment with fluticasone propionate-salmeterol (n=21) or fluticasone propionate alone (n=21). Spirometry, the methacholine provocation concentration causing a 20% decline in forced expiratory volume in 1 second (PC20), the adenosine 5'-monophosphate (AMP) PC20, and ENO levels were measured before and at the height of the pollen season after 6 weeks of treatment. RESULTS: Changes in the methacholine PC20, the AMP PC20, and ENO levels were not significantly different between treatment groups. No significant changes in the AMP PC20 were observed among the fluticasone propionate-salmeterol and fluticasone propionate groups during natural pollen exposure. However, a significant increase in the methacholine PC20 was observed in the fluticasone propionate-salmeterol group (P = .03) and in the fluticasone propionate group (P = .04); ENO concentrations decreased significantly in both groups during natural allergen exposure (P = .009 and .005). CONCLUSIONS: In patients with pollen-induced asthma, treatment with either fluticasone propionate or fluticasone propionate-salmeterol is associated with significant reductions in methacholine responsiveness and ENO concentrations, even during natural pollen exposure. Furthermore, at least in patients with mild asthma, natural allergen exposure and the regular use of fluticasone propionate-salmeterol are not associated with a greater increase in ENO levels and airway responsiveness than natural allergen exposure and fluticasone propionate use alone.

Adenosine Monophosphate↗
PubMed2005

Inhaled salmeterol/fluticasone propionate: a review of its use in asthma.

Salmeterol/fluticasone propionate, administered twice daily via a multidose dry powder inhaler (Seretide/Advair Diskus), Seretide Accuhaler or metered-dose hydrofluoroalkane (chlorofluorocarbon-free) inhaler (Seretide Evohaler), is a combination of the long-acting beta(2)-adrenoceptor agonist (beta(2)-agonist) [LABA] salmeterol and the corticosteroid fluticasone propionate. Maintenance therapy with combined salmeterol/fluticasone propionate is at least as effective in improving lung function and symptoms and is as well tolerated in patients with asthma as concurrent salmeterol plus fluticasone propionate. In patients previously receiving as-required short-acting beta(2)-agonists (SABAs) or inhaled corticosteroids, salmeterol/fluticasone propionate was significantly more effective in providing asthma control than fluticasone propionate and in improving lung function and asthma symptoms than inhaled corticosteroids (at equivalent or higher dosages), salmeterol or montelukast (as monotherapy or in combination with fluticasone propionate). Salmeterol/fluticasone propionate was more effective in improving asthma symptoms than adjusted-dose budesonide/formoterol in patients with uncontrolled asthma despite treatment with inhaled corticosteroids with or without a LABA in a well designed 1-year study. In pharmacoeconomic analyses, salmeterol/fluticasone propionate compared favourably with inhaled corticosteroids and mono- or combination therapy with oral montelukast. Salmeterol/fluticasone propionate is, therefore, an effective, well tolerated and cost-effective option for the maintenance treatment of patients with asthma.

Acetates↗
PubMed2002

Cost-effectiveness comparison of salmeterol/fluticasone propionate versus montelukast in the treatment of adults with persistent asthma.

OBJECTIVE: To compare the relative cost effectiveness of salmeterol (50 microg)/ fluticasone propionate (100 microg) with that of oral montelukast (10mg) as initial maintenance therapy in patients with persistent asthma uncontrolled on short-acting beta2-agonist therapy alone. STUDY DESIGN: A cost-effectiveness analysis was performed based on effectiveness and resource utilisation data that was prospectively collected from a randomised, double-blind, double-dummy, 12-week trial. PATIENTS AND METHODS: Patients (>15 years of age) who had asthma for at least 6 months. Effectiveness measurements in this analysis included improvement in forced expiratory volume in 1 second (FEV(1)) and symptom-free days (SFDs). Cost of asthma drug treatment as well as costs related to an asthma exacerbation were used in the cost analysis. The study assumed a payer's perspective. All costs are in 2001 US dollars. RESULTS: Of the 423 patients eligible for the study, 211 were randomised to salmeterol/fluticasone propionate and 212 to montelukast. Treatment with salmeterol/fluticasone propionate resulted in a significantly higher proportion of patients who achieved a 12% increase in FEV(1) (successful treatment) [salmeterol/fluticasone propionate: 71% vs montelukast: 39%; p < 0.001] and percentage of SFDs (salmeterol/fluticasone propionate: 46.8% vs montelukast: 21.5%; p < 0.001) compared with montelukast. The mean daily costs per successfully treated patient were lower in the salmeterol/fluticasone propionate group (US dollars 5.03, 95% CI US dollars 4.61 to US dollars 5.50) compared with the montelukast group (US dollars 8.25, 95% CI US dollars 6.98 to US dollars 9.93). Furthermore, per patient mean daily cost per SFD was lower with salmeterol/fluticasone propionate (US dollars 7.63, 95% CI US dollars 6.90 to US dollars 8.50) compared with montelukast (US dollars 14.89, 95% CI US dollars 12.36 to US dollars 17.98). Incremental cost-effectiveness ratios (ICERs) showed that the additional costs to achieve these benefits with salmeterol/fluticasone propionate were minimal. With regards to improvement in lung function, the ICER was US dollars 1.33 (95% CI US dollars 0.80 to US dollars 2.02) and with regards to SFD, the ICER was US dollars 1.69 (95% CI US dollars 1.01 to US dollars 2.48). Sensitivity analysis demonstrated the stability of the results over a range of assumptions. CONCLUSIONS: From a third-party payer perspective, this analysis shows that based on increased efficacy and only a slight increase in cost, twice-daily treatment with salmeterol/fluticasone propionate is more cost effective than once-daily treatment with montelukast as initial maintenance therapy for persistent asthma. This finding complements the results of the clinical analyses indicating that treatment of both inflammation and bronchoconstriction with products such as salmeterol/ fluticasone propionate may be more cost effective as initial maintenance asthma therapy than the use of leukotriene modifiers such as montelukast.

Acetates↗
PubMed1994

Once daily intranasal fluticasone propionate is effective for perennial allergic rhinitis.

The efficacy of intranasal fluticasone propionate 200 micrograms once daily or 100 micrograms twice daily in treating perennial allergic rhinitis was evaluated in a randomized, double-blind, placebo-controlled study of 24 weeks' duration in 365 patients. Clinician-rated and patient-rated total nasal symptom severity scores were improved within 1 week of treatment with either regimen of fluticasone propionate and improvement was maintained over the 24-week treatment period. Clinician-rated overall evaluation indicated a significantly better response in the two fluticasone propionate groups compared with the placebo group. All efficacy evaluations indicated no difference in response between the fluticasone propionate 200 micrograms once-daily and 100 micrograms twice-daily groups. Patients in both fluticasone propionate groups had significantly less nasal obstruction upon awakening than the placebo group at all assessment periods. Fewer patients in either fluticasone propionate group used antihistamine rescue medication compared with the placebo group. The percentage of patients with nasal eosinophils and basophils at the end of the 24-week treatment period was significantly lower in both fluticasone propionate groups compared with the placebo group. Safety evaluations indicated that intranasal fluticasone propionate was as safe as placebo when given as 200 micrograms once daily or 100 micrograms twice daily. The incidence of drug-related adverse events was similar among the fluticasone propionate and placebo groups except for the incidence of epistaxis and blood in nasal mucus which was somewhat higher in the fluticasone propionate twice-daily group. There was no changes in the opthalmic examinations to suggest corticosteriod-induced posterior subcapsular cataract formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗