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PubMed1997

Comparative efficacy and safety of twice daily fluticasone propionate powder versus placebo in the treatment of moderate asthma.

BACKGROUND: Fluticasone propionate, an inhaled corticosteroid with negligible systemic bioavailability via the oral route, is efficacious in the treatment of asthma when administered via metered-dose inhaler. OBJECTIVE: To evaluate the efficacy and safety of inhaled fluticasone propionate powder in patients with moderate asthma previously treated with an inhaled corticosteroid. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of 342 adolescent and adult patients with moderate asthma [forced expiratory volume in 1 second (FEV1) between 50% and 80% of predicted] treated previously by beclomethasone dipropionate or triamcinolone acetonide. Patients received fluticasone propionate powder 50 micrograms, 100 micrograms, 250 micrograms, or placebo via a breath-actuated inhalation device, the Diskhaler, twice daily for 12 weeks. RESULTS: Patients in the fluticasone propionate groups experienced a mean increase from baseline to endpoint in FEV1 ranging from 0.43 L to 0.47 L. Patients in the placebo group experienced a mean decrease from baseline of 0.22 L (P < .001). The probability of patients remaining in the study over time without developing signs of exacerbating asthma was significantly greater in the fluticasone propionate groups than in the placebo group (P = .001). Asthma symptom scores, supplemental rescue albuterol use, and number of nighttime awakenings due to asthma requiring treatment also improved significantly with all fluticasone propionate treatment regimens compared with placebo (P < .001). There were no statistically significant differences at endpoint among the three fluticasone propionate groups. No serious drug-related adverse events occurred. CONCLUSIONS: Fluticasone propionate powder (50, 100, and 250 micrograms) was well-tolerated and significantly improved lung function in patients with moderate asthma.

Administration, Inhalation↗
PubMed1998

Inhibition of interleukin-5 mediated eosinophil viability by fluticasone 17-propionate: comparison with other glucocorticoids.

BACKGROUND: Inhaled glucocorticoids are commonly employed to treat patients with asthma. Eosinophils are important effector cells in the pathogenesis of asthma, and, in vitro, glucocorticoids modulate eosinophil viability. OBJECTIVE: Using this glucocorticoid inhibition of eosinophil viability, we compared the in vitro potencies of several inhaled glucocorticoids with particular attention to fluticasone 17-propionate. METHODS: Eosinophils from normal or mildly atopic donors were purified, cultured with cytokines and glucocorticoids, and on day 4, after staining with propidium iodide, analysed by flow cytometry. RESULTS: Eosinophil viability was prolonged by interleukin (IL)-5 in a concentration-dependent manner; in contrast, dexamethasone inhibited the IL-5 effect. Fluticasone 17-propionate, 1.0-1000 nM, also inhibited the IL-5 effect in a concentration-dependent manner; interestingly, at 0.1 nM fluticasone 17-propionate modestly, but significantly, enhanced eosinophil survival. High concentrations of IL-5 and granulocyte-macrophage colony-stimulating factor essentially completely overcame the inhibitory effect of 1000 nM fluticasone 17-propionate on eosinophil survival. In contrast, although interferon-gamma-mediated eosinophil viability was inhibited by 1.0-1000 nM fluticasone 17-propionate, this inhibition was not overcome by increased concentrations of interferon-gamma. Comparison of the glucocorticoid inhibition of eosinophil viability in the presence of 10 pg/mL IL-5 resulted in these drug IC50 values (in nM): fluticasone 17-propionate, 1.3; budesonide, 8.5; triamcinolone acetonide, 25; flunisolide, 32; dexamethasone, 94; beclomethasone 17-monopropionate, 210; beclomethasone 17,21-dipropionate, 290; and hydrocortisone, >1000. CONCLUSION: Fluticasone 17-propionate's effect on cytokine-mediated eosinophil viability is similar qualitatively to other glucocorticoid preparations. However, quantitatively, fluticasone 17-propionate has the most potent suppressive effects on IL-5 mediated eosinophil viability among the currently available inhaled glucocorticoids in the United States.

Administration, Inhalation↗
PubMed1999

The cost-effectiveness of inhaled fluticasone propionate and budesonide in the treatment of asthma in adults and children.

Inhaled corticosteroids form the mainstay of the treatment and management of asthma and the results of a meta-analysis comparing two of the most frequently prescribed inhaled corticosteroids, fluticasone propionate and budesonide, administered in a clinically equivalent 1:2 dose ratio to 1980 patients with asthma, demonstrated that fluticasone propionate had an improved efficacy:safety ratio. However, limited data are available on the relative economic benefits of fluticasone propionate and budesonide. The database for clinically relevant parameters, for which the efficacy:safety meta-analysis had demonstrated statistical significance between the two corticosteroids, was used for this pharmacoeconomic analysis. Treatment with fluticasone propionate was more cost-effective than budesonide with respect to improvement in morning peak expiratory flow rate, successfully treated weeks, symptom-free days, symptom-free 24 h and episode-free days. The costs of treatment for fluticasone propionate and budesonide were 7.78 Pounds per week and 12.33 Pounds per week, respectively. The main contributing factor to the higher costs of budesonide was the higher cost of health care contacts, which were 4.53 Pounds per week for budesonide and 0.57 Pounds per week for fluticasone propionate. The pharmacoeconomic difference increased in favour of fluticasone propionate as the criteria for success were made more stringent. These results demonstrate that, for asthma patients requiring modification of therapy treatment with fluticasone propionate is more effective and also cheaper, in terms of overall health-care costs, than treatment with budesonide.

Adult↗
PubMed2001

Bacterial populations and processes involved in acetate and propionate consumption in anoxic brackish sediment.

Bacterial populations and pathways involved in acetate and propionate consumption were studied in anoxic brackish sediment from the Grosser Jasmunder Bodden, German Baltic Sea. Uptake of acetate and propionate from the porewater was studied using stable carbon isotope-labeled compounds. Labeled acetate was not produced as an intermediate during propionate uptake experiments, and propionate consumption was not affected by the addition of acetate. In parallel, incorporation of labeled acetate and propionate into phospholipid-derived fatty acids (PLFA) was studied to indicate bacterial populations involved in the consumption of these substrates. The (13)C-acetate label was mainly recovered in even-numbered PLFA (16:1omega7c, 16:0 and 18:1omega7c). In contrast, primarily odd-numbered PLFA (a15:0, 15:0, 17:1omega6 and 17:0) and the even-numbered i16:0 were labeled after incubation with (13)C-propionate. Although single PLFA labeled with propionate are commonly found in sulfate reducers, the complete PLFA-labeling pattern does not resemble any of the know strains. However, the acetate-labeling pattern is similar to Desulfotomaculum acetoxidans and Desulfofrigus spp., two acetate-consuming, sulfate reducers. In conclusion, our data suggest that acetate and propionate were predominantly consumed by different, specialized groups of sulfate-reducing bacteria.

Journal Article↗
PubMed1999

Addition of salmeterol versus doubling the dose of fluticasone propionate in patients with mild to moderate asthma.

BACKGROUND: The objective of this multicentre, randomised, double blind, parallel group study was to compare the efficacy and safety of the addition of salmeterol with that of doubling the dose of fluticasone propionate in asthmatic patients not controlled by a low or intermediate dose of inhaled corticosteroids. METHODS: After a four week run in period of treatment with fluticasone propionate (100 micrograms twice daily if pre-trial dose was 400-600 micrograms inhaled corticosteroids or 250 micrograms twice daily if pre-trial dose was 800-1200 micrograms inhaled corticosteroids), 274 patients were randomised to treatment for 12 weeks with either salmeterol 50 micrograms twice daily plus the run in dose of fluticasone propionate or twice the run in dose of fluticasone propionate (200 or 500 micrograms twice daily). Outcome measures were daily records of peak expiratory flow (PEF), symptom scores, and clinic lung function. RESULTS: The improvements in both the morning and evening PEF were better in the salmeterol than in the fluticasone propionate group, the mean increase in morning PEF being 19 l/min higher (95% CI 11.0 to 26.1) and in evening PEF being 16 l/min (95% CI 18.4 to 24.0) higher in the salmeterol group. The increase in forced expiratory volume in one second (FEV1) was 0.09 1 greater in the salmeterol group than in the fluticasone propionate group after four weeks of treatment (95% CI 0.01 to 0.18), but not after 12 weeks. Both regimens showed an increase in symptom free days and a reduction in the need for rescue salbutamol both during the day and the night, but these improvements were greater in the salmeterol group. There were no significant differences between the groups in adverse effects or in the number of rescue course of oral corticosteroids. CONCLUSIONS: In this group of patients still symptomatic despite 100 or 250 micrograms fluticasone propionate twice daily, the addition of salmetterol caused a greater improvement in lung function and symptom control than doubling the dose of fluticasone propionate.

Albuterol↗
PubMedDate not supplied

Bioavailability of clobetasol propionate in different vehicles.

Topical clobetasol propionate is widely used for the treatment of psoriasis. One formulation of clobetasol propionate, Skin Cap, was thought by some practitioners and patients to be more effective than other formulations. Differences in corticosteroid bioavailability could account for differences in efficacy. The purpose of this study is to compare the relative bioavailability of clobetasol propionate from Skin Cap to two FDA-approved formulations of clobetasol propionate (Olux foam and Temovate scalp application). The bioavailability was assessed by measuring the percutaneous absorption of clobetasol propionate in vitro on scalp skin, using the human cadaver skin model. There was no significant difference in the percutaneous absorption of clobetasol propionate between Olux foam and Skin Cap (2.09 and 1.93% at 48 h, respectively) or between Olux foam and Temovate scalp application (3.70 and 3.46%, respectively) when applied under unoccluded conditions. Under occluded conditions, there was greater absorption of clobetasol propionate from the Olux foam as compared with Skin Cap (4.94 and 1.57%, respectively; p < 0.05). The Skin Cap vehicle does not provide more bioavailable clobetasol propionate than currently available, FDA-approved products. Other differences, including those in patient compliance, could account for the perceived efficacy of the product.

Administration, Cutaneous↗
PubMed2004

Inhaled salmeterol/fluticasone propionate: a review of its use in chronic obstructive pulmonary disease.

The salmeterol/fluticasone propionate dry powder inhaler (DPI) [Advair Diskus, Seretide Accuhaler] contains the long-acting beta2-adrenoceptor agonist salmeterol and the inhaled corticosteroid fluticasone propionate. In the US, twice-daily salmeterol/fluticasone propionate 50/250 microg is approved for use in adults with chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis, and in the EU, the twice-daily 50/500 microg dosage is approved for use in patients with severe COPD, repeat exacerbations and significant symptoms despite bronchodilator therapy. In patients with moderate-to-severe COPD, twice-daily inhaled salmeterol/fluticasone propionate 50/250 or 50/500 microg for 24-52 weeks improves predose forced expiratory volume in 1 second (FEV1) significantly more than salmeterol monotherapy, improves postdose or postbronchodilator FEV1 significantly more than fluticasone propionate monotherapy and results in clinically significant improvements in health-related quality of life. Salmeterol/fluticasone propionate 50/500 microg significantly reduced annual COPD exacerbations, especially in severe COPD. Some corticosteroid-related adverse events were increased in recipients of fluticasone propionate with or without salmeterol versus salmeterol monotherapy or placebo; withdrawal from fluticasone propionate, including combination therapy, needs careful management to minimise COPD exacerbations. The DPI combining a corticosteroid and long-acting beta2-agonist provides benefits over monotherapy and may encourage patient compliance in COPD.

Administration, Inhalation↗
PubMed1990

Efficacy of laidlomycin propionate for increasing rate and efficiency of gain by feedlot cattle.

One thousand twenty steers and heifers were used in six feeding trials to examine the influence of laidlomycin propionate on feedlot performance and to determine the most efficacious dietary concentrations of that ionophore. Cattle were fed diets ranging in energy content from 1.08 to 1.49 Mcal NEg/kg of DM. Laidlomycin propionate improved rate of gain and feed conversion in both steers and heifers. Improvements in performance were not evident when laidlomycin propionate was fed at only 3 mg/kg. However, both average daily gain and feed conversion were improved by laidlomycin propionate within the range of 6 to 12 mg/kg of DM (P less than .001). Feed consumption was not substantially affected by inclusion of laidlomycin propionate in the diet. Improvements in ADG and feed conversion were greater on lower-energy diets than on higher-energy diets, but both these performance characteristics were improved regardless of the type of diet fed. Average daily gain was maximized with laidlomycin propionate at 6 mg/kg, whereas improvements in feed conversion were sustained through 12 mg/kg. Carcasses of cattle fed diets containing 6 to 12 mg/kg of laidlomycin propionate weighed 7.3 kg more (P less than .001) than carcasses of cattle fed the control diets. Yield grade and quality grade were not affected by laidlomycin propionate (P greater than .05).

Animal Feed↗
PubMed2001

Improved asthma control after changing from low-to-medium doses of other inhaled corticosteroids to low-dose fluticasone propionate.

OBJECTIVE: To evaluate the efficacy and safety of changing from low-to-medium doses of other inhaled corticosteroids to low-dose fluticasone propionate. METHODS: Data from 11 randomized, double-blind, parallel-group trials in adults (>= 12 years; n = 1453; % predicted FEV1 = 42% to 89%) and 4 trials in children (4-11 years; n = 161; % predicted FEV1 = 50% to 112%) with chronic asthma were retrospectively analyzed. Symptomatic adults (n = 1181) treated with low-to-medium doses of beclomethasone dipropionate (168-672 mcg/day), triamcinolone acetonide (400-1200 mcg/day), or flunisolide (>=1000 mcg/day) were switched to low-dose fluticasone propionate (176 or 200 mcg daily) for 6-26 weeks. Patients (n = 272) remaining on low-dose beclomethasone dipropionate (336 mcg daily) served as controls. Pediatric patients previously treated with low doses of triamcinolone acetonide (4-8 puffs/day), or low-to-medium doses of beclomethasone dipropionate (4-8 puffs/day) or flunisolide (2-6 puffs/day), were changed to low-dose fluticasone propionate (100 mcg daily) for 12-52 weeks. RESULTS: Improvements in FEV1, morning and evening peak expiratory flow (PEF), rescue albuterol use, asthma symptom scores, and symptom-free days were significantly greater in adults who changed from low-to-medium doses of beclomethasone dipropionate or triamcinolone acetonide to low-dose fluticasone propionate (P <.001). Regardless of the degree of asthma severity, these improvements were 1.5- to 4-fold greater in adult patients changed to low-dose fluticasone propionate vs those remaining on low-dose beclomethasone dipropionate. Significant improvements in lung function, albuterol use, and asthma symptoms (P <=.002) were also seen in pediatric patients who changed from beclomethasone dipropionate, flunisolide, or triamcinolone acetonide to a much lower dose of an inhaled corticosteroid (100 mcg fluticasone propionate daily). Drug-related adverse events were low in adults and children, and were comparable among adults receiving low-dose fluticasone propionate or beclomethasone dipropionate. CONCLUSIONS: Results indicate that patients with persistent asthma can change from other inhaled corticosteroids to a lower dose of fluticasone propionate and still maintain or improve asthma control.

Adult↗
PubMed1993

Fluticasone propionate aqueous nasal spray is safe and effective for children with seasonal allergic rhinitis.

INTRODUCTION: Fluticasone propionate aqueous nasal spray, a new topical corticosteroid preparation, is effective when given as 200 micrograms once daily in patients (> 12 years of age) with seasonal allergic rhinitis. STUDY OBJECTIVE: To evaluate the efficacy and safety of fluticasone proprionate aqueous nasal spray in children aged 4 to 11 years with seasonal allergic rhinitis. STUDY DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel-group. PATIENTS: Two hundred fifty children aged 4 to 11 years with moderate-to-severe nasal symptoms, a positive skin test reaction to a late-summer or autumn allergen, a history of seasonal allergic rhinitis, and documentation of an unsatisfactory response to conventional treatment. INTERVENTIONS: Children were randomly assigned to receive fluticasone propionate, either 100 micrograms or 200 micrograms, or placebo, given by intranasal spray once daily in the morning for 14 days. MEASUREMENTS AND RESULTS: Severity of nasal symptoms (obstruction, rhinorrhea, itching, and sneezing) was recorded on visual analog scales by investigators at weekly visits and by patients (or adult guardian) daily in the evening. According to investigator and patient ratings, both fluticasone propionate 100 micrograms/d and 200 micrograms/d lowered total nasal symptom scores when compared with placebo. Both dosages of fluticasone propionate were more effective than placebo on the basis of investigator-rated overall clinical evaluation of efficacy at the end of treatment, with significant improvement (as opposed to moderate or mild improvement, no change or worsening) noted in 21% to 29% of the active-treatment groups vs 9% in the placebo group. There were no significant differences between the two fluticasone propionate dosages in any efficacy measurement. Morning plasma cortisol concentrations and frequency of drug-related adverse events were similar in the fluticasone propionate and placebo groups. CONCLUSION: In children as young as 4 years, 100 micrograms of fluticasone propionate aqueous nasal spray given once daily is as effective as 200 micrograms given once daily, the usual adult dose for the treatment of seasonal allergic rhinitis. Both fluticasone propionate dosages were well tolerated and neither dosage appears to interfere with the hypothalamic-pituitary-adrenal axis in children.

Administration, Topical↗
PubMed1988

Propionic acid-induced calcium mobilization in human neutrophils.

The ability of propionic acid to elicit an increase in the level of cytoplasmic free calcium in human neutrophils was examined in detail. Propionic acid induced a rapid and dose-dependent mobilization of calcium that relied on both internal and external sources of calcium. The effects of propionic acid on the mobilization of calcium were inhibited by pertussis toxin, but not cholera toxin, implicating a guanine nucleotide binding protein. Furthermore, preincubation of the neutrophils with phorbol 12-myristate 13-acetate resulted in a decreased mobilization of calcium. This inhibitory activity of phorbol myristate acetate was antagonized by the protein kinase C inhibitor H-7. Preincubation of the cells with the synthetic chemotactic factor fMet-Leu-Phe caused a reduction in the magnitude of the calcium transient elicited by propionic acid. However, the calcium response to propionic acid was not affected by antagonists of fMet-Leu-Phe and platelet-activating factor binding or by an inhibitor of leukotriene synthesis. Propionic acid did not elicit a mobilization of calcium in monocytes, platelets, lymphocytes, or undifferentiated HL-60 cells. However, the treatment of the HL-60 cells with dimethylsulfoxide resulted in the appearance of a calcium response to propionic acid. The potential physiological significance of these findings are discussed.

Calcium↗
PubMed1994

Microbial production of propionic acid and vitamin B12 using molasses or sugar.

With a cell concentration of 125 g dry biomass l-1 and a dilution rate of 0.1 h-1, Propionibacterium acidipropionici produces 30 g propionic acid l-1 from sugar with a productivity of 3 g l-1 h-1. The yield of propionic acid is approx. 0.36-0.45 g propionic acid g-1 sucrose and is independent of the dilution rate and cell concentration. Acetic acid is an unwanted by-product in the production of propionic acid. The concentration of acetic acid only increases slightly when the cell concentration is increased. A two-stage fermentation process was developed for the conversion of sugar or molasses of various types to propionic acid and vitamin B12. By fermentation of blackstrap molasses (from sugar beet and sugar cane) in the first fermentation stage 17.7 g propionic acid l-1 with a yield of 0.5 g propionic acid g-1 carbohydrate was produced with a dilution rate of 0.25 h-1. In the second stage 49 mg vitamin B12 1-1 was produced at a dilution rate of 0.03 h-1.

Carbohydrate Metabolism↗
PubMed1990

The use of metronidazole in management of methylmalonic and propionic acidaemias.

Gut bacteria have been implicated as an important source of propionate in children with inborn errors of propionate metabolism. We have investigated the value of oral metronidazole (10-20 mg/kg per day) in five children with methylmalonic acidaemia (MMA) and four with propionic acidaemia (PA). Urinary excretion of propionate metabolites fell significantly during the treatment in all subjects, the mean decrease being 41% (range 12-76, P less than 0.01), while mean plasma propionate was reduced from 45.0 mumol/l to 25.1 mumol/l (P less than 0.05). Substantial reduction of the gut bacterial population was confirmed by lactulose breath hydrogen tests and by stool culture, and stool propionate concentration was reduced in most subjects. Clinical improvement was noted in three children. These results suggest that long-term antimicrobial therapy may offer significant clinical benefit to children with inborn errors of propionate metabolism.

Amino Acid Metabolism, Inborn Errors↗
PubMed1997

Propionate oxidation in Escherichia coli: evidence for operation of a methylcitrate cycle in bacteria.

Escherichia coli grew in a minimal medium on propionate as the sole carbon and energy source. Initially a lag phase of 4-7 days was observed. Cells adapted to propionate still required 1-2 days before growth commenced. Incorporation of (2-13C), (3-13C) or (2H3)propionate into alanine revealed by NMR that propionate was oxidized to pyruvate without randomisation of the carbon skeleton and excluded pathways in which the methyl group was transiently converted to a methylene group. Extracts of propionate-grown cells contained a specific enzyme that catalyses the condensation of propionyl-CoA with oxaloacetate, most probably to methylcitrate. The enzyme was purified and identified as the already-known citrate synthase II. By 2-D gel electrophoresis, the formation of a second propionate-specific enzyme with sequence similarities to isocitrate lyases was detected. The genes of both enzymes were located in a putative operon with high identities (at least 76% on the protein level) with the very recently discovered prp operon from Salmonella typhimurium. The results indicate that E. coli oxidises propionate to pyruvate via the methylcitrate cycle known from yeast. The 13C patterns of aspartate and glutamate are consistent with the further oxidation of pyruvate to acetyl-CoA. Oxaloacetate is predominantly generated via the glyoxylate cycle rather than by carboxylation of phosphoenolpyruvate.

Amino Acid Sequence↗
PubMed1985

Propionate transport in rat liver cells.

Propionate extraction by liver is generally in the range of 95%, which could depend on a transport process across the cell membrane. The study reports conditions in which [14C]propionate uptake can be measured with minimal interferences from metabolism. Propionate uptake by isolated hepatocytes was mediated by two components: a low-affinity component of limited physiological interest and a high-affinity (apparent Km about 0.15 mM) component. This last component displayed a high capacity but was not Na+-dependent nor concentrative. Propionate transport was not markedly affected by acetate, butyrate or other C3 glucogenic compounds; it was inhibited by halogenated monocarboxylates, monochloroacetate and 2-chloropropionate being the most potent. Classical inhibitors of anion transport and of functional-SH groups were ineffective. Propionate uptake was responsive to external pH: stimulated by acidic and depressed by alkaline pH. Hepatic uptake of propionate in vivo was practically quantitative up to 0.8-1.0 mM in afferent plasma, in keeping with the measured capacity of the high-affinity component. It is suggested that propionate uptake is essentially carrier mediated but this process should not be rate limiting for hepatic utilization in physiological conditions.

Animals↗
PubMed1986

Propionate and butyrate metabolism in rat or sheep hepatocytes.

The capacities of isolated hepatocytes to metabolize volatile fatty acids have been compared in rat and sheep hepatocytes. In both species, acetate utilization in vitro was quite limited. Significant species differences for propionate and butyrate consumption were found: propionate utilization by rat hepatocytes was relatively limited and plateaued at about 0.8-1.0 mM, whereas butyrate utilization was approx. 2-times higher. In contrast, ruminant hepatocytes exhibited a lower rate of butyrate utilization, but propionate metabolism was much more active than in rat liver cells. With relatively low concentrations of substrates (max. 2 mM), only propionate, compared to lactate or alanine, had a significant glucogenicity with hepatocytes from fed sheep. In both species, butyrate inhibited propionate consumption, although to a larger extent in sheep. The conversion of [2-14C]propionate to glucose by sheep hepatocytes was inhibited by 2 mM butyrate (60%) or ammonia (30%); 1 mM oleate or 10 mM glucose were ineffective. The basal rate of ammonia utilization by sheep hepatocytes was much lower than in rat and was unaffected upon addition of ornithine. Ammonia metabolism was markedly enhanced by butyrate and, in contrast to rat liver cells, also by propionate.

Ammonia↗
PubMed1983

Alteration in sensitivity of transmural electrical response to propionate in rat colon after chronic luminal infusion of short-chain fatty acids.

The colon is always exposed to abundant short-chain fatty acids (SCFA) produced by gut fermentation. In order to know an effect of chronic load of SCFA on colonic functions, we studied that the acute and chronic effects of SCFA on transmural potential difference (p.d.) across the proximal colon of germ-free (GF), gnotobiotic (GB) and conventionalized (CV) rats in vivo. Intravenous administration of SCFA (acute effect), such as propionate, butyrate, valerate or caproate, caused a transient increase in the p.d. The acute effects of propionate were studied in detail. The dose-response curve of CV rats shifted markedly to the right compared to that of GF rats, suggesting that CV rats were less sensitive to the acute effects of propionate than GF rats. Decreased sensitivity also appeared in GB rats (monocontamination with Fusobacterium varium). By chronic luminal infusion of isotonic sodium propionate or butyrate (25.5 ml/day) into the proximal colon of GF rats for 7 days (chronic effect), the acute effects of propionate were reduced. Atropine reduced the p.d. increment produced by propionate and shifted the dose-response curve of propionate to the right. These results suggest that chronic luminal load of SCFA resulted in a type of chronic refractoriness.

Animals↗
PubMed1994

Effect of propionate on in vivo carbohydrate metabolism in streptozocin-induced diabetic rats.

Undigested carbohydrates and some dietary fibers are fermented in the large intestine to form short-chain fatty acids (SCFA), including acetate, propionate, and butyrate. It has been suggested that some of the beneficial effects of high-carbohydrate, high-fiber diets on carbohydrate and lipid metabolism are mediated by the metabolism of SCFA in the liver. Propionate has been shown in vitro to decrease glucose production in rat hepatocytes. The aim of the present study was to investigate the effects of propionate on carbohydrate metabolism in normal and streptozocin (STZ)-induced diabetic male Sprague-Dawley rats. Rats were fed a high-fat diet with or without sodium propionate supplementation (either 0.5% or 5% wt/wt) for 4 weeks. At the completion of the feeding period, body weight and liver glycogen concentrations were significantly decreased in STZ-diabetic rats and were unaffected by propionate supplementation. Although STZ-diabetic animals had elevated fasting plasma glucose, cholesterol, and triglyceride levels relative to nondiabetic rats, propionate supplementation had no significant effect on these parameters in either group. Basal and insulin-stimulated carbohydrate metabolism were assessed using the euglycemic clamp technique in overnight-fasted animals with 3(H)-6-glucose infusion. As expected, basal hepatic glucose production (HGP) was higher and the metabolic clearance rate of glucose (MCR) was lower in STZ-diabetic rats. High-dose insulin infusion (3 mU.kg-1.min-1) suppressed HGP in nondiabetic and diabetic animals and increased the MCR in nondiabetic animals. However, propionate supplementation did not alter basal or insulin-stimulated HGP or the MCR in either nondiabetic or diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗