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PubMed1991

Regulation of in vitro metabolism of palmitate by carnitine and propionate in liver from dairy cows.

Regulation of in vitro palmitate metabolism by carnitine and propionate was investigated in liver obtained by biopsy from fasted nonlactating cows and from cows during early lactation. Liver slices from nonlactating cows during a 7-d fast esterified less palmitate than those from the same cows before fasting. Carnitine added in vitro increased hepatic oxidation and decreased esterification of palmitate in fed cows, but effects of carnitine were less during fasting. Propionate added in vitro decreased oxidation of palmitate; the effect was greater during fasting. In liver slices from cows during early lactation, carnitine increased oxidation and total utilization of palmitate and decreased palmitate esterification. Addition of tetradecylglycidic acid, an inhibitor of carnitine palmitoyltransferase I, prevented the carnitine-induced changes in palmitate metabolism. Substantial carnitine-independent oxidation of palmitate was observed in the presence of tetradecylglycidic acid. Tetradecylglycidic acid decreased esterification of palmitate to triglycerides but increased esterification to diglycerides. Effects of tetradecylglycidic acid and either propionate or pyruvate on palmitate oxidation were additive, indicating that propionate and pyruvate affect palmitate oxidation at sites other than carnitine palmitoyltransferase I. No interactions were detected between carnitine and propionate, but both compounds were potent regulators of palmitate metabolism in liver slices from cows during early lactation.

Animals↗
PubMed1994

Effect of isocaloric infusion of glucose in the rumen or propionate in the duodenum.

This study was undertaken to understand better the mechanisms causing increased milk protein. Cows fed steam-flaked sorghum have increased milk protein compared with that of cows fed dry-rolled sorghum because of a large shift of starch digestion from the intestine to the rumen. Five cannulated lactating cows were infused with glucose in the rumen or with propionate in the duodenum in two trials. The experimental design was a 2 x 2 Latin square with 7 d of adjustment and 7 d of infusion. During the experiment, cows received a TMR containing 19.3% CP and 1.56 Mcal/kg of NEL (on a DM basis); alfalfa hay and dry-rolled sorghum grain were the principal ingredients. Similar concentrations in feces of cows among propionate treatments suggested complete absorption of infused propionate. Milk yield did not differ, but protein percentage of milk was higher (2.88 versus 2.72%) for cows infused ruminally with glucose than for those infused in the duodenum with propionate. For the respective treatments, duodenal flows were 2.11 and 1.76 kg/d for microbial protein and 3.44 and 2.73 kg/d for total CP (or 85 and 74% of CP intake). These data demonstrate that increased propionate availability for gluconeogenesis and a possible sparing of essential AA did not result in increased milk protein content, but ruminal infusion of glucose, which tended to increase microbial protein synthesis, did increase the protein percentage of milk.

Adenosine Triphosphate↗
PubMed1996

Effects of the ratio of ruminal propionate to butyrate on milk yield and blood metabolites in dairy cows.

Four Ayrshire cows (mean = 56 DIM) were used in a 4 x 4 Latin square design to study the effects of the ratio of propionate to butyrate in the rumen on milk yield, milk composition, and blood metabolites. The cows were fed a basal diet (16.2% CP, 43.4% NDF) consisting of 50% grass silage, 6% grass hay, and 44% concentrate (percentage of DM). The diet supplied 44 Mcal/d of metabolizable energy and was supplemented with isoenergetic infusions of VFA (4.5 Mcal/d). Propionate (900 g/d) was replaced gradually with 33, 67, and 100% of butyrate on an energy basis. Replacement of propionate with butyrate in the infusate decreased propionate and increased butyrate concentrations in ruminal fluid and in blood plasma. Yields of milk and lactose decreased, and yield of milk fat increased, as butyrate increased. Milk fat content increased, and lactose content decreased, as butyrate increased. Increased ruminal supply of butyrate decreased plasma glucose concentration and increased blood ketone body concentration. When only butyrate was infused (750 g/d), either liver metabolism was changed or tissue mobilization was increased, as indicated by the increased production of long-chain milk fatty acids and increased plasma concentrations of acetate, Gly, and branched-chain AA. An increase in ruminal butyrate supply at the expense of propionate adversely affected milk yield and the repartitioning of nutrients between milk components. At a high percentage, increased butyrate might also adversely affect the overall metabolism of the cow.

3-Hydroxybutyric Acid↗
PubMed1975

A simplified and rapid quantitative assay for propionic and methylmalonic acids in urine.

Propionic and methylmalonic aciduria occur individually in inborn errors of metabolism and together in vitamin B12-deficient states. A method is described for the simultaneous and rapid extraction of these acids from urine and their quantification by a simple gas chromatographic technique. The assay is based upon the spontaneous and quantitative decarboxylation of methylmalonic acid (MMA) at 225 degrees C. to its monocarboxylic acid product, propionic acid. By utilizing another substituted malonic acid, ethylmalonic acid, as a specific internal standard, accurate quantitation is possible by peak height ratio analysis, Endogenous propionic acid is then measured at 130 degrees C., a temperature at which methylmalonic acid does not decarboxylate. The assay is rapid with a total running time of approximately 2 hours. The method provides excellent resolution of propionic acid excretion at or above 0.5 mg. per liter of urine. The level of resolution for methylmalonic acid, in the presence of propionic aciduria, was 5 mg. per liter of urine.

Chromatography, Gas↗
PubMed1991

[The effect of metabolites of the propionate pathway on the oxidative activity of liver mitochondria].

Methylmalonate and propionate, the major metabolites of the propionate pathway of fatty and amino acid metabolism used at 1-4 mM cause selective inhibition of succinate and palmitoyl carnitine oxidation in liver mitochondria. Methylmalonate is more specific towards succinate, whereas propionate--towards palmitoyl carnitine oxidation. Methylmalonate is transported to mitochondria at a high rate with no effect on succinate transport. Being injected intramusculary methylmalonate has no inhibiting effect on the oxidative activity of mitochondria but is able to activate succinate and palmitoyl carnitine oxidation. The inhibiting effect of propionate on palmitoyl carnitine oxidation is a long-term one. Injections of these metabolites precursors, isoleucine, methionine and valine, produce an activating effect on succinate oxidation. Thus, propionate pathway metabolites may participate in the regulation of lipid-carbohydrate metabolism.

Animals↗
PubMed1990

Effects of dietary propionate on carbohydrate and lipid metabolism in healthy volunteers.

Propionate produced in the colon from the fermentation of alpha-amylase-resistant starch and non-starch polysaccharides, is cholesterol lowering and gluconeogenic in animal models. In humans, little is known about the effect of propionate on metabolism. In a double-blind, paired-comparison, placebo-controlled study, the diet of 10 healthy female volunteers, aged 20-22 yr, was supplemented for a period of 7 wk with 7.5 g sodium propionate daily in capsule form, while the diet of the 10 control group members was supplemented with dibasic calcium phosphate in identical capsules as placebo. Propionate supplementation did not lower total serum cholesterol (TC), but increased HDLC (9.5%) (p less than 0.05) and triglyceride levels (16.7%, p less than 0.02) and decreased fasting serum glucose and maximum insulin increments during glucose tolerance tests (p less than 0.05). The results suggest that the improvement in glucose tolerance and insulin sensitivity and the known beneficial effect of dietary fiber on HDL metabolism may in part be mediated through effects of propionate on hepatic carbohydrate metabolism.

Adult↗
PubMed1989

[Determination of volatile fatty acids in the blood plasma of cattle before and after an infusion of propionate and butyrate].

Before and after infusion of propionate and butyrate the concentrations of volatile fatty acids (VFA) in the blood of heifers were determined by gas chromatography, in order to indicate activity and regulation of the carbohydrate metabolism. 14 heifers were loaded after food deprivation with intravenous infusions of propionate and butyrate. Concentrations of acetate, propionate, isobutyrate, butyrate, and valerate were measured in blood samples which were taken later on. The methods used for clearance and extraction as well as for gas chromatographic analysis are described. Retention times and blood concentrations are given for each VFA. Concentrations prior to infusion were for: acetate 10.14 +/- 2.51 microliters/ml; propionate 0.42 +/- 0.35 microliters/ml; iso-butyrate 3.72 +/- 1.37 microliters/ml; butyrate 3.44 +/- 0.68 microliters/ml blood plasma. The concentrations of the infused VFA showed a 100 (butyrate) to 1000 (propionate) fold increase followed by a subsequent decrease to the initial values. These investigations on the profile of VFA elucidated criteria of the energy metabolism.

Animals↗
PubMed1985

Propionate loading test for liver function in spontaneously ketotic dairy cows.

Propionate utilisation by the liver in spontaneously ketotic dairy cows was investigated by determining blood glucose levels after an intravenous sodium propionate load (2.5 mmol kg-1). In addition, blood ketone body concentrations were measured after propionate loading. Cows were divided into three groups (control, mildly ketotic and severely ketotic) by their blood acetoacetate concentrations. Plasma glucose concentrations increased significantly after sodium propionate injection in all three groups (P less than 0.05). The maximum glucose concentration occurred earlier in the control group than in the ketotic groups. Changes in glucose concentrations following propionate loading of control and ketotic cows differed significantly at 20 minutes and beyond. Differences in the change in glucose concentration between mildly ketotic and severely ketotic cows were not significant. Acetoacetate concentration was significantly decreased at five minutes and beyond after the injection in ketotic cows, whereas beta-hydroxybutyrate concentration decreased more slowly. A decrease in beta-hydroxybutyrate concentration was significant at 40 minutes and beyond in the severely ketotic group and at 10 minutes and beyond in the mildly ketotic group after loading.

3-Hydroxybutyric Acid↗
PubMed1983

Effect of propionic acid on urea synthesis by sheep liver.

Propionate reduced substantially the rate of ureagenesis by slices of sheep liver whereas butyrate did not inhibit urea synthesis. The site of inhibition of urea synthesis by propionate occurs at some point between the fixation of ammonia and the formation of citrulline since 0.5 mM propionate inhibited by 80 per cent the synthesis of citrulline by mitochondria isolated from sheep liver. Since the apparent Ki for propionate is approximately 1.7 mM, the inhibitory effect of propionate on urea synthesis could be of physiological significance in sheep.

Animals↗
PubMed1994

CT and MR of the brain in disorders of the propionate and methylmalonate metabolism.

PURPOSE: To present the CT and MR findings in children with propionic and methylmalonic acidemia. METHODS: Twenty-three new patients with methylmalonic and 20 with propionic acidemia were examined with CT and/or MR of the brain. In total 52 CT and 55 MR studies were done. Twenty-six previously published cases were also reviewed. RESULTS: The findings were similar in the two syndromes. During the first month of life the examinations were either normal or showed white matter attenuation. Later during the first year moderate or even severe widening of sulci and fissures was seen, especially in infants with propionic acidemia. During therapy, these changes often resolved, especially in the patients with methylmalonic acidemia. Mild to moderate delay in myelination was also a common finding in both disorders. Basal ganglia changes, predominately in the globus pallidus, were seen in five patients with methylmalonic acidemia and in two children with propionic acidemia; in two patients these changes were transient. CONCLUSION: Children who have methylmalonic or propionic acidemia, in addition to widening of cerebrospinal fluid spaces and some delay in myelination, also often show symmetric involvement of the basal ganglia.

Amino Acid Metabolism, Inborn Errors↗
PubMed1999

Effect of topical fluticasone propionate on the mucosal allergic response induced by ragweed allergen and diesel exhaust particle challenge.

Glucocorticoids block the local allergic response in a variety of ways. However, studies have also shown that glucocorticoids increase in vitro IgE synthesis and that treatment with corticosteroids may result in elevated serum IgE concentrations. The ability of topical glucocorticoids to modulate the mucosal IgE response has not been elucidated. We studied the effect of topical steroid (fluticasone propionate) treatment on the local allergic antibody response induced by challenge with either allergen or diesel exhaust particles (DEP). A parallel group study was performed with ragweed-allergic subjects, each subject serving as his/her own control. Nasal provocation challenges were performed on three groups. One group received ragweed allergen, another diesel exhaust particles, and the third saline. The study was repeated following 1 week of treatment with intranasal fluticasone propionate. Each group received the same challenge as before. The concentrations of total immunoglobulins (IgE, IgG, IgA, and IgM), anti-ragweed antibody, IgE- and IgA-secreting cells, epsilon (epsilon) mRNA, and cytokine mRNAs (IL-2, -4, -5, -6, TNF-alpha, INF-gamma) were measured in nasal lavages performed before and at various time points after challenge. Treatment with fluticasone propionate for 7 days caused a decrease in the concentrations of nasal IgE protein, IgE-producing cells, total epsilon mRNA, and all the cytokine mRNAs tested. Furthermore, treatment with fluticasone propionate inhibited the production of allergen-specific IgE and cytokine mRNAs following challenge with ragweed antigen. However, fluticasone treatment did not significantly inhibit the enhancement of mucosal IgE production or cytokine mRNAs observed following nasal challenge with DEP. These results indicate that 1-week treatment with topical fluticasone propionate was effective in blocking local effects of allergen exposure but was unable to inhibit the adjuvant-like effect of DEP.

Administration, Intranasal↗
PubMed1993

A placebo controlled trial of fluticasone propionate in asthmatic children.

Fluticasone propionate is a synthetic steroid for use by the inhaled route. It's high topical potency and low systemic bioavailability make it suitable for use in asthmatic children. A total of 258 children were randomised in a double-blind study to receive fluticasone propionate (50 micrograms bd) as the dry powder formulation inhaled via a Diskhaler inhaler, or matched placebo (with current therapy) for 4 weeks throughout which time diary cards were completed. During clinic visits lung function and adrenal function were measured. Fluticasone propionate produced a significantly greater increase in morning peak expiratory flow rate (PEFR) (adjusted mean difference over days 1-28, 17 l/min (95% CI; 10, 24); P < 0.001) and evening PEFR (adjusted mean difference over days 1-28, 16 l/min (95% CI; 9, 23); P < 0.001). In addition, diary card symptom scores, beta 2-agonist rescue and clinic lung function improved significantly on fluticasone propionate. There were few adverse events and basal plasma cortisol remained within the normal range. In conclusion fluticasone propionate at 50 micrograms bd is superior to placebo (current therapy) in the treatment of childhood asthma with no evidence of adverse effects.

Administration, Inhalation↗
PubMed1991

A double-blind, vehicle-controlled paired comparison of halobetasol propionate cream on patients with plaque psoriasis.

The efficacy and safety of halobetasol propionate 0.05% cream, an ultra high-potency corticosteroid preparation, was evaluated in a double-blind, vehicle-controlled, paired comparison study. Patients' psoriatic lesions were evaluated before treatment and after 1 and 2 weeks of twice-daily treatment with halobetasol propionate and vehicle. Response measures (plaque elevation, erythema, scaling, and pruritus) were evaluated with a 4-point severity scale whereby the sum provided a total score. Patient self-assessment measures were obtained at the 2-week visit by categorizing his or her global responses to queries about each treatment's "effectiveness" and "overall rating." All efficacy parameters, as judged by the physician, showed statistically significant (p = 0.0001) treatment differences favoring halobetasol propionate at both week 1 and week 2 evaluations. Patient global responses for "effectiveness" and "overall rating" favored halobetasol propionate 0.05% cream over vehicle after 2 weeks of use. No systemic adverse drug effects were reported during the study. No patient was discontinued from the study because of an adverse event, and there was no evidence of skin atrophy after 2 weeks of treatment with either agent. Patient reports of "stings" or "burns" were equally distributed between the active and vehicle treatment groups. This trial demonstrates that halobetasol propionate 0.05% cream is clinically beneficial and without evidence of significant risk in the treatment of plaque psoriasis.

Administration, Cutaneous↗
PubMed1991

A review of two controlled multicenter trials comparing 0.05% halobetasol propionate ointment to its vehicle in the treatment of chronic eczematous dermatoses.

The efficacy and safety of 0.05% halobetasol propionate ointment were evaluated in patients with chronic atopic or other eczematous dermatoses in two vehicle-controlled, double-blind studies: a paired-comparison study in 124 patients (study A) and a parallel-group study in 100 patients (study B). In study A, patients applied both treatments twice daily for 2 weeks and were evaluated by investigators on days 0, 7, and 14 with 0 to 3 severity scales and by self-assessment with two 5-step end-of-treatment rating scales. In study B, patients applied treatments twice daily for 2 weeks, and investigators made evaluations on days 0, 3, 7, and 14 with 0 to 6 scales and also made a 5-step end-of-treatment physician's global assessment. In study A, both severity scores and patient ratings favored halobetasol propionate significantly on days 7 (p less than or equal to 0.0013) and 14 (p less than 0.0001); in study B, severity scores on days 3 (p less than or equal to 0.045, pruritus, erythema, and overall lesion severity), 7, and 14 (p less than 0.001, all comparisons) also favored halobetasol propionate significantly, and global assessments showed complete resolution or marked improvement for 83% of patients using halobetasol propionate versus 28% of those using vehicle (p less than 0.0001). No instances of systemic effects or skin atrophy were reported in either study. We conclude that 0.05% halobetasol propionate ointment is highly effective and well tolerated in the treatment of the conditions studied, with the rapid action and high degree of clearing associated with superpotent corticosteroid formulations.

Adolescent↗
PubMed2006

Contribution of the heme propionate groups to the electron transfer and electrostatic properties of myoglobin.

The role of the heme propionate groups in determining the electron transfer and electrostatic properties of myoglobin have been studied by thermodynamic, kinetic, and spectroscopic studies of horse heart myoglobin in which the heme propionate groups are esterified. Spectroelectrochemical analysis has established that the E(m,7) of dimethylester heme-substituted Mb (DME-Mb) (E(m,7)=100.2(2)mV vs. NHE (Normal Hydrogen Electrode) (25 degrees C) is increased approximately 40mV relative to that of the native protein with DeltaH degrees =-12.9(2) kcal/mol and DeltaS degrees =-51.0(8) cal/mol/deg (pH 7.0, mu=0.1M (phosphate)). The second order rate constant for reduction of DME-metMb by Fe(EDTA)(2-) is increased >400-fold relative to that for reduction of native metMb to a value of 1.34(2)x10(3)M(-1)s(-1) with DeltaS(double dagger)=-13(1) cal/mol/deg and DeltaH(double dagger)=9.2(3) (pH 7.0, micro=0.1M (phosphate)). Analysis of the pH dependences of the reduction potential and rate constant for reduction by Fe(EDTA)(2-) demonstrates that heme propionate esterification introduces significant changes into the electrostatic interactions in myoglobin. These changes are also manifested by differences in the pH dependences of the (1)H NMR spectra of native and DME-metMb that reveal shifts in pK(a) values for specific His residues as the result of heme propionate esterification. In sum, the current results establish that heme propionate esterification not only affects the electron transfer properties of myoglobin but also influences the titration behavior of specific His residues.

Electron Transport↗
PubMed2005

Effects of inhaled ciclesonide and fluticasone propionate on cortisol secretion and airway responsiveness to adenosine 5'monophosphate in asthmatic patients.

The efficacy and systemic effects of ciclesonide, a novel glucocorticosteroid, inhaled via pressurized metered-dose inhaler (pMDI) were compared with fluticasone propionate pMDI in 26 patients with asthma, using a randomized, double blind, placebo-controlled, double dummy, 6-period crossover study design. Treatments were placebo, ciclesonide 320 microg (ex-actuator dose) once daily (o.d.), ciclesonide 640 microg o.d., ciclesonide 640 microg twice daily (b.i.d.), fluticasone propionate 440 microg (ex-actuator dose) b.i.d., and fluticasone propionate 880 microg b.i.d. The primary variable was area under the plasma cortisol concentration-time curve over 24 h (plasma cortisol AUC(0-24), relative to placebo) derived from samples taken every 2 h, on the 9th day of treatment. Secondary variables were 24-h urinary cortisol excretion and PC20 for adenosine 5'-monophosphate (AMP) (relative to placebo and expressed in doubling concentrations). Ciclesonide did not affect 24-h cortisol secretion. Fluticasone propionate suppressed cortisol secretion as demonstrated by a decrease in plasma cortisol AUC(0-24), relative to placebo, by 29% (95% CI 15-41) and 59% (95% CI 51-66) with 440 and 880 microg b.i.d., respectively. PC20 more than doubled with each active treatment, but no statistically significant dose-response effect could be established. It was concluded that moderate to high doses of fluticasone propionate suppressed cortisol secretion, that ciclesonide did not suppress cortisol secretion, and that all active treatments decreased hyperresponsiveness to AMP.

Adenosine Monophosphate↗
PubMed1992

Fluticasone propionate given once daily is as effective for seasonal allergic rhinitis as beclomethasone dipropionate given twice daily.

Fluticasone propionate was compared with beclomethasone dipropionate for the treatment of allergic rhinitis in a multicenter, double-blind, randomized, placebo-controlled study during the mountain cedar (Juniperus ashei) pollination season in central Texas. Adults (n = 313) with moderate to severe symptoms were treated with fluticasone propionate aqueous nasal spray 200 micrograms once a day or beclomethasone dipropionate aqueous nasal spray 168 micrograms twice a day or placebo for 2 weeks. Fluticasone propionate administered once daily and beclomethasone dipropionate administered twice daily were equally effective as assessed by clinician- and patient-rated scores for nasal obstruction, rhinorrhea, sneezing, and nasal itching throughout the treatment and follow-up periods. Both regimens were more effective than placebo. Adverse events were related to topical administration and were similar in frequency and nature in all three treatment groups. Fluticasone propionate and beclomethasone dipropionate displayed a similar safety profile that did not differ from placebo. We conclude that fluticasone propionate aqueous nasal spray administered as 200 micrograms once daily in the morning is as safe and effective as beclomethasone dipropionate aqueous nasal spray administered as 168 micrograms twice daily for seasonal allergic rhinitis.

Administration, Topical↗
PubMed1999

A comparison of multiple doses of fluticasone propionate and beclomethasone dipropionate in subjects with persistent asthma.

BACKGROUND: Inhaled corticosteroids are recommended for the treatment of persistent asthma. Comparative clinical studies evaluating 2 or more doses of these agents are few. OBJECTIVE: We sought to compare the efficacy and safety of 2 doses of fluticasone propionate (88 micrograms twice daily and 220 micrograms twice daily) with 2 doses of beclomethasone dipropionate (168 micrograms twice daily and 336 micrograms twice daily) in subjects with persistent asthma. METHODS: Three hundred ninety-nine subjects participated in this randomized, double-blind, parallel-group clinical trial. Eligible subjects were using daily inhaled corticosteroids and had an FEV1 of 45% to 80% of predicted value. Clinic visits, including spirometry, were conducted every 1 to 2 weeks. Subjects recorded symptoms, use of albuterol, and peak expiratory flows on daily diary cards. RESULTS: Fluticasone propionate treatment resulted in significantly (P </=.034) greater improvements in objective pulmonary function parameters than did beclomethasone dipropionate treatment and significantly greater reductions in daily albuterol use (P </=.010) and asthma symptoms (P </=.027). Both low-dose (88 micrograms twice daily) and medium-dose (220 micrograms twice daily) fluticasone propionate significantly increased FEV1 compared with higher doses of beclomethasone dipropionate (P =. 006). Low-dose and medium-dose fluticasone propionate improved FEV1 by 0.31 L (14%) and 0.36 L (15%), respectively, compared with improvements of 0.18 L (8%) and 0.21 L (9%) with low-dose and medium-dose beclomethasone dipropionate. The adverse event profiles were similar for both medications. CONCLUSION: Fluticasone propionate provides greater asthma control at roughly half the dose of beclomethasone dipropionate, with a comparable adverse event profile.

Adolescent↗