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Effect of propionate on pyruvate metabolism in adipose tissue.

Glyceride-glycerol formation in rat adipose tissue from pyruvate-2-(14)C is increased by fasting, while fatty acid synthesis is markedly depressed. In tissues of fasted animals glyceride-glycerol formation is maximal with concentrations of pyruvate exceeding 2.5 mM. With 0.25 mM pyruvate-2-(14)C, glyceride-glycerol formation is increased severalfold by the addition of 0.25 mM propionate. No further increase in synthesis is caused by propionate when pyruvate is supplied in optimal amounts. Addition of equimolar concentrations of acetate or pyruvate does not replace propionate. The effect of propionate on glyceride-glycerol synthesis from pyruvate is also given by a series of even-chain fatty acids. However, only propionate promotes fatty acid synthesis in tissues of fasted and fed animals. Fixation of (14)CO(2) in glyceride-glycerol is dependent on the presence of propionate and is maximal in tissues of fasted rats and when pyruvate is also added. Succinate has no significant effect. Actinomycin treatment blocks glyceride-glycerol synthesis in tissues of fed and fasted animals, in the presence and absence of propionate. At the same time, fatty acid synthesis in tissues of fasted rats is markedly increased.

Adipose Tissue↗

Effect of acetate and propionate on fasting hepatic glucose production in humans.

OBJECTIVE: Short chain fatty acids (SCFA, e.g. acetate and propionate) produced from bacterial colonic fermentation may be involved in the improvement of fasting glucose concentration observed with high dietary fibre diets. Because fasting blood glucose is related to hepatic glucose production, we have tested the effect of propionate and acetate on hepatic glucose production. SETTING: The study was carried out in the Clinical Research Center for Human Nutrition. SUBJECTS: Six healthy young volunteers. INTERVENTIONS: The subjects received, in a random order: acetate (12 mmol/h), or propionate (4 mmol/h), or acetate+propionate (12 mmol/h + 4 mmol/h), or an isotonic sodium salt solution (saline) in 3 h gastric infusions. Blood glucose and plasma insulin was monitored. Hepatic glucose production was measured with an isotopic method using [6,6-2H2] glucose. RESULTS: No changes were observed in blood glucose, plasma insulin concentrations or hepatic glucose production with any of the infused solutions. An increase in free fatty acid (FFA) plasma concentration related to the fasting state was observed with the saline solution, but not with the SCFA infusions (P < 0.05). There was also an increase in beta-hydroxybutyrate concentration with the saline and the acetate solutions, but not with the propionate or acetate+propionate solutions. CONCLUSIONS: SCFA, administered at a rate calculated on the basis of a continuous daily fermentation of 30 g dietary fibres, do not change hepatic glucose production or fasting blood glucose. Propionate and acetate decrease plasma FFA, and further studies are needed to explore this effect on glucose tolerance and insulin sensitivity.

Acetates↗

Applicability of an enzymatic quantitation of methylmalonic, propionic, and acetic acids in normal and megaloblastic states.

A rapid sensitive spectrophotometric assay for the measurement of methylmalonic and propionic acids in urine is described. The assay is based upon the quantitation of propionic acid using acetyl coenzyme A synthetase isolated from baker's yeast. This enzyme is highly specific for acetate and propionate, and acetate interference is eliminated by conversion to citrate. Methylmalonic acid was assayed by converting it to propionate by heat decarboxylation and then measuring the propionate increment over the endogenous amount in the noncarboxylated sample. Studies of urine obtained from normal subjects (by isolation, partial purification, and then assay by the isotope dilution technique) demonstrated urinary excretion of less than 1 mg of propionic acid and 1-5 mg of methylmalonic acid per day. In 22 consecutive patients with documented vitamin B12 deficiency, methylmalonic acid excretion in excess of 30 mg/24 hr was found. In four other patients, with only neurologic involvement methylmalonic aciduria aided in identifying B12 deficiency as an etiologic factor. Methylmalonic acid excretion was measured by direct assay of an aliquot of urine, requiring neither a valine load nor special extraction procedures. Propionic aciduria was variably increased in B12 deficiency and did not correlate either with the severity of the deficit or degree of methylmalonic aciduria. The assay was performed on urine, but it is potentially applicable to tissue extracts. In addition, this assay method can be utilized for the quantification of urine acetate levels as well.

Acetates↗

Inhibition of mitogen-activated proliferation of human peripheral lymphocytes in vitro by propionic acid.

Recurrent infections are common features in patients affected by propionic acidaemia (McKusick 232000) and methylmalonic acidaemia (McKusick 251000). Since these disorders are biochemically characterized by tissue accumulation of propionic acid and methylmalonic acid respectively, it is possible that these compounds may act as immunosuppressants. We therefore investigated the effect of propionate and methylmalonate on cellular growth of human peripheral lymphocytes stimulated in vitro by phytohaemagglutinin, concanavalin A and pokeweed mitogen, a recognized test of cellular immunocompetence. Lymphocytes were cultured in flat-bottomed 96-well microplates at 37 degrees C for 96 h (phytohaemagglutinin and concanavalin A) or 144 h (pokeweed mitogen) in the presence of one mitogen at different concentrations and of one acid added at doses of 1.0, 2.5 or 5.0 mM. Cell blastogenesis was measured by the incorporation of tritiated thymidine into cellular DNA and compared with that of identical cultures with no acid added (controls). A consistent and progressive inhibitory effect of propionic acid with increasing concentrations in culture was identified with all mitogens and was more pronounced with pokeweed mitogen. Lymphocyte blastogenesis was not altered in the presence of methylmalonic acid. The effect of propionate was observed only when the drug was added at the beginning (phytohaemagglutinin-activated) or until 24 h (concanavalin A- and pokeweed mitogen-activated) of culture. The viability of lymphocytes after treatment with the drug, as assessed by the Trypan Blue exclusion test, revealed no change when compared with the same untreated lymphocytes, indicating no lymphocytotoxic activity. In conclusion, propionic acid, which accumulates in tissues of patients with propionic acidaemia, causes 'in vitro' immunosuppression, which may be related to the recurrent infections characteristic of these patients.

Adult↗

Once daily fluticasone propionate is as effective for perennial allergic rhinitis as twice daily beclomethasone diproprionate.

BACKGROUND: Fluticasone propionate aqueous nasal spray, a new potent corticosteroid, is effective when given once or twice daily for seasonal allergic rhinitis. METHODS: Fluticasone propionate was compared with beclomethasone dipropionate in a multicenter double-blind, randomized, placebo-controlled, parallel-group study in 466 patients with perennial allergic rhinitis. Adults and adolescents (aged 12 to 71 years) with moderate to severe symptoms, nasal eosinophilia, and a positive skin test reaction (> or = 2+) to a perennial allergen received fluticasone propionate aqueous nasal spray 100 micrograms twice daily or 200 micrograms once daily, or beclomethasone dipropionate aqueous nasal spray 168 micrograms twice daily, or placebo for 6 months. RESULTS: Clinician- and patient-rated scores for nasal obstruction (including obstruction on awakening), rhinorrhea, sneezing, and nasal itching were reduced by the first visit at 7 days after initiation of active treatment and remained lower than those of patients receiving placebo throughout the 6-month treatment period. Nasal eosinophilia was reduced in significantly more patients receiving active treatment. The incidence of adverse events was similar in all four treatment groups except for blood in nasal mucus, which was reported by significantly more patients in the two twice-daily active treatment groups compared with the placebo group. There was no evidence of systemic effects of fluticasone propionate. There were no significant differences between fluticasone propionate given once or twice daily or beclomethasone dipropionate given twice daily for any efficacy or safety evaluation. CONCLUSIONS: Fluticasone propionate aqueous nasal spray given once daily in the morning is safe and effective therapy for perennial allergic rhinitis and is as effective as twice daily dosing with fluticasone propionate or beclomethasone dipropionate.

Administration, Topical↗

Fluticasone propionate powder and lack of clinically significant effects on hypothalamic-pituitary-adrenal axis and bone mineral density over 2 years in adults with mild asthma.

BACKGROUND: Although inhaled corticosteroids are widely used for the treatment of inflammation in asthma, prospective, long-term, placebo-controlled trials characterizing their systemic safety with chronic use are lacking. OBJECTIVE: This study was designed to prospectively evaluate the long-term safety of inhaled fluticasone propionate therapy. METHODS: Fluticasone propionate powder, 500 microgram, or placebo was administered twice daily by means of the Diskhaler for 104 weeks to 64 adults with mild persistent asthma in a randomized, double-blind, parallel-group study. Primary safety variables were measured at baseline and every 6 months thereafter. Although evaluation of efficacy was not an objective of this study, pulmonary function testing was performed at monthly intervals. RESULTS: Two years of treatment with fluticasone propionate had no significant effects on the skeletal system. No clinically significant changes were observed in ophthalmic parameters (glaucoma and posterior subcapsular cataracts). Mean change from baseline in lumbar spine (L1 to L4 ) bone density at week 104 was not significantly different between fluticasone propionate (-0.006 +/- 0.008 g/cm2) and placebo (-0.007 +/- 0.010 g/cm2). Markers of bone formation (serum osteocalcin) and resorption (urinary N-telopeptide) did not differ significantly between treatment groups. The effects of fluticasone propionate treatment on the hypothalamic-pituitary-adrenal axis were minimal, with no alterations in morning plasma cortisol concentrations and minor but statistically significant decreases in poststimulation mean peak plasma cortisol concentrations (P =.021) and 8-hour plasma cortisol area under the curve values (P =.020) at week 104. Drug-related adverse events were primarily topical effects of inhaled corticosteroids. Pulmonary function improved significantly during 2 years of fluticasone propionate treatment. CONCLUSION: Fluticasone propionate powder, 500 microgram twice daily for up to 2 years, was efficacious and well tolerated, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis, bone density, or ophthalmic parameters in adults with mild asthma.

Adolescent↗

Fluticasone propionate powder: oral corticosteroid-sparing effect and improved lung function and quality of life in patients with severe chronic asthma.

BACKGROUND: Many patients with severe asthma are dependent on oral corticosteroids for maintenance control of their disease. Treatments that allow patients to be weaned off oral corticosteroids may help to minimize the risk of side effects associated with their chronic use. OBJECTIVE: This study evaluated whether inhaled fluticasone propionate powder could maintain pulmonary function while reducing the dose of oral prednisone in patients with chronic, severe asthma. METHODS: Oral prednisone-dependent (5 to 40 mg/day) adolescents and adults with asthma (n = 111; mean FEV1 = 61% of predicted value) were randomized to placebo or twice daily fluticasone propionate 500 or 1000 microg administered by means of a multidose powder inhaler for 16 weeks in a double-blind, parallel-group study. Patients underwent controlled prednisone reduction on the basis of predetermined asthma stability criteria. RESULTS: Oral prednisone was eliminated by 75% and 89% of patients in the twice daily 500 and 1000 microg fluticasone propionate groups, respectively, versus 9% of the placebo group (P <.001). FEV1, morning and evening peak expiratory flow, asthma symptoms, albuterol use, and nighttime awakenings improved with fluticasone propionate treatment, achieving statistical significance (P </=.009) primarily in the 1000 microg twice daily group. Hypothalamic-pituitary-adrenal axis suppression observed at baseline improved when patients were weaned off oral prednisone to fluticasone propionate. Adverse events ascribed to drug treatment were primarily topical effects of inhaled corticosteroids or those associated with prednisone withdrawal. Patient quality of life assessed by means of the Asthma Quality of Life Questionnaire was clinically and significantly improved after fluticasone propionate treatment (P </=.003). CONCLUSION: Fluticasone propionate powder (500 or 1000 microg twice daily) effectively improved lung function, adrenal function, and asthma-specific quality of life in patients with severe chronic asthma previously treated with oral prednisone while allowing most patients to be weaned off oral corticosteroid therapy.

Administration, Inhalation↗

Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: a randomised crossover study.

BACKGROUND: Inhaled corticosteroids are currently the cornerstone of asthma treatment. Some studies of high-dose fluticasone propionate in patients with no or mild asthma have, however, suggested substantial systemic absorption. We investigated the pharmacokinetics of fluticasone propionate in patients with asthma receiving appropriate doses for severity. METHODS: We did a double-blind, randomised, crossover study in 11 patients with asthma and 13 matched healthy controls (age 20-65 years; asthma patients forced expiratory volume in 1 s <75% and stable on high-dose inhaled corticosteroids). Patients received one 1000 microg intravenous dose or 1000 microg daily for 7 days inhaled (via spacer device) fluticasone propionate. In the 12 h after dosing, we monitored plasma fluticasone propionate and cortisol concentrations by mass spectrometry and competitive immunoassay with use of direct chemiluminescence. Analysis was by intention to treat. FINDINGS: After inhalation, geometric mean values were significantly lower in the asthma group than in controls for fluticasone propionate plasma area under curve (1082 [95% CI 850-1451] vs 2815 pg mL(-1) h(-1) [2262-3949], -62% difference [45-72]; p<0.001), maximum concentrations (117 [91-159] vs 383 pg/mL [302-546], -68% [-50 to -81]; p<0.001), and systemic bioavailability (10.1 [7.9-14.0] vs 21.4% [15.4-32.2], -54% [-27 to -70]; p=0.001). Intravenous-dose clearance, volume of distribution at steady state, plasma half-life, and mean residence time, were similar in the two groups. Less suppression of plasma cortisol concentrations was seen in the asthma group than in controls 4-12 h after inhaled fluticasone propionate. INTERPRETATION: Systemic availability of fluticasone propionate is substantially less in patients with moderate to severe asthma than in healthy controls. Inhaled corticosteroids that are absorbed through the lungs need to be assessed in patients who are receiving doses appropriate for disease severity, and not in normal volunteers.

Administration, Inhalation↗

A comparison of costs and efficacy of intranasal fluticasone propionate and terfenadine tablets for seasonal allergic rhinitis.

This paper compares cost-efficacy ratios for intranasal fluticasone propionate and terfenadine tablets within a sample of patients with seasonal allergic rhinitis symptoms due to mountain cedar allergy. Efficacy was assessed using secondary data analysis of patient ratings of symptoms and their overall assessment of response to treatment within a previously conducted clinical trial. Costs include direct costs of the drugs used for therapy. Patients with documented mountain cedar allergy who were 12 years of age or older (N = 232) had been randomized to either receive intranasal fluticasone propionate, terfenadine, or placebo. The cost-efficacy ratios for intranasal fluticasone propionate 200 micrograms once daily were more favorable than the ratios for terfenadine 60 mg twice daily. This relationship remained throughout the sensitivity analysis. Because intranasal fluticasone propionate is only available in a fixed package size, the number of efficacy-adjusted days of terfenadine therapy that could be purchased to reach break-even costs for a 30-day supply of fluticasone was calculated. Cost efficacy-adjusted days ranged from 11 to 18 days. If cost-efficacy adjustments are not conducted, the upper end of the range increases from 18 to 22 days, since 22 days of terfenadine could be purchased for the price of a 30-day supply of intranasal fluticasone propionate. Depending on which of the efficacy measures the reader believes, if patients use terfenadine for longer than 11 to 22 days, fluticasone propionate is the more cost-efficacious choice. Because most allergies are seasonal and allergy seasons typically last longer than 11 to 22 days, it is likely that fluticasone propionate will frequently be the more cost-efficacious choice in the patient population represented in this study.

Adult↗

Efficacy and safety of inhaled fluticasone propionate chlorofluorocarbon in 2- to 4-year-old patients with asthma: results of a double-blind, placebo-controlled study.

BACKGROUND: Current asthma guidelines recommend inhaled glucocorticoids administered via pressurized metered-dose inhaler (MDI) with a holding chamber as the preferred therapy for young children with asthma. OBJECTIVE: To evaluate the efficacy and safety of fluticasone propionate chlorofluorocarbon MDI use in preschool-aged children with asthma. METHODS: Randomized, double-blind, placebo-controlled, parallel-group study of 332 children aged 24 to 47 months with asthma. Fluticasone propionate chlorofluorocarbon, 44 or 88 microg twice daily, or placebo (chlorofluorocarbon propellant alone) administered for 12 weeks via MDI with a valved holding chamber and an attached face mask. The primary efficacy measure was average change in 24-hour daily asthma symptom scores. Safety assessments included adverse events, 12-hour urinary cortisol excretion, and growth. RESULTS: Treatment failure (ie, asthma exacerbation) occurred in approximately half as many fluticasone propionate-treated patients (13%-14%) as placebo-treated patients (24%). Compared with placebo users, patients treated with fluticasone propionate, 88 microg twice daily, had a 13% greater improvement in the mean proportion of symptom- and albuterol-free days (P = .02); asthma symptom scores and albuterol use were also significantly reduced. Patients treated with fluticasone propionate, 44 microg twice daily, had greater improvements than placebo-treated patients; however, differences did not reach statistical significance. At end point, the growth velocities of fluticasone propionate-treated patients were within the range of those of placebo-treated patients. No clinically relevant changes in 12-hour overnight urinary cortisol excretion were observed. CONCLUSION: Compared with placebo use, fluticasone propionate, 88 microg administered twice daily, significantly reduced asthma exacerbations, asthma symptoms, and rescue albuterol use and was well tolerated, with no clinically relevant systemic effects, as measured by growth velocity or 12-hour urinary cortisol excretion levels.

Albuterol↗

Diskus and diskhaler: efficacy and safety of fluticasone propionate via two dry powder inhalers in subjects with mild-to-moderate persistent asthma.

BACKGROUND: Fluticasone propionate is a topically active glucocorticoid with potent antiinflammatory activity in the treatment of asthma. OBJECTIVE: This study evaluated the safety and efficacy of fluticasone propionate administered via the Diskus and Diskhaler powder delivery devices in subjects with mild-to-moderate asthma. METHODS: Fluticasone propionate (500 microg twice daily) or placebo was administered via the Diskus and Diskhaler to 213 adolescent and adult asthma subjects in a randomized, double-blind, double-dummy, parallel-group study for 12 weeks. Subjects were stratified according to baseline therapy of inhaled corticosteroids or beta2-agonists alone. Subjects were dropped from the study if they met predefined criteria for lack of efficacy. RESULTS: Fluticasone propionate improved pulmonary function both in subjects previously treated with inhaled corticosteroids or beta2-agonists alone. At endpoint, fluticasone propionate significantly improved forced expiratory volume in 1 second (P < .001), morning and evening peak expiratory flow (P < .001), and asthma symptom scores (P < or = .016), and significantly reduced nighttime awakenings (P = .016; Diskhaler group only) and rescue albuterol use (P < .001). Overall, efficacy measurements for the Diskus and Diskhaler were similar. More placebo-treated subjects (34%) withdrew from the study due to lack of efficacy than subjects in the Diskus (5%) or Diskhaler (5%) groups. The incidence and severity of adverse events were similar across groups. Measurement of plasma fluticasone propionate and cortisol concentrations showed no apparent influence of device on systemic exposure. CONCLUSION: Fluticasone propionate powder, administered via the Diskus or Diskhaler inhalation devices, was well tolerated and effective in the treatment of mild-to-moderate persistent asthma.

Administration, Inhalation↗

A randomized, double-blind, placebo-controlled study of clobetasol propionate 0.05% foam in the treatment of nonscalp psoriasis.

BACKGROUND: Topical corticosteroids are the primary treatment for mild to moderate psoriasis. Foam preparations of corticosteroids offer potential cosmetic and pharmacodynamic advantages over cream and ointment vehicles. A clobetasol propionate foam product is as effective as clobetasol propionate solution in the treatment of scalp psoriasis. AIM: To evaluate the safety and efficacy of clobetasol propionate foam in the treatment of psoriasis involving sites other than the scalp. METHODS: Eighty-one subjects with mild to moderate psoriasis were randomized in a 3 : 1 ratio to receive clobetasol propionate foam vs. placebo foam treatment in this double-blind study of psoriasis involving nonscalp sites. The investigator's and subject's global assessment of the response at week 2 (or at the end of treatment) and at week 4 (follow-up) and the severity of erythema, scaling, and plaque thickness were assessed. Safety was assessed from reported adverse events. RESULTS: After 2 weeks of treatment, there was significantly greater improvement with clobetasol propionate foam compared with placebo foam in both investigator's and subject's global assessment of the response (P < 0.0005). The improvement with clobetasol propionate foam was still present at the 4-week follow-up visit. Adverse effects were generally limited to mild to moderate application site reactions. No subjects withdrew because of adverse events. CONCLUSIONS: Clobetasol propionate foam is more effective than placebo in the treatment of nonscalp psoriasis. Twice-daily applications are well tolerated, compliance exceeds 90%, cosmetic characteristics are acceptable, and the medication may eliminate the need for separate scalp and body prescriptions.

Administration, Topical↗

The use of 0.25% zinc pyrithione spray does not enhance the efficacy of clobetasol propionate 0.05% foam in the treatment of psoriasis.

BACKGROUND: It was discovered that Skin Cap (Cheminova Internacional S.A., Madrid, Spain), an over-the-counter psoriasis therapy with zinc pyrithione, contained clobetasol propionate and it was withdrawn from the market by the US Food and Drug Administration review. Some suggested that there might be a synergistic effect of zinc pyrithione with clobetasol propionate. OBJECTIVE: We sought to evaluate the efficacy of clobetasol propionate 0.05% foam with and without the coadministration of a topical 0.25% zinc pyrithione spray in treating psoriasis involving sites other than the scalp. METHODS: We conducted a randomized, double-blind, right/left study of patients with mild to moderate, generally symmetric, plaque-type psoriasis. Patients were assigned to treatment with clobetasol propionate foam on all psoriatic lesions and then randomly assigned to use zinc pyrithione spray to either the right or left side of their body (vehicle spray to be applied to the opposite side). There was a 2-week treatment phase (visits at baseline, week 1, and week 2) and a follow-up phase (visit at week 4), and all treatments were administered twice daily for 2 weeks. The primary outcome measure was the change from baseline to week 2 in the composite score of the signs of psoriasis (erythema, scaling, plaque thickness) for symmetric target lesions. RESULTS: A total of 25 patients were enrolled; 24 completed the trial and 1 was lost to follow up. Of those who completed the study, 63% (15 of 24) were men, and the mean age (+/-SD) was 50 years (+/-12.2). After 2 weeks of therapy, the average decline in the composite score was 3.5 (+/-1.8) for monotherapy (clobetasol propionate foam and vehicle) and, similarly, 3.3 (+/-1.8) for clobetasol propionate foam plus zinc pyrithione spray (P =.5). DISCUSSION: Zinc pyrithione spray does not appear to enhance the efficacy of clobetasol propionate foam after 2 weeks of therapy.

Administration, Topical↗

Testosterone-propionate impairs the response of the cardiac capillary bed to exercise.

OBJECTIVE: Experimental application of anabolic-androgenic steroids and exercise training induce cardiac hypertrophy. This study quantifies for the first time, on microscopical level, the adaptation of the cardiac capillaries and myocytes to the concomitant application of testosterone-propionate and exercise training. METHODS: Female SPF-NMRI mice were studied over 3 and 6 wk. Experimental groups: (i) sedentary control (C); (ii) exercise (treadmill running, E); (iii) testosterone-propionate (TP); and (iv) testosterone-propionate+exercise (TPE). Morphometric parameters: 1) papillary muscles: capillary density, intercapillary distance, number of capillaries around a myocyte, and minimal myocyte diameter; and 2) left ventricular wall: capillary density and intercapillary distance. RESULTS: Papillary muscle: A striking suppression of the exercise-induced improvement in capillary supply occurs in the testosterone-propionate+exercise groups over 3 and 6 wk. Exercise without drugs increases significantly (P < 0.05) the capillary density, shortens significantly (P < 0.05) the intercapillary distance, whereas it increases the number of capillaries around a myocyte. These alterations are not observed in the testosterone-propionate treated sedentary animals; e.g., capillary density after 6 wk (mean values +/- standard deviation, capillaries x mm(-2)): C: 4272 +/- 287, E: 5411 +/- 758, TP: 4221 +/- 364, and TPE: 3997 +/- 397. Moreover, only in the testosterone-propionate+exercise groups occurs a mild myocyte hypertrophy after both time periods: there is a trend toward hypertrophy (P < 0.1) in comparison with the C groups and a significant hypertrophy (P < 0.05) in comparison with the E groups. CONCLUSIONS: Testosterone-propionate profoundly inhibits the exercise-induced augmented capillarization, whereas (under training conditions) it leads to a mild myocyte hypertrophy. The microvascular impairment could trigger an imbalance between the myocardial oxygen supply and demand, especially during physical exercise.

Animals↗

Comparison of the effects of pulsed dye laser, pulsed dye laser + salicylic acid, and clobetasole propionate + salicylic acid on psoriatic plaques.

BACKGROUND: Studies show that pulsed dye laser (PDL) has some clinical benefits on psoriasis with a low clearance rate. In addition, it has been suggested that applying keratolytics before treatment might be helpful in PDL therapy. Topical corticosteroids remain the most commonly prescribed agents for psoriasis. OBJECTIVE: This study was designed to compare the efficacy of the PDL treatment with that of PDL treatment after salicylic acid on psoriatic plaques. The other goal of this study was to compare the efficacy of the PDL treatment with that of clobetasol propionate treatment. METHODS: Twenty-two patients with chronic, stable psoriatic plaques that involved less than 20% of their body were included in the study. Three similar-appearing psoriasis plaques in these patients were selected. Whereas the first plaque received only PDL, the second plaque received PDL after salicylic acid, and the third plaque received clobetasol propionate ointment and salicylic acid. Evaluation of the study plaques was carried out by the modified Psoriasis Area and Severity Index (mPASI) score and by measuring the area of the plaques. RESULTS: Of the 21 patients, 19 completed the study. Although the decrease in mPASI scores was determined to be maximum for clobetasol propionate + salicylic acid-treated plaques and minimum for only PDL-treated plaques, the decrease was statistically significant in all groups when compared with baseline (p < .003). At the 3- and 6-week evaluations, there was a statistically significant difference between clobetasol propionate + salicylic acid-treated plaques and the two PDL-treated plaques (p < .003); however, the difference observed at the 9-, 12-, and 15-week evaluations was statistically significant only between clobetasol propionate + salicylic acid-treated plaques and PDL-treated plaques (p < .003). When the baseline and 15-week evaluations were compared, there was no statistically significant increase in the mean lesion areas of clobetasol propionate + salicylic acid-treated psoriatic plaques (p > .003), but there was a statistically significant increase in the mean lesion areas of two PDL-treated psoriatic plaques (p < .003). CONCLUSION: The results of this study showed that the effect of PDL could be increased when salicylic acid was added to treatment, although there was no statistically significant difference between both treatment protocols. However, clobetasol propionate + salicylic acid treatment is more effective than both PDL and PDL + salicylic acid treatment.

Adult↗

Pathways of propionate degradation by enriched methanogenic cultures.

A mixed methanogenic culture was highly enriched in a growth medium containing propionate as the sole organic carbon and energy source. With this culture, the pathways of propionate degradation were studied by use of C-radiotracers. Propionate was first metabolized to acetate, carbon dioxide, and hydrogen by nonmethanogenic organisms. Formate was not excreted. The carbon dioxide originated exclusively from the carboxyl group of propionate, whereas both [2-C]- and [3-C]propionate lead to the production of radioactive acetate. The methyl and carboxyl groups of the acetate produced were equally labeled, regardless of whether [2-C]- or [3-C]propionate was used. These observations suggest that in the culture, propionate was degraded through a randomizing pathway.

Journal Article↗

Propionate exchange reactions in methanogenic ecosystems.

Propionate degradation was measured with [1-C]- and [2-C]propionate in an anaerobic digestor. When [1-C]propionate was used, label disappeared more rapidly from the propionate pool than when [2-C]propionate was used. This indicated that an exchange reaction involving the carboxyl group of propionate occurred. Labeled propionate added to digestor samples which were equilibrated with H(2) lost label from the carboxyl group but not from the methylene group.

Journal Article↗

Growth of syntrophic propionate-oxidizing bacteria with fumarate in the absence of methanogenic bacteria.

Oxidation of succinate to fumarate is an energetically difficult step in the biochemical pathway of propionate oxidation by syntrophic methanogenic cultures. Therefore, the effect of fumarate on propionate oxidation by two different propionate-oxidizing cultures was investigated. When the methanogens in a newly enriched propionate-oxidizing methanogenic culture were inhibited by bromoethanesulfonate, fumarate could act as an apparent terminal electron acceptor in propionate oxidation. C-nuclear magnetic resonance experiments showed that propionate was carboxylated to succinate while fumarate was partly oxidized to acetate and partly reduced to succinate. Fumarate alone was fermented to succinate and CO(2). Bacteria growing on fumarate were enriched and obtained free of methanogens. Propionate was metabolized by these bacteria when either fumarate or Methanospirillum hungatii was added. In cocultures with Syntrophobacter wolinii, such effects were not observed upon addition of fumarate. Possible slow growth of S. wolinii on fumarate could not be demonstrated because of the presence of a Desulfovibrio strain which grew rapidly on fumarate in both the absence and presence of sulfate.

Journal Article↗