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Fluticasone Propionate Reduces Oral Prednisone Use While it Improves Asthma Control.

This study examined the effect of fluticasone propionate aerosol on oral prednisone requirements in patients with severe asthma. Ninety-six patients dependent on oral prednisone were treated with placebo or fluticasone propionate aerosol (750 or 1000 &mgr;g twice daily) for 16 weeks. The dosage of oral prednisone was adjusted weekly according to predetermined criteria. Fluticasone propionate 750 and 1000 &mgr;g twice daily resulted in 69% and 88% of patients (low and high doses, respectively) not using any prednisone compared to 3% of placebo-treated patients by the end of the study. In the fluticasone propionate groups, forced expiratory volume in 1 s (FEV(1)) and peak expiratory flow rates and the number of nighttime awakenings improved at the last evaluable visit. In addition, the number of nighttime awakenings and symptomatic albuterol use declined relative to placebo values (p < 0.05). Fluticasone propionate aerosol was well tolerated. Fluticasone propionate aerosol (750 or 1000 &mgr;g twice daily) effectively and safely allowed most asthmatics who were dependent on oral corticosteriods to reduce or eliminate oral prednisone use while improving pulmonary function.

Journal Article↗

Fluticasone propionate: topical or systemic effects?

Intranasal corticosteroids have been shown to be more effective than oral antihistamines for the treatment of seasonal allergic rhinitis. However, there are some who question whether intranasally administered corticosteroids should be used due to potential systemic effects. Fluticasone propionate, a potent corticosteroid with high specificity for the glucocorticoid receptor, is available as an aqueous nasal spray for the treatment of allergic rhinitis. To determine whether the efficacy of fluticasone propionate aqueous nasal spray (FPANS) was due to direct topical effects on the nasal mucosa or to indirect systemic effects following absorption from the nasal mucosa or from the swallowed portion of an intranasal dose, FPANS 200 micrograms once daily was compared with oral fluticasone propionate 5 mg or 10 mg once daily or placebo for 2 weeks in patients with seasonal allergic rhinitis. These oral dosages were chosen to yield low but consistent plasma fluticasone propionate concentrations. Both clinician- and patient-rated scores for nasal obstruction, rhinorrhoea, sneezing, and nasal itching were significantly lower in the intranasal fluticasone propionate group compared with both oral fluticasone propionate groups. A separate placebo-controlled study was conducted in patients with perennial rhinitis to determine if administration of FPANS 200 micrograms once daily for 1 year was associated with adverse systemic effects. At the 1-year assessment, there were no significant effects on bone mineral density or on biochemical markers of bone turnover. Similarly, there was no evidence of posterior subcapsular cataracts nor of glaucoma. Furthermore, there were no significant effects on hypothalamic-pituitary adrenal axis function as assessed by plasma cortisol and 24-h urinary cortisol response to the 6-h cosyntropin stimulation test. These data confirm that the efficacy of FPANS for the treatment of allergic rhinitis results from direct topical effects, thus reducing the likelihood of adverse systemic effects.

Administration, Intranasal↗

Ligand-binding properties and N-glycosylation of alpha 1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate(AMPA)-selective glutamate receptor channel expressed in a baculovirus system.

The alpha 1 subunit of the mouse alpha-amino-3-hydroxy-5-methyl-4-isoxazole- propionate(AMPA)-selective glutamate receptor channel has been expressed in insect Spodoptera frugiperda cells using a baculovirus system. The recombinant receptor proteins were identified by immunocytochemical detection, Western-blot analysis, and [35S]methionine/[35S]cysteine metabolic labeling experiments. The effect of tunicamycin on the metabolic labeling and immunoblots suggested that the two products, a major protein species of approximately 104 kDa and a minor species of approximately 100 kDa, correspond to glycosylated and non-N-glycosylated forms, respectively, which was also supported by the enzymic deglycosylation experiments. The lack of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate-binding activity of non-N-glycosylated glutamate receptor expressed in the presence of tunicamycin suggested that N-glycosylation is required, directly or indirectly, for functional expression in insect cells for ligand binding. Scatchard analysis of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate binding showed a single binding site with Kd 30 nM and a Bmax value of 2.6 x 10(5) binding sites/cell or 1.5 pmol/mg protein in the total particulate fraction. Among the compounds tested in the competition studies, beta-(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)-L-alanine (quisqualate) was the most potent inhibitor of the 3H-labeled alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate binding (IC50 = 30 nM), followed in decreasing order by alpha-amino-3-hydroxy-5- methyl-4-isoxazole propionate, L-glutamate, 6,7-dinitroquinoxaline-2,3-dione, 6-cyano-7-nitroquinoxaline-2,3-dione, and 2-carboxy-4-(1-methylethenyl)-3-pyrrolidineacetate (kainate). Thus, in this study we present detailed analysis of alpha-amino-3-hydroxy-5-methyl-4- isoxazole-propionate-binding activity of the homomeric (single subunit) glutamate receptor channel of mouse alpha 1 subunit and discuss possible roles of N-glycosylation of the glutamate receptor channel alpha 1 subunit.

Amino Acid Sequence↗

Enrichment of Thermophilic Propionate-Oxidizing Bacteria in Syntrophy with Methanobacterium thermoautotrophicum or Methanobacterium thermoformicicum.

Thermophilic propionate-oxidizing, proton-reducing bacteria were enriched from the granular methanogenic sludge of a bench-scale upflow anaerobic sludge bed reactor operated at 55 degrees C with a mixture of volatile fatty acids as feed. Thermophilic hydrogenotrophic methanogens had a high decay rate. Therefore, stable, thermophilic propionate-oxidizing cultures could not be obtained by using the usual enrichment procedures. Stable and reproducible cultivation was possible by enrichment in hydrogen-pregrown cultures of Methanobacterium thermoautotrophicum DeltaH which were embedded in precipitates of FeS, achieved by addition of FeCl(2) to the media. The propionate-oxidizing bacteria formed spores which resisted pasteurization for 30 min at 90 degrees C or 10 min at 100 degrees C. Highly purified cultures were obtained with either M. thermoautotrophicum DeltaH or Methanobacterium thermoformicicum Z245 as the syntrophic partner organism. The optimum temperature for the two cultures was 55 degrees C. Maximum specific growth rates of cultures with M. thermoautotrophicum DeltaH were somewhat lower than those of cultures with M. thermoformicicum Z245 (0.15 and 0.19 day, respectively). Growth rates were even higher (0.32 day) when aceticlastic methanogens were present as well. M. thermoautotrophicum DeltaH is an obligately hydrogen-utilizing methanogen, showing that interspecies hydrogen transfer is the mechanism by which reducing equivalents are channelled from the acetogens to this methanogen. Boundaries of hydrogen partial pressures at which propionate oxidation occurred were between 6 and 34 Pa. Formate had a strong inhibitory effect on propionate oxidation in cultures with M. thermoautotrophicum. Inhibition by formate was neutralized by addition of the formate-utilizing methanogen or by addition of fumarate. Results indicate that formate inhibited succinate oxidation to fumarate, an intermediate step in the biochemical pathway of propionate oxidation.

Journal Article↗

Fluticasone propionate in asthma: a long term dose comparison study.

BACKGROUND: Few dose ranging studies have investigated optimal dosing with inhaled corticosteroids in children with asthma. AIMS: To compare the efficacy and tolerability of fluticasone propionate 100 or 200 microg twice daily in children with moderate to severe asthma for one year. METHODS: One year, randomised, double blind, parallel group, multicentre study. Children aged 4-11 years (n = 528) with moderate to severe asthma who had previously received high dose inhaled corticosteroids were given fluticasone propionate 100 or 200 microg twice daily for the 52 week treatment period. Efficacy (exacerbations, lung function, and symptoms) and tolerability (adverse events and cortisol levels) were measured. RESULTS: There was a non-significant decreased risk of experiencing an exacerbation at any time with fluticasone propionate 200 microg twice daily compared with fluticasone propionate 100 microg twice daily. This difference reached significance among patients with more severe asthma (defined by previous inhaled corticosteroid dose >800 microg/day). Daily record card morning peak expiratory flow (PEF) in the total population improved significantly more with the higher dose of fluticasone propionate (between group difference, weeks 1-52: 11.4 l/min). Clinic visit mean PEF improved from baseline with both doses, but the response was significantly greater with the higher dose (between group difference, week 52: 17.8 l/min). Both doses were equally well tolerated and overnight urinary cortisol concentrations were unchanged or slightly increased during treatment with either dose. CONCLUSION: This long term dose comparison study shows that treatment with fluticasone propionate 200 micro g twice daily may offer benefits over a lower dose, particularly in children with more severe asthma.

Androstadienes↗

Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial.

OBJECTIVES: To determine the effect of long term inhaled corticosteroids on lung function, exacerbations, and health status in patients with moderate to severe chronic obstructive pulmonary disease. DESIGN: Double blind, placebo controlled study. SETTING: Eighteen UK hospitals. PARTICIPANTS: 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second (FEV(1)) 50% of predicted normal. INTERVENTIONS: Inhaled fluticasone propionate 500 microgram twice daily from a metered dose inhaler or identical placebo. MAIN OUTCOME MEASURES: Efficacy measures: rate of decline in FEV(1) after the bronchodilator and in health status, frequency of exacerbations, respiratory withdrawals. Safety measures: morning serum cortisol concentration, incidence of adverse events. RESULTS: There was no significant difference in the annual rate of decline in FEV(1 )(P=0.16). Mean FEV(1) after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo (P<0.001). Median exacerbation rate was reduced by 25% from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate (P=0.026). Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate (P=0.0043). Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group (25% v 19%, P=0.034). CONCLUSIONS: Fluticasone propionate 500 microgram twice daily did not affect the rate of decline in FEV(1) but did produce a small increase in FEV(1). Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status. These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease.

Administration, Inhalation↗

Comparison of the systemic effects of fluticasone propionate and budesonide given by dry powder inhaler in healthy and asthmatic subjects.

BACKGROUND: The potential for long term adverse effects from inhaled corticosteroids relates to their systemic absorption, usually assessed from proxy markers in short term studies. When fluticasone propionate and budesonide have been compared in this way the results have been inconsistent. To determine whether this is because of the subjects studied or the sensitivity of the systemic marker used, we have compared the effects of fluticasone propionate and budesonide in healthy and asthmatic subjects and investigated the effect of treatment on three systemic markers. METHODS: Forty six healthy subjects were randomised to receive inhaled fluticasone propionate 1500 microg/day (via an Accuhaler), budesonide 1600 microg/day (via a Turbuhaler), or placebo; 31 subjects with moderately severe asthma were randomised to receive the same doses of fluticasone propionate or budesonide but not placebo. Systemic effects in healthy and asthmatic subjects were compared after 7 days. Treatment was continued for another 21 days in the subjects with asthma when systemic effects and asthma control were assessed. RESULTS: At baseline healthy subjects had higher urinary levels of total cortisol metabolites (TCM) than subjects with asthma. After 7 days of treatment with fluticasone propionate urinary TCM levels in the healthy subjects were significantly lower than in the subjects with asthma (mean difference between groups 1663 microg/day, 95% CI 328 to 2938). This was not the case with budesonide, however, where urinary TCM levels in the healthy subjects remained above those in the asthmatic subjects (mean difference between groups 1210 microg/day, 95% CI -484 to 2904). Urinary TCM levels were considerably more sensitive to the effects of inhaled corticosteroids than morning serum cortisol or osteocalcin concentrations. Only budesonide reduced the serum level of osteocalcin. CONCLUSIONS: When given by dry powder inhaler for 7 days, fluticasone propionate 1500 microg/day has a greater effect on the hypothalamic-pituitary-adrenal axis in healthy subjects than in subjects with asthma, but this is not the case for budesonide 1600 microg/day. These findings, together with the differences in sensitivity between systemic markers, explain many of the discrepancies in the literature.

Administration, Inhalation↗

Early onset of effect of salmeterol and fluticasone propionate in chronic obstructive pulmonary disease.

BACKGROUND: Combined treatment with inhaled corticosteroids and long acting beta2 agonists is approved for the treatment of chronic obstructive pulmonary disease (COPD), but little is known about the onset of effect of the combination. METHODS: Data were used from 1465 patients with COPD entered into a large 1 year double blind trial with daily measurements of peak expiratory flow (PEF) and symptom scores. RESULTS: PEF was significantly higher after 1 day in patients treated with salmeterol 50 microg twice daily or the salmeterol/fluticasone propionate combination 50/500 microg twice daily than placebo. In patients treated with fluticasone propionate 500 microg twice daily alone, PEF differed from placebo after 2 days. The differences after 2 weeks compared with placebo were 16 l/min (95% confidence interval (CI) 11 to 21), 11 l/min (95% CI 6 to 16), and 27 l/min (95% CI 22 to 33) for salmeterol, fluticasone propionate, and the salmeterol/fluticasone propionate combination, respectively. For all treatments the effect on PEF after 2 weeks was comparable to that seen at the end of the study. The difference between the salmeterol/fluticasone propionate combination and placebo after 2 weeks as a percentage of baseline was similar for PEF and clinic forced expiratory volume in 1 second (FEV1). Differences in breathlessness scores were statistically significant after 1 day for the group treated with salmeterol alone and after 2 days for the combination group. The 2 week change in FEV1 was only partly indicative of a long term response in individual patients. CONCLUSIONS: The effects of salmeterol and fluticasone propionate, alone or in combination, on PEF and breathlessness are seen within days and most of the obtainable effect on these parameters is reached within 2 weeks.

Administration, Inhalation↗

A dose-ranging study of fluticasone propionate administered once daily via multidose powder inhaler to patients with moderate asthma.

STUDY OBJECTIVE: This dose-ranging study evaluated the clinical efficacy and safety of inhaled fluticasone propionate administered once daily via a multidose powder inhaler in patients with moderate asthma (FEV(1), 45 to 75% predicted). MATERIALS AND METHODS: In this multicenter trial, 330 patients (> or = 12 years old) previously receiving inhaled corticosteroids or beta(2)-agonists alone were randomized in a double-blind manner to receive fluticasone propionate at 100, 200, or 500 microg once daily or matching placebo for 12 weeks. RESULTS: Once-daily treatment with fluticasone propionate resulted in an improvement in efficacy variables, such as FEV(1), morning and evening peak expiratory flow (PEF), asthma symptom scores, nighttime awakenings, albuterol use, and duration of study participation. A dose-related trend was observed for improvements in morning and evening PEF and albuterol use. Statistical significance for pairwise comparisons was achieved for 200 microg and 500 microg fluticasone propionate vs placebo for all efficacy variables, and for 100 microg fluticasone propionate vs placebo for morning and evening PEF at most or all time points. Drug-related adverse events were few (< or = 5%) and mostly related to the topical effects of inhaled corticosteroids. No dose-response effect or clinically relevant differences were observed in morning plasma cortisol concentrations or after cosyntropin stimulation. CONCLUSION: Once-daily treatment with fluticasone propionate was well tolerated and demonstrated some dose-related trends in improvements in lung function and asthma control in patients with moderate asthma.

Administration, Inhalation↗

Intranasal fluticasone propionate. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in allergic rhinitis.

Fluticasone propionate is a potent topical anti-inflammatory corticosteroid with low systemic activity. Available pharmacodynamic data are only preliminary; however, large placebo- and drug-controlled clinical studies involving almost 4000 patients with seasonal allergic rhinitis and 1500 with perennial allergic and nonallergic rhinitis have confirmed the efficacy of intranasal fluticasone propionate in the control of nasal symptoms. Fluticasone propionate generally demonstrated similar efficacy compared with intranasal beclomethasone dipropionate, flunisolide acetonide and oral astemizole and better or a trend towards better efficacy compared with oral loratadine, terfenadine, cetirizine and intranasal sodium cromoglycate (cromolyn sodium) against nasal symptoms. The incidence of adverse effects in association with intranasal fluticasone propionate appears to be comparable to that observed with placebo; the most frequently reported effects are nasal dryness/burning, epistaxis and headache. Consistent with its minimal systemic availability, intranasal fluticasone propionate in a dosage of up to 4 mg/day does not cause adrenal suppression. Thus, based on early data from large clinical trials, fluticasone propionate administered once daily offers an effective and convenient treatment option in patients with seasonal and perennial allergic rhinitis, and is distinguished by its low oral bioavailability.

Administration, Intranasal↗

Effect of fluticasone propionate on interleukin-12 and interferon-gamma production in patients affected by allergic bronchial asthma.

Fluticasone propionate is a very effective topical treatment for asthma. Interleukin-12, which is produced by monocyte-macrophage and B lymphocytic cell lines, plays an important role in the induction of Th1 cells; whereas interferon-gamma (IFN-gamma), mainly produced by Th1 cells, exhibits a crucial effect on macrophage and natural killer cell activation. Since previous studies have demonstrated a reduced production of IL-12 and IFN-gamma in patients with allergic asthma, we examined whether fluticasone propionate therapy could influence the release of these cytokines in asthma. We selected two groups of subjects (15 per group): nonatopic healthy donors (group A) and asthmatic patients (group B). Cytokine release was assessed in sera as well as in supernatants of whole blood cultures after IFN-gamma priming and lipopolysaccharide stimulation. Venous blood and spirometric tests from patients in group B were obtained before and after treatment. Fluticasone propionate therapy significantly increased interleukin-12 levels in both supernatants of blood cultures (1,152.12 +/- 225.57 vs. 540.87 +/- 130.07 pg/ml; p < 0.05) or in sera (72.24 +/- 15.76 vs. 10.83 +/- 2.70 pg/ml; p < 0.05). Patients treated with fluticasone propionate also displayed increased levels of IFN-gamma in either blood culture supernatants (59.12 +/- 16.88 vs. 18.87 +/- 7.53 IU/ml; p < 0.05) or in sera (5.60 +/- 2.87 vs. < 1 IU/ml; p < 0.05). In addition, we observed a significant increase in FEV1 values in asthmatic patients after fluticasone propionate therapy (51.86 +/- 5.31 vs. 71.46 +/- 10.37% predicted). We propose that fluticasone propionate may exert at least in part of its antiinflammatory activity through the modulation of the cytokine output.

Adolescent↗

Fluticasone propionate compared with zafirlukast in controlling persistent asthma: a randomized double-blind, placebo-controlled trial.

OBJECTIVE: The objective of our study was to compare the efficacy and safety of fluticasone propionate (an inhaled corticosteroid) with zafirlukast (a leukotriene modifier) for persistent asthma. STUDY DESIGN: In this randomized placebo-controlled, parallel-group, double-blind, double-dummy trial, patients underwent an 8- to 14-day run-in period followed by 12 weeks of treatment with inhaled fluticasone propionate (88 mg twice daily by metered-dose inhaler), oral zafirlukast (20 mg twice daily), or placebo. POPULATION: We included a total of 338 persistent asthma patients, 12 years of age or older, using short-acting b2-agonists alone. OUTCOMES: measured Efficacy outcomes included changes in pulmonary function, asthma symptoms, rescue albuterol use, nighttime awakenings due to asthma, and quality of life. Safety outcomes included asthma exacerbations, adverse events, and clinically significant laboratory test results. RESULTS: After 12 weeks of treatment, patients taking fluticasone propionate experienced significantly greater improvements in all clinical parameters (symptom scores, percentages of symptom-free and albuterol-free days, albuterol use, and nighttime awakenings) compared with patients taking zafirlukast (P <.05) or placebo (P <.05). Treatment with fluticasone propionate resulted in significantly greater improvements in pulmonary function compared with zafirlukast (P <.05) or placebo (P <.05). Fewer fluticasone propionate patients (4%) had an exacerbation requiring oral corticosteroids compared with those taking zafirlukast (12%) or placebo (10%). CONCLUSIONS: Inhaled fluticasone propionate is more effective than zafirlukast in controlling asthma symptoms, improving pulmonary function, and improving quality of life for patients who are symptomatic with the use of short-acting b2-agonists alone.

Administration, Inhalation↗

Short-term safety assessment of clobetasol propionate 0.05% shampoo: hypothalamic-pituitary-adrenal axis suppression, atrophogenicity, and ocular safety in subjects with scalp psoriasis.

Clobetasol propionate is known to be a very effective treatment for psoriasis; however, its use is limited by potent corticosteroid class related side effects such as hypothalamic-pituitary-adrenal (HPA) axis suppression and atrophogenicity. The aim of this single-center, parallel group, randomized study was to assess the HPA axis suppression potential, atrophogenicity, and ocular tolerability of clobetasol propionate shampoo in 26 patients with scalp psoriasis. Suitable subjects were treated once daily for 4 weeks with clobetasol propionate shampoo, to be rinsed off after 15 minutes or with a leave-on clobetasol propionate gel. The study demonstrated that clobetasol propionate shampoo did not lead to HPA axis suppression or to skin atrophy. Conversely, the gel led to HPA axis suppression and a decrease in skin thickness. Neither formulation had an impact on ocular safety. Despite the short contact application time, the clobetasol propionate shampoo provides similar efficacy results to the gel.

Administration, Cutaneous↗

Overview of anaerobic treatment: thermophilic and propionate implications.

Difficulties in achieving low propionate concentrations in anaerobically treated effluents are frequently reported in the literature (Ahring, 1994; Kugelman and Guida, 1989; Rimkus et al., 1982), especially at thermophilic temperatures, with concentrations as high as 1000 to 9600 mg/L sometimes produced. This paper will detail the effect of several variables on the performance of both mesophilic and thermophilic regimes. Studies concerning the effect of the following four important factors on performance are included: reactor configuration, inorganic nutrient supplementation, substrate characteristics, and the unique role of microbial consortia proximity in enhancing performance. Reactor configuration modifications, essential nutrient additions, and the importance of close microbial proximity were all found to contribute to improvement in thermophilic anaerobic digestion in all the studies. It was found that, in substrates that shunt significant amounts of the electron donor through propionate, performance was critically related to reactor optimization, with propionate removal efficiency considerably improved using intact upflow anaerobic sludge blanket granules, less so in a homogenized granule slurry blanket, and noticeably reduced even more when the completely stirred reactor configuration of homogenized granules was used. The critical importance of extremely close microbial consortia proximity in maintaining hydrogen intermediates at very low levels to efficiently convert propionate to hydrogen and acetate was demonstrated. Compared to mesophilic digestion, thermophilic digestion manifested elevated levels of propionate, except in the nonmixed reactors, which had close microbial consortia proximity. The reactor configuration with the best results was the anaerobic digestion elutriated phased treatment (ADEPT) scheme, in which the raw sludge was elutriated of its fermenting volatile fatty acids, as they are generated in a short 5- to 8-day solids retention time (SRT) in one reactor and the elutriate then metabolized by passing up through a methanogenic granule or slurry blanket (with its close microbial consortia proximity) in a separate reactor with a 20- to 50-day SRT. Loading rates and performance of the ADEPT reactor configuration were superior to the standard continuously stirred tank reactor, and ADEPT thermophilic temperatures allowed higher organic loading rates without high propionate concentrations in the effluent.

Anaerobiosis↗

Evaluation of the efficacy and safety of clobetasol propionate spray in the treatment of plaque-type psoriasis.

Treatment of the inflammatory component of plaque psoriasis is an important part of psoriasis management. A new and unique spray formulation of clobetasol propionate 0.05% may provide advantages over the currently available formulations through easy application to hard-to-reach areas and the ability to deliver a fixed dose of corticosteroid per spray. The purpose of this study was to evaluate the efficacy and safety of clobetasol propionate spray 0.05% in the treatment of moderate to severe plaque-type psoriasis. This study was conducted as a multicenter, randomized, double-blinded, vehicle-controlled, parallel-group, comparative study in subjects with plaque psoriasis. Subjects were randomized to receive either clobetasol propionate spray 0.05% (n=60) or vehicle spray (n=60) twice daily for 4 weeks, followed by a 4-week treatment-free follow-up period. Efficacy evaluations at all visits included assessment of scaling, erythema, plaque elevation, pruritus, and overall disease severity. Success rates for each of the signs and symptoms evaluated, as well as for the overall disease severity assessment, were significantly in favor of clobetasol propionate (P<.001). The additional 2 weeks of treatment from weeks 2 to 4 increased the number of cleared subjects from 2% to 25%; treatment success was still in favor of clobetasol propionate (P<.001) at week 8 (4 weeks post-treatment). No treatment-related serious adverse events occurred during the course of the study. Mild application site burning/stinging was the most common treatment-related adverse event, with similar frequency and severity for both active and vehicle groups. There were no reports of skin atrophy, telangiectasia, folliculitis, or hypothalamus-pituitary-adrenal axis suppression. Overall, clobetasol propionate spray 0.05% administered twice daily for 4 weeks was effective and safe in reducing scaling, erythema, plaque elevation, and overall disease severity and demonstrates durable clinical response up to 4 weeks after treatment end.

Administration, Cutaneous↗

Once daily fluticasone propionate aqueous nasal spray is an effective treatment for seasonal allergic rhinitis.

A multicenter double-blind, randomized, parallel group study was conducted to evaluate the once daily administration of fluticasone propionate, a potent, new corticosteroid preparation, for the treatment of seasonal allergic rhinitis. Adult patients (n = 227) were treated for 2 weeks with fluticasone propionate aqueous nasal spray 200 micrograms QD or 100 micrograms BID or matching placebo during the autumn pollen season. Overall, the administration of fluticasone propionate once daily in the morning was as effective as the twice daily dosage regimen, and either regimen was more effective than placebo. Improvement in clinician-rated and patient-rated nasal symptom scores, including morning nasal obstruction, was evident within three days of fluticasone propionate therapy and continued throughout the treatment period. Fewer patients receiving fluticasone propionate used rescue medication and had nasal eosinophilia compared with patients receiving placebo. Adverse events were similar in frequency and nature in all three treatment groups. Morning plasma cortisol concentrations and response to cosyntropin stimulation were similar across groups and offered no evidence of HPA axis suppression. We conclude that fluticasone propionate aqueous nasal spray administered once daily is a safe and effective treatment for seasonal allergic rhinitis. The convenience of a once daily regimen may encourage better compliance.

Administration, Intranasal↗

[Propionic acid cocci and their taxonomic position].

In order to determine the taxonomic position of propionic cocci, the authors studied their morphological, cultural and biochemical properties, the fatty acid composition of cells, and established the degree of homology for the DNAs of cocci and classical propionic bacteria using the method of molecular hybridization. The cocci were found to have the activities of catalase and superoxide dismutase which were higher than in the studied propionic bacteria. The propionic cocci and propionic bacteria were shown to be similar in terms of their fatty acid composition and to contain the C15-saturated acid in the form of anteiso isomer as the main type of fatty acids. Their fatty acid composition was most similar to that of the species Propionibacterium jensenii (P. technicum). The propionic cocci and bacteria are related in the structure of their genomes, particularly, in the case of the bacterium P. jensenii (P. raffinosaceum)--49%. On the basis of studying the phenotypic characteristics, the fatty acid composition, the nucleotide composition of DNA, and the high degree of homology between the DNAs of the cocci and the bacterial species P. jensenii (P. raffinosaceum), the authors propose to assign the cocci to the genus Propionibacterium as a new species Propionibacterium coccoides.

DNA, Bacterial↗

Fluticasone propionate nasal spray is more effective and has a faster onset of action than placebo in treatment of rhinitis medicamentosa.

BACKGROUND: Controversy still exists about the treatment of rhinitis medicamentosa and treatment has never been objectively evaluated. OBJECTIVE: To study the effect of fluticasone propionate aqueous nasal spray compared to placebo nasal spray in the treatment of rhinitis medicamentosa. METHODS: A parallel randomized, double-blind study was conducted to evaluate the treatment of rhinitis medicamentosa. Two groups containing 10 patients with rhinitis medicamentosa in each group stopped their overuse of nasal vasoconstrictor spray immediately and were treated with either fluticasone propionate nasal spray once daily 200 micrograms, or placebo nasal spray for 14 days. The nasal mucosal swelling was recorded with rhinostereometry, acoustic rhinometry and a peak inspiratory flow meter. Nasal stuffiness was estimated on a visual analogue scale in the morning and in the evening of each day. RESULTS: The mucosal swelling decreased after 7 and 14 days of treatment with fluticasone propionate as well as placebo, but the reduction was significantly greater after treatment with fluticasone propionate. The symptom scores for nasal stuffiness showed a marked reduction during the treatment period in both groups, but there was a faster onset of symptom reduction after treatment with fluticasone propionate. CONCLUSION: Fluticasone propionate is more effective and has a faster onset of action than placebo in the treatment of rhinitis medicamentosa. An adequate treatment of these patients consists of a combination of vasoconstrictor withdrawal and a topical corticosteroid to alleviate the withdrawal process.

Administration, Intranasal↗