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At least 19 recordsLinked to original sources
PubMed2003

Treatment of recurrent chronic hyperplastic sinusitis with nasal polyposis.

OBJECTIVE: To demonstrate the long-term efficacy of intranasal furosemide, an inhibitor of the sodium chloride cotransporter channel at the basolateral surface of the respiratory epithelial cell, vs no therapeutic intervention vs intranasal mometasone furoate, a corticosteroid, in preventing relapses of chronic hyperplastic sinusitis with nasal polyposis. DESIGN: Randomized prospective controlled study. Patients were examined every 6 months during follow-up (range, 1-9 years). PATIENTS: One hundred seventy patients with bilateral obstructive or minimally obstructive chronic hyperplastic sinusitis with nasal polyposis. INTERVENTION: All patients were surgically treated in the ENT Department, University of Siena Medical School. One month after surgery, group 1 patients (n = 97) started treatment with intranasal furosemide, group 2 (n = 40) received no therapeutic treatment, and group 3 (n = 33) were treated with mometasone. MAIN OUTCOME MEASURES: Clinical and instrumental evaluation of postoperative outcomes. RESULTS: Seventeen (17.5%) of 97 patients in group 1, 12 (30.0%) of 40 patients in group 2, and 8 (24.2%) of 33 patients in group 3 experienced nasal polyposis relapses. We noted a prevalence of early-stage relapse in patients treated with furosemide or mometasone, whereas patients who did not receive any treatment experienced more severe grades of chronic hyperplastic sinusitis with nasal polyposis (P<.005). CONCLUSION: Use of intranasal furosemide represents a valid therapeutic treatment in the prevention of chronic hyperplastic sinusitis with nasal polyposis.

Administration, Intranasal↗
PubMed2004

Influence of preservatives and topical steroids on ciliary beat frequency in vitro.

OBJECTIVE: To measure the influence of topical steroids and the preservative potassium sorbate on the ciliary beat frequency (CBF) of human nasal mucosa in vitro. DESIGN: In vitro study of cultured ciliated cells of human nasal mucosa. METHODS: Human nasal mucosa was removed endoscopically and cultured for 10 days. Cell cultures with ciliated cells grown on an object slide were exposed to benzalkonium chloride and topical steroids in an exposure chamber. The CBF was measured with a photometer. RESULTS: The preservative potassium sorbate did not influence CBF in different concentrations. The glucocorticoid budesonide spray containing potassium sorbate did not affect CBF at 10% dilution and showed moderate reversible decrease of CBF at 50% dilution. The glucocorticoid sprays fluticasone propionate and mometasone fuorate containing the preservative benzalkonium chloride caused a reversible decrease of CBF at 10% dilution and a complete irreversible standstill at 50% dilution. CONCLUSIONS: In vitro, the steroid sprays containing fluticasone or mometasone, both with benzalkonium chloride, caused slowing or standstill of CBF depending on the concentration. The isolated preservative potassium sorbate and the budesonide nasal spray containing this preservative did not have negative influence on CBF in vitro. Potassium sorbate can therefore be considered harmless to the motility of ciliated cells.

Administration, Inhalation↗
PubMed2006

A randomized controlled trial of mometasone furoate nasal spray for the treatment of nasal polyposis.

OBJECTIVE: To evaluate the efficacy and safety of mometasone furoate nasal spray (NS) for the treatment of nasal polyposis. DESIGN: Randomized, double-blind, placebo-controlled, parallel-group, multicenter study. SETTING: A total of 24 centers in 17 countries. PATIENTS: A total of 310 subjects 18 years or older with bilateral nasal polyps. INTERVENTIONS: (1) A 200-microg dose of mometasone furoate NS in the morning and matching placebo in the evening; (2) 200-microg doses of mometasone furoate NS in the morning and evening; or (3) matching placebo in the morning and evening. All 3 regimens were administered as a nasal spray for 4 months. MAIN OUTCOME MEASURES: Primary end points were change from baseline to last assessment in physician-assessed bilateral polyp grade and change from baseline in subject-assessed congestion and/or obstruction score averaged over the first month of treatment. Analysis of variance was used for all efficacy end points except for change in bilateral polyp grade, for which baseline polyp grade was added as a covariate to the analysis of variance model to account for any between-group baseline differences in this variable. RESULTS: Mometasone furoate NS doses of 200 microg administered once or twice daily produced greater reductions in bilateral polyp grade at the end point than placebo, with differences reaching statistical significance with twice-daily dosing (P = .04). Over 1 month, both mometasone furoate NS regimens produced statistically superior improvements from baseline in congestion and/or obstruction score vs placebo (P = .01 for once-daily dosing; P<.001 for twice-daily dosing). The drug was well tolerated. CONCLUSION: Mometasone furoate NS is an effective and well-tolerated treatment for bilateral nasal polyposis in adults, reducing nasal polyp size and symptoms of nasal congestion and/or obstruction.

Administration, Intranasal↗
PubMed1997

Cutaneous toxicity following the administration of dactinomycin.

Dactinomycin (AMD) is an effective drug in the management of several malignant disorders and has been used for almost 40 years. Skin and subcutaneous toxicities following extravasation are well known and can be harmful. Similarly radiation-recall is a well established phenomenon following the administration of AMD. We report a patient who developed a localized brawny erythema in the crural folds and the axillae, likely due to AMD. This rare skin complication of AMD seems to benefit from topical corticosteroid treatment, although postinflammatory hyperpigmentation may take months to disappear.

Administration, Cutaneous↗
PubMed2003

Mometasone furoate degradation and metabolism in human biological fluids and tissues.

The in vitro metabolic and non-metabolic degradation kinetics of mometasone furoate (MF) was investigated in selected human biological fluids and subcellular fractions of tissues. Qualitative and quantitative differences in transformation profiles of MF were observed among human biological media. Degradation was the major event in plasma and urine with four new degradation products identified; A: 21-chloro-17alpha-hydroxy-16alpha-methyl-9beta,11beta-oxidopregna-1,4-diene-3,20-dione 17-(2-furoate), B: 9alpha,21beta-dichloro-11beta,21alpha-dihydroxy-16alpha-methylpregna-1,4,17,20-tetraen-3-one 21-(2-furoate), C: 21beta-chloro-21alpha-hydroxy-16alpha-methyl-9beta,11beta-oxidopregna-1,4,17,20-tetraen-3-one 21-(2-furoate), and D: 21-chloro-17alpha-hydroxy-16alpha-methyl-9beta,11beta-oxidopregna-1,4-diene-3,20-dione. A, B and C were predominant and D was minor in plasma while A and C were predominant in urine. Hydrolysis of the 17-ester bond of MF was not a major event in plasma. The turnover of MF in plasma was faster than that in phosphate buffers of pH 7.4. Metabolism of MF occurred primarily and rapidly in liver, appreciably in intestine, but negligibly in in vitro lung tissue. While 6beta-hydroxylation was a major metabolic pathway for MF in microsomes of both human liver and intestine, other parallel and subsequent metabolism pathways could also be involved. If these degradation and metabolic products are also formed and active in humans in vivo, both MF and its 'active' products need to be taken into account when determining the systemic bioavailability of MF and in establishing concentration-effect relationships with this drug.

Adult↗
PubMed2004

Human receptor kinetics, tissue binding affinity, and stability of mometasone furoate.

Mometasone furoate (MF) is a topically used glucocorticoid with high anti-inflammatory potency. In contrast to the wealth of data derived from clinical studies, information about the molecular pharmacology of the compound is lacking or contradictory. Thus, we elucidated the characteristics of receptor binding kinetics and receptor affinity in a bioassay. Metabolite formation was determined in human plasma and lung tissue as well as binding affinity to human lung tissue. Fast and extensive association of MF to the human glucocorticoid receptor was observed while the dissociation of the MF-receptor complex was faster compared to fluticasone propionate (FP). The relative receptor affinity of MF was calculated as 2200 (dexamethasone = 100, FP = 1800) and confirmed in a bioassay measuring the induction of the glucocorticoid regulated protein CD163 in human monocytes. In plasma and human lung tissue MF formed a 9,11-epoxy degradation product. The binding affinity of MF to human lung tissue was low compared to FP due to fast redistribution from tissue into plasma. These molecular pharmacological properties are in accordance with clinical data.

Antigens, CD↗
PubMed2005

Solid state characterization of mometasone furoate anhydrous and monohydrate forms.

Mometasone furoate is a potent glucocorticoid anti-inflammatory agent. Its anhydrous Form 1 and monohydrate form were characterized by X-ray crystallography, X-ray powder diffraction at ambient and elevated temperature, thermal analysis, FT-IR, and dynamic moisture adsorption. In Form 1, mometasone furoate molecules pack tightly with molecules interlocked in a space group of P2(1)2(1)2(1). The monohydrate form crystallizes in space group P1. The unit cell of the monohydrate contains one water molecule and one mometasone furoate molecule. The water molecules form channels along the a axis and mometasone furoate molecules pack in layers in the same direction. Dehydration was observed between 60 and 100 degrees C by thermogravimetric analysis with a heating rate of 10 degrees C/min. It corresponds to a broad endotherm over the same temperature range in the differential scanning calorimetry with the same heating rate. Variable temperature X-ray powder diffraction reveals that a new anhydrous form (Form 2) was fully produced above 90 degrees C. This crystalline form was converted to Form 1 after being heated above 150 degrees C; and was totally converted to the monohydrate after 1 day at 23 degrees C, 45% RH.

Anti-Inflammatory Agents↗
PubMed2002

Investigation of an enhanced resolution triple quadrupole mass spectrometer for high-throughput liquid chromatography/tandem mass spectrometry assays.

Triple quadrupole mass spectrometers, when operated in multiple reaction monitoring (MRM) mode, offer a unique combination of sensitivity, specificity, and dynamic range. Consequently, the triple quadrupole is the workhorse for high-throughput quantitation within the pharmaceutical industry. However, in the past, the unit mass resolution of quadrupole instruments has been a limitation when interference from matrix or metabolites cannot be eliminated. With recent advances in instrument design, triple quadrupole instruments now afford mass resolution of less than 0.1 Dalton (Da) full width at half maximum (FWHM). This paper describes the evaluation of an enhanced resolution triple quadrupole mass spectrometer for high-throughput bioanalysis with emphasis on comparison of selectivity, sensitivity, dynamic range, precision, accuracy, and stability under both unit mass (1 Da FWHM) and enhanced (<or=0.1 Da FWHM) resolution. The advantage of enhanced resolution was demonstrated in the case of mometasone with polypropylene glycol (PPG) interference. At unit mass resolution, the transmitted precursor ion from the first quadrupole contained not only protonated molecules from mometasone, but also PPG interference. At enhanced resolution only selected mometasone peaks were transmitted, and no interference from PPG was detected. Sensitivity of the instrument was demonstrated with 10 femtograms of descarboethoxyloratadine injected on-column, for which a signal-to-noise (S/N) ratio of 24 was obtained for MRM chromatograms at both unit and enhanced resolution. Absolute signals obtained at enhanced resolution were about one-third those obtained at unit mass resolution. However, S/N was maintained at enhanced resolution due to the proportional decrease in noise level. Finally, the stability of the instrument operating at enhanced resolution was demonstrated during an overnight 17 h period that was used to validate a liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay for the quantitation of loratadine and descarboethoxyloratadine in human plasma. Assay performances (dynamic range, correlation coefficients for standard curves, precision and accuracy for QC samples) under unit and enhanced resolution were both within current pharmaceutical and regulatory guidelines demonstrating the stability of the mass spectrometer operating at enhanced resolution for typical bioanalytical high-throughput applications.

Calibration↗
PubMed2005

Influence of low glycolytic activities in gcr1 and gcr2 mutants on the expression of other metabolic pathway genes in Saccharomyces cerevisiae.

A complex of the transcription factors Gcr1p and Gcr2p coordinately regulates the expression of glycolytic genes in Saccharomyces cerevisiae. To understand the effects of gcr mutations on other metabolic pathways, genome-wide gene expression profiles in gcr1 and gcr2 mutants were examined. The biggest effects of gcr1 and gcr2 mutations were observed on the glycolytic genes and the expressions of most of the glycolytic genes were substantially decreased compared to those in the wild-type strain in both glucose and glycerol+lactate growth conditions. On the other hand, the expressions of genes encoding the TCA cycle and respiration were increased in gcr mutants when the cells were grown in glucose. RT-PCR analyses revealed that the expression of SIP4 and HAP5, which are known to affect the expression of some of the gluconeogenic, TCA cycle and respiratory genes, were also increased under this condition. The growth of gcr mutants on glucose was impaired by adding respiration inhibitor antimycin A, whereas the growth of the wild-type strain was not. The conversion of glucose to biomass was higher and, to the contrary, ethanol yield was lower in the gcr2 mutant compared to those in the wild-type strain. These results suggest the possibility that the gcr mutants, in which glycolytic activities are low, changed their metabolic patterns under glucose growth condition to enhance the expression of TCA cycle and respiratory genes to produce more energy.

Adenosine Triphosphate↗
PubMed1997

Use of a radioimmunoassay which detects C21 steroids with a 17, 20beta-dihydroxyl configuration to identify and measure steroids involved in final oocyte maturation in female plaice (Pleuronectes platessa).

A radioimmunoassay (RIA) has been developed to detect a range of C21 (pregnane) steroids with a 17,20beta-dihydroxyl (17,20beta) configuration. In conjunction with reverse-phase high-performance liquid chromatography (HPLC), it identifies and quantifies the metabolites of 17,20beta-dihydroxy-4-pregnen-3-one, the putative "maturation-inducing steroid" in female plaice Pleuronectes platessa. Total levels of 17,20beta metabolites which can be extracted from plasma or urine with diethyl ether (i.e., free steroids) are very low (<3 ng/ml). However, total levels of 17,20beta metabolites which can be released by solvolysis (i.e., sulphated steroids) are very high (up to 1 microg/ml in plasma and 10 microg/ml in urine). On HPLC, these sulphated metabolites have been identified (in order of abundance in plasma) as: 5beta-pregnane-3alpha,17,20beta-triol, 5beta-pregnane-3beta,17,20beta-triol, 17, 20beta-dihydroxy-4-pregnen-3-one, and 17, 20beta-dihydroxy-5beta-pregnan-3-one. These steroids are absent from plasmas of fish which have not yet begun final oocyte maturation. The results support the hypothesis that 17, 20beta-dihydroxy-4-pregnen-3-one is the maturation-inducing steroid in plaice but that it is rapidly metabolised to render it inactive. The results also show that the '17,20beta'-RIA, in combination with an overnight acid solvolysis procedure, is a useful procedure for monitoring the effects of exogenous factors (such as gonadotrophin injections) on final oocyte maturation in female plaice.

Animals↗
PubMed2002

Review of the molecular and cellular mechanisms of action of glucocorticoids for use in asthma.

Asthma is characterized by inflammation in the lung and glucocorticoids (GCs) are the most clinically effective treatment available. The success of chronic GC therapy for asthma stems largely from the ability of the GC-GC receptor (GR) complex to alter transcription of a wide array of molecules involved in the inflammatory process. Many of the adverse effects of elevated systemic GC levels have been reduced through the use of inhalation as a method of administration, as opposed to oral GC. GCs exert their effects by binding to the wild-type GR, GR(alpha). The GR(alpha) complex can directly or indirectly alter gene transcription by binding to specific DNA sites or by activating transcription factors. There is also evidence to support GR(alpha) involvement in post-translational activities. In the management of asthma, the GR(alpha) down-regulates proinflammatory mediators such as interleukin-(IL)-1, 3, and 5, and up-regulates anti-inflammatory mediators such as IkappaB [inhibitory molecule for nuclear factor kappaB1 IL-10, and 12. Newer GCs are being designed to increase potency and topical activity. Mometasone furoate (MF), has recently been developed for the treatment of asthma and inhibits key anti-inflammatory processes with a potency equal to or greater than that of fluticasone propionate. A better understanding of the molecular mechanisms involved might provide strategies for optimizing the effectiveness of GC in the treatment of asthma.

Anti-Inflammatory Agents↗
PubMed1995

Randomised crossover comparison of adrenal suppressive effects of dermal creams containing glucocorticosteroids.

To compare the effect of multiple dose treatment with fatty cream 0.1% hydrocortisone-17-butyrate (LLFC) and fatty cream 0.1% mometasone furoate (EFC), under occlusion on adrenal function, we performed an open label, randomised, two-period crossover study, lasting 30 days, in 12 healthy, male volunteers (age 18-45 y). Morning plasma cortisol and ACTH concentrations were determined before, during, and after the treatments, and a Synacthen test was performed before and during the treatments. Both agents suppressed plasma cortisol concentrations, EFC significantly more than LLFC. ACTH concentrations were normal and were comparable between the two treatments throughout the studies, while the Synacthen tests showed normal rises in cortisol levels. Both treatments were well tolerated. We conclude that EFC has a stronger suppressive effect on plasma cortisol values than LLFC, although for short duration treatments both suppressive effects are transient.

Administration, Topical↗
PubMed1977

The influence of fluocortolone treatment on the collagen content in guinea pig skin.

Specific pathogen free guinea pigs were treated with varying dosis of fluocortolone for 15 days. The treated animals showed the same per cent weight gain as the controls. The total hydroxyproline content of the skin and the hydroxyproline content in different collagen fractions was the same in treated and untreated animals. Thus fluocortolone seems to have no specific effect on the synthesis or the breakdown of collagen in the guinea pig skin. Also the physical development of the animals, kept under defined conditions, failed to show a catabolic effect of of fluorcortolone.

Animals↗
PubMedDate not supplied

An easy-to-use dry-powder inhaler.

The mometasone furoate dry-powder inhaler is a novel device designed to support compliance by delivering a topical corticosteroid in a simple three-step operation. This breath-actuated inhaler uses a stabilized agglomerate formulation to measure and deliver accurate, uniform, and precise doses of drug over a range of inspiratory flow rates. Laboratory and clinical data have shown that the design produced a simple, clinically effective inhaler for the treatment of adults and children 12 years of age and older with mild, moderate, or severe persistent asthma.

Administration, Inhalation↗