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PubMed2005

The efficacy and safety of fluticasone propionate in very young children with persistent asthma symptoms.

We aimed to evaluate the efficacy and safety of fluticasone propionate (FP) in children aged 12-47 months with recurrent/persistent asthma symptoms. One hundred and sixty children (12-47 months) were randomised into this multicentre, double-blind, placebo-controlled, parallel-group study, and treated with either FP (100 microg bd) or placebo (2 puffs bd), both administered by metered-dose-inhaler and Babyhaler for 12 weeks. The primary endpoint was percentage of symptom-free 24h periods. Over weeks 1-12, FP-treated patients had significantly more percentage symptom-free 24-h periods compared with placebo (odds ratio 0.53; 95% CI 0.29-0.95; P = 0.035). Relative to baseline, where all patients were symptomatic for at least 21/28 days of the run-in, the improvement equated to one additional symptom-free 24 h period per week. FP patients also had a significantly higher percentage of 24 h periods with no wheeze or cough, the odds ratio for treatment difference corresponding to two additional wheeze-free and one additional cough-free periods per week. FP was well-tolerated, with similar reported adverse events in both groups. Urinary cortisol-creatinine ratio was slightly decreased among FP patients after 12 weeks, but with no clinical correlates. FP is effective for the treatment of chronic persistent asthma symptoms in very young children.

Administration, Inhalation↗
PubMed2005

Control of mild to moderate asthma over 1-year with the combination of salmeterol and fluticasone propionate.

OBJECTIVE: The aim of this study was to assess asthma control using salmeterol plus fluticasone propionate (FP) in combination (SFC) versus salmeterol or FP as monotherapy in patients with mild to moderate asthma. METHODS: In this randomised, double-blind, parallel-group study, 322 symptomatic patients were recruited, of which 282 were randomised to receive either salmeterol (50 microg), FP (250 microg), or SFC (50 microg/250 microg), via a single Diskus inhaler twice daily for 12 months. Outcome variables included the number of patients requiring an increase in study medication and the number experiencing 2 exacerbations during the 12-month treatment period. Airway hyper-responsiveness (AHR) and lung function tests were performed at clinic visits. Peak expiratory flow, rescue medication use, symptom scores and adverse events were recorded in diary cards. RESULTS: Fewer patients required an increase in study medication with SFC (10.5%) than with either FP (34.8%) or salmeterol (61.1%) (P<0.001). Significantly fewer patients experienced 2 exacerbations with SFC (4.2%), compared with FP (17.4%; P<0.01) or salmeterol (40%; P<0.001). SFC improved AHR to a significantly greater extent than FP (methacholine PC20=1.8 mg/ml vs. 1.1 mg/ml; P<0.05) or salmeterol (methacholine PC20=1.8 mg/ml vs. 0.7 mg/ml; P<0.001). CONCLUSIONS: The protection against exacerbations may be attributed to better control of inflammation, AHR and lung function parameters achieved with salmeterol and FP in combination, compared with either treatment alone.

Administration, Inhalation↗
PubMed2006

EXCEL: A randomised trial comparing salmeterol/fluticasone propionate and formoterol/budesonide combinations in adults with persistent asthma.

OBJECTIVES: This multicentre, parallel group, double-blind, double-dummy, randomised 24-week study was designed to compare the efficacy of salmeterol/fluticasone propionate combination (SFC) 50/250 microg one inhalation twice daily (bid) with formoterol/budesonide combination (FBC) 6/200 microg two inhalations bid in patients with persistent asthma, currently receiving 1000-2000 microg/day of inhaled corticosteroids. METHODS: The intent-to-treat population comprised 694 patients in the SFC group and 697 patients in the FBC group. RESULTS: The primary endpoint, mean rate of all exacerbations over 24 weeks, was similar in both treatment groups (SFC: 2.69; FBC: 2.79; SFC/FBC ratio 0.96; 95% CL 0.84, 1.10; P=0.571). A reduction in the rate of exacerbations over time was observed in both treatment groups. Overall, there was a 30% lower annual rate of moderate/severe exacerbations in the SFC group compared with the FBC group (95% CI 0-49%, 52% reduction vs. 1% increase; P=0.059). This effect increased with time: in weeks 17-24 the moderate/severe exacerbation rate was 57% lower in the SFC group compared with the FBC group (95% CI 21-77% reduction; P=0.006). Similar improvements in lung function, asthma symptoms and rescue medication usage were seen with both treatments and both were well tolerated. CONCLUSIONS: Twice-daily treatment with SFC and FBC over 6 months significantly improved asthma symptoms and lung function in patients with persistent asthma. The rate of exacerbations was significantly reduced over time on both treatments but SFC was found to be significantly superior to FBC in reducing the rate of moderate/severe exacerbations with sustained treatment.

Administration, Inhalation↗
PubMed2006

A comparison of the relative growth velocities with budesonide and fluticasone propionate in children with asthma.

There have been no previous large, well-designed direct comparisons of the effects of fluticasone propionate (FP) and budesonide (BUD) on growth in children. This randomised, double-blind study compared the effects on growth of FP and BUD in children aged 6-9 years with persistent asthma. Following a 6-month run-in period (without inhaled corticosteroids), patients with normal growth velocity were randomised to 12 months' treatment with FP 100 micro g bd (n=114) or BUD 200 micro g bd (n=119). Growth velocity was determined by stadiometric height measurement. Lung function, asthma symptoms and use of relief medication were also assessed. Annualised mean growth velocity during run-in was comparable in the two groups (FP: 5.9 cm/yr; BUD: 6.0 cm/yr). During the treatment period, adjusted mean growth velocity was significantly higher in the FP than the BUD group (5.5 cm/yr vs 4.6 cm/yr; P<0.001). Asthma control improved similarly in both treatment groups. Bone mineral density and overnight urinary cortisol:creatinine ratios were similar in the two groups. Drug-related adverse events were reported among 3% of FP-treated children, compared with 2% for BUD. In conclusion, this study demonstrates that FP for childhood asthma has significantly less impact on childhood growth velocity than a therapeutically equivalent dose of BUD.

Androstadienes↗
PubMed2006

Potency ratio fluticasone propionate (Flixotide Diskus)/budesonide (Pulmicort Turbuhaler).

In the choice of, or switch between, various inhaled corticosteroids (ICS) it is important to know equipotent doses for clinical treatment effects of the alternatives. Various ICS do have different inherent potency. Further, the ICS are delivered from inhalers that may differ markedly in output characteristics and drug delivery to intrapulmonary airways. Therefore, clinical efficacy comparisons must include drug-inhaler comparisons. We estimated the therapeutic potency ratio of the Flixotide Diskus (fluticasone propionate, FP) and the Pulmicort Turbuhaler (budesonide, BUD) in steroid-naive asthma patients, using a dose-reduction technique (FP 500-0 mcg/day, BUD 800-0 mcg/day). The dose defining end point was loss of asthma control in this paper denoted as exacerbation. In total, 282 patients with proven asthma were enrolled in the study, and 103 in the FP group and 98 in the BUD group completed the study per protocol. In total, 80 patients in the FP-group and 79 in the BUD-group experienced a dose defining exacerbation. The exacerbation frequency increased in a dose-dependent way as the dose was titrated down. From these data the potency difference between the present drug inhaler combinations, Flixotide Diskus and Pulmicort Turbuhaler, was calculated to be between 1.50:1 (95% CI 1.10:1-2.05:1) and 1.75:1 (CI 1.26:1-2.43:1) depending on if patients with insufficient steroid-response were excluded from the calculations or not. In these steroid-naïve patients, the potency difference was evident only at low daily doses, below 200 mcg.

Administration, Inhalation↗
PubMed2005

Propionicicella superfundia gen. nov., sp. nov., a chlorosolvent-tolerant propionate-forming, facultative anaerobic bacterium isolated from contaminated groundwater.

A novel strain, designated as BL-10(T), was characterized using a polyphasic approach after isolation from groundwater contaminated by a mixture of chlorosolvents that included 1,1,2-trichloroethane, 1,2-dichloroethane, and vinyl chloride. Stain BL-10(T) is a facultatively anaerobic bacterium able to ferment glucose to form propionate, acetate, formate, lactate, and succinate. Fermentation occurred in the presence of 1,2-dichloroethane and 1,1,2-trichloroethane at concentrations to at least 9.8 and 5.9 mM, respectively. Cells are Gram-positive, rod-shaped, non-motile, and do not form spores. Oxidase and catalase are not produced and nitrate reduction did not occur in PYG medium. Menaquinone MK-9 is the predominant respiratory quinone and meso-diaminopimelic acid is present in the cell wall peptidoglycan layer. Major cellular fatty acids are C(15:0), iso C(16:0), and anteiso C(15:0). Genomic DNA G + C content is 69.9 mol%. Phylogenetic analysis based on 16S rRNA gene sequence comparisons showed strain BL-10(T) to fall within the radiation of genera Propionicimonas and Micropruina. On the basis of the results obtained in this study, it is proposed that strain BL-10(T) should be classified as a novel taxon, for which the name Propionicicella superfundia gen. nov., sp. nov. is proposed. The type strain of Propionicicella superfundia is BL-10(T) (=ATCC BAA-1218(T), =LMG 23096(T)).

Biodegradation, Environmental↗
PubMed2002

Efficacy and safety of low-dose fluticasone propionate compared with zafirlukast in patients with persistent asthma.

To compare the efficacy and safety of fluticasone propionate and zafirlukast in patients with relatively stable persistent asthma who were previously treated with inhaled corticosteroids and short-acting beta(2)-agonists.A total of 440 patients (> or =12 years of age) previously treated with inhaled corticosteroids (beclomethasone dipropionate or triamcinolone acetonide) and short-acting beta(2)-agonists were included in this randomized double-blind study. After an 8-day run-in period, patients were treated with fluticasone (88 microg) or zafirlukast (20 mg) twice daily for 6 weeks. Outcome measures included pulmonary function (forced expiratory volume in 1 second [FEV(1)], peak expiratory flow [peak flow]), albuterol use, asthma symptoms, withdrawals due to lack of efficacy, and asthma exacerbations. Patients treated with fluticasone (n = 224) experienced greater mean increases in FEV(1) (0.24 L vs. 0.08 L, P <0.001), morning peak flow (30 L/min vs. 6 L/min, P <0.001), and evening peak flow (23 L/min vs. 5 L/min, P <0.001) during the study than did those treated with zafirlukast (n = 216). Fluticasone-treated patients had significantly greater increases in the mean percentages of symptom-free days (22% vs. 8%, P <0.001), rescue-free days (23% vs. 10%, P = 0.002), nights with uninterrupted sleep (<1% vs. -5%, P = 0.006), and fewer asthma exacerbations (1% vs. 6%, P = 0.005). Fewer fluticasone-treated patients were withdrawn due to lack of efficacy (2% vs. 13%, P <0.001).Inhaled fluticasone was more effective than zafirlukast in maintaining or improving asthma control in patients with relatively stable asthma who were switched from low-dose inhaled corticosteroids.

Adrenal Cortex Hormones↗
PubMed1998

Clobetasol dipropionate 0.05% versus testosterone propionate 2% topical application for severe vulvar lichen sclerosus.

OBJECTIVE: Our goal was to evaluate short-term (3 months) and long-term (1 year) treatment of vulvar lichen sclerosus, by comparing topical application of testosterone propionate 2% in petrolatum with the corticosteroid clobetasol dipropionate 0.05%. STUDY DESIGN: There were 20 women in each treatment group. The patients' symptoms and the gynecologist's examination findings were recorded before treatment, at 3 months, and at 1 year after initiation of therapy. RESULTS: The symptomatic (subjective) effect of clobetasol treatment was similar to that of testosterone at the 3-month follow-up (p < or = 0.34), although objectively the signs of lichen sclerosus had improved more in the clobetasol group (p < or = 0.033). Both symptoms and signs were significantly more improved in the clobetasol-treated group at the 1-year follow-up examination (p < or = 0.02). Seventy percent of women treated by testosterone discontinued treatment because of a lack of response, whereas only 10% of the women treated with clobetasol stopped the treatment for that reason (p < or = 0.00042). CONCLUSION: Clobetasol is more effective than testosterone in the treatment of women with lichen sclerosus, especially in the long term.

Administration, Topical↗
PubMed1998

Characterization of a pH-sensitive surfactant, dodecyl-2-(1'-imidazolyl) propionate (DIP), and preliminary studies in liposome mediated gene transfer.

The inefficiency of non-viral gene delivery systems, relative to viral systems, is likely due, in part, to the failure of endosomes to release DNA before reaching degradative lysosomes. A solution is to incorporate compounds in a delivery vector that will selectively increase the release of endosomally encapsulated DNA. To meet the above criteria, we designed, synthesized, and characterized the physicochemical and biological properties of such a compound, dodecyl-2-(1'-imidazolyl) propionate (DIP) to enhance cationic liposome mediated gene delivery. Several surface active techniques were used to characterize DIP lysing membranes. The critical micelle concentration of DIP was between 0.10-0.18 mM and the effective release and solubilization ratios were 1.0 and 4.0, respectively. DIP facilitated membrane disruption in both a pH and concentration dependent manner. In the presence of esterase at pH 7.0, the hydrolysis rate increased 32-fold indicating DIP can be degraded in the biological milieu. Toxicity of DIP by MTT assay in the SKnSH cell line demonstrated an ID50 of 1.2 mM, which is 30-fold higher than the concentration of DIP used to enhance gene transfection. When incorporated into cationic-liposomes, DIP enhanced transgene expression in vitro by 5-fold. The results of the study indicate that DIP may be a useful adjuvant to increase non-viral gene delivery to cells.

Fluoresceins↗
PubMed1995

In vitro insulinotropic action of a new non-sulfonylurea hypoglycemic agent, calcium (2s)-2-benzyl-3-(cis-hexahydro-2-isoindolinyl-carbonyl) propionate dihydrate (KAD-1229), in rat pancreatic B-cells.

We examined the in vitro insulinotropic action of a novel non-sulfonylurea compound, calcium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinyl-carbonyl) propionate dihydrate (KAD-1229), which is a succinate derivative, using rat pancreatic islets and perfused pancreas. The sodium salt of KAD-1229 free acid (KAD-1229-Na) stimulated insulin secretion from isolated rat islets and perfused rat pancreas in a concentration-dependent manner at 0.1 to 10 microM. It produced a predominant first phase and a less prominent second phase response in the presence of 5.55 mM glucose. An ATP-sensitive K+ (K+ATP) channel activator, diazoxide, eliminated the insulinotropic effect of KAD-1229-Na. Glucose primed the B-cell in the perfused pancreas, but KAD-1229-Na did not. When the insulinotropic effects of 16.7 mM glucose on isolated rat islets were inhibited submaximally by 1 microM norepinephrine, the addition of 1 microM KAD-1229-Na reversed this inhibition. All of these insulinotropic effects of KAD-1229-Na were qualitatively indistinguishable from those of sulfonylurea compounds. We conclude that KAD-1229-Na acts on K+ATP channels of pancreatic B-cells despite its non-sulfonylurea structure.

Animals↗
PubMed1997

Immunoautoradiographic evidence for a loss of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate-preferring non-N-methyl-D-aspartate glutamate receptors within the medial temporal lobe in schizophrenia.

Decreased expression of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-preferring non-N-methyl-D-aspartate (non-NMDA) glutamate receptors (GluRs) occurs in the medial temporal lobe of schizophrenics in terms of reduced abundance of GluR1 and GluR2 subunit mRNAs. To investigate further these receptors in schizophrenia, we have performed a quantitative immunoautoradiographic study in medial temporal lobe sections of 11 schizophrenics and 10 well-matched controls. GluR1 and GluR2/3 were detected with polyclonal antisera coupled to 35S-labeled secondary antibodies. Both subunits were vulnerable to a prolonged postmortem interval and poor agonal state as indicated by brain pH. GluR1 also tended to decline with increasing age. These factors were therefore used as covariates. GluR1 abundance was reduced in schizophrenics in parahippocampal gyrus (p < .025), while GluR2/3 was lower in most subfields in the schizophrenics, significantly so in CA4 (p < .02). The present data extend the evidence for decreased expression of the AMPA subtype of non-NMDA receptors in the medial temporal lobe in schizophrenia, although the magnitude and spatial extent of the loss is smaller than that affecting the encoding mRNAs. Impaired AMPA receptor expression is consistent with a neurodevelopmental origin and with hypotheses of glutamatergic hypofunction in the disease; however, its true pathophysiological significance and relationship to the other neuropathological and pathochemical abnormalities in the medial temporal lobe in schizophrenia remain to be determined.

Adult↗
PubMed1997

Enhancement of contextual fear-conditioning by putative (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor modulators and N-methyl-D-aspartate (NMDA) receptor antagonists in DBA/2J mice.

Previous studies demonstrated that DBA/2J (DBA) mice performed poorly while C57BL/6J (C57) mice performed normally on a number of complex learning and memory tasks. Chronic oxiracetam treatment dramatically improved the performance of DBA mice but not that of C57 mice on the Morris water task and in contextual fear conditioning. The present study demonstrates that acute treatment with nootropics, oxiracetam (10-1000 mg/kg) or aniracetam (10-100 mg/kg), and N-methyl-D-Aspartate (NMDA) antagonists, (+)-MK-801 (0.1-3 microg/kg), CPP (0.01-0.3 mg/kg), and (+)-HA-966 (0.1-3 mg/kg), administered prior to training and testing, reversed the contextual learning impairment in DBA mice in a dose-dependent manner without affecting auditory cue conditioning. These effects appeared to be independent of testing order (context vs. auditory cue tests) and were not due to state-dependent learning. The inactive stereoisomers, (-)-MK-801 and (-)-HA-966, were incapable of increasing contextual freezing in DBA mice. In DBA mice, the effects of 30 mg/kg oxiracetam and 100 mg/kg aniracetam were inhibited by the (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonists, NBQX, and GYKI-52466. The combined administration of 30 mg/kg oxiracetam and 1 microg/kg (+)-MK-801 produced an additive response. None of the pharmacological treatments altered performance in C57 mice at doses that were effective in DBA mice. These results suggest that DBA mice may be learning impaired due to altered glutamatergic receptor function.

Acoustic Stimulation↗
PubMed1997

Prenatal exposure of female rhesus monkeys to testosterone propionate increases serum luteinizing hormone levels in adulthood.

OBJECTIVE: To determine whether prenatal androgenization of the developing primate hypothalamohypophyseal unit induces irreversible changes in LH secretion. DESIGN: Prospective nonrandomized study. SETTING: An academic research environment. ANIMALS: Forty-one adult ovulatory female rhesus monkeys. INTERVENTION(S): Seventeen female rhesus monkeys exposed prenatally to testosterone propionate (female pseudohermaphrodites) and 24 normal females underwent blood sampling over two ovulatory menstrual cycles. MAIN OUTCOME MEASURE(S): Serum FSH, LH, E2, and T were determined by RIA; P was determined by enzyme immunoassay. Serum bioactive LH was measured by mouse Leydig cell bioassay. RESULT(S): Tonic immunoactive LH hypersecretion and normal FSH release occurred in female pseudohermaphrodites compared with normal females. Periovulatory immunoactive LH and FSH secretion was similar in both female types, whereas a relative increase in the amount of circulating bioactive LH to immunoactive LH was found at midcycle in female pseudohermaphrodites versus normal females. The length of the follicular phase was unaffected by prenatal androgen exposure, but the slopes of serum T and E2 concentrations versus follicular phase cycle day were significantly lower in female pseudohermaphrodites than normal females. Luteal phase length and P secretion were comparable in both types of females. CONCLUSION(S): Androgen exposure during primate neural differentiation may alter permanently the pattern of LH secretion in the presence of cyclic gonadotropin release.

Animals↗
PubMed1989

Chromatographic approaches to the quality control of chiral propionate anti-inflammatory drugs and herbicides.

The chiral analysis of a range of propionate anti-inflammatory drugs and herbicides was accomplished by gas chromatographic separation of their R-alpha-phenylethylamide diastereomeric derivatives. Using a packed column (3% OV-l on Chromosorb G) good separations were obtained but analysis times were rather long. Examination of the same crystalline derivatives using a capillary column (bonded methylsilicone) resulted in good separations together with much reduced total analysis times. The technique was validated through the analysis of several derivatives prepared on a micro scale and examined directly by gas chromatography without any crystallisation step. Racemic materials all gave virtually 50:50 response ratios while the analysis of optically pure samples produced no evidence of significant racemization. Derivatives of phenoxyacetic acid and myristic acid were also prepared and chromatographed as potential internal standards.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1999

Efficacy and safety of high-dose inhaled steroids in children with asthma: a comparison of fluticasone propionate with budesonide.

OBJECTIVE: To compare the efficacy and adverse effects of inhaled fluticasone propionate (FP), 400 microgram/d, with those of budesonide (BUD), 800 microgram/d, in children with moderate to severe asthma. METHODS: Three hundred thirty-three children, ages 4 to 12 years, receiving inhaled corticosteroids were enrolled in a double-blind, double-dummy, randomized, parallel-group study. After a 2-week run-in phase, 166 children received FP and 167 received BUD for 20 weeks. The primary outcome variable was mean morning peak expiratory flow; the 2 treatments were to be regarded as equivalent if the 90% CI for the treatment difference was within +/- 15 L/min. Pulmonary function, height, and diary cards were assessed at each visit; and morning serum cortisol levels were determined before and after treatment. RESULTS: Baseline peak expiratory flow was similar, FP 236 +/- 72 (SD) L/min and BUD 229 +/- 74, increasing after treatment to 277 +/- 41 and 257 +/- 28, a difference between treatments of 12 L/min (90% CI 6-19 L/min; P =.002). Symptom control and use of rescue medication were the same. Cortisol levels after treatment were 199 nmol/L (FP) and 183 nmol/L (BUD) (treatment ratio = 1.09; 90% CI 0.98-1.21; P =.172). Linear growth was less in those receiving BUD (mean difference, 6.2 mm; 95% CI 2.9-9.6; P =.0003). CONCLUSION: FP at half the dose was superior to BUD in improving peak expiratory flow and comparable in controlling symptoms. Growth was reduced with BUD compared with FP, but there was no difference in serum cortisol suppression or hepatic or renal function.

Androstadienes↗
PubMed1998

Effect of testosterone propionate treatment on thyrotropin secretion of young and old rats in vitro.

The aim of this study was to evaluate the influence of androgens on TSH secretion during aging in Dutch rats. Male young (2 months) and old (16-21 months) rats were castrated (Cx) or sham-operated (C) and received testosterone propionate (TP--4 mg/Kg B.W., i.m., 7 days) or vehicle. Female adult (3 months) and old (12 and 17 months) intact rats received TP or corn oil in the same dose. The rats were decapitated, trunk blood was collected and anterior pituitaries were dissected out for in vitro incubation. In Cx young male rats, only TSH pituitary content showed lower levels than in their controls. Cx TP-treated rats showed higher serum TSH and in vitro basal and TRH-induced TSH secretion, but TP only partially reversed the decrease in pituitary TSH promoted by castration. The old male rats showed lower basal in vitro TSH secretion and pituitary TSH content. In Cx old male rats, serum and basal in vitro TSH concentrations were higher than those of old controls and TP treatment further increased basal in vitro TSH secretion, as well as, stimulated TRH-induced TSH secretion. Interestingly, TP had no effect on intact young or old male rats. However, in intact old female rats, TP stimulated in vitro TSH secretion but, as observed in the intact male, TP had no effect on adult female rats. These results suggest a stimulatory role of testosterone on TSH secretion of young and old male rats. Thereafter, it seems that the testes of old rats secrete some testicular factor that inhibits TSH secretion. However, in male rats with normal testosterone levels TP treatment did not increase further TSH secretion, but in old female rats it had a stimulatory effect.

Aging↗
PubMed1983

In vivo patterns of circulating testosterone following castration and intramuscular testosterone propionate injections of adult male rats.

In vivo patterns of circulating testosterone (T) were investigated in castrated and in intact male rats following a single intramuscular injection of 1mg testosterone propionate (TP). In addition, the in vivo clearance pattern of T was investigated following castration. The injection of TP into intact rats resulted in a rapid, statistically significant increase in circulating T which lasted for 12h and returned to normal by 24h post-injection. Circulating T decreased to nondetectable levels by 6h following orchiectomy. Injection of TP into castrated rats caused a rapid increase in circulating T which reached highest levels 60 min after administration. The concentrations of T in TP-treated orchiectomized rats remained elevated for 12h with a gradual decline which persisted for the experimental period of 6 days post-injection and provided moderate maintenance of sex accessory organ weights. TP injections increased circulating T levels in both groups of rats, but the magnitude of elevation was greater in intact animals where the normal T diurnal variations were disturbed. The elevation in circulating T persisted longer in the castrate-TP-treated animals than in intact animals, suggesting a difference in clearance, distribution and metabolism of T in orchiectomized rats.

Animals↗
PubMed1996

Intranasal fluticasone propionate versus loratadine in the treatment of adolescent patients with seasonal allergic rhinitis.

Fluticasone propionate (FP) is a topical corticosteroid with minimal systemic activity. We examined safety and compared the efficacy of FP aqueous nasal spray, 200 micrograms every day with loratadine tablets, 10 mg by mouth every day in 240 adolescents with ragweed pollen-induced seasonal allergic rhinitis for 4 weeks in a randomized, double-blind, parallel-group study. Nasal and eye symptoms were recorded daily on a 4-point (0 to 3) scale. A higher percentage of symptom-free days was observed for nasal blockage on waking during treatment with FP (p < 0.0001). Significant results were also obtained for all other nasal symptoms when analyzed for both symptom-free days and symptom scores. No differences were found for eye irritation symptoms (p = 0.14). Morning and evening nasal peak inspiratory flow (PIF) was recorded daily by 57 subjects. FP treatment was associated wit significantly higher PIF values than loratadine both morning (p = 0.0051) and evening (p = 0.0036). A greater improvement over 4 weeks was observed for PIF morning values in the FP group (p = 0.008) but not for evening values (p = 0.358). Statistically significant correlations were found for nasal blockage and PIF in the morning (r = -0.54, p = 0.0001) and in the evening (r = -0.46, p = 0.008).

Administration, Intranasal↗