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PubMed1997

A randomized, double-blind dose reduction study to compare the minimal effective dose of budesonide Turbuhaler and fluticasone propionate Diskhaler.

BACKGROUND: New inhaled glucocorticosteroids and inhalers are being developed. Their clinical equipotency is difficult to assess and is often discussed. OBJECTIVE: This study was carried out to compare the effect of budesonide Turbuhaler and fluticasone propionate (FP) Diskhaler in a dose reduction study in children (ages 5 to 16 years) with asthma. METHODS: Children treated with budesonide administered through a pressurized metered-dose inhaler with a large volume spacer had their budesonide dose gradually reduced to define the minimal effective dose with this delivery system. After this period, 217 children were randomly allocated to treatment with half the dose of either budesonide Turbukaler or FP Diskhaler for 5 weeks in a double-blind trial. If no deterioration in asthma control was seen, the dose was further reduced by 50% at 5-week intervals until deterioration in asthma control was seen. Throughout the study, morning and evening peak expiratory flow, symptoms, and use of rescue beta 2-agonist were recorded in diaries. Lung function tests and a standardized exercise test were performed at the clinic at the end of each treatment period. Urine cortisol excretion (24 hours) was measured before and after the first 5-week treatment period. Standardized criteria for deterioration in asthma control, based on diary card variables and exercise testing, were used to determine the minimal effective dose for each patient; and from this, the number of dose reduction steps was calculated. RESULTS: No statistically significant difference was seen in number of dose reduction steps from baseline or in minimal effective dose between the two treatments; mean reduction was 1.59 dose steps for budesonide Turbuhaler and 1.65 dose steps for FP Diskhaler (p = 0.52), and minimal effective dose was 188 micrograms for budesonide Turbuhaler and 180 micrograms for FP Diskhaler. After these dose reductions, the same level of asthma control was observed in the budesonide Turbuhaler and FP Diskhaler groups. Furthermore, no statistically significant differences between the two inhaler-drug combinations were seen in daytime or nighttime symptoms, morning and evening peak expiratory flow, use of rescue beta 2-agonist, lung functions at the clinic, exercise-induced fall in lung function, or 24-hour urinary cortisol excretion during the first 5-week period. CONCLUSION: Microgram for microgram, budesonide Turbuhaler and FP Diskhaler are equally effective in treatment of children with moderate asthma.

Administration, Inhalation↗
PubMed1998

The effect of fluticasone propionate on functional status and sleep in children with asthma and on the quality of life of their parents.

BACKGROUND: Although in the past drug interventions were measured primarily on the basis of their efficacy and safety, today we are increasingly interested in what impact treatments have on the patient's day-to-day activities and quality of life. OBJECTIVES: We sought to assess the effect of treatment with fluticasone propionate (FP) on functional status and sleep disturbances in children with asthma and to evaluate possible changes in the quality of life of the parents of these children after treatment. METHODS: As part of a randomized, double-blind, parallel-group, placebo-controlled, multicenter study on the effects of FP powder (50 or 100 microg twice daily) on growth in children aged 4 to 11 years with mild-to-moderate asthma (n = 325), parents/caregivers completed the following questionnaires at baseline and at weeks 24 and 52 of treatment: Functional Status IIR (FSII), Sleep Scale-Children (SLP-C), and Quality of Life of Parents of Asthmatic Children (QOL-PAC). Change from baseline to weeks 24 and 52 within each treatment group was analyzed by using paired t-tests, and differences between treatment groups were analyzed by using analysis of covariance. RESULTS: Mean FSII and SLP-C scores improved significantly over baseline values with either 50 or 100 microg FP at weeks 24 and 52 (p < 0.05) and were significantly better than scores in the placebo group (p < 0.05). In contrast, FSII scores at week 52 and SLP-C scores at weeks 24 and 52 decreased significantly in the placebo group (p < 0.05). QOL-PAC results revealed that scores on the Burden scale were significantly improved in both FP groups at weeks 24 and 52. Subjective Norms and Social scales improved significantly only in the 100 microg FP group at week 52. CONCLUSIONS: The results of this study show that FP (either 50 or 100 microg twice a day) was associated with significant improvements in functional status and decreased sleep disturbances in children with asthma. In addition, treatment of children with FP was associated with a decreased burden on the parents of these children with asthma.

Administration, Topical↗
PubMed1998

Development of fluticasone propionate and comparison with other inhaled corticosteroids.

Fluticasone propionate (FP) is a trifluorinated glucocorticoid based on the androstane nucleus. It was selected for development from structure-activity relationships (topical anti-inflammatory, cutaneous vasoconstriction, and hypothalamic-pituitary-adrenal axis suppression) of a series of 17beta-carbothioates. FP is 3-, 300-, and 1000-fold more lipophilic than beclomethasone dipropionate, budesonide, and triamcinolone acetonide, respectively. FP has an absolute affinity (KD) for the glucocorticoid receptor of 0.5 nmol/L and a relative receptor affinity 1.5-fold higher than beclomethasone-17-monopropionate (17-BMP) and mometasone furoate, 3-fold higher than budesonide, and 20-fold higher than flunisolide and triamcinolone acetonide. The rate of association of FP with the receptor is faster and the rate of dissociation slower than other corticosteroids. The resulting half-life of the FP active steroid-receptor complex is >10 hours, compared with approximately 5, 7.5, and 4 hours for budesonide, 17-BMP, and triamcinolone acetonide, respectively. FP has high selectivity for the glucocorticoid receptor, with little or no activity at other steroid receptors. FP is more potent than beclomethasone dipropionate, budesonide, triamcinolone acetonide, and mometasone furoate in inhibiting human T-cell migration and proliferation, inhibiting CD4+ T-cell cytokine and basophil histamine release, attenuating adhesion molecule expression, stimulating inflammatory cell apoptosis, and inducing cellular antiprotease release. In asthma patients, FP decreases the number of CD3+, CD4+, CD8+, and CD25+ T cells, mast cells, and eosinophils in bronchial biopsies, in addition to suppressing CD1a-dendritic and IgE+ cells and HLA-DR. FP, therefore, has a good pharmacologic profile for a topical steroid with increased intrinsic glucocorticoid potency and potent anti-inflammatory activity.

Administration, Inhalation↗
PubMed1998

The common cold: effects of intranasal fluticasone propionate treatment.

OBJECTIVE: A double-blind, randomized, placebo-controlled trial was conducted to study the effect of the intranasal corticosteroid, fluticasone propionate (FP), in the naturally occurring common cold. METHODS: One hundred ninety-nine young adults received high-dose FP (200 microg four times daily) or placebo beginning 24 to 48 hours after onset of the common cold for 6 days. All symptoms were recorded on diary cards on days 1 to 20, and clinical examinations were carried out on days 1, 7, and 21. Nasopharyngeal aspirates were collected on days 1 and 7 for detection of rhinoviruses (found in 105 subjects) and Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis (found in 52 subjects) in the nasopharynx. RESULTS: In general, FP treatment had no clinically recognizable effects on the symptoms of the common cold, although it significantly reduced nasal congestion and cough on some study days. After treatment, rhinoviruses were cultured more often in the FP treatment group (37% vs 14%, p < 0.001), but this had no effect on the symptoms of common cold. FP treatment produced no changes in the colonization of pathogenic bacteria in the nasopharynx. Some symptoms of common cold were significantly more severe during days 1 to 10 (p < 0.05) in subjects found to have positive cultures for S. pneumoniae, H. influenzae, or M. catarrhalis in the nasopharynx on day 1 (n = 33). CONCLUSION: FP treatment does not have any marked effects on the symptoms of the common cold. FP treatment induced prolonged shedding of viable rhinoviruses. Some symptoms of the common cold were significantly more severe in subjects with pathogenic bacteria in the nasopharynx.

Administration, Intranasal↗
PubMed1999

In vivo modulation of glucocorticoid receptor mRNA by inhaled fluticasone propionate in bronchial mucosa and blood lymphocytes in subjects with mild asthma.

BACKGROUND: In vivo regulation of the glucocorticoid receptor (GR) by glucocorticoids provides a means of modulating sensitivity of targeted cells. OBJECTIVE: We sought to determine the in vivo modulation of GR mRNA expression by fluticasone propionate (FP) in subjects with mild asthma. METHODS: Ten atopic asthmatic subjects were treated with FP 250 microg twice daily for 4 weeks. Before and after treatment, the patients underwent fiberoptic bronchoscopy with endobronchial biopsy and sampling of venous blood for measurements of GR mRNA levels. A solution hybridization assay was used for quantitative analysis of GR mRNA. In addition, a 24-hour urinary cortisol excretion and an adrenocorticotropic hormone test before and after treatment with FP were performed. RESULTS: A high interindividual variation in GR mRNA expression was seen. However, we detected a significant reduction of the GR mRNA levels in the endobronchial biopsy specimens after FP treatment (36.6 +/- 23.1 and 25.0 +/- 10.9 amol GR mRNA/microg RNA, respectively; P <.01). In the peripheral blood lymphocytes an even more striking downregulation of the GR by its cognate ligand was documented (30.3 +/- 26.5 and 8.8 +/- 5 amol GR mRNA/microg RNA, respectively; P <.001), possibly reflecting differences in glucocorticoid sensitivity between tissues. A small but significant reduction of the 24-hour urinary cortisol excretion was observed (233 +/- 109 and 157 +/- 66 nmol/L, respectively; P <.01), whereas the feedback regulation of glucocorticoid synthesis by means of the hypothalamic-pituitary-adrenal axis as assessed by the adrenocorticotropic hormone test remained normal after treatment with FP. CONCLUSION: The results in this study confirm the potency of the inhaled corticosteroid FP and provide evidence for a considerable tissue-specific interindividual variation in the expression of the GR.

Adrenocorticotropic Hormone↗
PubMed1999

Time to onset of effect of fluticasone propionate in patients with asthma.

BACKGROUND: The effectiveness of inhaled glucocorticoids in the treatment of asthma is well documented; however, times to onset and maximal treatment effects of these agents have been poorly described. OBJECTIVE: We sought to determine the time to onset of effect and the time to the best observed effect of inhaled fluticasone propionate (FP) in patients with asthma. METHODS: Data from 8 randomized, double-blind, placebo-controlled clinical trials of at least 8 weeks' duration were analyzed. Corticosteroid-naive patients (n = 1461) were treated with either FP (25 micrograms to 500 micrograms) or placebo twice daily. Efficacy evaluations included morning peak expiratory flow (PEF), asthma symptom scores, supplemental albuterol use, and FEV1. RESULTS: Statistically significant improvements in PEF, asthma symptom scores, and supplemental albuterol use were observed beginning on day 1 of treatment in the FP group versus the placebo group (P <.001); significant increases in FEV1 were observed at the first measurement at week 1 (P <.001). The best observed effect occurred within 3 weeks of the start of FP treatment for PEF (+36 L/min) and FEV1 (+0.52 L) and within 2 weeks for reduction in supplemental albuterol use and asthma symptom scores. Patients with the most severe airflow obstruction had the greatest change in PEF (+56 L/min) and fastest time to 50% of best observed effect (3 days) compared with patients with mild or moderate airflow obstruction; however, time to best observed effect was similar in the 3 groups (20 to 27 days). CONCLUSION: In patients with asthma, the onset of significant benefit of FP on PEF, symptoms, and rescue albuterol use occurred within 1 day of the start of therapy. FEV1 improved within 1 week of the start of therapy (the first measurement after randomization). There was no effect of sex, age, or dose of FP on the time to response. The best observed response in PEF varies with the degree of baseline airflow obstruction; however, the degree of airflow obstruction has no effect on the time to best observed response.

Administration, Inhalation↗
PubMed2000

Cost-efficacy comparison of inhaled fluticasone propionate and budesonide in the treatment of asthma.

BACKGROUND: The results of a recent meta-analysis comparing 2 inhaled corticosteroids, fluticasone propionate (FP) and budesonide, demonstrated that FP had an improved efficacy-to-safety ratio compared with budesonide. However, limited data are available on the relative economic benefits of these 2 regimens. OBJECTIVE: This pharmacoeconomic analysis used individual patient data from studies in the meta-analysis to compare the relative cost-efficacy of 2 asthma regimens from the perspective of a US third-party payer. METHODS: This analysis included all 7 studies in the meta-analysis that compared budesonide with FP dosed at approximately half the dose of budesonide and that included measurement of daily morning peak expiratory flow (PEF). RESULTS: The total daily per-person cost of asthma management was higher for patients treated with budesonide than with FP ($3.00 vs $2.25, respectively). Treatment with FP had greater cost-efficacy than treatment with budesonide, based on a range of outcome measures that included improvement in morning PEF, symptom-free days, and episode-free days. The daily cost per effectively treated patient (an increase in PEF of > or = 10%) was $5.62 with FP and $10.05 with budesonide. The cost per symptom-free day was $4.36 with FP, compared with $6.67 with budesonide. The cost per episode-free day was $5.60 with FP and $9.42 with budesonide. The pharmacoeconomic difference continued to favor FP as the criteria for success were made more stringent and the cost of budesonide was lowered. CONCLUSION: Based on data from the 7 randomized, controlled trials, treatment of asthma with FP was more effective and less expensive, using US health care assumptions and costs, than treatment with budesonide.

Administration, Inhalation↗
PubMed2003

Two multicenter, randomized, single-blind, single-dose, crossover studies of specific sensory attributes of budesonide aqueous nasal spray and fluticasone propionate nasal spray.

BACKGROUND: Intranasal corticosteroids are effective for the treatment of allergic rhinitis. Sensory attributes associated with these sprays may affect patient preference and adherence to treatment regimens. OBJECTIVES: These 2 studies compared patients' perceptions of and preferences for specific sensory attributes of budesonide aqueous nasal spray (BANS) and fluticasone propionate nasal spray (FPNS). METHODS: In 2 multicenter, randomized, single-blind (patient), single-dose, 2-period, 1-day crossover studies, adults with mild to moderate allergic rhinitis received single doses of BANS (one 32-pg spray per nostril in both studies, 64-microg total dose) and FPNS (two 50-microg sprays per nostril in study 1, 200-pg total dose; one 50-microg spray per nostril in study 2, 100-microg total dose). Study 1 compared the once-daily recommended starting doses of BANS and FPNS, and study 2 compared BANS with half the once-daily recommended dose of FPNS to balance the number of actuations for delivery of study drug. Patients completed the 23-item Sensory Perceptions Questionnaire and indicated their product preference (if any). RESULTS: A total of 110 women and 71 men in study 1 and 136 women and 54 men in study 2 were randomized to treatment. None had previously used BANS or FPNS. In both studies, fewer patients perceived scent or taste (both P < 0.001 in both studies), forceful spray (P < 0.001 in both studies), and a wet feel in both the nose and throat (study 1, P < 0.004; study 2, P < 0.002) with BANS than with FPNS. In addition, more patients in both studies liked the spray force (study 1, P < 0.01; study 2, P < 0.001) and moisture content in the throat (study 1, P < 0.001; study 2, P < 0.006) of BANS and indicated a greater overall satisfaction with the sensory features of BANS than those of FPNS (study 1, P < 0.001; study 2, P < 0.015). In analyses that included all responding patients, 54.4% of patients in study 1 preferred BANS and 37.8% preferred FPNS (P < 0.022). In study 2, 47.4% preferred BANS and 41.1% preferred FPNS (not significant). Of the 92.2% of patients in study 1 and 88.4% in study 2 who specified a product preference, 59.0% preferred BANS and 41.0% preferred FPNS in study 1 (P = 0.021), and 53.6% preferred BANS and 46.4% preferred FPNS in study 2 (not significant). CONCLUSIONS: On the basis of perceptions of specific sensory attributes reported after 1 administration in these 2 studies, BANS was rated as more pleasing and preferred over the recommended QD starting dose of FPNS, and was also rated as more pleasing than half the QD recommended starting dose of FPNS.

Administration, Intranasal↗
PubMed1995

Treatment of periocular capillary hemangioma with topical clobetasol propionate.

BACKGROUND: Hemangiomas pose a therapeutic challenge because they can threaten vision in infancy and early childhood. Intralesional injection of corticosteroid is widely regarded as the treatment of choice for hemangiomas which induce strabismus or significant refractive error, or occlude the visual axis. Ocular and systemic complications such as eyelid necrosis, central retinal artery occlusion, and adrenal suppression have been reported rarely after corticosteroid injection. METHODS: Three infants were treated with clobetasol propionate (Temovate) cream for vision-threatening eyelid hemangiomas. RESULTS: Treatment with this topical fluorinated corticosteroid produced a measurable reduction in the size of the hemangiomas, which permitted clearing of the visual axis. No regional side effects were noted. In addition, the patients did not demonstrate evidence of hypothalamic-pituitary-adrenal axis suppression. CONCLUSIONS: This treatment modality appears to provide an additional alternative for managing superficial periocular hemangiomas which threaten vision.

Administration, Topical↗
PubMed1998

The effect of fluticasone propionate on respiratory syncytial virus-induced chemokine release by a human bronchial epithelial cell line.

Respiratory syncytial virus (RSV) is an important cause of bronchiolitis in infants, is an important trigger of asthma exacerbation, and stimulates chemokine production by human respiratory epithelial cells in vitro. We tested the effect of the corticosteroid fluticasone propionate (FP) on RSV-stimulated production of the chemokines interleukin 8 (IL-8) and RANTES (regulated upon activation, normal T cell expressed and secreted) by a human bronchial epithelial cell line, BEAS-2B. Confluent BEAS-2B cultures were inoculated with RSV at approximately 1 plaque-forming unit/cell, and media were collected at 24 h intervals. Concentrations of IL-8 and RANTES were measured in supernatants using ELISA. The effect of FP at varying concentrations on RSV-induced chemokine release was determined. RSV stimulated increased release of both IL-8 and RANTES, particularly at 24-48 h after virus inoculation. Significant but incomplete inhibition of RSV-stimulated increases for both chemokines was found when cultures were treated with FP at > or = 10(-8) M (for IL-8) or > or = 10(-7) M (for RANTES). There was no significant effect of FP on release of RSV itself from infected BEAS-2B cells. We conclude that a possible mechanism for the efficacy of inhaled corticosteroids in reducing the frequency or severity of asthma exacerbations is inhibition of virus-induced chemokine production by airway cells.

Androstadienes↗
PubMed1986

Topical clobetasol-17-propionate: review of its clinical efficacy and safety.

Clobetasol-17-propionate, the most potent of currently available topical steroids as predicted by the vasoconstrictor assay, has just been approved in the United States. In psoriasis, it has proved significantly more effective than class II steroids and as or more effective than the only marketed class I steroid. In the more steroid-responsive eczemas, the superior efficacy of clobetasol is also apparent, but less striking. Clobetasol prolongs remission rates, making intermittent treatment schedules feasible and minimizing inherent potential steroid side effects. Clobetasol may also be useful in the treatment of a myriad of other skin conditions. A review of the pharmacology, efficacy, and side effects of this addition to our dermatologic armamentarium is presented here.

Administration, Topical↗
PubMed2003

Triamcinolone acetonide aqueous nasal spray and fluticasone propionate are equally effective for relief of nasal symptoms in patients with seasonal allergic rhinitis.

OBJECTIVE: We compared 220 microg daily intranasal aqueous triamcinolone acetonide (TAA AQ) with 200 microg daily fluticasone propionate (FP) for relief of seasonal allergic rhinitis symptoms. Study design and setting Randomized, parallel-group, investigator-blind study included patients with symptomatic seasonal allergic rhinitis. After a baseline period, TAA AQ or FP was taken for about 21 days. Nasal symptom (discharge, stuffiness, itching, sneezing) severity was recorded twice daily; total nasal symptom score was calculated. Health-related quality of life was assessed by Rhinoconjunctivitis Quality of Life Questionnaire. RESULTS: Reductions in individual symptoms and total nasal symptom score were statistically significant versus baseline and were equivalent between treatments: -3.15 +/- 0.19 with TAA AQ (n = 148) and approximately 3.17 +/- 0.18 with FP (n = 147) (95% confidence interval for the difference, -0.7391 to 0.3693). Clinically and statistically significant improvements in Rhinoconjunctivitis Quality of Life Questionnaire scores were comparable. CONCLUSION: TAA AQ and FP were equally efficacious in relieving seasonal allergic rhinitis symptoms and improving health-related quality of life. SIGNIFICANCE: Differences in molecular potency of intranasal steroids do not confer differences in efficacy.

Administration, Intranasal↗
PubMedDate not supplied

Fluticasone propionate and budesonide do not influence bone metabolism in the long term treatment of asthma.

BACKGROUND: Inhaled corticosteroids (ICS) are recommended in the treatment of asthmatic patients. They have been said to be efficacious in the treatment of asthma in respect to cortisol and bone metabolism. METHODS: The effects of the two inhaled corticosteroid, budesonide (BUD) and fluticasone propionate (FP) on bone metabolism, morning cortisol and their effects on the clinical parameters (FEV1, diurnal variation of peak expiratory flow rate = PEFR and log PC20) were examined in a group of 16 asthmatic patients. Eight patients used 800 micrograms/daily BUD and 8,400 micrograms/daily FP during 6 months period. RESULTS: Both BUD and FP improved clinical parameters as determined by FEV1 (p < 0.05) and PEFR (p < 0.01). There was no difference in respect to log PC20 values in either group (p > 0.05). Both treatments didn't change morning cortisol (p < 0.05). Both FP and BUD didn't change any indices of bone formation as determined by serum alkaline phosphatase, bone alkaline phosphatase, osteocalcin and carboxyterminal propeptide of type 1 procollagen and bone resorption as determined by urinary calcium and deoxypyridinoline (p > 0.05). In addition there was no significant effect on calcium and phosphate metabolism (serum calcium, phosphate and parathyroid hormone). CONCLUSION: As a result, having no adverse effect on bone metabolism and adrenal function, in the regard to clinical efficacy, FP is as effective as the double dose of BUD on PEFR and FEV1.

Administration, Inhalation↗
PubMedDate not supplied

The comparison of the efficacy of fluticasone propionate with cetirizine in perennial allergic rhinitis.

BACKGROUND: Allergic rhinitis is an IgE mediated hypersensitivity reaction of the nasal mucosa characterised by nasal discharge, obstruction, and pruritus. PATIENTS AND METHODS: In this study, 43 patients with perenneal allergic rhinitis were enrolled in order to compare the efficacy of Fluticasone Propionate (FP), a corticosteroid nasal spray, with Cetirizine, a systemic oral antihistaminic preparation, which is supposed to have nonsteroidal antiinflammatory activity. Cetirizine (10 mg daily as a single dose) was administered to 22 patient for 45 days. On the other hand, FP (400 micrograms/day) was administered into each nostril twice a day in the remaining 21 patients for 45 days. Skin test was obtained from each patient before therapy. Total eosinophil count, eosinophil count in nasal smear, electrorhinomanometric investigation, PGE2 and ratio of LTC4 to LTD4 both in the serum and in the nasal secretions were determined before and after therapy. In addition, percentage of eosinophils, and mast cells count in the biopsy specimens taken from anterior edge of middle choncha were evaluated before and after therapy, and than the results were graded for each patients. RESULTS: When we compared the eosinophil count in nasal smear, eosinophil percentage and total eosinophil parameters between two groups, it was shown that FP was more effective than Cetirizine. On the other hand, when we compared the ratio of LTC4 to LTD4 in serum and nasal smear, level of PGE2 and mast cell and nasal airway resistance measured by ERM, there were non statistical difference between two groups. CONCLUSION: These results suggest that FP and Cetirizine may be used alternatively in case of an adverse reaction to any of them.

Administration, Intranasal↗
PubMed1998

Slight promotion effects of intermittent administration of testosterone propionate and/or diethylstilbestrol on 3,2'-dimethyl-4-aminobiphenyl-initiated rat prostate carcinogenesis.

In order to determine the effects of intermittent hormonal manipulation on the promotion stage of rat prostate carcinogenesis, testosterone and/or estrogen were administered to F344 rats for 40 weeks after 20-weeks treatment with the prostate carcinogen, 3,2'-dimethyl-4-aminobiphenyl. For this purpose testosterone propionate (TP) and diethylstilbestrol (DES) were introduced into silastic tubes, 2- and 0.5-cm long, respectively, and implanted into the subcutis for seven repeated cycles of 30 days treatment and 10 days withdrawal. Intermittent administration of TP resulted in suppression of ventral prostate adenocarcinoma development and slight but non-significant increases in the incidences of invasive carcinomas of the lateral prostate and seminal vesicles. Intermittent administration of DES completely suppressed tumorigenesis in all sites and the combination of TP and DES generally inhibited prostate tumor development. Thus, under the present experimental conditions, no strong enhancing effects of cyclic hormonal manipulation were observed on rat prostate carcinogenesis. Indeed, the opposite appeared to be the case.

Aminobiphenyl Compounds↗
PubMed1999

Carcinogenicity of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in the rat prostate and induction of invasive carcinomas by subsequent treatment with testosterone propionate.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) at 400 ppm in the diet for 52 weeks was found to induce non-invasive microscopic carcinomas in the ventral prostate of the treated rats, in addition to colon and mammary carcinomas. The current experimental data demonstrate that only a 20-week period of PhIP treatment is sufficient for induction of ventral carcinomas and that long-term pharmacological dosing with testosterone propionate which applied through a Silastic tube embedded in the subcutis after PhIP treatment can induce invasive carcinomas in the anterior prostate and seminal vesicles. Thus, PhIP may provide the basis for a good two stage carcinogenesis model for investigation of prostate carcinogenesis.

Animals↗
PubMed2001

Functional expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors precedes the development of cholinergic phenotype in embryonic rat septal cells in culture.

We examined the development of cholinergic neuronal functions and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) responses in cultured embryonic rat septal cells. Choline acetyltransferase activity was increased from 4 to 6 days in culture and reached a plateau at day 8. Acetylcholine release was increased from 6 to 8 days in culture. AMPA-induced increase in intracellular Ca(2+) level was observed at 3 days in culture and most of the AMPA-responsive cells coincided with high-K(+) responsive cells. These results suggest that cholinergic neurons develop their neuronal functions about 8 days under cultured conditions, and functional expression of AMPA receptors precedes the cholinergic functional development.

Acetylcholine↗