The reservoir effect of topical steroids in vitiliginous skin: A cross-sectional study.

Background: Prolonged and frequent use of topical steroids may lead to decrease in effi cacy as well as many local adverse effects. Stratum corneum has a unique property of reservoir effect. Aims: To study the reservoir effect of topical steroids in a steroid-responsive condition which may enable a decrease in the dosing frequency of topical steroids. Methods: A cross-sectional study design was used. Patients with at least three vitiliginous patches of more than 2 cm2 present over the trunk or limbs were included. Exclusion criteria were topical or systemic corticosteroid use within the previous 4 weeks, antihistamine use within the previous 7 days, history of any allergy in the past and immunosuppression. Clobetasol propionate cream was applied on the fi rst vitiliginous area (site A) and fl uticasone propionate ointment was applied on the second vitiliginous area (site B). The third vitiliginous area, site C (control site) was left without applying any medication. Histamine-induced wheal suppression test was performed on each site, at the same time of the day, on every consecutive day following steroid application, until the values obtained at sites A and B approached those obtained at site C. SPSS software for Windows, version 16.0 was used for statistical analysis. The mean and standard deviation of the various studied parameters were calculated for various treatment groups and compared using analysis of variance (ANOVA) test. Results: Forty patients were included in the study. The average wheal volumes and average erythema sizes at sites A and B were signifi cantly smaller than the corresponding values at site C for up to 5 days after applying medication (P < 0.001). Limitations: The presence of a cutaneous reservoir of topical steroid was confi rmed based on its suppressive effect on the wheal and fl are response to histamine. It is not certain that the concentration that suppresses histamine-induced wheal and fl are is suffi cient for therapeutic effi cacy in vitiligo. Conclusion: The reservoir effect of topical clobetasol propionate and fl uticasone propionate persisted for 5 days in vitiliginous skin. Hence, it may be possible to reduce the frequency of topical steroid application in vitiligo.

Efficacy and safety of the single-capsule combination of fluticasone/formoterol in patients with persistent asthma: a non-inferiority trial / Eficácia e segurança da associação fluticasona/formoterol em cápsula única em pacientes com asma persistente: estudo de não inferioridade

OBJECTIVE: Fluticasone and formoterol are effective in the treatment of asthma. When a corticosteroid alone fails to control asthma, combination therapy is the treatment of choice. The objective of this study was to compare the efficacy and safety of formulations containing budesonide/formoterol (BUD/FOR), fluticasone alone (FLU), and the single-capsule combination of fluticasone/formoterol (FLU/FOR) on lung function in patients with mild-to-moderate persistent asthma. METHODS: This was a randomized, multicenter, open phase III trial conducted in Brazil. The primary efficacy analysis was the assessment of non-inferiority between FLU/FOR and BUD/FOR combinations regarding FEV1 (in L) at the final visit. The secondary analyses were PEF, level of asthma control, serum cortisol levels, frequency of adverse events, adherence to treatment, and appropriate inhaler use. RESULTS: We randomized 243 patients to three groups: FLU/FOR (n = 79), BUD/FOR (n = 83), and FLU (n = 81). In terms of the mean FEV1 after 12 weeks of treatment, the difference between the FLU/FOR and BUD/FOR groups was 0.22 L (95% CI: −0.06 to 0.49), whereas the difference between the FLU/FOR and FLU groups was 0.26 L (95% CI: −0.002 to 0.52). Non-inferiority was demonstrated by the difference between the lower limits of the two 95% CIs (−0.06 vs. −0.002). The level of asthma control and PEF were significantly greater in the FLU/FOR and BUD/FOR groups than in the FLU group. There were no significant differences among the groups regarding patient adherence, patient inhaler use, or safety profile of the formulations. CONCLUSIONS: The single-capsule combination of FLU/FOR showed non-inferiority to the BUD/FOR and FLU formulations regarding efficacy and ...

OBJETIVO: A fluticasona e o formoterol são efetivos no tratamento da asma. A terapia combinada é o tratamento de escolha quando o corticosteroide isolado não controla a asma. O objetivo deste estudo foi comparar a eficácia e segurança de formulações contendo budesonida/formoterol (BUD/FOR), fluticasona (FLU) e fluticasona/formoterol (FLU/FOR) em cápsula única sobre a função pulmonar em pacientes com asma persistente leve e moderada. MÉTODOS: Estudo de fase III multicêntrico brasileiro, aleatorizado e aberto. A análise primária de eficácia foi a avaliação de não inferioridade da combinação FLU/FOR perante a combinação BUD/FOR em relação ao VEF1 (em L) na visita final. As análises secundárias foram PFE, nível de controle da asma, nível de cortisol sérico, frequência de eventos adversos, aderência ao tratamento e uso adequado do inalador. RESULTADOS: Foram randomizados 243 pacientes nos grupos FLU/FOR (n = 79), BUD/FOR (n = 83) e FLU (n = 81). Após 12 semanas de tratamento, a média da diferença do VEF1 foi de 0,22 L (IC95%: −0,06 a 0,49) entre os grupos FLU/FOR e BUD/FOR e de 0,26 L (IC95%: −0,002 a 0,52) entre os grupos FLU/FOR e FLU. A não inferioridade ficou demonstrada pela diferença de limite inferior do IC95% (−0,06 vs. −0,002). O nível de controle da asma e o PFE foram significativamente maiores nos grupos FLU/FOR e BUD/FOR em comparação com o grupo FLU. Não houve diferenças significativas em relação a adesão, uso do inalador e perfil de segurança entre os grupos. CONCLUSÕES: ...

Comparative Efficacy of Generic Salmeterol Xinafoate/Fluticasone Propionate MDI Fixed Dose Combination and Seretide ® MDI in Asthmatic Patients: An Open Label, Randomized, Phase III Study.

The addition of an inhaled long-acting β2-agonist (LABA) to an inhaled corticosteroid (ICS) gives optimal control of asthma in most patients. The long-acting β2-agonist (LABA) Salmeterol xinafoate (Salmeterol) and inhaled corticosteroid (ICS) fluticasone propionate (fluticasone) are being made available as a combination product Seretide® pMDI (Salmeterol/ Fluticasone) in a single aerosol inhaler. This randomized, open label, non-inferior, multicentric, 12-week, phase III study compared the efficacy and safety of generic Salmeterol/Fluticasone with commercially available product Seretide®. Materials and methods:Patients aged > 12 years inclusive of either sex (N = 372) with persistent asthma as defined by NHLBI for > 6 months prior to screening were included in the study. After a screening phase (1 week), eligible patients were enrolled in the trial with 2 weeks run in period. Eligible patients were randomized to receive either of the two treatment groups [HFA-Propelled pMDI Salmeterol/Fluticasone (25/250mcg) or HFA-Propelled Seretide® (25/250mcg) pMDI] in a ratio of 1:1 for the 12- week treatment period. The primary objective was to demonstrate non-inferiority of Salmeterol/Fluticasone versus Seretide®, measured by mean pre-dose forced expiratory volume in the first second (FEV1), at week 12. Results: This study provides evidence for the primary efficacy endpoint that Salmeterol/Fluticasone was statistically as well as clinically non-inferior to Seretide® in the treatment of patients with persistent asthma. This was supported by secondary endpoints which demonstrate that Salmeterol/Fluticasone appeared to be comparable to Seretide® in terms of efficacy for the secondary efficacy endpoints (morning PEFR, evening PEFR, diurnal variability of PEFR, daytime and night-time asthma symptoms score, average need for short acting-β2-agonists, proportion of patients that required rescue medication, patients with nocturnal asthma, patients without asthma symptoms of score 0 and average number of days without asthma symptoms of score 0). Salmeterol/Fluticasone was safe and well tolerated; and safety profile is comparable to comparator Seretide®. Conclusion: The results of study demonstrate that generic and innovator HFA formulations of Salmeterol/Fluticasone are clinically interchangeable. Overall, the study indicates that HFA-Propelled Salmeterol/ Fluticasone (25/250mcg) pMDI was safe, well tolerated and non-inferior in efficacy compared to HFA-Propelled Seretide® (25/250mcg) pMDI.

Comparação do corticoide inalatório e oral no tratamento da disfonia aguda / Use of inhaled versus oral steroids for acute dysphonia

A disfonia aguda é um quadro comum na prática clínica. Seu tratamento, principalmente em adultos, não é bem definido na literatura. O corticoide é o tratamento medicamentoso mais recomendado. Os estudos existentes, entretanto, não são suficientes para a determinação da superioridade entre diferentes corticoides e a melhor forma de administração. OBJETIVO: Este estudo clínico prospectivo teve como objetivo comparar o efeito do corticoide inalatório na forma de pó seco com o efeito do corticoide oral, no tratamento da disfonia aguda. MÉTODO: Foram avaliados 32 pacientes adultos, divididos em dois grupos de 16 pacientes para cada um dos tratamentos, antes e após sete dias do uso da medicação. Os pacientes foram submetidos à videolaringosocpia e avaliação perceptiva e acústica da voz. RESULTADOS: O tratamento inalatório e oral reduziram significativamente a hiperemia, o edema e melhorou o movimento muco-ondulatório; entretanto, a redução do edema foi estatisticamente mais significativa (p = 0,012) nos pacientes tratados com a forma inalatória. A comparação dos valores da análise perceptiva auditiva e das medidas acústicas após tratamento entre os grupos, entretanto, não apresentou significância estatística. CONCLUSÃO: Houve melhora significativa da laringite aguda nas avaliações realizadas, em todos os pacientes estudados, com os dois tratamentos. O tratamento com corticoide inalatório foi significativamente mais efetivo na redução do edema.

Acute dysphonia is a frequent condition in clinical practice. Its treatment, especially in adults, is not well established in the literature. Steroids are the most recommended drug treatment. However, the existing studies are not enough to establish superiority among the different steroids and the best route of administration. OBJECTIVE: This prospective clinical study aimed at comparing the effect of inhaling steroids as a dry powder with the effect of oral steroids to treat acute dysphonia. METHOD: We assessed 32 adult patients, broken down into two groups of 16 patients in each one of the treatments, before and seven days after the use of the medication. The patients were submitted to videolaryngoscopy and perceptive and acoustic voice assessment. RESULT: Oral and inhalation treatment significantly reduced hyperemia and edema, and improved the muco-ondulatory movement; nonetheless, edema reduction was statistically more significant (p = 0.012) in the patients treated with the inhalation form of the drug. However, comparing the values of the auditory perceptive analysis and the acoustic measures after treatment between the groups was not statistically significant. CONCLUSION: There was a significant improvement in the acute laryngitis concerning the assessments carried out in all the patients assessed, concerning the two treatments. The inhalation steroid treatment was significantly more effective in reducing the edema.

Inhibir la contractilidad sin provocar necrosis: ¿sería útil en miocardiopatía hipertrófica? Modelo experimental de administración intramiocárdica de toxina botulínica y de wortmanina / Inhibiting contractility without necrosis: Would it be helpful for hypertrophic cardiomyopathy? Experimental model of intramyocardial botulinum toxin and wortmannin

En este artículo se presenta una idea original: inhibir la contracción miocárdica en forma regional y selectiva sin inducir necrosis. Se propone como una posible opción terapéutica en miocardiopatía hipertrófica asimétrica obstructiva, y se plantean 2 modelos farmacológicos basados en la administración intramiocárdica de toxina botulínica y de wortmanina.

The purpose of this paper is to introduce a new idea: local inhibition of contractility without necrosis. It's potential usefulness in hypertrophic cardiomyopathy treatment is discussed and 2 pharmacological models, administrating botulinum toxin and wortmannin directly in the myocardium are disclosed.

Diagnóstico endoscópico y manejo de la esofagitis eosinofílica / Endoscopic diagnosis and management of eosinophilic esofagitis

Eosinophilic esophagitis is a clinico pathologic entity that has been increasingly recognized over the past two decades. It affects all ages, preferably men, with a history of atopy and is characterized by eating disorders, dysphagia and heartburn. It has elements in common with gastroesophageal reflux disease and the distinction between them can be a challenge for the clinician. It has several typical endoscopic features, such as longitudinal grooves, rings, plaques and stenosis, but none of them is pathognomonic of the disease. The correlation of history, endoscopic and histology are essential for a correct diagnosis. Management includes a period of use of proton pump inhibitors to rule out concomitant reflux disease. Treatment with topical corticosteroids such as fluticasone and budesonide are successful in the short term, but recurrence is common. Some cases may require endoscopic dilatation. Data is still insufficient to establish optimal management at short and long-term, therefore therapeutic decisions should be evaluated on a case-by-case basis.

La esofagitis eosinofílica es una entidad clínico patológica que ha sido reconocida en forma cada vez más frecuente en las últimas dos décadas. Afecta a todas las edades, de preferencia a hombres con antecedentes de atopia y se caracteriza por presentar trastornos alimentarios, disfagia y pirosis. Presenta elementos comunes con la enfermedad por reflujo gastroesofágico y la distinción entre ellas puede ser un desafío para el médico. Tiene varias características endoscópicas típicas, como los surcos longitudinales, anillos, placas y estenosis, pero ninguna de ellas es patognomónica de la enfermedad. La correlación de la historia, imagen endoscópica e histología son imprescindibles para el diagnóstico correcto. El manejo incluye un período de uso de inhibidores de la bomba de protones para descartar una enfermedad por reflujo concomitante. El tratamiento con corticoides tópicos como la fluticasona y budesonida da buenos resultados a corto plazo, pero la recidiva es frecuente. Algunos casos pueden requerir dilatación endoscópica. Faltan datos para establecer un manejo óptimo a corto y largo plazo, por lo que las decisiones terapéuticas deben ser evaluadas caso a caso.

The reno-protective effect of a phosphoinositide 3-kinase inhibitor wortmannin on streptozotocin-induced proteinuric renal disease rats

Diabetic nephropathy (DN) is a progressive kidney disease that is caused by injury to kidney glomeruli. Podocytes are glomerular epithelial cells and play critical roles in the glomerular filtration barrier. Recent studies have shown the importance of regulating the podocyte actin cytoskeleton in early DN. The phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin, simultaneously regulates Rac1 and Cdc42, which destabilize the podocyte actin cytoskeleton during early DN. In this study, in order to evaluate the reno-protective effects of wortmannin in early DN by regulating Rac1 and Cdc42, streptozotocin (STZ)-induced proteinuric renal disease (SPRD) rats were treated with wortmannin. The albuminuria value of the SPRD group was 3.55 +/- 0.56 mg/day, whereas wortmannin group was 1.77 +/- 0.48 mg/day. Also, the albumin to creatinine ratio (ACR) value of the SPRD group was 53.08 +/- 10.82 mg/g, whereas wortmannin group was 20.27 +/- 6.41 mg/g. Changes in the expression level of nephrin, podocin and Rac1/Cdc42, which is related to actin cytoskeleton in podocytes, by wortmannin administration were confirmed by Western blotting. The expression levels of nephrin (79.66 +/- 0.02), podocin (87.81 +/- 0.03) and Rac1/Cdc42 (86.12 +/- 0.02) in the wortmannin group were higher than the expression levels of nephrin (55.32 +/- 0.03), podocin (53.40 +/- 0.06) and Rac1/Cdc42 (54.05 +/- 0.04) in the SPRD group. In addition, expression and localization of nephrin, podocin and desmin were confirmed by immunofluorescence. In summary, we found for the first time that wortmannin has a reno-protective effect on SPRD rats during the early DN. The beneficial effects of wortmannin in SPRD rats indicate that this compound could be used to delay the progression of the disease during the early DN stage.

Cortisol basal em asmáticos em uso de duas diferentes doses de propionato de fluticasona / Basal cortisol in asthmatics on two different doses of fluticasone propionate

OBJETIVOS: Avaliar os valores de cortisol basal em asmáticos persistentes em uso de propionato de fluticasona inalatório na dose de 200 ou 300 mcg/dia. MÉTODOS: O diagnóstico e a classificação da gravidade da asma basearam-se nas recomendações do Global Initiative for Asthma. Pacientes menores de 11 anos receberam fluticasona na dose de 200 mcg/dia, e aqueles com mais de 11 anos receberam 300 mcg/dia. Após 10 semanas de tratamento, a dosagem do cortisol foi realizada para avaliação da função adrenal. RESULTADOS: Foram avaliados 41 pacientes (65,9 por cento do sexo masculino) entre 6 e 18 anos. Não houve diferença significativa entre as médias de cortisol basal nos pacientes que receberam 200 mcg/dia de propionato de fluticasona (n = 13) e naqueles que receberam 300 mcg/dia (n = 28). CONCLUSÕES: Os achados mostram que doses baixas a moderadas de propionato de fluticasona não causam supressão adrenal.

OBJECTIVES: To evaluate basal plasma cortisol in persistent asthmatics on inhaled fluticasone propionate 200 mcg/day and 300 mcg/day. METHODS: Asthma diagnosis and classification was based on Global Initiative for Asthma recommendations. Patients aged 11 years old or less received fluticasone propionate 200 mcg/day and those older than 11 years received 300 mcg/day. After 10 weeks of treatment, plasma cortisol levels were monitored to evaluate the hypothalamic-pituitary-adrenal axis. RESULTS: Forty-one patients (65.9 percent males) aged 6 to 18 years old were evaluated. No statistical differences were found between plasma cortisol levels in patients who received 200 mcg/day (n = 13) and those who received 300 mcg/day (n = 28). CONCLUSIONS: Our results show that low and moderate doses of fluticasone propionate do not cause adrenal suppression.

Comparison of chemical cautery (AgNo3) and steroid spray against SMD (submucosal diathermy) in the treatment of symptomatic inferior turbinate hypertrophy (ITH).

OBJECTIVE: To compare the efficacy of chemical cautery (AgNo3) and steroid nasal spray against SMD (submucosal diathermy) in the treatment of symptomatic Inferior Turbinate Hypertrophy (ITH). MATERIALS AND METHODS: Patients attending OPD in the department of ENT &HNS at KMCTH with symptomatic Inferior turbinate Hypertrophy were taken with their approval included for the study. Patients were divided into 2 Groups: in the first Group 25 patients were included and treated with chemical cautery (AgNo3) under Local Anaesthesia (LA), followed by steroid nasal spray for 3 months; in the second Group 25 patients were included and were treated with SMD (submucosal diathermy) under General Anaesthesia (GA).They all had history of use of topical nasal decongestant for different time period. Patients were followed up for 6 months. RESULTS: In Group 1, 16 patients complain of burning sensation for first week and 8 patients complain of continuous nasal blockage for 6 weeks.1 patient complain about inosmia for 2 weeks. In Group 2, nasal pain was complained by 17 patient for 2 weeks. 3 patients complain of persistent nasal blockage for 4 weeks. 3 patients complain of anosmia for 4 weeks. After completion of 6 months in Group 1, 20 patient has recurrent nasal blockage, whereas in Group 2, 10 patient has recurrent nasal blockage. Besides these, other symptoms noticed during initial phase did not appear. CONCLUSION: Chemical cautery (AgNo3) and steroid nasal spray is easy to follow, has less complication ,but failure rate is high, whereas SMD is procedure with less failure rate, but has to carried out under GA and has more discomfort postoperatively. For symptomatic inferior turbinate hypertrophy, where topical nasal decongestant has little role SMD is the choice of treatment for longer relief.

Efficacy and safety of combination ointment "fluticasone propionate 0.005% plus mupirocin 2.0%" for the treatment of atopic dermatitis with clinical suspicion of secondary bacterial infection: an open label uncontrolled study.

BACKGROUND: The skin of patients with atopic dermatitis is colonized with Staphylococcus aureus. Reduction of bacterial colonization has been reported to be effective in the treatment of atopic dermatitis. AIM: To assess the efficacy and safety of a combination of fluticasone propionate 0.005% and mupirocin 2.0% ointment twice daily for 2 weeks in patients with atopic dermatitis clinically suspected of secondary bacterial infection. METHODS: An open-label, non-randomized study of 122 patients (64 males and 58 females) from 20 centers was conducted. Atopic dermatitis was diagnosed by clinical assessment and scoring was done on the visual analogue scale (VAS). Clinical evaluation of the lesions was done on day 1 (baseline), day 8 and on day 15 of study visits. RESULTS: At baseline, many patients had moderate itching (41.8%), moderate dryness (41.8%) and mild weeping lesions (49.2%). The baseline proportions of the clinicians' global impressions (CGI) scale for mild, moderate and severe atopic dermatitis lesions were 19.7%, 55.7% and 12.2% respectively. At the end of the treatment period, 67.2% patients had mild disease, whereas only 9% and 0.8% patients had moderate and severe disease respectively. At baseline, only 33.65% patients were comfortable with the existing lesions when assessed on visual analog scale (VAS). However, after the treatment, this proportion increased to 51.77% and 78.60% patients on day 8 and on day 15 respectively. CONCLUSION: Twice daily topical application of a fluticasone propionate 0.005% and mupirocin 2.0% ointment is an effective and safe therapeutic regimen in atopic dermatitis.