Supramolecular aggregates of cyclodextrins with co-solvent modulate drug dispersion and release behavior of poorly soluble corticosteroid from chitosan membranes.

In this study, the ability of different beta-cyclodextrins to facilitate homogeneous dispersion of triamcinolone acetonide (TA) into chitosan membranes is assessed. Drug loading was assessed through atomic force microscopy (AFM), scanning electron microscopy (MEV-FEG), and X-ray diffraction analyses. Drug interactions with the co-polymer were investigated with Fourier transform infrared spectroscopy, thermal analyses. Swelling assay, and in vitro drug release experiment were used to assess TA release behavior. Undispersed particles of drug were observed to remain in the simple chitosan membranes. Hydroxypropyl-ß-cyclodextrin enabled the dispersion of TA into chitosan membranes and subsequent sustained drug release. In addition, the membrane performance as a drug delivery device is improved by adding specified amounts of the co-solvent triethanolamine. The experimental data presented in this study confirm the utility of our novel and alternative approach for obtaining a promising device for slow and controlled release of glucocorticoids, such as triamcinolone acetonide, for topical ulcerations.

[Does corticosteroid treatment during the pre and postnatal periods affect the neurodevelopmental outcome of premature newborns?]

INTRODUCTION: Glucocorticoids, widely used in the perinatal period, may be associated with adverse neurodevelopmental effects. OBJECTIVES: To analyze neurodevelopmental outcomes in a cohort of very low birth weight newborns treated with antenatal and/or postnatal corticosteroids. MATERIALS AND METHODS: This was a prospective cohort study in which we included all very low birth weight babies admitted to the neonatal intensive care unit of a tertiary hospital between 2008 and 2013. We compared the neurodevelopment among very low birth-weight newborns who did not receive prenatal corticosteroid therapy and those who received a complete course (two doses of 12 mg betamethasone) and an incomplete course (one dose), and between those who did not receive postnatal corticosteroid therapy and those who received it (systemic dexamethasone after the first week of life). Motor, neurosensory and cognitive functions, as well as behavior disorders during the first two years of age were evaluated. RESULTS: A total of 225 very low birth weight newborns were analyzed; 83.6% received prenatal corticosteroid therapy (24% incomplete treatment schedule and 59.6% complete schedule). Only 13.3% received systemic dexamethasone during the postnatal period. Neurological monitoring was performed corticosteroid therapy and more neurological disorders, and no significant differences were found among those who received complete and incomplete courses of prenatal corticosteroid therapy. CONCLUSION: These results did not demonstrate an association between perinatal corticosteroid therapy and worse neurodevelopmental outcomes in very low birth weight newborns.

¿Afecta el tratamiento con corticoides en los periodos prenatal y posnatal el neurodesarrollo del recién nacido prematuro? / Does corticosteroid treatment during the pre and postnatal periods affect the neurodevelopmental outcome of premature newborns?

Resumen Introducción. Los glucocorticoides, ampliamente utilizados en el periodo perinatal, pueden asociarse con efectos adversos en el neurodesarrollo. Objetivo. Analizar los resultados del tratamiento con corticoides en el periodo prenatal y en el posnatal en el neurodesarrollo de una cohorte de recién nacidos de muy bajo peso. Materiales y métodos. Se hizo un estudio prospectivo de cohortes en los recién nacidos de muy bajo peso hospitalizados en la unidad de cuidados intensivos neonatales de un hospital de tercer nivel entre el 2008 y el 2013. Se comparó el neurodesarrollo entre aquellos que no recibieron tratamiento prenatal con corticoides y quienes recibieron el esquema completo (dos dosis de 12 mg de betametasona) o el incompleto (una dosis). También, se compararon los resultados en el neurodesarrollo de los recién nacidos que no recibieron tratamiento posnatal y aquellos que sí (dexametasona sistémica a partir de la primera semana de vida). Se evaluó la función motora, la neurosensorial y la cognitiva, así como los trastornos de conducta durante los dos primeros años de vida. Resultados. Se analizaron 225 recién nacidos de muy bajo peso; 83,6 % de las madres había recibido tratamiento prenatal con corticoides (esquema incompleto: 24 %; esquema completo: 59,6 %). Durante el periodo posnatal solamente el 13,3 % había recibido dexametasona sistémica. El seguimiento neurológico se llevó a cabo en 194 neonatos. En el análisis de regresión logística no se detectó que el tratamiento prenatal no el posnatal se asociara con más trastornos neurológicos, ni hubo diferencias significativas entre quienes recibieron el esquema completo y los que recibieron el incompleto durante el periodo prenatal. Conclusión. Los resultados de este estudio no pudieron demostrar que el tratamiento perinatal con corticoides se asociara con peores resultados en el neurodesarrollo en recién nacidos de muy bajo peso.

Abstract Introduction: Glucocorticoids, widely used in the perinatal period, may be associated with adverse neurodevelopmental effects. Objectives: To analyze neurodevelopmental outcomes in a cohort of very low birth weight newborns treated with antenatal and/or postnatal corticosteroids. Materials and methods: This was a prospective cohort study in which we included all very low birth weight babies admitted to the neonatal intensive care unit of a tertiary hospital between 2008 and 2013. We compared the neurodevelopment among very low birth-weight newborns who did not receive prenatal corticosteroid therapy and those who received a complete course (two doses of 12 mg betamethasone) and an incomplete course (one dose), and between those who did not receive postnatal corticosteroid therapy and those who received it (systemic dexamethasone after the first week of life). Motor, neurosensory and cognitive functions, as well as behavior disorders during the first two years of age were evaluated. Results: A total of 225 very low birth weight newborns were analyzed; 83.6% received prenatal corticosteroid therapy (24% incomplete treatment schedule and 59.6% complete schedule). Only 13.3% received systemic dexamethasone during the postnatal period. Neurological monitoring was performed in 194 infants. Logistic regression analysis did not detect an association between prenatal and postnatal corticosteroid therapy and more neurological disorders, and no significant differences were found among those who received complete and incomplete courses of prenatal corticosteroid therapy. Conclusion: These results did not demonstrate an association between perinatal corticosteroid therapy and worse neurodevelopmental outcomes in very low birth weight newborns.

[Utility of challenge test in immediate hypersensitivity to hydrocortisone sodium succinate]. / Utilidad de la prueba de reto en hipersensibilidad inmediata a succinato sódico de hidrocortisona.

Corticosteroid hypersensitivity is a complex phenomenon in which many factors interact, such as idiosyncrasy, intolerance or allergic reactions. The prevalence of immediate hypersensitivity reactions to corticosteroids is 0.2%-0.5%. Corticosteroids have major therapeutic implications; thus, when hypersensitivity is suspected, in-vitro and/or in-vivo testing can be performed to confirm diagnosis, being the drug challenge the gold standard. After definitive diagnosis, cross-reactivity among the different corticosteroid groups should be considered, to choose wisely if corticosteroid therapy is still required. In Coopman classification, steroids belonging to groups A, B and D2 have high cross-reactivity, however, more studies are needed to determine the degree of cross-reaction among these drugs. This paper presents the case of a woman, in who hypersensitivity to hydrocortisone succinate was confirmed by drug challenge test.

La hipersensibilidad a corticoesteroides es un fenómeno complejo en el que interactúan múltiples factores como idiosincrasia, intolerancia o alergia. La prevalencia de las reacciones de hipersensibilidad inmediata a corticoesteroides es de 0.2 a 0.5%. Debido a la relevancia terapéutica de los esteroides, es importante confirmar el diagnóstico de hipersensibilidad con pruebas in vivo, in vitro, o ambas, el patrón de referencia es la prueba de reto con el fármaco implicado. Una vez realizado el diagnóstico y en caso de que se requiera continuar con el tratamiento con esteroides, deberá considerarse la reactividad cruzada entre los diferentes grupos propuestos en la clasificación de Coopman, en la que los corticoesteroides pertenecientes a los grupos A, B y D2 tienen una elevada reactividad cruzada entre sí; sin embargo, hacen falta más estudios para determinar el grado de reactividad cruzada entre estos fármacos. Comunicamos el caso de una paciente en la que se confirmó el diagnóstico de hipersensibilidad a succinato de hidrocortisona con la prueba de reto.

Uso antenatal do corticosteroide e hemorragia peri-intraventricular: [revisão] / Antenatal corticosteroids and intraventricular hemorrhage: [review]

OBJETIVO: Realizar uma revisão bibliográfica sobre o uso antenatal do corticosteroide na prevenção da hemorragia peri-intraventricular. FONTES DE DADOS: Levantamento bibliográfico por meio do Pubmed e SciELO abrangendo os últimos 20 anos. Foram utilizadas as palavras chaves no idioma inglês: "cerebral hemorrhage", "steroids" e "newborn, infant". SÍNTESES DE DADOS: A hemorragia peri-intraventricular é uma importante patologia nos prematuros, sobretudo nos menores de 34 semanas, devido a suas graves sequelas neurológicas. Uma vez ocorrido o sangramento, não há tratamento específico. Desta forma, a prevenção torna-se o maior objetivo das pesquisas. O resultado da meta-análise de estudos randomizados demonstrou que o corticosteroide antenatal reduz a mortalidade e a incidência da doença de membrana hialina e da hemorragia peri-intraventricular. O efeito protetor na redução do risco da hemorragia peri-intraventricular não está completamente esclarecido. Além de acelerar a maturidade pulmonar, o corticosteroide antenatal estimula a maturação da microvasculatura da matriz germinativa, promove o espessamento da membrana basal, acelera a formação proteica nas junções firmes e estabiliza o fluxo sanguíneo cerebral. Também melhora as condições de nascimento dos fetos pré-termo. CONCLUSÕES: O uso antenatal do corticosteroide associado à implementação de melhores práticas de atendimento ao prematuro tem sido responsável pela evidente redução dos índices dessa doença. Apesar de comprovada eficácia e segurança, não é amplamente utilizado. Medidas devem ser tomadas para estimular seu uso como prática rotineira no atendimento de gestantes com risco de parto prematuro.

OBJECTIVE: To conduct a literature review on the use of antenatal corticosteroids for the prevention of peri-intraventricular hemorrhage. DATA SOURCE: Bibliography search in Pubmed and SciELO databases covering the past 20 years using the following key-words: "cerebral hemorrhage", "steroids" and "newborn infant". DATA SYNTHESIS: The peri-intraventricular hemorrhage is an important disease of preterm infants, especially those with less than 34 weeks, due to its serious neurological sequelae. Once the bleeding occurs, there is no specific treatment. Thus, prevention becomes the main goal of the research. Meta-analysis of randomized studies showed that antenatal corticosteroids reduce mortality and the incidence of hyaline membrane disease and peri-intraventricular hemorrhage. The physiologic basis for this protective effect in reducing the risk of peri-intraventricular hemorrhage is not completely clear. Besides accelerating lung maturity, antenatal steroids stimulate the maturation of the microvasculature of the germinal matrix, promote the thickening of the basement membrane, accelerate the formation of protein in tight functions and stabilize the cerebral blood flow. They also improve the birth conditions of preterm babies. CONCLUSIONS: The use of antenatal corticosteroids associated with implementing best practices to assist preterm infants reduces the frequency of peri-intraventricular hemorrhage. Despite its proven efficacy and safety, it is not widely used. Measures should be taken to encourage its use as a routine practice in the care of pregnant women at risk of premature birth.

Ciclesonide, a hypotonic intranasal corticosteroid.

Intranasal corticosteroids (INCSs) are established as the first-line treatment of moderate to severe allergic rhinitis (AR) in both adults and children. Compared with other nasal allergy medications, INCSs are the most effective at providing symptom relief and increasing quality of life. Ciclesonide nasal spray is the most recently approved INCS. The formulation of ciclesonide does not contain benzylalkonium chloride or phenyl ethyl alcohol, excipients that have been associated with reduced mucociliary transport, and unpleasant sensory perceptions. Additionally, ciclesonide has been formulated in a hypotonic suspension that has been shown to optimize intranasal absorption and it has a lower volume of spray compared with most other INCS products. Systemic exposure to ciclesonide and its active metabolite desisobutyryl-ciclesonide is low after intranasal administration. High protein binding ( approximately 99%) and rapid first-pass clearance further reduce systemic exposure to the drug. Studies up to 1 year have shown that intranasal ciclesonide does not cause cortisol suppression as monotherapy and does not have an additive effect on the hypothalamic-pituitary-adrenal axis function when administered in combination with inhaled corticosteroids. The efficacy of ciclesonide, 200 microg/day, has been shown in pediatric, adolescent, and adult patients with moderate to severe seasonal AR and perennial AR treated for up to 1 year. Additionally, environmental exposure unit studies have established an onset of action as early as 1 hour after administration. Ciclesonide nasal spray has also been shown to have an acceptable safety profile in patients with AR as young as 2 years of age. Thus, intranasal ciclesonide appears to provide an additional effective treatment option for patients with AR.

Spectrophotometric and HPLC determination of deflazacort in pharmaceutical dosage forms

Deflazacort (DFZ) is a glucocorticoid used as an anti-inflammatory and immunosuppressant drug. No official methods are available for DFZ determination in pharmaceutical formulations. The objective of this study was to develop, validate and compare spectrophotometric (UV and colorimetric) and high-performance liquid chromatography (HPLC) methods, for the quantitative determination of DFZ in tablets and oral suspension. For the UV method, ethanol was used as the solvent, with detection at 244 nm. The colorimetric method was based on the redox reaction with blue tetrazolium in alkaline medium, with detection at 524 nm. The method by HPLC was carried out using a C18 column, mobile phase consisting of acetonitrile:water (80:20, v/v) with a flow rate of 1.0 mL min-1 and detection at 244 nm. The methods proved linear (r > 0.999), precise (RSD < 5 percent) and accurate (recovery > 97 percent). Statistical analysis of the results indicated that the UV and HPLC methods were statistically equivalent, while the values obtained for the colorimetric method differed significantly from the other methods.

O deflazacorte (DFZ) é um fármaco glicocorticóide usado como antiinflamatório e imunossupressor. Métodos oficiais não estão disponíveis para a determinação de DFZ em formas farmacêuticas. Este estudo teve como objetivo desenvolver, validar e comparar métodos por espectrofotometria (UV e colorimetria) e cromatografia líquida de alta eficiência (CLAE), na determinação quantitativa de DFZ em comprimidos e suspensão oral. O método por UV utilizou etanol como solvente, com detecção em 244 nm. O método colorimétrico foi baseado na reação de redução com azul de tetrazólio em meio alcalino, com detecção em 524 nm. O método por CLAE utilizou coluna C18; fase móvel constituída de acetonitrila:água (80:20, v/v), com fluxo de 1,0 mL min-1 e detecção em 244 nm. Os métodos foram lineares (r > 0,999); precisos (RSD < 5 por cento), e exatos (recuperação > 97 por cento). As análises estatísticas dos resultados obtidos indicaram que os métodos por UV e por CLAE foram estatisticamente equivalentes, enquanto os valores obtidos para o método colorimétrico diferiram significativamente dos demais métodos.

Recent developments in capillary electrokinetic chromatography with replaceable charged pseudostationary phases or additives.

Although electrochromatography in packed beds or monolithic columns has gained enormous interest, techniques based on charged pseudostationary phases like micelles are of high practical importance in electrically driven separation science. However, nonmicellar alternatives, e.g., using charged soluble polymers or smaller additives are still attractive, as they allow high concentrations of organic solvents, and their application is not limited by the critical micellar concentration. This review discusses the developments in the field of electrokinetic chromatography with these additives in the last three years, covering ionic polymeric pseudostationary phases, dendrimers and so-called micelle polymers, but also small molecules which implement separation selectivity due to their specific interaction with the analytes.

Los corticoides: medicamentos con riesgo / Corticoids: risk medicines

Los medicamentos corticoides o corticosteroides son esteroides semejantes a los aislados de los extractos de la corteza suprarenal, con funciones multiples, de los que se hace facil uso y abuso, incluso en enfermedades triviales, que bien pueden ser tratadas con otros antiinflamatorios. El proposito del presente articulo es el de informar sobre estas sustancias de prescripcion delicada, que en buenas y competentes manos son favorables, cuando su manejo es correcto, maximalizando y racionalizando sus efectos

Síndrome de Vogt-Koyanagi-Harada: revisäo de 16 casos / Vogt-koyanagi-Harada syndrome: a review of 16 cases

Este trabalho realiza uma análise crítica percentual em um grupo de 16 pacientes portadores da síndrome de Vogt-Koyanagi-Harada, no período de 1977-1994, atendidos no serviço de uveítes de clínica oftalmológica do HGV-CCS-FUFPI.