RESUMEN
Topical glucocorticoids (TG) such as dexamethasone (DEX) have been used for decades for the treatment of skin diseases. However, TG present well-documented side effects and their delivery to the skin is often insufficient. Therefore, many efforts have been undergone to improve the amount of drug delivered to the skin and to reduce side effects at the same time. In this work, the feasibility of DEX-submicron polymeric particles (SP) prepared by vibrational spray-drying as an approach to overcome the challenges associated with the topical administration of this drug class was evaluated. DEX was homogeneously dispersed in the SP matrix, according to confocal Raman microscopy analysis. Drug-loaded SP were incorporated into the oil phase of oil-in-water emulsions (creams). The formulation containing polymeric submicron particles (C-SP) showed controlled drug release kinetics and a significant drug accumulation in skin compared to formulations containing non-polymeric particles or free drug. DEX accumulation in the stratum corneum was evaluated by tape stripping and a depot effect over time was observed for C-SP, while the formulation containing the free drug showed a decrease over time. Similarly, C-SP presented higher drug retention in epidermis and dermis in skin penetration studies performed on pig skin in Franz diffusion cells, while drug permeation into the receptor compartment was negligible. It was demonstrated, for the first time, the advantageous application of submicron polymeric particles obtained by vibrational spray-drying in semisolid formulations for cutaneous administration to overcome challenges related to the therapy with TG such as DEX.
Asunto(s)
Dexametasona/administración & dosificación , Portadores de Fármacos/química , Glucocorticoides/administración & dosificación , Polímeros/química , Absorción Cutánea , Piel/metabolismo , Animales , Dexametasona/farmacocinética , Composición de Medicamentos/métodos , Liberación de Fármacos , Emulsiones , Glucocorticoides/farmacocinética , Técnicas In Vitro , Microscopía Confocal , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Piel/efectos de los fármacos , Propiedades de Superficie , Sus scrofa , Distribución Tisular , VibraciónRESUMEN
The oxidizing capacity and skin penetration of a commercial nanosized ZnO, Nanosun™ (Micronisers-Australia), were evaluated in vitro using porcine skin. Nanosun™ was initially characterized regarding its photo-reactivity and size distribution. An assay using methylene blue was performed to confirm the Nanosun™ photo-reactivity by exposing the labile molecule to UVA irradiation in the presence and absence of the nanosized ZnO. The nanosized ZnO was photo-reactive, reducing the methylene blue concentration to 7% while its concentration remained constant in the control formulation (without ZnO). The product label states that the average particle size is 30 nm. X-ray diffraction, nitrogen sorption and UV-spectrophotometry confirmed the presence of nanometric particles of approximately 30 nm. On the other hand, laser diffractometry showed micrometric particles in the size distribution profile. These analyses indicated that the nanoparticles are arranged as agglomerates and aggregates of micrometric proportions ranging from 0.6 to 60 µm. The skin lipid peroxidation was determined by the formation of thiobarbituric acid reactive species (TBARS) and quantified by UV-spectrophotometry. When exposed to UVA radiation the nanosized ZnO applied porcine skin showed a lower production of TBARS (7.2 ± 1.5 nmol g(-1)) than the controls, the MCT applied porcine skin (18.4 ± 2.8 nmol g(-1)) and the blank porcine skin (14.0 ± 2.0 nmol g(-1)). The penetration of ZnO nanoparticles was studied by scanning electron microscopy and energy dispersive X-ray spectroscopy. The tested ZnO particles did not penetrate into viable layers of the intact porcine skin. The particles tend to accumulate on the skin folds and in these regions they may penetrate into the horny layer.
Asunto(s)
Óxido de Zinc/química , Animales , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/efectos de la radiación , Nanopartículas del Metal/química , Nanopartículas del Metal/toxicidad , Azul de Metileno/química , Microscopía Electrónica de Transmisión , Tamaño de la Partícula , Piel/efectos de los fármacos , Piel/efectos de la radiación , Espectrometría por Rayos X , Porcinos , Rayos UltravioletaRESUMEN
The aim of this study was to assess the reliability and external validity of the Previous Day Food Questionnaire (PDFQ) designed to obtain a report of the foods eaten on the previous day by schoolchildren. Participants were 7-10-year-old school children of the first four grades of a public school in Southern Brazil (N=227). Test-retest reliability was evaluated by kappa coefficient for two administrations of the PDFQ on the same day to the same children. External validity of the PDFQ was evaluated via sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) using trained observers of the food eaten on the previous day as gold standard. The association between responses from observed food intake with those from reported food intake on PDFQ was evaluated by multivariate logistic regression, controlled for school grade, gender, time of the eating, and the variation between first and second PDFQ applications. For the reliability study, the analyses stratified by school eating occasions (3 a day) indicated that agreement level was moderate or better for all food categories. PDFQ's sensitivity ranged from 57.1% (vegetables) to 93.3% (rice), whereas its specificity ranged from 77.8% (bread/pasta) to 98% (meats). Both, PPV and NPV were reasonably high. PDFQ was highly associated with observed food intake, with effect magnitude several times larger than any other factor analyzed for all foods. PDFQ also showed good test-retest reliability, suggesting that it may generate reliable and valid data for assessing food intake at the group (school) level.
Asunto(s)
Encuestas sobre Dietas , Dieta , Encuestas y Cuestionarios/normas , Brasil , Niño , Fenómenos Fisiológicos Nutricionales Infantiles , Conducta Alimentaria , Femenino , Humanos , Modelos Logísticos , Masculino , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The science of voice evaluation and assessment has profited from technological advancement and objective measurement of voice parameters has become an integral part of the voice examination, however, subjective voice evaluation remains a vital component of any voice examination. The Towne-Heuer Reading Passage was developed in 1970 to provide a reading sample that would facilitate subjective voice evaluation. The reliability of the passage was established using three judges listening to 15 normal Philadelphia speakers and 15 vocal abuse-misuse clients with verified vocal nodules. The frequency of hard glottal attack (HGA) was determined for the two groups and high interjudge and intrajudge correlation was found. A difference in the frequency of HGA was found between the two groups.
Asunto(s)
Lectura , Trastornos de la Voz/diagnóstico , Calidad de la Voz , Voz/fisiología , Adolescente , Adulto , Niño , Humanos , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
Hard or abrupt glottal attack (HGA) is one of the vocal behaviors often associated with benign lesion of the vocal folds. This study was designed to determine whether the frequency of HGA was different in hyperfunctional voice patients with and without vocal fold masses. One hundred and forty-seven subjects were studied. All subjects received a complete otolaryngological evaluation including strobovideolaryngoscopy, objective voice measures, and evaluation by a speech-language pathologist. Thirty-two patients were diagnosed with muscle tension dysphonia (19 male, 13 female) without vocal fold masses. Fifty-seven patients were diagnosed with unilateral vocal fold masses (29 male, 28 female), most of which were cysts. Fifty-eight patients were diagnosed with bilateral vocal fold masses (13 male, 45 female). Of the 45 females with bilateral vocal fold masses. 26 had a vocal cyst and reactive nodule and 19 had bilateral vocal fold nodules. The control group was balanced and matched based on sex and on percentage of singers and nonsingers. It consisted of 49 subjects with no vocal fold pathology (20 male, 29 female). The group was composed of professional speakers, singers, and nonprofessional speakers. All voice disordered groups demonstrated higher frequencies of HGA than the control group. Differences were found between the male and female subjects in this study. No differences were found between the various disorders. Differences were also found between the subgroups of bilateral masses, where the bilateral nodules group presented a higher frequency of HGA than the cyst and contralateral reactive nodule.
Asunto(s)
Quistes/diagnóstico , Glotis/fisiopatología , Enfermedades de la Laringe/diagnóstico , Músculos Laríngeos/fisiopatología , Trastornos de la Voz/diagnóstico , Trastornos de la Voz/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Quistes/complicaciones , Femenino , Humanos , Enfermedades de la Laringe/complicaciones , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Trastornos de la Voz/etiología , Calidad de la VozRESUMEN
BACKGROUND: Some studies have identified and selected factors that were associated with prognosis in patients with gastrointestinal fistulas, but a multivariate analysis to determine their relative importance and independent predictive value has not been done. The aim of this study was to determine independent prognostic factors for fistula closure and death in patients with gastrointestinal fistulas using a multivariate model. STUDY DESIGN: Several variables were assessed related to spontaneous closure, surgical closure, and mortality in 188 patients with digestive fistulas (duodenal 22.3%, jejunoileal 28.7%, colonic 23.9%, biliopancreatic 25%). Selection of the variables was done through a forward stepwise logistic regression procedure; the final models were used to estimate the probability of closure, either spontaneous or surgical, and the probability of death. RESULTS: Variables significant for spontaneous closure were: cause of the fistula (p = 0.027), fistula output (p = 0.037), institutional origin of the patient (p = 0.026), and occurrence of complications (p<0.001). Organ of origin of the fistula was only marginally significant (p = 0.068). Successful surgical closure was significantly associated with the presence of complications (p = 0.001) and was marginally associated with age (p = 0.069). Variables significant for death were fistula output (p = 0.009) and the presence of complications (p<0.001). CONCLUSIONS: We conclude that the likelihood of spontaneous fistula closure is higher for fistulas with surgical causes, low output, and with no complications. Mortality is higher in patients with complications and with high-output fistulas.