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ABSTRACT Purpose The study was conducted to compare intralesional methylprednisolone acetate 40 mg/ml (Depo-Medrol) injection with incision and curettage in the treatment of chalazia. Method A prospective, interventional clinical study was conducted. Seventy-seven patients that met the inclusion criteria and gave informed consent were randomized to receive either intralesional methylprednisolone injection or incision and curettage. Patients were followed up at two weeks and at one month, and the treatment was repeated when indicated. Results Seventy-three patients completed the study. At two weeks, after one treatment, there was a significant difference in outcome (p = 0.002) between the two groups: 10 (27%) chalazia resolved after intralesional methylprednisolone injection and 23 (64%) after incision and curettage. At one month however, there was no statistical difference (p = 0.223) in outcome between the two groups: resolution occurred in 24 patients (65%) after intralesional methylprednisolone injection, and in 28 patients (78%) after incision and curettage. In cases that were successfully treated at one month, 58% required a second treatment with intralesional injection, which was significantly more (p = 0.020) than the 18% with incision and curettage. In both groups, the initial chalazion size and duration did not significantly influence the outcome of treatment. The average time to perform intralesional injection (39 seconds) was significantly quicker (p = 0.000) than the average time for incision and curettage (2 minutes 46 seconds). In 3 out of 37 injected patients, a slight subcutaneous methylprednisolone deposit was visible at one month. Conclusion Incision and curettage remains the gold standard in the treatment of chalazia, but intralesional methylprednisolone (Depo-Medrol) injection is an useful alternative treatment modality.

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Orientador: Gilberto de Nucci / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-12T13:53:54Z (GMT). No. of bitstreams: 1 Oliveira_LinaSayuriOdoBuenode_M.pdf: 1845448 bytes, checksum: 4fea923152025c316ca4c99487b21970 (MD5) Previous issue date: 2008 / Resumo: Betametasona é um corticosteróide sintético designado para exercer a função de um glicocorticóide ativo. Como um álcool livre, betametasona apresenta uma vasta aplicação clínica com atividade antiinflamatória e imunossupressora. A betametasona foi extraída com 0,5mL de plasma humano por extração líquido-líquido (ELL) utilizando Cloranfenicol como padrão interno. O método utilizou uma corrida cromatográfica de 2,5min, com a coluna analítica C18 (100mm×2.1mm i.d.), a calibração da curva linear de 0,05ng/mL a 50ng/mL (r2 > 0,993). A exatidão inter-corrida dos controles de qualidade foi 92.3% (CQA 0.15ng/mL), 90.7% (CQB 4.0ng/mL) e 97.2% (CQC 40ng/mL). A precisão inter-corrida dos controles de qualidade foi 8.7% (CQA 0.15ng/mL), 9.0% (CQB 4.0ng/mL) e 9.8% (CQC 40ng/mL). O método aqui descrito foi empregado em estudo de biodisponibilidade relativa de duas formulações contendo dexclorfeniramina/betametasona 2mg/0.25mg comprimido. A razão da média geométrica e dos respectivos intervalos de confiança (IC) de Betametasona/Celestamine® foram 107.61% (101.62-113.95%) para AUClast, 106.93% 102.08-112.00% para AUC0-inf e 105.06% (96.56-114.31%) para Cmax. O intervalo deconfiança de 90% calculado para a razão individual das médias de Cmax, ASC0-72h, ASClast e ASC0-inf para betametasona/celestamine® estavam dentro do intervalo de 80- 125% definido pela Agência Vigilância Sanitária (ANVISA). No presente estudo um método, rápido, sensível e robusto foi desenvolvido para a determinação e quantificação de betametasona em plasma humano através da cromatografia líquida acoplada a espectrometria de massas usando fotoionização à pressão atmosférica em modo negativo. / Abstract: Betamethasone is a synthetic corticosteroid designed to exert a marked glucocorticoid activity. As the free alcohol, betamethasone finds widespread clinical applications related to its anti-inflammatory and immunosuppressant activity. Betamethasone was extracted from 0.5 ml human plasma by liquid-liquid extraction (LLE) using chloramphenicol as internal standard. The method has a chromatographic run of 2.5 min using a C18 analytical column (100mm×2.1mm i.d.) and the linear calibration curve over the range was linear from 0.05 to 50 ng ml-1 (r2 > 0.993). The between-run accuracy, based on the relative standard deviation replicate quality controls was 92.3% (0.15 ng ml-1), 90.7% (4.0 ng ml-1) and 97.2% (40 ng ml-1). The between-run precision for the above-mentioned concentrations was 8.7, 9.0 and 9.8%, respectively. The method herein described was employed in a bioequivalence study of two formulations of dexchlorpheniramine/betamethasone 2 mg/0.25 mg tablets. The geometric mean and respective 90% confidence interval (Cl) of betamethasone/Celestamine® percent ratios were 107.61% (101.62-113.95%) for AUClast, 06.93% 102.08-112.00%for AUC0-inf and 105.06% (96.56-114.31%) for Cmax. In adition, the calculated 90% Cl for mean Cmax, AUClast and AUCinf betamethasone/celestamine® individual ratios were within the 80-125% interval defined by the Agência Vigilância Sanitária - ANVISA. In the present study, a fast, sensitive, robust method was developed for the determination and quantification of betamethasone in human plasma by liquid chromatography coupled with tandem mass spectrometry, using photospray ionization in negative mode. / Mestrado / Mestre em Farmacologia

Orientadores: Carlos Takahiro Chone, Eulalia Sakano / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T21:36:35Z (GMT). No. of bitstreams: 1 Dias_ArethusaIngriddeLizMedeiros_M.pdf: 1854166 bytes, checksum: ba03fb9925b6895d98d898626cbb0986 (MD5) Previous issue date: 2013 / Resumo: Existem poucos estudos que correlacionam os aspectos histopatológicos dos pólipos nasossinusais após tratamento com corticosteróide nasal. O objetivo do presente estudo foi analisar as alterações histopatológicas dos pólipos nasais antes e após o uso de corticosteróide tópico nasal por três meses. Foi utilizado ensaio clínico, sem grupo controle. Biópsias de pólipos nasais de pacientes com polipose nasossinusal foram realizadas antes e após três meses de uso de budesonida 50 mcg, duas vezes ao dia, para análise histopatológica. Nos 35 pacientes incluídos, observou-se, após corticoterapia, um aumento da intensidade do edema na submucosa, sendo que 50% destes apresentavam edema intenso, uma redução de 47% de pacientes com infiltrado intenso de eosinófilos (p= 0,07) e não houve alteração quanto ao infiltrado de linfócitos, neutrófilos e plasmócitos. Com relação à presença dos cistos glandulares, houve aumento estatisticamente significante (p=0,031). Não se observou variação na espessura da membrana basal (p=0,344). Concluiu-se que o uso de corticosteróide tópico nasal por três meses mostrou variações no estroma e na intensidade das células dos pólipos nasossinusais / Abstract: There are few papers regarding the effect of corticosteroids on histopathology of sinonasal polyps. The aim of this study was to analyze the histopathology of nasal polyps before and after three months of nasal topical corticosteroids. It was used a non-controlled clinical trial. Nasal polyps biopsies of patients with sinonasal polyposis were performed before and after three months of budesonide 50 mcg BID for histopathological analysis. Among the 35 patients included, after steroid therapy, it was observed an increase in submucosal edema intensity, half of them presenting intense edema, a 47% reduction of cases with intense eosinophils infiltration (p = 0.07). Lymphocytes, neutrophils and plasma cells infiltration in polyps was not altered by treatment. It was observed statistically significant increase in presence of glandular cysts after treatment (p = 0.031). The thickness of the basement membrane did not changes (p=0.344). This study concluded that three months use of topical nasal corticosteroids resulted in stromal and cellular variations of sinonasal polyps / Mestrado / Otorrinolaringologia / Mestra em Ciências Médicas

The objective was to compare the effects of three corticosteroids at various equimolar concentrations on equine articular explant co-cultures in an inflammatory environment. Synovial and osteochondral explant co-cultures from 6 equine cadavers were exposed to IL-1β (10 ng/mL) and various concentrations (10-4, 10-7, or 10-10 M) of MPA, TA, IPA. Concentrations of PGE2, MMP-13, LDH, and GAG in media were determined at 48 and 96 hours. Results indicated wells with low concentrations of MPA (10-7 and 10-10 M at 48 and 96 hours), TA (10-7 M at 48 hours and 10-7 and 10-10 M at 48 and 96 hours), and IPA (10-10 M at 48 hours) had significantly less PGE2 than positive control samples. Groups with low concentrations (10-7 and 10-10 M) of MPA and TA had significantly less PGE2 than the highest concentration (10-4 M) at 48 hours. Significantly less MMP-13 was detected for all concentrations of MPA, TA, and IPA at 96 hours. The LDH assay results indicated cytotoxicity only for samples treated with IPA at 10-4 M at 48 and 96 hours. GAG was significantly lower for samples treated with TA 10-7 M at 48 hours and MPA 10-10 M at 96 hours versus positive controls. These findings suggest corticosteroids at low concentrations mitigated the inflammatory and catabolic effects of IL-1β to a greater extent than high concentrations. Effects of IPA and MPA were similar to TA at clinically relevant low equimolar concentrations. / Master of Science / Recent data suggest that isoflupredone acetate is commonly administered intra-articularly for treatment of joint disease (osteoarthritis) in horses. Although much data has been published regarding effects of other corticosteroids on cartilage, to our knowledge there have been no similar studies of the effects of isoflupredone acetate. With increased scrutiny from the general public and more stringent control of medication use by regulatory agencies, determination of information regarding such common intra-articular therapies is imperative. In addition, prior studies have only evaluated the effects of corticosteroids on cartilage, whereas other joint tissues (subchondral bone and synovium) have been shown to be important to the biological responses of joints. Therefore, to more closely simulate the natural joint environment, this study was conducted with a co-culture model incorporating synovial tissue, articular cartilage, and subchondral bone within an inflammatory environment (via stimulation with interleukin-1β). The effects of various concentrations of methylprednisolone acetate, triamcinolone acetonide, and isoflupredone acetate on joint tissues were determined via measurement of selected biomarkers. This study provided the first data regarding biological effects of IPA on joint tissues of horses, and the first comparison of such effects with those of other corticosteroids commonly used intra-articularly for the treatment of joint disease in horses.

La mucoviscidose (ou cystic fibrosis, CF) est une maladie caractérisée par une inflammation pulmonaire chronique qui contribue à la dégradation progressive de l’épithélium des voies aériennes des patients. Les glucocorticoïdes (GC) représentent un outil essentiel pour le traitement du patient mais leur efficacité et leur rapport bénéfice/risque restent cependant controversés. Les effets secondaires provoqués par l’administration de ces molécules pourraient être diminués par l’utilisation de leur protéine d’adressage, la corticosteroid-binding globulin (CBG). L’objectif de ce travail était d’étudier l’expression de la CBG chez les patients CF, afin d’optimiser leur traitement anti-inflammatoire par GC. Nous avons montré, dans un premier temps, que la synthèse hépatique de CBG était augmentée, tandis que son taux plasmatique était conservé chez les patients CF, comparé aux patients non-CF. Dans un second temps, nous nous sommes intéressés à l’expression de la CBG au niveau pulmonaire. L’inflammation chez les patients CF étant principalement pulmonaire, l’expression locale de CBG à ce niveau pourrait moduler l’efficacité du GC, en le recaptant. Nos données montrent que l’expression de cette CBG pulmonaire est diminuée chez les patients CF. Les études sur des modèles in vitro hépatiques et pulmonaires n’ont pas permis d’expliquer les résultats obtenus et ont souligné la limite des modèles et des outils à disposition. Le maintien de la concentration plasmatique de CBG et la diminution de la CBG pulmonaire chez les patients CF suggèrent ainsi que la CBG pourrait être utilisée comme outil thérapeutique dans le contexte de la mucoviscidose, afin d’optimiser le traitement par GC. / Cystic fibrosis (CF) is characterized by a chronic pulmonary inflammation, responsible of the progressive degradation of the airways epithelium. In CF, glucocorticoids (GC) are widely used but their efficiency and benefit/risk ratio are still discussed. The side effects, caused by the administration of these molecules, might be decreased by the use of their delivery protein, corticosteroid-binding globulin (CBG). The aim of the work was to study the expression of CBG in CF patients, in order to optimise their anti-inflammatory treatment by GC. First, we showed that the hepatic synthesis of CBG was increased while its plasmatic level was preserved in CF patients, compared to non-CF. Second, we were interested by the expression of CBG at the pulmonary level. The inflammation in CF patients being primarely pulmonary, the local expression of CBG in the lung could modulate the efficiency of GC through recapture. Our data showed that this expression of this pulmonary CBG was decreased in CF patients. The studies conducted in vitro on hepatic and pulmonary models did not explained our results and highlighted the limit of the models and tools at our disposal. The maintained plasmatic concentration of CBG and the decrease of pulmonary CBG in CF patients suggest that CBG might be useful as a therapeutic tool in the CF context, in order to optimise the GC treatment.