Desenvolvimento de sistemas farmacêuticos emulsionados para veiculação gênica

Broadly speaking, the concept of gene therapy involves the transfer of a genetic material into a cell, tissue, or organ in order to cure a disease or at least improve the clinical status of a patient. Making it simple, gene therapy consists in the insertion of functional genes into cells containing defective genes by substituting, complementing or inhibiting them. The achievement of a foreigner DNA expression into a population of cells requires its transfer to the target. Therefore, it is a key issue to create systems able to transfer and protect the DNA until it reaches the target, the vectors. The disadvantages related to the use of viral vectors have encouraged efforts to develop emulsions as non-viral vectors. In fact, they are easily produced, present controllable stability and enable transfection. The aim of this work was to develop an emulsion for gene therapy and evaluate its ability to compact nucleic acids by the development of a complex with the plasmid pIRES2-EGFP. The first step was to determine the Hydrophilic Lipophilic Balance (HLB) of the Captex® 355 (oily internal phase of the emulsion) through long and short term stability assays. Based on the results, emulsions composed of Captex® 355, Tween 20® and Span 60® with 10.7 HLB were produced by three different methods: phase inversion, spontaneous emulsification and sonication. The results showed that the lowest diameter and best stability of the emulsions were achieved by the sonication method. The cationic emulsions were made by adding DOTAP to the basic emulsion. Its association with pIRES2-EGFP was evaluated by electrophoresis. Several rates of emulsion and DNA were evaluated and the results showed that 100% of the complex was formed when the rate DOTAP/DNA(nmol/µg) was 130. In conclusion, the overall results show the ability of the proposed emulsion to compact pIRES2-EGFP, which is a requirement to a successful transfection. Therefore, such formulation may be considered a promising candidate for gene therapy

Modelos de sobrevivência com fração de cura e erro de medida nas covariáveis

In this work, we study the survival cure rate model proposed by Yakovlev et al. (1993), based on a competing risks structure concurring to cause the event of interest, and the approach proposed by Chen et al. (1999), where covariates are introduced to model the risk amount. We focus the measurement error covariates topics, considering the use of corrected score method in order to obtain consistent estimators. A simulation study is done to evaluate the behavior of the estimators obtained by this method for finite samples. The simulation aims to identify not only the impact on the regression coefficients of the covariates measured with error (Mizoi et al. 2007) but also on the coefficients of covariates measured without error. We also verify the adequacy of the piecewise exponential distribution to the cure rate model with measurement error. At the end, model applications involving real data are made

Modelos de sobrevivência com fração de cura e omissão nas covariáveis

In this work we study the survival cure rate model proposed by Yakovlev (1993) that are considered in a competing risk setting. Covariates are introduced for modeling the cure rate and we allow some covariates to have missing values. We consider only the cases by which the missing covariates are categorical and implement the EM algorithm via the method of weights for maximum likelihood estimation. We present a Monte Carlo simulation experiment to compare the properties of the estimators based on this method with those estimators under the complete case scenario. We also evaluate, in this experiment, the impact in the parameter estimates when we increase the proportion of immune and censored individuals among the not immune one. We demonstrate the proposed methodology with a real data set involving the time until the graduation for the undergraduate course of Statistics of the Universidade Federal do Rio Grande do Norte

Recidiva de câncer labial em pacientes atendidos no hospital DR. Luiz Antônio (Natal-RN) entre 1997-2004

Introduction: Cancer of the lip is very common in tropical countries, being noticeable the squamous cell carcinoma as the main histological type. Objective: Evaluate the socialdemographic profile, habits, occupation, clinical characteristics of the cancer lesions and the aftermath of treatment of the patients treated on the Luiz Antônio Hospital (Natal-RN). Design: Retrospective cohort. Methods: We analyzed 181 medical records of patients from the Luiz Antônio Cancer Hospital (Natal-RN) in the period between 1997 and 2004. The statistic evaluation of time between the diagnosis and the relapse or the cure of the patient were done through the Kaplan-Meier method and the comparison of survivor functions were done through the Log-rank test. Later, was estimated the proportional risk model of Cox. Results: The study population were composed by 69,1% males, 95,2% unlettered, the mean age of 66,5 years, 89,0% of smokers and 64,1% had an occupation involving sun exposure. In regard to the clinical characteristics, most lesions were in the lower lip (77,9%), the size of the tumor was smaller than 2 cm (51,8%), 92,6% had localized lesions. Were verified 16,3% of local relapse and 13% of regional. Almost the totally of the cases corresponded to squamous cell carcinoma (97,2%). We observed smaller accumulated probability of not occurrence of local relapse when the base and borders were free of lesions (p=0,041), as well as a smaller probability of regional relapse when the sort of treatment was surgery, associated with other therapeutics modalities (p=0,001). The patients with advanced pathologic stage (p=0,016), treated with surgery associated with other therapeutics modalities (p=0,001) and diameter above 4cm (p=0,019) presented a bigger possibility of any kind of relapse. The multivariable analysis pointed the complex treatments (surgery plus other therapeutics modalities) as a predictor variable for occurrence of new local lesions (p=0,001) and total (p=0,046), besides the age above 70 years to the regional relapse (p=0,050). Conclusion: Cancer of the lip occur in the lower lip, in males, smokers and individuals exposed to Sun light. The relapse was frequent, even being localized and without great consequences to the patient s health. The probability of relapse is related to the size and borders of the lesion and to the histological exam, as well as to the patient s age and complexity of the treatment chosen