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- ItemAcesso aberto (Open Access)Análise morfológica dos fígados e rins no binômio materno-fetal após tratamento de ratas prenhes com Ritonavir durante toda a prenhez(Federação Brasileira das Sociedades de Ginecologia e Obstetrícia, 2007-07-01) Carvalho, Adelino Moreira De; Simões, Ricardo Santos [UNIFESP]; Oliveira, Fábio Hideo Martins; Simões, Manuel de Jesus [UNIFESP]; Oliveira-filho, Ricardo Martins; Nakamura, Mary Uchiyama [UNIFESP]; Kulay Júnior, Luiz [UNIFESP]; Universidade José do Rosário Vellano Faculdade de Ciências Médicas; Universidade Federal de São Paulo (UNIFESP); Irmandade da Santa Casa de Misericórdia de São Paulo Faculdade de Ciências Médicas Departamento de Obstetrícia; Universidade de São Paulo (USP)PURPOSE: to evaluate the effect of the chronic administration of three different doses of Ritonavir in the liver and kidneys of pregnant albino rats and their concepts from a morphological standpoint. METHODS: forty pregnant albino EPM-1 Wistar rats were randomly divided into four groups: Contr (vehicle control), and three experimental groups, Exp20, Exp60, Exp180, which received daily 20, 60 or 180 mg/kg of Ritonavir, respectively. The drug and the vehicle (propyleneglycol) were orally administered by gavage, from the first up to the 20th day of pregnancy. At the last experimental day, all the animals were sacrificed under deep anesthesia, and fragments from the maternal and fetal liver and kidneys were taken and prepared for histological analysis by light microscope. RESULTS: no morphological changes were identified in Exp20 and control group. In the Exp60 group, we found hepatocytes with signs of atrophy and apoptosis (eosinophilic cytoplasm and picnotic nuclei) and marked sinusoid capillary vasodilation (congestion). The proximal convoluted tubules of maternal kidneys and liver showed eosinophilic areas and hyperchromatic nuclei, as well as signs of vasodilation. The maternal kidneys and livers of the Exp180 rats presented more prominent morphological changes than the ones of Exp60. Regarding the fetal organs, no histomorphological abnormalities were observed in all the groups. CONCLUSIONS: our results show that the administration of Ritonavir to pregnant rats, in higher than conventional doses causes morphological changes in the maternal liver and kidneys. On the other hand, the lack of abnormalities in the fetal organs may be due to the protective role of glycoprotein P.
- ItemAcesso aberto (Open Access)Análise por sequenciamento paralelo maciço da resistência aos antirretrovirais em pacientes infectados pelo HIV-1 em terapia de resgate(Universidade Federal de São Paulo (UNIFESP), 2017-06-21) Castro, Daniela Funayama de [UNIFESP]; Komninakis, Shirley Vasconcelos [UNIFESP]; Lattes http://lattes.cnpq.br/6529080329230878; http://lattes.cnpq.br/8695544517472892; Universidade Federal de São Paulo (UNIFESP)Antiretroviral Therapy (ART) has improved the quality and life expectancy of HIV-1 infected individuals, reducing both mortality and morbidity. However, along with ART there was the emergence of resistant viral populations selected by the selective pressure of the drugs. These viral populations may lead the patient to virological failure. Although the success rates of ART are high, patients with virologic failure usually require changes in their antiretroviral regimens, which is called a "rescue therapy". Objectives: 1 - Analyze resistance mutations in samples of patients who failed ART and using rescue antiretrovirals: Darunavir, Etravirine and / or Raltegravir; 2 - Compare the mutational profile obtained by the Massive Parallel Sequencing with the one identified by conventional sequencing - Sanger's method. METHODS: Twenty-eight samples with HIV genotyping results with virological failure of antiretroviral drugs were selected between March 2014 and May 2015. The selected samples were from patients with failed ART and one or more antiretroviral drugs from this study. For the analysis of the samples the Massive Parallel Sequencing was done. Results: The most prevalent mutation among all analyzed was I84V in the protease (39.1%). Among the mutations that reduced susceptibility to Darunavir, after I84V, the most common was L33F, accounting for 26%. In mutations that confer reduced susceptibility to Etravirine, mutations K101P, Y181I and Y181V were identified, representing a frequency of 4.3% each. With regard to Raltegravir, a frequency above 21% of the N155H mutation was observed, which gives a significant reduction in the susceptibility to this drug. Mutations with minority prevalence and TAMs M41L, D67N, K70R, L210W, T215F, T215Y and K219Q were also identified. Conclusion: Minority resistance mutations are not currently identified by the method used in clinical practice, such as population sequencing (Sanger's method), whose detection limit is higher than 20-30%. Massive Parallel Sequencing makes it possible to identify mutations with frequency up to 1%. The analysis of minority mutations could, in some situations, help in the choice of a more adequate antiretroviral.The analysis of minority mutations could, in some situations, help in the choice of a more adequate antiretroviral.
- ItemAcesso aberto (Open Access)Efeitos da administração diária da associação estavudina/nelfinavir sobre os fetos e placentas da rata albina(Federação Brasileira das Sociedades de Ginecologia e Obstetrícia, 2011-05-01) Carvalho, Gisela Maria Vieira Rodrigues De [UNIFESP]; Nakamura, Mary Uchiyama [UNIFESP]; Simões, Ricardo Santos; Antonio, Eliana Maria Restum [UNIFESP]; Wagngner, Adriana [UNIFESP]; Fontes, Tereza Maria Pereira [UNIFESP]; Kulay Júnior, Luiz [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)PURPOSE: to evaluate the effect of administration of a stavudine/nelfinavir combination on the rat pregnancy by assessing maternal and concepts weights, as well as the number of implantations, fetuses, placentas, resorptions and maternal and fetal mortality. METHODS: forty adult pregnant Wistar rats of the EPM-1 strain were randomly divided into four groups: control (GCtrl - drug vehicle control, n=10), and three experimental groups, which were treated with an oral solution of stavudine/nelfinavir (ExpI - 1/40 mg/kg b.w., n=10; ExpII - 3/120 mg/kg b.w., n=10; ExpIII - 9/360 mg/kg b.w., n=10) from day 0 to the 20th day of pregnancy. Maternal body weights were determined at the start of the experiment and on the 7th, 14th and the 20th day thereafter. At term (20th day) the rats were anesthetized and, upon laparotomy and hysterotomy, the number of implantations, resorptions, living fetuses, placentae and intrauterine deaths were recorded. The collected fetuses and placentae were weighed and the concepts were examined under a stereomicroscope for possible external malformations. Statistical analysis was performed by analysis of variance (ANOVA) complemented by the Kruskal-Wallis test (p<0.05). RESULTS: there was a progressive and gradual increase in body weight during the course of pregnancy in all groups, which was more evident in the final period, but with no significant difference between groups. The mean number of fetuses, placentas, implantations, and fetal and placental weights showed no significant differences between groups. Also, no resorptions or external malformations were found in the experimental groups. However, between the 8th and 14th days of gestation, there was one case of maternal mortality in each experimental group. CONCLUSIONS: the administration of a stavudine/nelfinavir combination had no deleterious effects on the concepts.
- ItemAcesso aberto (Open Access)Evolução da função renal de pacientes portadores do Vírus da Imunodeficiência Humana/ Síndrome da Imunodeficiência Adquirida(Escola Paulista de Enfermagem, Universidade Federal de São Paulo (UNIFESP), 2009-01-01) Friedl, Daniane Bornea; Aprile, Daniele Cristina Bosco; Fino, Luana Camargo; Barbosa, Dulce Aparecida [UNIFESP]; Belasco, Angélica Gonçalves Silva [UNIFESP]; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)OBJECTIVE: To evaluate the renal function in patients with Human Immunodeficiency Virus who were attending the Center for Infectious Diseases Control of the São Paulo Hospital of the Federal University of São Paulo. METHODS: This retrospective study consisted of the review of 200 randomly selected medical records. RESULTS: Patients were predominant white males with a mean age of 45 years. They had been diagnosed with the disease over 50 months ago, had from 0 to up 9 comorbidities, and a mean creatinine of .93mg/dl. The majority of patients were receiving antiviral medication. CONCLUSION: There was no significant alteration in renal function in the patients between the first and last visit.