Navegando por Palavras-chave "Ritonavir"

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    Acao cronica do lopinavir associado ao ritonavir sobre a prenhez da rata albina
    (Universidade Federal de São Paulo (UNIFESP), 2003) Hagemann, Cristiane Cadore de Farias [UNIFESP]
    Objetivo: avaliar os efeitos da acao cronica da associacao lopinavir e ritonavir sobre a prenhez da rata albina. Metodo: foram utilizadas 62 ratas albinas, da linhagem EPM-1 Wistar, com 3 meses de idade, pesando aproximadamente 200g, que aleatoriamente foram divididas em 5 grupos, sendo dois grupos controle - Contr 1 (grupo controle de estresse - n = 10) e Contr 2 (grupo controle de veiculo - n = 10) - e tres grupos submetidos a experimentacao - Exper 1 (n = 14), Exper 2 (n = 14) e Exper 3 (n = 14) - que receberam a solucao oral de lopinavir / ritonavir respectivamente nas doses de 12,8 / 3,2 mg; 38,4 / 9,6 mg; e 115,2 / 28,8 mg por kilograma de peso corporal. A droga e o veiculo (propilenoglicol) foram ministrados por gavagem. Nos dias zero, 7, 14 e 20 da prenhez, os animais foram pesados. No vigesimo dia, as matrizes foram sacrificadas. Apos incisao xifo-pubica e exposicao dos orgaos internos, foi realizada histerotomia, seguida de avaliacao do numero de implantacoes, de reabsorcoes, de fetos, de placentas, de obitos intra-uterinos, peso dos fetos e das placentas, alem da pesquisa de malformacoes maiores com auxilio de lupa. Resultados: As matrizes de todos os grupos apresentaram ganho de peso quando comparado o dia zero com o dia 20 da prenhez. O ganho percentual de peso das ratas nesse periodo foi de 45,1 por cento, 42,8 por cento, 47,9 por cento, 55,8 por cento e 53,9 por cento em Contr 1, Contr 2, Exper 1, Exper 2 e Exper 3 respectivamente. Nos grupos expostos ao medicamento foi verificado obito estatisticamente significante entre as matrizes quando comparado com os grupos controle (p = 0,002). A administracao da associacao lopinavir / ritonavir nao afetou significativamente o tamanho da ninhada, o numero de reabsorcoes, o peso dos fetos, o peso das placentas, como tambem nao determinou obito e / ou malformacoes entre as crias. Conclusoes: a combinacao lopinavir / ritonavir pode interferir negativamente sobre a rata albina, causando dano letal. As crias de matrizes expostas a droga nao apresentaram efeito deleterio
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    Ação crônica do ritonavir sobre a prenhez da rata albina (Rattus norvegicus albinus, Rodentia, Mammalia)
    (Universidade Federal de São Paulo (UNIFESP), 2003) Carvalho, Adelino Moreira de [UNIFESP]; Kulay Júnior, Luiz [UNIFESP]
    Objetivos: Geral - avaliar os efeitos da acao cronica do ritonavir sobre a rata prenhe e seus conceptos. Especificos: avaliar a influencia do ritonavir sobre: o peso e mortalidade das matrizes, o numero de implantacoes e de reabsorcoes, o peso dos fetos e das placentas, o aspecto histologico dos figados e rins maternos e fetais, a funcao hepatica e renal das matrizes. Metodos: 40 ratas albinas, EPM1 Wistar, 3 meses de idade, pesando cerca de 200g, aleatoriamente divididas em grupos de 10: controle (C) e experimentais: E,, E2 e E3. Apos teste de prenhez positivo, foi administrado, via gavagem, diariamente, durante toda a prenhez, 1 mL do veiculo (propilenoglicol + etanol) ao grupo C e 1 mL de ritonavir, em diferentes concentracoes, aos grupos E, (20mg/Kg), E2 (60mg/Kg) e E3(180mg/Kg). No 20.°. dia de prenhez, as ratas foram anestesiadas (eter sulfurico) e sacrificadas. Feito puncao ventricular cardiaca, recolhido sangue em tubo seco e dosados aspartato aminotransferase, alanina aminotransferase, ureia e creatinina. Retiradas as placentas e fetos. Observado seu aspecto, tamanho, presenca ou nao de malformacoes, reabsorcoes; avaliado peso das ratas, placentas e fetos; avaliado o indice de mortalidade. Encaminhados fragmentos de figados e rins de matrizes e crias para microscopia de luz. Estatistica feita pelo Teste de Kruskall-Wallis. Para resultados de p < 0,05, aplicou-se o Teste de Comparacoes Multiplas de Dunn. O nivel de rejeicao da hipotese de nulidade fixado em 0,05 (5 por cento). Resultados: todos os grupos ganharam peso em relacao ao dia zero de prenhez; o E1 (dose terapeutica) ganhou mais peso que todos os outros grupos e mais que o esperado pela prenhez; o E2 ganhou proporcionalmente mais peso que o C; o E3 ganhou menos peso que o esperado pela prenhez; o E1 apresentou ganho de peso medio nas placentas; 20 por cento das ratas do grupo E2 e 40 por cento do E3 foram a obito. Nao houve nos fetos: obito, malformacoes; perda de peso ou lesoes histologicas. Nos figados e rins do grupo E3 houve intensa conGestão vascular e picnose; nos figados do grupo E2: conGestão sinusoidal e hepatocitos hipercromaticos; rins do grupo E2: dilatacao de vasos sanguineos peritubulares; reabsorcoes: presentes em E3; 180mg/Kga(au)
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    Ação da associação lopinavir/ritonavir sobre a prenhez da rata albina: aspectos microscópicos e bioquímicos
    (Universidade Federal de São Paulo (UNIFESP), 2005) Cunha, Andre Marquez [UNIFESP]; Kulay Júnior, Luiz [UNIFESP]
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    Administration of lopinavir/ritonavir association during rat pregnancy: maternal and fetal effects
    (I R O G Canada, Inc, 2013-01-01) Kulay Júnior, Luiz [UNIFESP]; Hagemann, Cristiane Cadore de Farias [UNIFESP]; Nakamura, Mary Uchiyama [UNIFESP]; Simoes, Ricardo Santos [UNIFESP]; Carvalho, Adelino Moreira de [UNIFESP]; Oliveira-Filho, Ricardo Martins [UNIFESP]; Espiridião, Silvia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Jose do Rosario Vellano Univ; ABC Med Fdn FUABC
    Purpose: To evaluate the effects of the association of lopinavir and ritonavir administered during the whole period of rat pregnancy. Methods: 62 Wistar rats of the EPM-1 variant weighing about 200 g were randomly divided into five groups: two controls (Ctr1 = stress control, n = 10; and Ctr2 = drug vehicle control, n = 10) and three experimental ones which were treated with an oral solution of lopinavir/ritonavir (Exp1 = 12.8/3.2 mg/kg b.w., n = 14; Exp2 = 38.4/9.6 mg/kg b.w., n = 14; Exp3 = 115.2/28.8 mg/kg b.w., n = 14) from 'day 0' up to the 20th day of pregnancy. Maternal body weight was recorded at the start of the experiment and on the 7th, 14th and 20th day thereafter. At term (20th day), upon laparotomy and hysterotomy, the rats were anesthetized and the amount of implantations, reabsorptions, living fetuses, placentae and intrauterine deaths were recorded. The collected fetuses and placentae were weighed and the concepts were examined under a stereoscope microscope for external malformations. Results: An apparent dose-unrelated lethal effect of the antiviral association on the pregnant rats was observed; notwithstanding, the body weight gain of the surviving rats had no changes, independent of the considered group. It was noted that the quantitative and qualitative intrauterine content of living term rats was indistinguishable from that of the controls. Conclusion: There was some degree of deleterious effects of the administration of the lopinavir/ritonavir association on pregnant rats; such effects eventually led to maternal death. However, neither the surviving rats showed toxicity nor did their concepts present any detectable change which could be related to the drug association.
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    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.
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    Análise morfológica e fisiológica dos fígados e rins de ratas prenhes e seus fetos tratados pela associação zidovudina, lamivudina e ritonavir durante toda a prenhez
    (Federação Brasileira das Sociedades de Ginecologia e Obstetrícia, 2010-11-01) Wagner, Adriana; Carvalho, Adelino Moreira de; Nakamura, Mary Uchiyama [UNIFESP]; Simões, Ricardo Santos; Fontes, Tereza Maria Pereira [UNIFESP]; Espiridião, Silvia [UNIFESP]; Kulay Júnior, Luiz [UNIFESP]; Universidade José do Rosário Vellano Departamento de Obstetrícia e Ginecologia; Universidade José do Rosário Vellano Serviço de Clínica Médica; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Universidade Gama Filho Departamento de Ginecologia e Obstetrícia; ABC Faculdade de Medicina Departamento de Obstetrícia e Pediatria
    PURPOSE: to evaluate the effect of administration of three different doses of the zidovudine/lamivudine/ritonavir combination on the liver and kidneys of pregnant rats and their concepts from a morphological and physiological standpoint. METHODS: 40 pregnant EPM-1 Wistar rats were randomly divided into 4 groups: 1 control (Ctrl: drug vehicle control, n=10) and 3 experimental groups: Exp1x, Exp3x and Exp9x. An oral solution of the zidovudine/lamivudine/ritonavir combination was administered to the experimental groups from the day 0 to day 20 of pregnancy: Exp1x=10/5/20 mg/kg; Exp3x=30/15/60 mg/kg; Exp9x=90/45/180 mg/kg. On the 20th pregnancy day the rats were anesthetized and blood was taken directly from the ventricular chambers for further biochemical determinations: aspartate-(AST) and alanine-(ALT) aminotransferases (Calorimetric method), urea nitrogen (BUN) by an enzymatic-kinetic method, and creatinine by a kinetic-calorimetric method. Maternal and fetal liver and kidney samples were taken, fixed in 10% formaldehyde and processed histologically for paraffin embedding. Five µm-thick fragments of maternal and fetal livers and kidneys were stained with hematoxilyn-eosin, being analyzed by light microscopy. To interpret the results, the well-known pattern of normality for livers and kidneys was considered on the basis of the following structures: hepatocytes, portal structure, hepatic veins, renal corpuscles, renal tubules and loop of Henle. Regarding the fetal livers, we also considered the erythrocytes in their different stages of development as well as the megacariocytes. If there was a change in the established staining pattern for liver and kidney structures, changes in nuclear morphology, rupture of some cytoplasmic organelles, and presence of vascular congestion, this was considered to be due to the drug doses. Results were submitted to analysis of variance (ANOVA) and to the Tukey-Kramer multiple comparisons test (p<0.05). RESULTS: no morphological changes were observed in the maternal livers of the Ctrl, Exp1x and Exp3x groups. In the maternal liver of the Exp9x group, hepatocytes showed signs of atrophy and apoptosis (eosinophilic cytoplasm and pycnotic nuclei) and marked sinusoid capillary vasodilation (congestion) was observed. The maternal kidneys of the Ctrl and Exp1x groups were normal, with renal corpuscles, convoluted tubules and typical loops of Henle. In contrast, the Exp3x and Exp9x groups showed vascular congestion and small glomeruli rich in cells containing hyperchromatic nuclei which were more intense in Exp9x. Regarding the fetal organs, no morphological or physiological changes were observed. A significant increase of AST (305.70±55.80, p<0.05) and creatinine (0.50±0.09, p<0.05) was observed in group Exp9x. CONCLUSIONS: our results show that the administration of the zidovudine, lamivudine and ritonavir combination to pregnant rats at high doses caused morphological and physiological changes in the maternal liver and kidneys. On the other hand, there were no changes in fetal organs.
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    Antiretroviral drugs saquinavir and ritonavir reduce inhibitory concentration values of itraconazole against Histoplasma capsulatum strains in vitro
    (Elsevier Brazil, 2016) Nogueira Brilhante, Raimunda Samia; Caetano, Erica Pacheco; Riello, Giovanna Barbosa; de Melo Guedes, Glaucia Morgana; Collares Maia Castelo-Branco, Debora de Souza; Bezerra Fechine, Maria Auxiliadora; de Oliveira, Jonathas Sales; de Camargo, Zoilo Pires [UNIFESP]; Lima de Mesquita, Jaco Ricarte; Monteiro, Andre Jalles; Cordeiro, Rossana de Aguiar; Gadelha Rocha, Marcos Fabio; Costa Sidrim, Jose Julio
    Recent studies have shown that some drugs that are not routinely used to treat fungal infections have antifungal activity, such as protease inhibitor antiretroviral drugs. This study investigated the in vitro susceptibility of Histoplasma capsulatum var. capsulatum to saquinavir and ritonavir, and its combination with the antifungal itraconazole. The susceptibility assay was performed according to Clinical and Laboratory Standards Institute guidelines. All strains were inhibited by the protease inhibitor antiretroviral drugs. Saquinavir showed minimum inhibitory concentrations ranging from 0.125 to 1 mu g mL(-1) for both phases, and ritonavir presented minimum inhibitory concentrations ranging from 0.0312 to 4 mu g mL(-1) and from 0.0625 to 1 mu g mL(-1) for filamentous and yeast phase, respectively. Concerning the anti fungal itraconazole, the minimum inhibitory concentration values ranged from 0.0019 to 0.125 mu g mL(-1) and from 0.0039 to 0.0312 mu g mL(-1) for the filamentous and yeast phase, respectively. The combination of saquinavir or ritonavir with itraconazole was synergistic against H. capsulatum, with a significant reduction in the minimum inhibitory concentrations of both drugs against the strains (p < 0.05). These data show an important in vitro synergy between protease inhibitors and itraconazole against the fungus H. capsulatum. (C) 2016 Published by Elsevier Editora Ltda.
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    Chronic action of association of zidovudine, lamivudine and ritonavir on pregnant rats. A biologic assay
    (I R O G Canada, Inc, 2011-01-01) Wagner, A.; Nakamura, Mary Uchiyama [UNIFESP]; Simoes, Ricardo Santos [UNIFESP]; Oliveira-Filho, Ricardo Martins [UNIFESP]; Fontes, Tereza Maria Pereira [UNIFESP]; Carvalho, Luisa Patricia Fogarolli de [UNIFESP]; Espiridião, Silvia [UNIFESP]; Kulay Júnior, Luiz [UNIFESP]; Univ Jose do Rosario Vellano; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Purpose: To evaluate at term the effects of a highly active antiretroviral (HAAR) drug association administered during the entire period of rat pregnancy. Methods: Three groups (n = 10 each) of adult pregnant rats were treated with an oral solution of HAAR (Exp 1 = 10/5/20 mg/kg b.w.; Exp 2 = 30/15/60 mg/kg b.w.; Exp 3 = 90/45/180 mg/kg b.w.) from day 0 up to the 20th day of pregnancy. A fourth group served as a control. At term (20th day) the rats were killed under deep anesthesia and the number of implantations, resorptions, living fetuses, placentae and intrauterine deaths were recorded. Results: The highest HAAR doses caused lower maternal weight gain, lower litter weights, and lower placental weights compared to the control group. Conclusions: HAAR during the entire period of rat pregnancy can reduce maternal body weight gain and lower term placental weight.
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    Efeito crônico da associação zidovudina e lopinavir/ritonavir sobre a prenhez de ratas albinas: manuscrito ensaio biológico, aspectos histológicos e bioquímicos
    (Universidade Federal de São Paulo (UNIFESP), 2011) Carvalho, Luisa Patricia Fogarolli de [UNIFESP]; Nakamura, Mary Uchiyama [UNIFESP]
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    Effects of combined zidovudine/lopinavir/ritonavir therapy during rat pregnancy: morphological aspects
    (I R O G Canada, Inc, 2013-01-01) Carvalho, Luisa Patricia Fogarolli de [UNIFESP]; Simoes, Ricardo Santos [UNIFESP]; Wagner, A.; Tavella, J. S.; Oliveira-Filho, Ricardo Martins [UNIFESP]; Kulay Júnior, Luiz [UNIFESP]; Nakamura, Mary Uchiyama [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Jose do Rosario Velano; Universidade de São Paulo (USP)
    Purpose: To evaluate the morphological aspects in rats subjected to an association of the antiretroviral drugs zidovudine/lopinavir/ritonavir in different doses administered throughout the gestational period. Materials and Methods: Forty pregnant rats were randomly allocated into four groups: control (Ctrl) and experimental (Exp1, Exp2, and Exp3), which received zidovudine/lopinavir/ritonavir in the doses of 10/13.3/3.3, 30/39.9/9.9, and 90/119.7/29.7 mg/kg per day from the first to the 20th day of pregnancy, respectively. At term, the animals were euthanized and maternal and fetal organ samples were removed for morphological analysis. Results: No major changes were identified in the group treated with the lowest dosing compared with the control. In group Exp2, the authors found hepatocytes with eosinophilic cytoplasm, pyknotic nuclei, and vasodilation. The proximal convoluted tubules of maternal kidneys showed eosinophilic areas and hyperchromatic nuclei, as well as signs of vasodilation. In the group treated with the highest dose (Exp3); the morphological changes in the maternal kidneys and livers were similar and more pronounced than those found in Exp2. The maternal pancreas of groups Exp2 and Exp3 evidenced moderate and progressive signs of tissue damage. The morphological features of all fetal livers, kidneys, and pancreases were normal. Conclusion: High doses of zidovudine/lopinavir/ritonavir association during the entire rat pregnancy period can cause definite morphological changes in maternal liver, kidneys, and pancreas. On the other hand, the corresponding fetal organs were not affected.