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An. acad. bras. ciênc ; 90(1): 73-84, Mar. 2018. tab
Artigo em Inglês | LILACS | ID: biblio-886885


ABSTRACT The adhesion ability of bacteria to abiotic surfaces has important implications in food industries, because these organisms can survive for long periods through the biofilm formation. They can be transferred from one place to another in the industry causing contamination of the food processing environment. In this study, the antibacterial and antibiofilm activities of the antimicrobial peptide P34, characterized as a bacteriocin-like substance (BLS P34) were tested against planktonic and sessile cells of Staphylococcus aureus and Enterococcus faecalis isolated from foods. The BLS P34 showed inhibitory effect against all planktonic cells of E. faecalis. The inhibition of biofilm formation and the eradication of pre-formed biofilm were evaluated with the crystal violet assay and with the reduction of 3-bromide [4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium. The BLS P34 promoted a reduction of percentage of adhered microbial cells on the surface, not being able to perform the complete elimination of biofilm formation. The metabolic activity of S. aureus biofilms decreased considerably between 41-95%. However, E. faecalis cells showed up metabolically stimulated. The BLS P34 has the potential antibiofilm for the species S. aureus. Studies suggest more detailed approaches to a better understanding of the interactions between the antimicrobial and bacterial cells within the biofilm structure.

Animais , Oligopeptídeos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Bacteriocinas/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Bacillus/isolamento & purificação , Bacillus/metabolismo , Bacteriocinas/isolamento & purificação , Aderência Bacteriana/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Análise de Variância
Clinics ; 72(6): 378-385, June 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-840088


OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.

Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Antivirais/administração & dosagem , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Inibidores de Proteases/administração & dosagem , Brasil , Estudos Transversais , Genótipo , Hepatite C Crônica/virologia , Interferon-alfa/administração & dosagem , Oligopeptídeos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Prolina/administração & dosagem , Prolina/análogos & derivados , Proteínas Recombinantes/administração & dosagem , RNA Viral/genética , Resultado do Tratamento
Braz. j. med. biol. res ; 49(3): e5043, Mar. 2016. graf
Artigo em Inglês | LILACS | ID: lil-771931


Ovarian cancer is one of the most common causes of death from gynecologic tumors and is an important public health issue. Ghrelin is a recently discovered bioactive peptide that acts as a natural endogenous ligand of the growth hormone secretagogue receptor (GHSR). Several studies have identified the protective effects of ghrelin on the mammalian reproductive system. However, little research has been done on the effects of ghrelin on ovarian cancer cells, and the underlying mechanisms of these effects. We sought to understand the potential involvement of mitogen-activated protein kinases (MAPKs) in ghrelin-mediated inhibition of growth of the ovarian line HO-8910. We applied different concentrations of ghrelin and an inhibitor of the ghrelin receptor (D-Lys3-GHRP-6) to HO-8910 cells and observed the growth rate of cells and changes in phosphorylation of the MAPKs ERK1/2, JNK and p38. We discovered that ghrelin-induced apoptosis of HO-8910 cells was though phosphorylated ERK1/2, and that this phosphorylation (as well as p90rsk phosphorylation) was mediated by the GHSR. The ERK1/2 pathway is known to play an essential part in the ghrelin-mediated apoptosis of HO-8910 cells. Hence, our study suggests that ghrelin inhibits the growth of HO-8910 cells primarily through the GHSR/ERK pathway.

Humanos , Feminino , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica/genética , Grelina/farmacologia , Sistema de Sinalização das MAP Quinases/fisiologia , Neoplasias Ovarianas/genética , Apoptose/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Oligopeptídeos/metabolismo , Neoplasias Ovarianas/metabolismo , Fosforilação/efeitos dos fármacos , Receptores de Grelina/antagonistas & inibidores , Receptores de Grelina/metabolismo , Células Tumorais Cultivadas
Braz. j. med. biol. res ; 49(7): e5300, 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-785056


The aim of this study was to determine risk factors for adverse events (AE)-related treatment discontinuation and severe anemia among patients with chronic hepatitis C virus (HCV) genotype 1 infection, treated with first-generation protease inhibitor (PI)-based therapy. We included all patients who initiated treatment with PI-based therapy at a Brazilian university hospital between November 2013 and December 2014. We prospectively collected data from medical records using standardized questionnaires and used Epi Info 6.0 for analysis. Severe anemia was defined as hemoglobin ≤8.5 mg/dL. We included 203 patients: 132 treated with telaprevir (TVR) and 71 treated with boceprevir (BOC). AE-related treatment discontinuation rate was 19.2% and anemia was the main reason (38.5%). Risk factors for treatment discontinuation were higher comorbidity index (OR=1.85, CI=1.05-3.25) for BOC, and higher bilirubin count (OR=1.02, CI=1.01-1.04) and lower BMI (OR=0.98, CI=0.96-0.99) for TVR. Severe anemia occurred in 35 (17.2%) patients. Risk factors for this outcome were lower estimated glomerular filtration rate (eGFR; OR=0.95, CI=0.91-0.98) for patients treated with TVR, and higher comorbidity index (OR=2.21, CI=1.04-4.67) and ribavirin dosage (OR=0.84, CI=0.72-0.99) for those treated with BOC. Fifty-five (57.3%) patients treated with TVR and 15 (27.3%) patients treated with BOC achieved sustained virological response (SVR). Among patients who received TVR and interrupted treatment due to AE (n=19), only 26.3% (n=5) achieved SVR (P=0.003). Higher number of comorbidities, lower eGFR and advanced liver disease are associated with severe anemia and early treatment cessation, which may compromise SVR achievement.

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Anemia/etiologia , Hepatite C Crônica/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Prolina/análogos & derivados , Inibidores de Proteases/administração & dosagem , Antivirais/administração & dosagem , Taxa de Filtração Glomerular , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Interferon-alfa/administração & dosagem , Modelos Logísticos , Oligopeptídeos/efeitos adversos , Polietilenoglicóis/administração & dosagem , Prolina/administração & dosagem , Prolina/efeitos adversos , Estudos Prospectivos , Inibidores de Proteases/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Ribavirina/administração & dosagem , Fatores de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Resposta Viral Sustentada , Fatores de Tempo , Falha de Tratamento
Rev. Esc. Enferm. USP ; 49(6): 937-943, Dec. 2015. graf
Artigo em Português | LILACS | ID: lil-767809


Abstract OBJECTIVE Comparing Health-Related Quality of Life (HRQoL) scores in patients with chronic hepatitis C undergoing double and triple antiviral therapy and analyzing possible factors related to HRQoL. METHOD HRQoL was assessed using the Short Form 36 and Chronic Liver Disease Questionnaire, which were applied at baseline and at weeks 4, 12 and 16 of treatment to 32 patients divided into two groups: double therapy with pegylated interferon (IFN-PEG) and ribavirin, and triple therapy with PEG-IFN, ribavirin and telaprevir. RESULTS The reduction of HRQoL was greater in patients receiving triple therapy compared to those treated with two drugs, the most critical time is at 12 weeks in both groups. After removal of telaprevir, the triple therapy group significantly improved their HRQoL scores. Anxiety and depression before treatment, employment status and race are significantly related to diminished HRQoL. CONCLUSION Patients undergoing double and triple therapy have diminished HRQoL indexes, but the addition of telaprevir chooses a more significant decrease.

Resumen OBJETIVO Comparar los puntajes de Calidad de Vida Relacionada con la Salud (CVRS) en pacientes con hepatitis C crónica sometidos a la terapia antiviral doble y triple y analizar los posibles factores relacionados con la CVRS. MÉTODO La CVRS fue evaluada utilizando el Short Form 36 y elChronic Liver Disease Questionnaire , que fueron aplicados antes y en las semanas 4, 12 y 16 de tratamiento, en 32 pacientes divididos en 2 grupos: terapia doble con interferón pegilado (IFN-PEG) y ribavirina, y triple con IFN-PEG, ribavirina y telaprevir. RESULTADOS La reducción de la CVRS fue mayor en pacientes en terapia triple cuando comparados con los tratados con dos drogas, siendo el momento más crítico la 12ª semana en ambos grupos. Después de la retirada del telaprevir, el grupo de terapia triple mejoró de modo significativo los puntajes de CVRS. Ansiedad y depresión en el pre tratamiento, situación de empleo y raza se mostraron relacionados con la reducción de la CVRS. CONCLUSIÓN Pacientes sometidos a la terapia doble y triple presentan reducción de los índices de CVRS, pero la adición del telaprevir les proporciona una caída más expresiva.

Resumo OBJETIVO Comparar os escores de Qualidade de Vida Relacionada à Saúde (QVRS) em pacientes com hepatite crônica C submetidos à terapia antiviral dupla e tripla e analisar os possíveis fatores relacionados à QVRS. MÉTODO A QVRS foi avaliada utilizando o Short Form 36 e oChronic Liver Disease Questionnaire , que foram aplicados antes e nas semanas 4, 12 e 16 de tratamento, em 32 pacientes divididos em 2 grupos: terapia dupla com interferon peguilado (IFN-PEG) e ribavirina e tripla com IFN-PEG, ribavirina e telaprevir. RESULTADOS A redução da QVRS foi maior em pacientes em terapia tripla quando comparados àqueles tratados com duas drogas, sendo o momento mais crítico a 12ª semana em ambos os grupos. Após a retirada do telaprevir, o grupo terapia tripla melhorou de modo significativo os escores de QVRS. Ansiedade e depressão no pré-tratamento, status empregatício e raça se mostraram relacionados à redução da QVRS. CONCLUSÃO Pacientes submetidos à terapia dupla e tripla apresentam redução dos índices de QVRS, mas a adição do telaprevir confere uma queda mais expressiva.

Feminino , Humanos , Masculino , Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Oligopeptídeos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Qualidade de Vida , Ribavirina/administração & dosagem , Quimioterapia Combinada , Proteínas Recombinantes/administração & dosagem
Arq. gastroenterol ; 52(1): 14-17, Jan-Mar/2015. graf
Artigo em Inglês | LILACS | ID: lil-746485


Background Chronic hepatitis C has great impact on world’s health. Current therapy for genotype 1 hepatitis C virus includes protease inhibitors boceprevir and telaprevir, associated to standard therapy - peginterferon alfa + ribavirin. There are no published data in Brazil on the results of this new therapy, and it is interesting an evaluation of what was accomplished up to this moment. Objectives To evaluate virologic response to triple therapy, as well as the safety profile and tolerability. Method This study is a clinical series of patients receiving triple therapy for C hepatitis in a single center of a Public Health System of South Brasil. Out of the 121 patients that initiated the triple therapy, the first patients that finished the treatment and evaluated the sustained virological response (24 weeks after the end of treatment) were included. Results Twenty four genotype 1 chronic hepatitis C monoinfected patients were included. Nineteen (79.2%) patients had been previously treated. Thirteen (54.2%) patients were cirrhotic. Nineteen (79.2%) patients completed the planned therapy. By the end of the treatment, 14 (58.3%) out of 24 patients had undetectable viral load. Sustained virologic response occurred in 12 (50.0%) out of 24 patients, 07 (58.3%) in telaprevir group and 05 (41.7%) in boceprevir group. Out of 24 patients under triple therapy, 58% (n=14) presented anemia. Conclusions In conclusion, despite the small number of patients treated with triple therapy evaluated in the current study, it possibly reflects the population under this therapy in real-life. .

Contexto A hepatite crônica pelo vírus C tem grande impacto na saúde mundial. A terapia atual do genótipo 1 inclui os inibidores de protease (IP) boceprevir e telaprevir, associados à terapia padrão - alfapeginterferona + ribavirina (PR). No Brasil ainda não há estudos publicados sobre os resultados dessa nova terapia, sendo de interesse uma avaliação do que foi realizado até o momento. Objetivos Avaliar a resposta virológica ao tratamento triplo, bem como o perfil de segurança e tolerabilidade. Métodos O estudo consta de série de casos dos pacientes em uso de terapia tripla para o tratamento da hepatite C em um polo de tratamento da Secretaria Estadual da Saúde do Estado do Rio Grande do Sul, Brasil. Dentre os 121 pacientes que estão em uso de terapia tripla (PR e IP) foram apresentados os dados referentes aos primeiros que finalizaram o tratamento e realizaram avaliação da resposta virológica sustentada na semana 24 pós-tratamento. Resultados Foram incluídos 24 pacientes monoinfectados por hepatite C crônica genótipo 1. Dezenove (79%) pacientes eram previamente experimentados. Treze (54,2%) pacientes apresentavam cirrose. Dezenove (79,2%) pacientes completaram o tratamento planejado. Ao final do tratamento, 14 (58,3%) dos 24 pacientes apresentaram carga viral indetectável. Resposta virológica sustentada ocorreu em 12 (50%) dos 24 pacientes, sendo 07 (58,3%) no grupo telaprevir e 05 (41,7%) no grupo boceprevir. Dos 24 pacientes submetidos à terapia tripla, 58% (n=14) apresentaram anemia. Conclusões Embora o presente estudo tenha avaliado um pequeno número de casos, possivelmente reflete a população submetida à terapia tripla na vida real, despida das restrições dos estudos de registro. .

Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Antivirais/efeitos adversos , Brasil , Quimioterapia Combinada/métodos , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Programas Nacionais de Saúde , Oligopeptídeos/efeitos adversos , Oligopeptídeos/uso terapêutico , Saúde Pública , Estudos Retrospectivos , Ribavirina/efeitos adversos , Ribavirina/uso terapêutico , Carga Viral
Braz. dent. j ; 25(6): 502-507, Nov-Dec/2014. tab
Artigo em Inglês | LILACS | ID: lil-732258


This aim of this study was to assess the ability of manual or rotary instrumentation associated with photodynamic therapy (PDT) to reduce Enterococcus faecalis using three combinations of light/photosensitizers: toluidine blue O/laser, fuchsin/halogen light and fuchsin/LED. Twenty deciduous molars were selected and contaminated with Enterococcus faecalis (McFarland 0.5 scale). Working length determination was performed by visual method. The teeth were randomly divided into two groups: G1 (n=10): manual instrumentation (Kerr-type files) and G2 (n=10): rotary instrumentation (ProTaper system). The bacteria were collected three times using sterile paper cones compatible with the anatomic diameter of the root canal for 30 s before and after instrumentation and after PDT. The samples were diluted in peptone water, seeded on blood agar plates and incubated in an oven at 37 °C for colony-forming units counting. The decrease of E. faecalis counts after instrumentation and after PDT was compared using the Wilcoxon test, t-test and Kruskal Wallis test. A significant reduction of E. faecalis occurred after manual and rotary instrumentation and after PDT using the three combinations of light/photosensitizer (p<0.05). It may be concluded that both rotary and manual instrumentation reduced E. faecalis. Fuchsin with halogen light or LED irradiation and toluidine blue O with laser irradiation can be used to reduce E. faecalis in root canals of primary molars. PDT can be used as an adjuvant to conventional endodontic treatment.

O objetivo do presente estudo foi avaliar a redução de Enterococcus faecalis após instrumentação manual ou rotatória associada à terapia fotodinâmica (PDT) utilizando 3 combinações luz/fotossensibilizante: azul de toluidina O/laser, fucsina/luz halógena e fucsina/LED. Foram selecionados 20 molares decíduos que foram contaminados com Enterococcus faecalis (escala 0,5 de McFarland). A odontometria foi feita através do método visual. Os dentes foram divididos aleatoriamente em dois grupos: G1 (n=10): instrumentação manual (limas tipo Kerr) e G2 (n=10): instrumentação rotatória (sistema ProTaper). Foram realizadas coletas com cone de papel estéril compatível com o diâmetro anatômico do canal durante 30 s antes e após a instrumentação e a PDT. As amostras foram diluídas em água peptonada, semeadas em placas de agar-sangue e incubadas em estufa a 37 °C para contagem das unidades formadoras de colônias. As comparações antes da redução de E. faecalis após a instrumentação e após a realização da PDT foram realizadas pelo teste de Wilcoxon, teste t e Kruskal Wallis. Houve redução significante de E. faecalis após a instrumentação manual ou rotatória e após realização da PDT com as três combinações de luz/fotossensibilizante (p<0,05). Pode-se concluir que a instrumentação rotatória e manual acarretou a redução de E. faecalis. A fucsina irradiada com luz halógena ou led e o azul de toluidina irradiado com laser podem ser utilizados para redução de E. faecalis do sistema de canais radiculares de molares decíduos. A terapia fotodinâmica pode ser utilizada como coadjuvante ao tratamento endodôntico convencional.

Animais , Camundongos , Fosfatase Ácida/biossíntese , Catepsina B/biossíntese , Leucina/análogos & derivados , Leupeptinas/farmacologia , Melanoma Experimental/enzimologia , Oligopeptídeos/farmacologia , Pepstatinas/farmacologia , Peptídeo Hidrolases/biossíntese , Inibidores de Proteases/farmacologia , Indução Enzimática , Leucina/farmacologia , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/enzimologia , Células Tumorais Cultivadas
Rev. bras. enferm ; 67(6): 920-927, Nov-Dec/2014.
Artigo em Português | LILACS, BDENF - Enfermagem | ID: lil-732823


Este estudo objetivou compreender as práticas de cuidado dos profissionais de saúde que assistem os idosos Kaingang. Estudo qualitativo, apoiado na etnografia, realizado com dez profissionais à que atuam na atenção primária saúde da Terra Indígena Faxinal, Paraná, Brasil. Os dados foram coletados no período de novembro de 2010 a fevereiro de 2012 por meio da observação participante e entrevistas, e, analisados à luz da Teoria Transcultural do Cuidado. Identificaram-se como práticas de cuidado a medicação e imunização, bem como, cuidados da medicina tradicional. Para realização destes cuidados, os profissionais dispunham de estratégias que proporcionavam manutenção dos idosos na assistência. Conclui-se que valores culturais e científicos necessitam integrar a assistência para melhoria da saúde dos idosos indígenas.

This research aims to understand the care practices of health professionals who assist the elderly Kaingang. It is a qualitative study, supported in ethnography, conducted by ten professionals working in primary health care in the indigenous land of Faxinal, Paraná, Brazil. The data was collected from November 2010 to February 2012 by participant observation and interviews, and analyzed based on the Transcultural Care Theory. Was identified the preoccupation of the carers practices with the medication and immunization, as well as traditional medical care. To achieve these, care professionals had strategies that implemented maintenance of older people in care. We conclude that cultural values and integrate scientific need assistance to improve the health of elderly indigenous.

Este estudio tuvo como objetivo entender las prácticas de cuidado de los profesionales de la salud que asisten a los ancianos Kaingang. Estudio cualitativo, apoyado en la etnografía, llevado a cabo con diez profesionales que trabajan en la atención primaria de la salud de la tierra indígena de Faxinal, Paraná, Brasil. Los datos fueron recogidos a partir de noviembre 2010 a febrero 2012 a través de la observación participante y las entrevistas, y analizado con base en la Teoría del Cuidado Transcultural. Se identificaron las prácticas de atención médica y imunizacion,el cuidado de la medicina, así tradicional. Para lograrlo, los profesionales tenían estrategias que proporcionaban el mantenimiento de las personas mayores en su atención. Se concluye que los valores culturales y científicos necesitan ayuda para mejorar la salud de los ancianos indígenas.

Animais , Ratos , Fígado/enzimologia , Lisossomos/enzimologia , Fosfolipases A/metabolismo , Fosfolipases/metabolismo , Inibidores de Proteases/farmacologia , Células Cultivadas , Quimotripsina/antagonistas & inibidores , Inibidores de Cisteína Proteinase/farmacologia , Leucina/análogos & derivados , Leucina/farmacologia , Leupeptinas/farmacologia , Oligopeptídeos/farmacologia , Pepstatinas/farmacologia , Fosfolipases A1 , Fatores de Tempo
Arq. bras. endocrinol. metab ; 58(3): 288-291, abr. 2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-709354


Objective : The present study investigated the effects of different dosages of a GHS-R antagonist [D-Lys3] on some serum hormonal (cortisol, T3 and T4) and biochemical parameters in a rat.Materials and methods : Thirty-six 60-day-old male rats were assigned to four treatments. [D-Lys3]-GHRP-6 solutions were infused via intraperitoneal injections. Blood was collected and analyzed.Results : The large dosages of a GHS-R antagonist (200 ng/kg BW) caused increases in cortisol, whereas no significant changes occurred when low dosages were injected. There were no significant changes in T3 and T4 following the administration of the GHS-R antagonist, but a considerable increase was observed in blood glucose levels of the groups (G50, G100, and G200 ng/kg BW). There was a significant increase in total protein when the greatest dose was administrated (G200 ng/kg BW). However, total cholesterol, triglycerides, and albumin showed no significant changes.Conclusions : Exogenous GHS-R antagonist can cause an increase in glucose and moderate increases in cortisol and total protein, yet it has no significant effect on T3 and T4 levels or on the concentrations of serum lipids. The effect of GHS-R antagonist is not completely adverse to the effects of ghrelin. Further molecular studies are necessary to identify the physiological effects of the peptidic GHS-R antagonist. Arq Bras Endocrinol Metab. 2014;58(3):288-91.

Objetivo : O presente estudo investigou os efeitos de diferentes doses do antagonista do GHS-R [D-Lys3] sobre alguns parâmetros hormonais (cortisol, T3 e T4) e bioquímicos em ratos.Materiais e métodos : Trinta e seis ratos machos com 60 dias de idade foram alocados para quatro tratamentos. Soluções de [D-Lys3]-GHRP-6 foram administradas por meio de injeções intraperitoneais e foram coletadas e analisadas amostras.Resultados : Doses altas de antagonista de GHS-R (200 ng/kg PC) levaram a aumento do cortisol, enquanto não houve diferença significativa quando foram injetadas doses baixas. Não houve alterações significativas em T3 e T4 depois da administração do antagonista do GHS-R, mas foi observado aumento considerável nos níveis de glicose sanguínea dos grupos (G50, G100 e G200 ng/kg PC). Houve aumento significativo na proteína total quando foi administrada a maior dose (G200 ng/kg PC), entretanto, não foram observadas alterações no colesterol total, nos triglicérides e na albumina.Conclusões : O antagonista do GHS-R exógeno pode causar aumento da glicose e aumento moderado do cortisol e proteína total, embora não haja efeitos significativos nos níveis de T3 e T4 ou na concentração de lipídios séricos. O efeito do antagonista de GHS-R não é completamente adverso aos efeitos da grelina. Devem ser feitos outros estudos moleculares para se identificar os efeitos fisiológicos do peptídeo antagonista do GHS-R. Arq Bras Endocrinol Metab. 2014;58(3):288-91.

Animais , Masculino , Hidrocortisona/sangue , Oligopeptídeos/administração & dosagem , Receptores de Grelina/antagonistas & inibidores , Tiroxina/sangue , Tri-Iodotironina/sangue , Glicemia/análise , HDL-Colesterol/sangue , Injeções Intraperitoneais , Distribuição Aleatória , Ratos Wistar , Albumina Sérica/análise , Triglicerídeos/sangue
J. bras. med ; 102(1)jan.-fev. 2014. graf, ilus, tab
Artigo em Português | LILACS | ID: lil-712210


A infecção pelo vírus da hepatite C (HCV) é importante causa de hepatite crônica, cirrose e carcinoma hepatocelular, sendo razão para a indicação de transplante hepático no mundo industrializado (Sherlock, 1995). Várias estratégias de tratamento da hepatite C foram empregadas ao longo dos últimos anos. O interferon peguilado em monoterapia ou combinado à ribavirina tornou-se tratamento padrão. Em 2011, foram introduzidos os inibidores de protease. Em dezembro de 2013, uma nova geração de drogas tem conferido resultados auspiciosos à terapia.

The hepatitis C virus infection (HCV) is an important cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, which leads indication for liver transplantation in the industrialized world (Sherlock, 1995). Many treatment strategies for hepatitis C were used for the latest years. Pegylated interferon monotherapy or combined to the ribavirin became a standard treatment. In 2011, protease inhibitors were introduced. In December 2013, a new generation drugs have been presented auspicious results to the therapy.

Humanos , Masculino , Feminino , Hepacivirus , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Inibidores de Proteases/uso terapêutico , Antivirais/uso terapêutico , Quimioterapia Combinada , Inibidores de Proteases/administração & dosagem , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Oligopeptídeos/administração & dosagem , Oligopeptídeos/uso terapêutico , Prolina/análogos & derivados , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico
Braz. j. infect. dis ; 17(6): 657-660, Nov.-Dec. 2013. tab
Artigo em Inglês | LILACS | ID: lil-696966


OBJECTIVE: To evaluate the factors associated with plasma concentrations of atazanavir (ATV) in a cohort of well-controlled HIV infected subjects (undetectable viremia). Design: Cross-sectional study where 69 subjects were consecutively enrolled between April and November, 2011. METHODS: Patients had to be on atazanavir for at least six months, undetectable viral load for a period equal to or longer than 12 months, T CD4+ lymphocyte count higher than 200 cells/mm³, and aged between 18 years and 70 years old. Exclusion criteria were pregnancy, any neurologic disease, active opportunistic disease, hepatitis or cancer. Atazanavir plasma levels were measured by ultra-performance liquid chromatography. RESULTS AND DISCUSSION: Overall, 54 patients (mean age of 47 years and 50% women) were included in the analysis. Those without ritonavir (unboosted atazanavir) had statistically lower plasma concentrations than those with ritonavir boosted atazanavir (p = 0.001) and total and indirect bilirubin were statistically associated with plasma concentration of atazanavir (r = 0.32 and r = 0.33 respectively; p < 0.05 in both cases). no statistical association was found among gender, ethnicity, age, weight, body mass index (BMI), lipid profile, and the plasma concentration of atazanavir. CONCLUSION: in summary, as expected, concomitant ritonavir use was the only factor associated with atazanavir plasma levels. prospective studies with a larger sample size might help to observe an association of atazanavir concentrations to other characteristics such as body weight, since the p-value showed to be close to significance (p = 0.068).

Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Fármacos Anti-HIV/sangue , Infecções por HIV/sangue , Oligopeptídeos/sangue , Piridinas/sangue , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/uso terapêutico , Cromatografia Líquida , Estudos de Coortes , Estudos Transversais , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Oligopeptídeos/farmacocinética , Oligopeptídeos/uso terapêutico , Estudos Prospectivos , Piridinas/farmacocinética , Piridinas/uso terapêutico , Carga Viral
Braz. j. infect. dis ; 17(2): 194-204, Mar.-Apr. 2013. ilus, tab
Artigo em Inglês | LILACS | ID: lil-673199


The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3) and 50% (geno 3 type 1) were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

Humanos , Antivirais/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Oligopeptídeos/efeitos adversos , Prolina/análogos & derivados , Inibidores de Proteases/efeitos adversos , Interações Medicamentosas , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Prolina/efeitos adversos
Clinics ; 67(2): 163-170, 2012. ilus, graf, tab
Artigo em Inglês | LILACS | ID: lil-614641


OBJECTIVES: Scintigraphy is generally not the first choice treatment for prostate cancer, although successful studies using bombesin analog radiopeptides have been performed. Recently, a novel peptide obtained using a phage display library demonstrated an affinity for prostate tumor cells. The aim of this study was to compare the use of a bombesin analog to that of a phage display library peptide (DUP-1) radiolabeled with technetium-99m for the treatment of prostate carcinoma. The peptides were first conjugated to S-acetyl-MAG3 with a 6-carbon spacer, namely aminohexanoic acid. METHODS: The technetium-99m labeling required a sodium tartrate buffer. Radiochemical evaluation was performed using ITLC and was confirmed by high-performance liquid chromatography. The coefficient partition was determined, and in vitro studies were performed using human prostate tumor cells. Biodistribution was evaluated in healthy animals at various time points and also in mice bearing tumors. RESULTS: The radiochemical purity of both radiotracers was greater than 95 percent. The DUP-1 tracer was more hydrophilic (log P = -2.41) than the bombesin tracer (log P = -0.39). The biodistribution evaluation confirmed this hydrophilicity by revealing the greater kidney uptake of DUP-1. The bombesin concentration in the pancreas was greater than that of DUP-1 due to specific gastrin-releasing peptide receptors. Bombesin internalization occurred for 78.32 percent of the total binding in tumor cells. The DUP-1 tracer showed very low binding to tumor cells during the in vitro evaluation, although tumor uptake for both tracers was similar. The tumors were primarily blocked by DUP1 and the bombesin radiotracer primarily targeted the pancreas. CONCLUSION: Further studies with the radiolabeled DUP-1 peptide are recommended. With further structural changes, this molecule could become an efficient alternative tracer for prostate tumor diagnosis.

Animais , Humanos , Masculino , Camundongos , Aminocaproatos/química , Bombesina , Oligopeptídeos/química , Peptídeos , Neoplasias da Próstata , Compostos Radiofarmacêuticos , Tecnécio , Aminocaproatos/farmacocinética , Bombesina/análogos & derivados , Meios de Cultura , Modelos Animais de Doenças , Marcação por Isótopo/métodos , Camundongos Nus , Oligopeptídeos/farmacocinética , Pâncreas , Distribuição Aleatória , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Receptores da Bombesina/análise , Receptores da Bombesina/metabolismo , Biomarcadores Tumorais/metabolismo
Clinics ; 67(3): 265-272, 2012. graf, tab
Artigo em Inglês | LILACS | ID: lil-623102


OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormonereleasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/litmice, which represent a model of GH deficiency arising frommutated growth hormone-releasing hormonereceptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice. RESULTS: After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (p<0.001). In comparison, an intermediate growth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions. CONCLUSIONS: Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a.

Animais , Feminino , Masculino , Camundongos , Hormônio do Crescimento/metabolismo , Oligopeptídeos/farmacologia , Receptores de Neuropeptídeos/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética , Análise de Variância , Modelos Animais de Doenças , Grelina/sangue , Hormônio do Crescimento/deficiência , Heterozigoto , Leptina/sangue , Camundongos Mutantes , Oligopeptídeos/administração & dosagem , Distribuição Aleatória
Gastroenterol. latinoam ; 22(2): 148-151, abr.-jun. 2011. tab, graf
Artigo em Espanhol | LILACS | ID: lil-661807


The patient who fails to an interferon based treatment with or without ribavirin represents a major challenge for the clinician. In the initial evaluation a detailed history of the first course of treatment is critical, since it largely determines the likelihood of response to retreatment. In addition, the use of adequate doses of ribavirin and excellent adherence are key for a successful therapy. During re-treatment, a viral load detectable at 12 weeks at any level is considered an indication to discontinue treatment because of the low probability of achieving sustained response. There are new direct antiviral agents (protease inhibitors) that have been shown to increase response rate in patients who previously failed treatment, nevertheless, these drugs have limitations, such as high cost, activity restricted to certain genotypes, additional adverse effects and low response in previous null-responders. There is great optimism in the development of multiple new therapies with different mechanisms of action that promise to significantly increase the chances of eradicating the virus in these difficult to treat patients.

El paciente que ha fallado a un tratamiento sobre la base de interferón, con o sin ribavirina representa un desafío importante para el clínico. En su enfrentamiento inicial es clave una historia detallada del primer curso de tratamiento, ya que en gran parte determina la posibilidad de respuesta a un re-tratamiento. Por otro lado, el uso de dosis adecuadas de ribavirina y una excelente adherencia son claves en el éxito de la terapia. Durante un re-tratamiento, una carga viral a las 12 semanas detectable en cualquier nivel se considera indicación de suspender el tratamiento por la baja probabilidad de lograr respuesta sostenida. Se debe considerar que existen nuevas drogas antivirales directas (inhibidores de proteasa) que han demostrado aumentar la tasa de respuesta en pacientes que previamente han fallado al tratamiento, no obstante, estas drogas tienen limitaciones tales como alto costo, efectividad restringida a algunos genotipos, efectos adversos adicionales y baja respuesta en pacientes respondedores nulos a un tratamiento previo. Existe gran optimismo en el desarrollo de múltiples nuevas terapias con diferentes mecanismos de acción que prometen aumentar en forma significativa la posibilidad de erradicar el virus en este grupo de pacientes difícil de tratar.

Humanos , Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Oligopeptídeos/uso terapêutico , Prolina/uso terapêutico , Ribavirina/uso terapêutico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Prolina/análogos & derivados , Retratamento
Acta cir. bras ; 26(1): 58-63, jan.-fev. 2011. ilus, graf, tab
Artigo em Inglês | LILACS | ID: lil-572235


Purpose: Angiogenesis involves many mediators including integrins, and the tripeptide RGD is a target amino acid recognition sequence for many of them. Hindlimb ischemia is a simple and convenient animal model however standardization of the injection procedures in the devascularized and control limb is lacking, thus rendering difficult the interpretation of results. The aim of this investigations was to evaluate neovascularization in a hindlimb murine model by means of 99mTc-HYNIC-ß-Ala-RGD. Methods: 99mTc-HYNIC-RGD analog was prepared using coligands. Ischemia was induced in Wistar rats by double- ligation of the common femoral artery. Radiolabeled RGD was injected after 2h, as well as 1, 3, 5, 7, 10 and 14 days. Uptake was evaluated by planar imaging and biodistribution studies. Results: The highest ratio between ischemia and control was achieved at the 7th day (2.62 ± 0.95), with substantial decrease by the 14th day. For pertechnetate the 7th day ratio was 0.87 ± 0.23. Scintigraphic image confirmed different uptakes. Conclusion: 99mTc-HYNIC-RGD analog concentrated in ischemic tissue by the time of widespread angiogenesis and pertechnetate confirmed reduction in blood flow. In this sense, the protocol can be recommended for ischemic models.

Objetivo: A angiogênese em resposta a fenômenos isquêmicos envolve vários mediadores como as integrinas, sendo que o tripeptídeo RGD possui uma seqüência de aminoácidos com reconhecimento para este alvo. O modelo animal de isquemia de pata traseira é simples e conveniente, porém não há uma padronização do procedimento de injeção e controle radioisotópico em membro desvascularizado, dificultando, portanto a interpretação de resultados. O objetivo deste estudo foi avaliar a neovascularização em modelo murino de isquemia de pata traseira através do radiotraçador 99mTc-HYNIC-ß-Ala-RGD. Métodos: O análogo 99mTc-HYNIC-RGD foi preparado usando coligantes. A isquemia foi induzida em ratos Wistar por dupla-ligação da artéria femoral comum na prega inguinal. Peptídeo RGD radiomarcado foi injetado após 2h, assim como 1, 3, 5, 7, 10 e 14 dias. A captação foi avaliada por imagem planar e estudos de biodistribuição. Resultados: A maior diferença de captação entre isquemia e pata controle foi obtida no 7º dia (2,62 ± 0,95), com decréscimo acentuado no 14º dia. Para o pertecnetato a razão no 7º dia foi 0,87 ± 0,23. A imagem cintilográfica confirmou as diferentes captações. Conclusões: O análogo 99mTc-HYNIC-RGD concentrou-se no tecido isquêmico na etapa em que a angiogênese é mais acentuada, e o estudo do pertecnetato confirmou a redução no fluxo sanguíneo. Desta maneira, este protocolo diagnóstico pode ser recomendado para modelos isquêmicos.

Animais , Masculino , Ratos , Membro Posterior/irrigação sanguínea , Isquemia/fisiopatologia , Neovascularização Fisiológica/fisiologia , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Sequência de Aminoácidos , Sequência Conservada , Membro Posterior/metabolismo , Membro Posterior , Isquemia , Oligopeptídeos , Compostos de Organotecnécio/farmacocinética , Ratos Wistar , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual