Curcumin, but not Prima-1, decreased tumor cell proliferation in the syngeneic murine orthotopic bladder tumor model

OBJECTIVE: Cigarette smoking is the main risk factor for bladder cancer development. Among the mediators of this effect of smoking is nuclear factor-kappa B. Curcumin suppresses cellular transformation by downregulating the activity of nuclear factor-kappa B. Prima-1 is a compound that induces apoptosis in human tumor cells, restoring the function of mutant p53. Our study aimed to evaluate the effects of curcumin and prima-1 in an animal model of bladder cancer. METHODS: Tumor implantation was achieved in six- to eight-week-old female C57BL/6 mice by introducing MB49 bladder cancer cells into the bladder. Intravesical treatment with curcumin and Prima-1 was performed on days 2, 6, 10, and 14. On day 15, the animals were sacrificed. Immunohistochemistry was used to determine the expression of cyclin D1, Cox-2, and p21. Cell proliferation was examined using PCNA. RESULTS: Animals treated with curcumin exhibited a higher degree of necrosis than animals in other groups. Immunohistochemistry showed reduced expression of cyclin D1 in the curcumin-treated group. All of the cells in mice treated with curcumin were p21 positive, suggesting that the p53 pathway is induced by this compound. Prima-1 did not induce any change in tumor size, necrosis, cell proliferation, or the expression of proteins related to the p53 pathway in this animal model. CONCLUSION: Curcumin showed activity in this animal bladder cancer model and probably acted via the regulation of nuclear factor-kappa B and p53. Therefore, curcumin is a good choice for the use in clinical trials to treat superficial bladder cancer as an alternative to bacillus Calmette-Guerin. In contrast, Prima-1 does not seem to have an effect on bladder cancer

Incidence of HIV vertical transmission among HIV-positive pregnant women treated at a regional reference service

Objective: surveying and to characterizing the incidence of HIV vertical transmission, from 2004 to 2013, among pregnant women accompanied by a referral service in STD, HIV/AIDS and Viral Hepatitis in the countryside of Minas Gerais. Method: it is a quantitative descriptive study. Data were obtained from the medical records of women infected by HIV registered in the unit. For analysis, there was used the simple descriptive statistics. It was approved by the Research Ethics Committee of the Higher Education Foundation of Passos (FESP), with CAAE: 28399314.8.0000.5112. Results: of the 33 pregnancies treated at the service, 60,6% (20) knew the diagnosis before pregnancy and 39,4% (13) of them obtained it during the prenatal period. In the first group there was no vertical transmission, while in the second group, there was one case, 8%. Conclusion: it is recommended that pregnant women do the test still in the first three months of pregnancy, because late diagnosis makes difficult doing prophylaxis

Curcumin, but not Prima-1, decreased tumor cell proliferation in the syngeneic murine orthotopic bladder tumor model

OBJECTIVE: Cigarette smoking is the main risk factor for bladder cancer development. Among the mediators of this effect of smoking is nuclear factor-kappa B. Curcumin suppresses cellular transformation by downregulating the activity of nuclear factor-kappa B. Prima-1 is a compound that induces apoptosis in human tumor cells, restoring the function of mutant p53. Our study aimed to evaluate the effects of curcumin and prima-1 in an animal model of bladder cancer. METHODS: Tumor implantation was achieved in six- to eight-week-old female C57BL/6 mice by introducing MB49 bladder cancer cells into the bladder. Intravesical treatment with curcumin and Prima-1 was performed on days 2, 6, 10, and 14. On day 15, the animals were sacrificed. Immunohistochemistry was used to determine the expression of cyclin D1, Cox-2, and p21. Cell proliferation was examined using PCNA. RESULTS: Animals treated with curcumin exhibited a higher degree of necrosis than animals in other groups. Immunohistochemistry showed reduced expression of cyclin D1 in the curcumin-treated group. All of the cells in mice treated with curcumin were p21 positive, suggesting that the p53 pathway is induced by this compound. Prima-1 did not induce any change in tumor size, necrosis, cell proliferation, or the expression of proteins related to the p53 pathway in this animal model. CONCLUSION: Curcumin showed activity in this animal bladder cancer model and probably acted via the regulation of nuclear factor-kappa B and p53. Therefore, curcumin is a good choice for the use in clinical trials to treat superficial bladder cancer as an alternative to bacillus Calmette-Guerin. In contrast, Prima-1 does not seem to have an effect on bladder cancer

Incidência de transmissão vertical do HIV entre gestantes soropositivas cadastradas em um serviço de referência regional Incidence of HIV vertical transmission among HIV-positive pregnant women treated at a regional reference service

Objetivo: Levantar e caracterizar a incidência de transmissão vertical do HIV, no período de 2004 a 2013, entre gestantes acompanhadas por serviço de referência em DST, HIV/Aids e Hepatites Virais no interior de Minas Gerais. Método: Estudo quantitativo descritivo. Os dados foram obtidos em prontuários de mulheres soropositivas para o HIV. Para análise, utilizou-se a estatística descritiva simples. Aprovado pela Comissão de Ética em pesquisa da Fundação de Ensino Superior de Passos (FESP), com CAAE: 28399314.8.0000.5112. Resultados: Das 33 gestações acompanhadas no serviço, 60,6% (20) conheciam o diagnóstico antes da gravidez e 39,4% (13) o obtiveram durante o pré-natal. No primeiro grupo não houve transmissão vertical, enquanto que no segundo houve um caso, 8%. Conclusão: Recomenda-se realização de teste ainda no primeiro trimestre gestacional, pois o diagnóstico tardio dificulta a profilaxia. Descritores: Transmissão vertical de doença infecciosa, HIV, Prevenção de doenças transmissíveis, Serviços de saúde materno-infantil

Incidência de transmissão vertical do HIV entre gestantes soropositivas cadastradas em um serviço de referência regional Incidence of HIV vertical transmission among HIV-positive pregnant women treated at a regional reference service

Objetivo: Levantar e caracterizar a incidência de transmissão vertical do HIV, no período de 2004 a 2013, entre gestantes acompanhadas por serviço de referência em DST, HIV/Aids e Hepatites Virais no interior de Minas Gerais. Método: Estudo quantitativo descritivo. Os dados foram obtidos em prontuários de mulheres soropositivas para o HIV. Para análise, utilizou-se a estatística descritiva simples. Aprovado pela Comissão de Ética em pesquisa da Fundação de Ensino Superior de Passos (FESP), com CAAE: 28399314.8.0000.5112. Resultados: Das 33 gestações acompanhadas no serviço, 60,6% (20) conheciam o diagnóstico antes da gravidez e 39,4% (13) o obtiveram durante o pré-natal. No primeiro grupo não houve transmissão vertical, enquanto que no segundo houve um caso, 8%. Conclusão: Recomenda-se realização de teste ainda no primeiro trimestre gestacional, pois o diagnóstico tardio dificulta a profilaxia. Descritores: Transmissão vertical de doença infecciosa, HIV, Prevenção de doenças transmissíveis, Serviços de saúde materno-infantil

Production and release of heat-labile toxin by wild-type human-derived enterotoxigenic Escherichia coli

Production and release of heat-labile toxin (LT) by wild-type enterotoxigenic Escherichia coli (ETEC) strains, isolated from diarrheic and asymptomatic Brazilian children, was studied under in vitro and in vivo conditions. Based on a set of 26 genetically diverse LT+ enterotoxigenic E. coli strains, cell-bound LT concentrations varied from 49.8 to 2415 ng mL(-1). the amounts of toxin released in culture supernatants ranged from 0% to 50% of the total synthesized toxin. the amount of LT associated with secreted membrane vesicles represented < 5% of the total toxin detected in culture supernatants. ETEC strains secreting higher amounts of LT, but not those producing high intracellular levels of cell-bound toxin, elicited enhanced fluid accumulation in tied rabbit ileal loops, suggesting that the strain-specific differences in production and secretion of LT correlates with symptoms induced in vivo. However, no clear correlation was established between the ability to produce and secrete LT and the clinical symptoms of the infected individuals. the present results indicate that production and release of LT by wild-type human-derived ETEC strains are heterogeneous traits under both in vitro and in vivo growth conditions and may impact the clinical outcomes of infected individuals.Univ São Paulo, Dept Microbiol, Inst Ciencias Biomed, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilFdn Oswaldo Cruz, Escola Nacl Saude Publ, Rio de Janeiro, BrazilUniv São Paulo, Dept Patol, Fac Med Vet & Zootecn, São Paulo, BrazilInst Butantan, Div Desenvolvimento Tecnol & Prod, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilWeb of Scienc

Underexpression of MMP-2 and its Regulators, TIMP2, MT1-MMP and IL-8, is Associated with Prostate Cancer

Objective: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specific regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome of prostate cancer (PCa). Materials and Methods: MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profile of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the final outcome of the PCa. Results: The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (&gt;= 7) over-expressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (&lt; 7). Conclusion: We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) [2009/50368-9]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP

Síndrome de Guillain Barre, uma complicação da Covid-19? Guillain Barre Syndrome, a Covid-19 cure?

A doença ocasionada pelo vírus da COVID-19, a qual se consuma em estado pandêmico desde 2020, trouxe consigo sintomas respiratórios característicos. Além desses quadros já conhecidos, foi observado que tal patógeno pode gerar também manifestações extrapulmonares, como as de cunho neurológico. Uma intercorrência neurológica relatada foi a Síndrome de Guillain-Barré (SGB), que possivelmente se associa com a infecção por COVID-19, devido à capacidade do vírus em induzir autoanticorpos. Estudo descritivo de revisão de literatura do tipo integrativa foi realizado mediante análise nas bases de dados da Biblioteca Virtual em Saúde (BVS), U. S. National Library of Medicine (Pubmed) e Scientific Electronic Library Online (SciELO) sobre essa temática e, aplicou-se critérios de inclusão e exclusão e obteve-se 150 artigos, dentre os quais foram selecionados 05 estudos, que passaram por um processo de leitura minucioso. Na pesquisa foi observado que, dentre as síndromes autoimunes relacionadas a pós-infecção por sars-cov-2, a SGB foi a principal. Ademais, a ocorrência de SGB é preponderante em pacientes COVID positivo em comparação com as pessoas que testaram negativo para o vírus. Em relação a sintomatologia, observou-se que o padrão sensório-motor clássico foi o mais frequente da SGB. Além disso, considerando-se a variável idade evidenciou-se maior ocorrência da SBG em pacientes infectados por COVID-19 naqueles com idade superior a 63 anos. Há muitas evidências clínicas que correlacionam a infecção por COVID-19 com sequelas neurológicas e, a SBG é relevante nesse contexto. Contudo, há poucos estudos que investigam essa doença como complicação da COVID-19, o que denota ser necessária mais pesquisas que busquem relacionar tais doenças

Analysis of the effect of Prima-1 in the expression of genes involved in programmed cell death in bladder cancer cell lines

Introdução: O carcinoma urotelial de bexiga (CUB) é o segundo tumor mais frequente do trato urinário. A perda da função do p53 é a alteração mais conhecida do carcinoma urotelial de alto grau invasivo. Prima-1 é uma pequena molécula, a qual restaura a função do p53 mutado promovendo a morte celular em vários tipos celulares. O objetivo do nosso estudo foi analisar o efeito do Prima-1 na indução da apoptose mediada por p53 após indução do dano ao DNA em linhagens de CUB. Material e métodos: O mecanismo de ação do Prima-1 foi avaliado em duas linhagens celulares de câncer de bexiga, T24 que tem como característica a mutação do p53 e RT4 que possui p53 intacto. Características morfológicas da apoptose, alterações no potencial de membrana mitocondrial e análise da expressão de treze genes envolvidos na apoptose mediada por p53 foram avaliados através de observação microscópica e reação em cadeia da polimerase em tempo real quantitativa (qRT-PCR). Resultados: Prima-1 foi capaz de reativar a função da P53 na linhagem de câncer de bexiga com p53 mt, promovendo a apoptose através da expressão de Bax e Puma, ativação da cascata das caspases e ruptura da membrana mitocondrial, independente de Bax, na linhagem celular T24 (p53 mt). Conclusão: Prima-1 foi capaz de restaurar a atividade transcricional de p53. Estudos experimentais in vivo poderiam ser conduzidos no intuito de testar essa molécula como um novo agente terapêutico do CUB de alto grau, invasivo, que apresenta caracteristicamente mutação de p53Introduction: Urothelial carcinoma of the bladder is the second most common tumor of the urinary tract. Loss of p53 function is the main genetic alteration related to the development of high-grade muscle-invasive disease. Prima-1 is a small molecule that restores tumor suppressor function to mutant p53 and induces cell death in various cancer types. Our aim is to investigate the ability of Prima-1 to induce apoptosis after DNA damage in BC cancer cell lines. Material and Methods: The therapeutic effect of Prima-1 was studied in two BC cell lines, T24, characterized by p53 mutation, and RT4, with no mutation in the p53 gene. Morphological features of apoptosis, mitochondrial membrane potential changes and expression of thirteen genes involved in p53-induced apoptosis were assessed by microscopic observation and quantitative real-time PCR (qRT-PCR) Results: Prima-1 is able to reactivate P53 function in p53-mutated bladder cancer cell line promote apoptosis through the induction of Bax and Puma expression, activating the caspase cascade and disruption of mitochondrial membrane, independent of Bak, in T24 cell line (p53 mt). Conclusion: Prima-1 is able to restore the transcriptional activity of p53. Experimental studies in vivo could be conducted in order to test this molecule as a new therapeutic agent of the urothelial carcinoma of the bladder, which characteristically presents p53 mutatio