Retinoic acid and cAMP inhibit rat hepatocellular carcinoma cell proliferation and enhance cell differentiation.

Hepatocellular carcinoma (HCC) is the third highest cause of cancer death worldwide. In general, the disease is diagnosed at an advanced stage when potentially curative therapies are no longer feasible. For this reason, it is very important to develop new therapeutic approaches. Retinoic acid (RA) is a natural derivative of vitamin A that regulates important biological processes including cell proliferation and differentiation. In vitro studies have shown that RA is effective in inhibiting growth of HCC cells; however, responsiveness to treatment varies among different HCC cell lines. The objective of the present study was to determine if the combined use of RA (0.1 µM) and cAMP (1 mM), an important second messenger, improves the responsiveness of HCC cells to RA treatment. We evaluated the proliferative behavior of an HCC cell line (HTC) and the expression profile of genes related to cancer signaling pathway (ERK and GSK-3ß) and liver differentiation (E-cadherin, connexin 26 (Cx26), and Cx32). RA and cAMP were effective in inhibiting the proliferation of HTC cells independently of combined use. However, when a mixture of RA and cAMP was used, the signals concerning the degree of cell differentiation were increased. As demonstrated by Western blot, the treatment increased E-cadherin, Cx26, Cx32 and Ser9-GSK-3ß (inactive form) expression while the expression of Cx43, Tyr216-GSK-3ß (active form) and phosphorylated ERK decreased. Furthermore, telomerase activity was inhibited along treatment. Taken together, the results showed that the combined use of RA and cAMP is more effective in inducing differentiation of HTC cells.

Characteristics of Lactobacillus and Gardnerella vaginalis from women with or without bacterial vaginosis and their relationships in gnotobiotic mice.

The objectives of the present study were to evaluate in vitro the production of antagonistic compounds against Gardnerella vaginalis by Lactobacillus strains isolated from women with or without bacterial vaginosis (BV), and to select one of the better Lactobacillus producers of such a substance to be tested in vivo using a gnotobiotic animal model challenged with one of the more sensitive G. vaginalis isolates. A total of 24 isolates from women with and without BV were identified as G. vaginalis. A higher frequency (P<0.05) of this bacterium was observed in women with BV (56.7%) when compared to healthy women (17.6%). A total of 86 strains of Lactobacillus were obtained from healthy women and women with BV. Lactobacillus strains were more frequently present (P<0.05) in healthy women (97.5%) than in women with BV (76.7%). Lactobacillus crispatus was the predominating strain in both healthy women and women with BV. Lactobacillus jensenii, Lactobacillus johnsonii, Lactobacillus gasseri and Lactobacillus vaginalis were isolated with an intermediate frequency in the two groups. In vitro antagonism assays were performed using as indicators 17 reference strains and the G. vaginalis strains isolated from women with BV and from healthy women. Lactobacillus isolated from healthy women showed the higher antagonistic activity against all the indicator strains when compared with isolates from women with BV. Concerning the indicator strains, G. vaginalis found in women with BV was more resistant to the antagonism, particularly when Lactobacillus isolates from women with BV were used as producer strains. A high vaginal population level of G. vaginalis was obtained by intravaginal inoculation of germ-free mice, and this colonization was accompanied by vaginal histopathological lesions. A tenfold decrease in vaginal population level of G. vaginalis and a reduction of histological lesions were observed when the pathogenic challenge was performed in mice previously monoassociated with an L. johnsonii strain. Concluding, results of the present study suggest that progression of G. vaginalis-associated BV depends in part on a simultaneous presence of Lactobacillus populations with a low antagonistic capacity and of a G. vaginalis strain with a high resistance to this antagonism. The results could also explain why G. vaginalis is frequently found in the vaginal ecosystem of healthy women.

Antagonism and synergism in Gardnerella vaginalis strains isolated from women with bacterial vaginosis.

Antagonistic and synergistic substances are important for interactions between micro-organisms associated with human body surfaces, either in healthy or in diseased conditions. In the present study, such compounds produced by Gardnerella vaginalis strains isolated from women with bacterial vaginosis (BV) were detected in vitro and the antagonistic ones were partially characterized. Among 11 G. vaginalis strains tested, all showed antagonistic activity against at least one of the 22 indicator bacteria assayed. Interestingly, for some of these strains, antagonism reverted to synergism, favouring one of the indicator strains (Peptostreptococcus anaerobius) when the growth medium was changed. Partial characterization of antagonistic substances suggested a bacteriocin-like chemical nature. Depending on growth conditions, G. vaginalis isolated from women with BV produced antagonistic or synergistic compounds for other bacterial components of the vaginal ecosystem. This is the first report to our knowledge of the production of antagonistic and/or synergistic substances by G. vaginalis. This ability may be a pivotal factor in understanding BV and the ecological role of this bacterium in the vaginal environment.

Ensino farmacêutico no Brasil na perspectiva de uma formação clínica / Pharmacist education in brazil from a clinical perspective

O objetivo deste estudo foi discutir a interação entre ensino e prática farmacêutica voltada para a formação clínica. A metodologia consistiu na busca, leitura e discussão de materiais impressos ou em formato eletrônico relacionados à temática. Os resultados apresentam uma pequena introdução sobre a evolução da profissão farmacêutica, que foi acompanhada pelo ensino, para, então, discutir as propostas que vêm sendo empregadas para garantir o desenvolvimento das diversas habilidades necessárias à práxis farmacêutica, sobretudo no âmbito clínico. Por muito tempo, o ofício farmacêutico esteve relacionado com a manipulação dos medicamentos, mas, com a ascensão da indústria farmacêutica, o profissional perdeu esse papel, indo atuar nas análises clínicas e na indústria. Na tentativa de reaproximar o farmacêutico da farmácia, resgatando o seu papel social, surgiram diversas propostas, como a Farmácia Clínica e a Atenção Farmacêutica. Entretanto, a incorporação da dimensão clínica na prática profissional exige uma adequação dos cursos de formação. Algumas experiências foram adotadas e são praticadas há muito tempo, como projetos de extensão e Farmácia-Escola. Entretanto, nos últimos anos, tem se difundido o uso de metodologias ativas, como as estratégias de ensino e aprendizagem baseadas na problematização, uso de realidade virtual, jogos e outros tipos de simulação. Todas essas práticas pedagógicas, inovadoras ou não, são úteis no processo ensino-aprendizagem, mas apenas se forem utilizadas na perspectiva de otimizar os resultados da farmacoterapia, melhorando a qualidade de vida dos usuários de medicamentos...

The aim of this study was to discuss the interaction between education and the practice of pharmacy, with a focus on clinical training. The methodology consisted in the discussion of papers and books related to the theme. The findings constitute a short introduction to the development of the pharmaceutical profession, which evolved side-by-side with teaching, and then discuss the measures that have been proposed to ensure the development of the various skills necessary for pharmaceutical practice, above all in the clinical setting. For a long time, the pharmacist was related to the handling of medicines, but the rise of the pharmaceutical industry led to the loss of this role, so that the pharmacist went to work in the industry and clinical analysis. In an attempt to bring pharmacists back to the pharmacy, rescuing their social role, several proposals were put forward, such as Clinical Pharmacy and Pharmaceutical Care. However, the incorporation of the clinical dimension into professional practice requires adjustments in the training courses. Some experiments were put into practice long ago, such as Faculty extension and Faculty-Pharmacy projects. In recent years, the use of active methods has been spreading, such as strategies for teaching and learning based on the use of problems, virtual reality, games and other types of simulation. All these teaching practices, innovative or not, are useful in the teaching-learning process, but only if used with a view to enhancing the results of pharmacotherapy, thus improving the quality of life of patients...

Retinoic acid and cAMP inhibit rat hepatocellular carcinoma cell proliferation and enhance cell differentiation

Hepatocellular carcinoma (HCC) is the third highest cause of cancer death worldwide. In general, the disease is diagnosed at an advanced stage when potentially curative therapies are no longer feasible. For this reason, it is very important to develop new therapeutic approaches. Retinoic acid (RA) is a natural derivative of vitamin A that regulates important biological processes including cell proliferation and differentiation. In vitro studies have shown that RA is effective in inhibiting growth of HCC cells; however, responsiveness to treatment varies among different HCC cell lines. The objective of the present study was to determine if the combined use of RA (0.1 µM) and cAMP (1 mM), an important second messenger, improves the responsiveness of HCC cells to RA treatment. We evaluated the proliferative behavior of an HCC cell line (HTC) and the expression profile of genes related to cancer signaling pathway (ERK and GSK-3β) and liver differentiation (E-cadherin, connexin 26 (Cx26), and Cx32). RA and cAMP were effective in inhibiting the proliferation of HTC cells independently of combined use. However, when a mixture of RA and cAMP was used, the signals concerning the degree of cell differentiation were increased. As demonstrated by Western blot, the treatment increased E-cadherin, Cx26, Cx32 and Ser9-GSK-3β (inactive form) expression while the expression of Cx43, Tyr216-GSK-3β (active form) and phosphorylated ERK decreased. Furthermore, telomerase activity was inhibited along treatment. Taken together, the results showed that the combined use of RA and cAMP is more effective in inducing differentiation of HTC cells.