Xyloglucan and Concanavalin A based dressings in the topical treatment of mice wound healing process

For medical biomaterials, xyloglucan dispersions can form films or gels to be applied as a wound dressing. For this purpose, the structural characterization of xyloglucan dressing (XG) and xyloglucan dressing containing 0.5 mg/mL of concanavalin A (XGL) was performed. The lectin release capacity and stability, cytotoxicity, and pro-wound healing effects were also investigated. XG and XGL films were prepared by mixing 0.5 % (w/v) xyloglucan with 0.3 % (v/v) glycerol. The ConA incorporated in the xyloglucan dressing maintained its biological activity for fourteen days in a controlled-release manner. The films were non-toxic, homogeneous, flexible, and accelerated the wound contraction compared with the control group, promoting less infiltration of inflammatory cells, angiogenesis, remodeling, and early epithelization. The films also alleviate the inflammation phase by reducing the production of pro-inflammatory cytokines (IFN-, TNF-, IL-1, IL-6, and IL-12), especially the XGL film, which promoted the up- and down-regulation of important proteins associated with the wound repair. All these findings suggest that XG and XGL films may represent a good therapeutic approach for wound healing applications.The authors are grateful for the financial support for research grants from the Conselho Nacional de Desenvolvimento Científico e Tecnol ´ogico (CNPq), Coordenaç˜ao de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and the Fundaç˜ao de Amparo `a Ciˆencia e Tecnologia do Estado de Pernambuco (FACEPE). We are grateful to the Centro de Tecnologias Estrat´egicas do Nordeste (CETENE) and to the Laborat´orio de Imunopatologia Keizo Asami-LIKA at the Universidade Federal de Pernambuco (UFPE) for access to its installation and technical assistance.info:eu-repo/semantics/publishedVersio

Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)

BACKGROUND:Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS:Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS:Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators

Interleukin-6 increases the expression and activity of insulin-degrading enzyme

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOImpairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and activity. IL-6 KO mice displayed lower insulin clearance in the liver and skeletal muscle, compared with wild type (WT), due to reduced IDE expression and activity. We also observed that after 3-h incubation, IL-6, 50 and 100 ng ml(-1), increased the expression of IDE in HEPG2 and C2C12 cells, respectively. In addition, during acute exercise, the inhibition of IL-6 prevented an increase in insulin clearance and IDE expression and activity, mainly in the skeletal muscle. Finally, IL-6 and IDE concentrations were significantly increased in plasma from humans, after an acute exercise, compared to pre-exercise values. Although the increase in plasma IDE activity was only marginal, a positive correlation between IL-6 and IDE activity, and between IL-6 and IDE protein expression, was observed. Our outcomes indicate a novel function of IL-6 on the insulin metabolism expanding the possibilities for new potential therapeutic strategies, focused on insulin degradation, for the treatment and/or prevention of diseases related to hyperinsulinemia, such as obesity and T2DM.Impairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and act7112FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2014/24719-7; 2015/12611-

Agricultura e biodiversidade nas ciências sociais brasileiras: alimentando a comunicação entre ciência e políticas públicas.

O presente artigo decorre de uma reflexão sustentada em dois pressupostos: a) que as ciências e, em particular, as sociais, podem contribuir para informar as tomadas de decisão e a formulação de políticas públicas visando a melhoria da vida das pessoas no planeta e b) que o papel da agricultura na conservação da biodiversidade é uma questão atual de extrema relevância e que merece ser aprofundada. A relação entre a agricultura e a biodiversidade tem sido objeto de questionamentos recentes na sociedade e no campo das políticas públicas. Contudo, se os estudos relacionados à biodiversidade e à agricultura, separadamente, têm observado um considerável crescimento no Brasil, poucos são os investimentos de pesquisa sobre a relação entre esses dois grandes temas. A partir dessas considerações, seguimos dois objetivos principais: 1) investigar como o papel da agricultura familiar na preservação da biodiversidade tem sido abordado pelas Ciências Sociais no Brasil, particularmente nos artigos publicados em periódicos brasileiros nos últimos 20 anos; 2) testar uma metodologia de revisão bibliográfica, criteriosa, que possa ser útil aos tomadores de decisão em políticas públicas e demais interessados

Effects of bromopride on the healing of left colon anastomoses of rats

Objetivo: Avaliar os efeitos da bromoprida sobre a formação de aderências e a cicatrização de anastomoses de cólon esquerdo de ratos. Métodos: Foram incluídos 40 ratos, divididos em dois grupos contendo 20 animais, para administração de bromoprida (grupo de estudo- E) ou solução fisiológica (grupo controle- C). Cada grupo foi dividido em subgrupos contendo 10 animais cada, para eutanásia no terceiro (E3 e C3) ou no sétimo dia (E7 e C7) de pós-operatório. Os ratos foram submetidos à secção do cólon esquerdo e anastomose término-terminal. No dia da relaparotomia, foi avaliada a quantidade total de aderências e removido um segmento colônico contendo a anastomose para análise histopatológica, da força de ruptura e da concentração de hidroxiprolina. Resultados: Não houve diferença entre os grupos em relação à evolução clínica. Dois animais do grupo de estudo apresentaram deiscência de anastomose bloqueada. Os animais que receberam bromoprida apresentaram número de aderências intracavitárias e aderências à anastomose semelhantes ao grupo controle. As anastomoses dos animais do grupo E3 apresentaram menor resistência de ruptura do que as do grupo C3 (p=0,04). Este efeito não ocorreu no sétimo dia de pós-operatório (p=0,37). Não houve diferença significativa entre os grupos em relação à histopatologia ou concentração de hidroxiprolina das anastomoses. Conclusão: O uso da bromoprida está associado à diminuição da resistência tênsil de anastomoses do cólon esquerdo de ratos no terceiro dia de pós-operatório.Objective: To evaluate the effects of bromopride on the formation of adhesions and anastomotic healing in the left colon of rats. Methods: We divided 40 rats into two groups of 20 animals, administration of bromopride (study group-E) or saline (control group- C). Each group was divided into subgroups containing 10 animals each for euthanasia in the third (C3 and E3) or the seventh (E7 and C7) postoperative days. The rats were submitted to section of the left colon and end-to-end anastomosis. On the day of reoperation, we evaluated the total amount of adhesions and removed a colonic segment containing the anastomosis for histopathological analysis, assessment of rupture strength and hydroxyproline concentration. Results: There was no difference between groups in relation to clinical outcome. Two animals in the study group had blocked anastomotic leakage. The animals that received bromopride had the number of intracavitary adhesions and adhesions to the anastomosis similar to the control group. The anastomoses from the group E3 animals showed lower resistance to rupture the one from the C3 group (p = 0.04). This effect did not occur on the seventh postoperative day (p = 0.37). There was no significant difference between groups in relation to histopathology and hydroxyproline concentration in the anastomoses. Conclusion: The use of bromopride was associated with decreased tensile strength of left colon anastomosis in rats in the third postoperative day