5 research outputs found

    Insulin crystals grown in short-peptide supramolecular hydrogels show enhanced thermal stability and slower release profile

    No full text
    [EN] Protein therapeutics have a major role in medicine in that they are used to treat diverse pathologies. Their three-dimensional structures not only offer higher specificity and lower toxicity than small organic compounds but also make them less stable, limiting their in vivo half-life. Protein analogues obtained by recombinant DNA technology or by chemical modification and/or the use of drug delivery vehicles has been adopted to improve or modulate the in vivo pharmacological activity of proteins. Nevertheless, strategies to improve the shelf-life of protein pharmaceuticals have been less explored, which has challenged the preservation of their activity. Herein, we present a methodology that simultaneously increases the stability of proteins and modulates the release profile, and implement it with human insulin as a proof of concept. Two novel thermally stable insulin composite crystal formulations intended for the therapeutic treatment of diabetes are reported. These composite crystals have been obtained by crystallizing insulin in agarose and fluorenylmethoxycarbonyl-dialanine (Fmoc-AA) hydrogels. This process affords composite crystals, in which hydrogel fibers are occluded. The insulin in both crystalline formulations remains unaltered at 50 °C for 7 days. Differential scanning calorimetry, high-performance liquid chromatography, mass spectrometry, and in vivo studies have shown that insulin does not degrade after the heat treatment. The nature of the hydrogel modifies the physicochemical properties of the crystals. Crystals grown in Fmoc-AA hydrogel are more stable and have a slower dissolution rate than crystals grown in agarose. This methodology paves the way for the development of more stable protein pharmaceuticals overcoming some of the existing limitations.The research leading to these results has received funding from the “la Caixa” Banking Foundation CaixaImpulse program, EIT-Health PocPlus program, and the Ministry of Economy and Competitiveness of Spain, acknowledged through the following projects: BIO2016-74875-P, BFU2014-57736-P, AGL2014-58883-R, SAF2017-88457-R, AGL2017-85270-R, and FIS2017-85954-R co-funded by Fondo Europeo de Desarrollo Regional, ERDF, European Union, and FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidades (Spain) projects P18-FR-3533, P12-FQM-2721, P12-FQM-790, CTS235, and CTS164. M.A.-A. and M.C.M.-T. were supported by fellowships from the Ministry of Education. CIBERehd is funded by Instituto de Salud Carlos III.Peer reviewe

    "A incorporação do proletariado à sociedade moderna": a Escola de Aprendizes Artífices de Minas Gerais (1910-1941) "The proletariat's integration into the modern society": the School for Apprentice Craftsmen of Minas Gerais (1910-1941)

    No full text
    Este artigo trata da criação de uma instituição escolar, a Escola de Aprendizes Artífices de Minas Gerais, inaugurada em Belo Horizonte em 1910. Apresentamos aqui algumas reflexões acerca da produção dessa escola como lugar de formação do cidadão trabalhador da república brasileira. Discutimos também as implicações da sua localização na trama social e espacial da cidade, bem como da produção do espaço a ela destinada em espaço escolar. Utilizando como fonte principal os primeiros relatórios de direção dessa escola e jornais mineiros do período, este trabalho aborda a constituição da Escola de Aprendizes Artífices e sua configuração na cultura urbana e no ambiente de trabalho da capital mineira.<br>This article deals with the creation of an educational institution, the School for Apprentice Craftsmen of Minas Gerais, installed in Belo Horizonte in 1910. We present here some reflections about the production of this school as a place of formation for the working citizen in the Brazilian republic. We also discuss the implications of its location in the social and spatial fabric of the city, as well as the production of its destined space into a schooling space. Using as primary sources the first reports from the school´s Principal and newspapers published in Minas Gerais in that period of time, this work approaches the constitution of the School for Apprentice Craftsmen and its configuration in the urban culture and the working environment of the Minas Gerais capital

    Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

    No full text
    Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis. Methods: We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, hadCD4+ cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4+ cell count and HIV-RNA via inverse probability weighting. Results: Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis. Conclusion: With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries
    corecore