Diabetic rats lose A2A receptor-mediated facilitation of ileal myenteric cholinergic neurotransmission

Enteric dysmotility is a long-term complication of Diabetes mellitus that causes significant discomfort in 76% of diabetic outpatients. Knowing that purines may be involved in synaptic transmission modifications in the CNS of diabetic rats, we decided to investigate if purinergic dysfunction could also play a role in diabetic enteric neuropathy in rats.info:eu-repo/semantics/publishedVersio

ITs in engineering education: joining efforts between SPEE and IGIP

The International Society for Engineering Education (IGIP) and The Portuguese Society for Engineering Education (SPEE), the first being the oldest European Society for Engineering Education in Europe and the second the very young Society for Engineering Education in Portugal, have been intensifying the collaboration between the two societies as well as the exchange and dissemination of information about their relevant activities, whilst promoting understanding and cooperation between their respective members. One possible way is to create joint working groups, open to the members of both societies, on common topics of interest. In fact, both societies already kicked off this activity. The first initiative happened during the 1st World Engineering Education Flash Week (WEE), Lisbon, 2011. The SPEE-IGIP Flash Moment was a one day event integrated in the main Conference, which was dedicated to “Information & Communication Technologies in Engineering Education”. ITs allow the development of different teaching strategies which contribute to enhance the learning outcomes of students. ITs are also particularly suited to develop Life Long Learning tools, in a broad range of Engineering subjects, either open to the general market or oriented to a very specific public. Examples of teaching strategies involving ITs have been addressed during the Flash Moment SPEE-IGIP which took place during WEE, and some are described in detail in the present work

Histamine Induces ATP Release from Human Subcutaneous Fibroblasts, via Pannexin-1 Hemichannels, Leading to Ca2+Mobilization and Cell Proliferation

Changes in the regulation of connective tissue ATP-mediated mechano-transduction and remodeling may be an important link to the pathogenesis of chronic pain. It has been demonstrated that mast cell-derived histamine plays an important role in painful fibrotic diseases. Here we analyzed the involvement of ATP in the response of human subcutaneous fibroblasts to histamine. Acute histamine application caused a rise in intracellular Ca(2+) ([Ca(2+)]i) and ATP release from human subcutaneous fibroblasts via H1 receptor activation. Histamine-induced [Ca(2+)]i rise was partially attenuated by apyrase, an enzyme that inactivates extracellular ATP, and by blocking P2 purinoceptors with pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt and reactive blue 2. [Ca(2+)]i accumulation caused by histamine was also reduced upon blocking pannexin-1 hemichannels with (10)Panx, probenecid, or carbenoxolone but not when connexin hemichannels were inhibited with mefloquine or 2-octanol. Brefeldin A, an inhibitor of vesicular exocytosis, also did not block histamine-induced [Ca(2+)]i mobilization. Prolonged exposure of human subcutaneous fibroblast cultures to histamine favored cell growth and type I collagen synthesis via the activation of H1 receptor. This effect was mimicked by ATP and its metabolite, ADP, whereas the selective P2Y1 receptor antagonist, MRS2179, partially attenuated histamine-induced cell growth and type I collagen production. Expression of pannexin-1 and ADP-sensitive P2Y1 receptor on human subcutaneous fibroblasts was confirmed by immunofluorescence confocal microscopy and Western blot analysis. In conclusion, histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to [Ca(2+)]i mobilization and cell growth through the cooperation of H1 and P2 (probably P2Y1) receptors.info:eu-repo/semantics/publishedVersio

Bradykinin-induced Ca2+ signaling in human subcutaneous fibroblasts involves ATP release via hemichannels leading to P2Y12 receptors activation

Chronic musculoskeletal pain involves connective tissue remodeling triggered by inflammatory mediators, such as bradykinin. Fibroblast cells signaling involve changes in intracellular Ca2+ ([Ca2+]i). ATP has been related to connective tissue mechanotransduction, remodeling and chronic inflammatory pain, via P2 purinoceptors activation. Here, we investigated the involvement of ATP in bradykinin-induced Ca2+ signals in human subcutaneous fibroblasts. Bradykinin, via B2 receptors, caused an abrupt rise in [Ca2+]i to a peak that declined to a plateau, which concentration remained constant until washout. The plateau phase was absent in Ca2+-free medium; [Ca2+]i signal was substantially reduced after depleting intracellular Ca2+ stores with thapsigargin. Extracellular ATP inactivation with apyrase decreased the [Ca2+]i plateau. Human subcutaneous fibroblasts respond to bradykinin by releasing ATP via connexin and pannexin hemichannels, since blockade of connexins, with 2- octanol or carbenoxolone, and pannexin-1, with 10Panx, attenuated bradykinin-induced [Ca2+]i plateau, whereas inhibitors of vesicular exocytosis, such as brefeldin A and bafilomycin A1, were inactive. The kinetics of extracellular ATP catabolism favors ADP accumulation in human fibroblast cultures. Inhibition of ectonucleotidase activity and, thus, ADP formation from released ATP with POM-1 or by Mg2+ removal from media reduced bradykinin-induced [Ca2+]i plateau. Selective blockade of the ADP-sensitive P2Y12 receptor with AR-C66096 attenuated bradykinin [Ca2+]i plateau, whereas the P2Y1 and P2Y13 receptor antagonists, respectively MRS 2179 and MRS 2211, were inactive. Human fibroblasts exhibited immunoreactivity against connexin-43, pannexin-1 and P2Y12 receptor. Bradykinin induces ATP release from human subcutaneous fibroblasts via connexin and pannexin-1-containing hemichannels leading to [Ca2+]i mobilization through the cooperation of B2 and P2Y12 receptors

Grand Challenges Scholars Program - GCSP at the Engineering School, Universidade Federal de Minas Gerais / Programa Acadêmico Grandes Desafios para a Engenharia, Escola de Engenharia, Universidade Federal de Minas Gerais

The structure of the Grand Challenges Scholars Program (GCSP) of the Universidade Federal de Minas Gerais -UFMG, School of Engineering, linked to the National Academy of Engineering (NAE) former initiative, is presented. This academic program has an aspirational vision of educating professionals for facing the challenges of engineering in the twenty-first century. The approach is based on an integrative methodology, geared toward the formation of critical competencies, with a focus on solutions to global problems. It creates opportunities for cooperation, as well as develops multicultural and multidisciplinary competencies, social ability, and commitment. Currently, the courses at the UFMG School of Engineering are adapting to meet the new national guidelines for Engineering courses in Brazil, published in January 2019, and the GCSP is a pilot program, capable of transforming the methodology, the mentality, and the educational and technological tools it uses, into an alternative for all engineering courses at UFMG. The Program started its activities in the School of Engineering in 2020, despite the challenges and limitations imposed by the Covid-19 pandemic. The operational criteria and the internal organization were defined, and the Program was introduced to the students. The first initiatives of the Program - with broad access to engineering students and open to the participation of students from other areas - included the Call No.01/2020 - Covid-19 and the I Sustainability Workshop, held in 2021

Immunogenicity and Reactogenicity of 2009 Influenza A (H1N1) Inactivated Monovalent Non-Adjuvanted Vaccine in Elderly and Immunocompromised Patients

Background\ud \ud Immunosuppressed individuals present serious morbidity and mortality from influenza, therefore it is important to understand the safety and immunogenicity of influenza vaccination among them.\ud Methods\ud \ud This multicenter cohort study evaluated the immunogenicity and reactogenicity of an inactivated, monovalent, non-adjuvanted pandemic (H1N1) 2009 vaccine among the elderly, HIV-infected, rheumatoid arthritis (RA), cancer, kidney transplant, and juvenile idiopathic arthritis (JIA) patients. Participants were included during routine clinical visits, and vaccinated according to conventional influenza vaccination schedules. Antibody response was measured by the hemagglutination-inhibition assay, before and 21 days after vaccination.\ud Results\ud \ud 319 patients with cancer, 260 with RA, 256 HIV-infected, 149 elderly individuals, 85 kidney transplant recipients, and 83 with JIA were included.\ud \ud The proportions of seroprotection, seroconversion, and the geometric mean titer ratios postvaccination were, respectively: 37.6%, 31.8%, and 3.2 among kidney transplant recipients, 61.5%, 53.1%, and 7.5 among RA patients, 63.1%, 55.7%, and 5.7 among the elderly, 59.0%, 54.7%, and 5.9 among HIV-infected patients, 52.4%, 49.2%, and 5.3 among cancer patients, 85.5%, 78.3%, and 16.5 among JIA patients. The vaccine was well tolerated, with no reported severe adverse events.\ud Conclusions\ud \ud The vaccine was safe among all groups, with an acceptable immunogenicity among the elderly and JIA patients, however new vaccination strategies should be explored to improve the immune response of immunocompromised adult patients. (ClinicalTrials.gov, NCT01218685)Fundação Butantan funded the study, and employed several of the authors. The funder had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript