RESUMEN
Porcine islet xenotransplantation is a viable strategy to treat diabetes. Its translation has been limited by the pre-clinical development of a clinically available immunosuppressive regimen. We tested two clinically relevant induction agents in a non-human primate (NHP) islet xenotransplantation model to compare depletional versus nondepletional induction immunosuppression. Neonatal porcine islets were isolated from GKO or hCD46/GKO transgenic piglets and transplanted via portal vein infusion in diabetic rhesus macaques. Induction therapy consisted of either basiliximab (n = 6) or rhesus-specific anti-thymocyte globulin (rhATG, n = 6), combined with a maintenance regimen using B7 costimulation blockade, tacrolimus with a delayed transition to sirolimus, and mycophenolate mofetil. Xenografts were monitored by blood glucose levels and porcine C-peptide measurements. Of the six receiving basiliximab induction, engraftment was achieved in 4 with median graft survival of 14 days. All six receiving rhATG induction engrafted with significantly longer xenograft survival at 40.5 days (P = 0.03). These data suggest that depletional induction provides superior xenograft survival to nondepletional induction, in the setting of a costimulation blockade-based maintenance regimen.
Asunto(s)
Suero Antilinfocítico , Trasplante de Islotes Pancreáticos , Animales , Suero Antilinfocítico/farmacología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Inmunosupresores/farmacología , Macaca mulatta , Porcinos , Trasplante HeterólogoRESUMEN
INTRODUCTION: We performed a systematic review of the literature to determine the value of bronchoalveolar lavage (BAL) in evaluating the pulmonary involvement of systemic sclerosis (SSc). METHODS: Articles published between 1980 and 2019 were retrieved from the databases: PubMed and Scielo. The search was restricted to clinical trials published in English, utilizing the keywords "scleroderma, systemic sclerosis, interstitial lung disease, and bronchoalveolar lavage". RESULTS: Twenty-two papers were analyzed. A positive correlation was observed between increased BAL cellularity (alveolitis) and worsening clinical symptoms, pulmonary function, and radiological pattern in 2, 11, and 15 studies, respectively. The majority of BAL studies that evaluated interleukin levels, including TNF-α, IL-6, IL-7, and IL-8, observed higher levels in patients with impaired pulmonary function and increased lung involvement. CONCLUSIONS: Alveolitis and the increase of some cytokines/chemokines in BAL were related to more severe pulmonary disease in SSc in the majority of the studies and seemed to be markers of worse prognosis, but it is unknown whether BAL adds clinical value to the use of the other non-invasive diagnostic procedures.
Asunto(s)
Lavado Broncoalveolar , Enfermedades Pulmonares Intersticiales/diagnóstico , Esclerodermia Sistémica/complicaciones , Humanos , Enfermedades Pulmonares Intersticiales/etiologíaRESUMEN
O objetivo deste trabalho consiste em comparar a percentagem da área preenchida pela guta-percha, nos níveis de 2 e 4 mm do terço apical de canais distais de molares inferiores, valendo-se de três técnicas de obturação: Sistema Termoplástico TC, Thermafil e CondensaçãoLateral. Trinta raízes distais de molares inferiores humanos foram utilizadas. Os canais foram instrumentados pela técnica manual coroa-ápice com limas Flexofile e, para uma melhor conicidade,foi utilizada como lima final a rotatória ProTaper F4 (Dentsply Maillefer). Em seguida, os canais foram obturados pelas técnicas a serem avaliadas e as raízes seccionados nos níveis 2 e 4 mm do ápice radicular. Os cortes foram analisados no aumento de 80 vezes. Imagens digitais foramanalisadas com auxilio de software (Image Pro Plus, Media Cybernetics, Inc). Os resultados obtidos, segundo o teste estatístico ANOVA, complementado pelo de Tukey?s, revelaram diferenças significantes entre os sistemas de obturação no nível de 2 mm do ápice (P < 0,001), com maior preenchimento de guta-percha nas técnicas de condensação lateral e TC. Concluiu-se que as técnicas TC e condensação lateral obtiveram os melhores resultados, apresentando diferenças estatísticassignificantes quando comparados ao Thermafil no nível de 2 mm. No nível de 4 mm, não foram encontradas diferenças entre as técnicas.
To compare the area filled by gutta-percha at 2 and 4 mm from the apex in distal canals of lower molars, using three obturation techniques: Termoplastic TC System, Thermafill and Lateral Condensation. Thirty distal roots of human lower molars were used in this study. The canalswere instrumented using Flexofiles in a crown-down technique, complemented by a ProTaper F4 (Dentsply Maillefer) rotary instrument to improve tapering. The canals were then obturated with the tested techniques, and the roots were sectioned at 2 and 4 mm from the apex. The samples were analyzed with 80× magnification. The percentage of the area filled with gutta-percha was assessed using a computer software (Image Pro Plus, Media Cybernetics, Inc). Statistical analysis (ANOVA and Tukey's post test) revealed significant differences between the obturation techniques tested at 2 mm from the apex (P < 0.001), with more gutta-percha present in Lateral Condensation and TC System techniques. The Lateral Condensation and TC System techniques presented the best results, showing significant differences when compared to the Thermafill at the 2 mm level. No differences between techniques were found at the 4 mm level.