In vitro and in vivo delivery of a sustained release nanocarrier-based formulation of an MRTF/SRF inhibitor in conjunctival fibrosis

Abstract Background Sustained drug delivery is a large unmet clinical need in glaucoma. Here, we incorporated a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor, CCG-222740, into slow release large unilamellar vesicles derived from the liposomes DOTMA (1,2-di-O-octadecenyl-3-trimethylammonium propane) and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), and tested their effects in vitro and in vivo. Results The vesicles were spherical particles of around 130 nm and were strongly cationic. A large amount of inhibitor could be incorporated into the vesicles. We showed that the nanocarrier CCG-222740 formulation gradually released the inhibitor over 14 days using high performance liquid chromatography. Nanocarrier CCG-222740 significantly decreased ACTA2 gene expression and was not cytotoxic in human conjunctival fibroblasts. In vivo, nanocarrier CCG-222740 doubled the bleb survival from 11.0 ± 0.6 days to 22.0 ± 1.3 days (p = 0.001), decreased conjunctival scarring and did not have any local or systemic adverse effects in a rabbit model of glaucoma filtration surgery. Conclusions Our study demonstrates proof-of-concept that a nanocarrier-based formulation efficiently achieves a sustained release of a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor and prevents conjunctival fibrosis in an established rabbit model of glaucoma filtration surgery.https://deepblue.lib.umich.edu/bitstream/2027.42/146540/1/12951_2018_Article_425.pd

Full remission and relapse of obsessive-compulsive symptoms after cognitive-behavioral group therapy: a two-year follow-up Remissão completa e recaídas dos sintomas obsessivo-compulsivos depois da terapia cognitivo-comportamental em grupo: dois anos de acompanhamento

OBJECTIVE: The aim of this study was to assess whether the results obtained with 12 sessions of cognitive-behavioral group therapy with obsessive-compulsive patients were maintained after two years, and whether the degree of symptom remission was associated with relapse. METHOD: Forty-two patients were followed. The severity of symptoms was measured at the end of cognitive-behavioral group therapy and at 18 and 24 months of follow-up. The assessment scales used were the Yale-Brown Obsessive-Compulsive Scale, Clinical Global Impression, Beck Depression Inventory, and Beck Anxiety Inventory. RESULTS: The reduction in symptom severity observed at the end of treatment was maintained during the two-year follow-up period (F = 57.881; p < 0.001). At the end of the treatment, 9 (21.4%) patients presented full remission, 22 (52.4%) presented partial remission, and 11 (26.2%) had unchanged scores in the Yale-Brown Obsessive-Compulsive Scale. After two years, 13 patients (31.0%) presented full remission, 20 (47.6%) had partial remission, and 9 (21.4%) had unchanged Yale-Brown Obsessive-Compulsive Scalescores. The full remission of symptoms at the end of the treatment was a protective factor against relapse (&#967;2 = 4,962; df = 1; p = 0.026). CONCLUSION: Our findings underscore the importance of attaining full remission of obsessive-compulsive symptoms during treatment and the need for new therapeutic strategies to achieve this.<br>OBJETIVO: Avaliar se os resultados obtidos com 12 sessões de terapia cognitivo-comportamental em grupo para pacientes com transtorno obsessivo-compulsivo foram mantidos depois de dois anos do final do tratamento e se o grau de remissão dos sintomas esteve associado às recaídas. MÉTODO: Quarenta e dois pacientes foram acompanhados. A gravidade dos sintomas foi avaliada no final da terapia cognitivo-comportamental em grupo, 18 e 24 meses após o término do tratamento. As escalas utilizadas para avaliação foram Yale-Brown Obsessive-Compulsive Scale, Clinical Global Impression, Beck Depression Inventory e Beck Anxiety Inventory. RESULTADOS: A redução da gravidade dos sintomas observada no final do tratamento foi mantida durante o período de dois anos de acompanhamento (F = 57,881; p < 0,001). Ao final do tratamento, 9 (21,4%) pacientes apresentaram remissão completa, 22 (52,4%) remissão parcial e 11 (26,2%) não apresentaram mudança na Yale-Brown Obsessive-Compulsive Scale. Dois anos depois, 13 pacientes (31,0%) apresentaram remissão completa dos sintomas, 20 (47,6%) apresentaram remissão parcial, e 9 (21,4%) não apresentaram mudança na Yale-Brown Obsessive-Compulsive Scale. A remissão completa dos sintomas ao final do tratamento foi protetora contra recaídas (&#967;2 = 4,962; df = 1; p = 0,026). CONCLUSÃO: Nossos achados apontam para a importância da obtenção da remissão completa dos sintomas obsessivo-compulsivos e para a necessidade de novas estratégias terapêuticas que tenham como meta atingir tal objetivo