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1.
Ocul Surf ; 20: 185-194, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33607323

RESUMO

Corneal transplantation is a routine procedure for patients with corneal blindness. Despite the streamlining of surgical techniques and deeper understanding of the cellular and molecular pathways mediating rejection, corticosteroids are still the main immunosuppressive regimen in corneal transplantation, and the 15-year survival of corneal transplants remains as low as 50%, which is poorer than that for most solid organ transplants. Recently, mesenchymal stromal cells (MSCs) with unique regenerative and immune-modulating properties have emerged as a promising cell therapy to promote transplant tolerance, minimize the use of immunosuppressants, and prevent chronic rejection. Here, we review the literature on preclinical studies of MSCs for corneal transplantation and summarize the key findings from clinical trials with MSCs in solid organ transplantation. Finally, we highlight current issues and challenges regarding MSC therapies and suggest strategies for safe and effective MSC-based therapies in clinical transplantation.


Assuntos
Transplante de Córnea , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Rejeição de Enxerto , Humanos , Imunossupressores
2.
Br J Ophthalmol ; 105(6): 862-868, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32703786

RESUMO

BACKGROUND: To investigate the relationship between estimated mean ocular perfusion pressure (MOPP) and peripapillary perfusion density (PD) or vessel density (VD) as measured by spectral-domain optical coherence tomography angiography (OCTA) in young healthy eyes. METHODS: 132 healthy participants (264 eyes) under 45 years of age underwent optic disc OCTA scan sized 3×3 mm to acquire PD and VD in the superficial vascular complex (SVC). Optic nerve head (ONH) parameters including retinal nerve fibre layer (RNFL) thickness, rim area and disc area were measured. MOPP was estimated from systemic blood pressure and intraocular pressure (IOP). A linear mixed model was used to find the systemic and ocular factors associated with PD and VD. RESULTS: The average age of the subjects was 25.8±6.5 years. PD and VD showed a significant correlation with RNFL thickness (r=0.224, p<0.001 and r=0.214, p<0.001, respectively), but with MOPP, the correlation was only marginally significant (r=0.105, p=0.09 and r=0.112, p=0.07, respectively). After controlling for confounding factors, including age, sex, IOP, central corneal thickness, axial length and OCTA signal strength, PD and VD were significantly associated with ONH parameters (all p<0.05) but not with estimated MOPP (all p>0.05). CONCLUSION: PD and VD in the SVC were significantly associated with ONH parameters while showing no association with estimated MOPP. OCTA-derived VD may not represent perfusion pressure, but is rather more dependent on peripapillary structure.


Assuntos
Angiofluoresceinografia/métodos , Pressão Intraocular/fisiologia , Disco Óptico/irrigação sanguínea , Células Ganglionares da Retina/patologia , Vasos Retinianos/fisiopatologia , Tomografia de Coerência Óptica/métodos , Campos Visuais , Adolescente , Adulto , Feminino , Fundo de Olho , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/fisiopatologia , Voluntários Saudáveis , Humanos , Masculino , Fibras Nervosas/patologia , Estudos Prospectivos , Vasos Retinianos/diagnóstico por imagem , Tonometria Ocular , Adulto Jovem
3.
Korean J Ophthalmol ; 34(5): 375-382, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33099559

RESUMO

PURPOSE: To evaluate the prevalence of the prism adaptation response in patients with intermittent exotropia (IXT) using the short-term prism adaptation test (PAT) and to assess factors associated with prism adaptation response in IXT patients. METHODS: A case-controlled retrospective analysis was performed on 113 patients with IXT without prior surgical treatment. Age, sex, visual acuity, refraction, stereoacuity, control scale, type of exotropia, history of occlusion, and presence of accompanying visual symptoms were recorded. Prism alternate cover test (PACT) was performed with fixation targets at 6 m and 1/3 m. All patients underwent short-term PAT wearing prism glasses that offset the exodeviation previously measured by PACT. After 30 minutes, angle deviation was measured, and patients were classified into either an increase group, which had an increase in deviation ≥5 prism diopters after short-term PAT, or a no-change group. Analysis was performed to investigate the clinical factors influencing the increase in exodeviation after short-term PAT. RESULTS: Fifty patients (44.2%) showed an increase ≥5 prism diopters during distance or near fixation after short-term PAT compared to the previous PACT: 12 patients (10.6%) showed an increment at distance fixation, and 45 patients (39.8%) showed an increase at near fixation. At distance fixation, the increase-group had a significantly smaller maximum angle measured by PACT. At near distance, age at PAT, maximum distance angle, minimum distance angle, maximum near angle, minimum near angle, angle fluctuation at near, and IXT type showed significant associations with positive short-term PAT response. In the multivariate analysis, older age and smaller maximum near angle were significantly associated with positive short-term PAT response at near fixation. CONCLUSIONS: Short-term PAT could be helpful in older IXT patients with a small maximum angle of deviation at near fixation to mitigate the vergence aftereffect and show the maximum angle of deviation.


Assuntos
Exotropia/terapia , Movimentos Oculares/fisiologia , Óculos , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos/métodos , Acuidade Visual , Estudos de Casos e Controles , Criança , Pré-Escolar , Doença Crônica , Progressão da Doença , Exotropia/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Músculos Oculomotores/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento
5.
Neurol Sci ; 41(10): 2755-2760, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32277391

RESUMO

BACKGROUND: The aim of this study was to determine important clinical and radiological features that aid in distinguishing presumed idiopathic optic perineuritis (OPN) from optic neuritis (ON) associated with antibody against myelin oligodendrocyte glycoprotein (MOG-Ab). METHODS: This retrospective, case-control study recruited patients with MOG-Ab-associated ON from 2011 through 2018 and idiopathic OPN from 2009 through 2011. The presence of MOG-Ab was not investigated in idiopathic OPN, because MOG-Ab testing was not available until 2011. The clinical and radiological features and the disease course were compared between the two patient groups. RESULTS: A total of 48 patients with MOG-Ab-associated ON were identified. These included 15 patients showing optic nerve sheath enhancement (ONSE) and 33 with only optic nerve enhancement. Ocular pain with ocular movement and optic disc swelling were more common in patients with ONSE, who also exhibited a poorer initial visual acuity than did those without ONSE. However, the response to steroid treatment, incidence of relapse after steroid treatment, and visual outcome at the last visit were similar between subgroups. The clinical and radiological features and treatment outcome were similar between these patients with OPN and patients with MOG-Ab-associated ON with ONSE. On the other hand, the clinical features of MOG-Ab-associated ON without ONSE differed from those of idiopathic OPN. CONCLUSION: Our findings showed a substantial proportion of ONSE in patients with MOG-Ab-associated ON. In view of the similarities between these patients and patients with OPN, MOG-Ab testing should be performed in all patients with idiopathic OPN.


Assuntos
Autoanticorpos , Neurite Óptica , Estudos de Casos e Controles , Humanos , Glicoproteína Mielina-Oligodendrócito , Neurite Óptica/diagnóstico por imagem , Estudos Retrospectivos
6.
Clin Transplant ; 32(9): e13376, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30098071

RESUMO

Randomized, open-label, comparative, single-center, Phase 4, 24-week study comparing pharmacokinetics (PK), safety, and efficacy of once-daily, prolonged-release tacrolimus (PR-T) with twice-daily, immediate-release tacrolimus (IR-T) in adult de novo living-donor liver transplant (LDLT) recipients in Korea. All patients received intravenous tacrolimus from Day 0 (transplantation) for 4 days and were randomized (1:1) to receive oral PR-T or IR-T from Day 5. PK profiles were taken on Days 6 and 21. Primary endpoint: area under the concentration-time curve over 24 hour (AUC0-24 ). Predefined similarity interval for confidence intervals of ratios: 80%-125%. Secondary endpoints included: tacrolimus concentration at 24 hour (C24 ), patient/graft survival, biopsy-confirmed acute rejection (BCAR), treatment-emergent adverse events (TEAEs). One-hundred patients were included (PR-T, n = 50; IR-T, n = 50). Compared with IR-T, 40% and 66% higher mean PR-T daily doses resulted in similar AUC0-24 between formulations on Day 6 (PR-T:IR-T ratio of means 96.8%), and numerically higher AUC0-24 with PR-T on Day 21 (128.8%), respectively. Linear relationship was similar between AUC0-24 and C24 , and formulations. No graft loss/deaths, incidence of BCAR and TEAEs similar between formulations. Higher PR-T vs IR-T doses were required to achieve comparable systemic exposure in Korean de novo LDLT recipients. PR-T was efficacious; no new safety signals were detected.


Assuntos
Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Fígado/efeitos adversos , Doadores Vivos/provisão & distribuição , Complicações Pós-Operatórias/tratamento farmacológico , Tacrolimo/administração & dosagem , Tacrolimo/farmacologia , Adulto , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Imunossupressores/farmacologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Prognóstico , Tacrolimo/farmacocinética , Distribuição Tecidual
7.
PLoS One ; 12(10): e0186229, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29040280

RESUMO

In this retrospective cross-sectional study, we quantitatively analyzed the tomographic features in the neural tissues around the optic disc in patients with diabetic retinopathy with and without panretinal photocoagulation. We analyzed 206 eyes, comprising 33 normal eyes in subjects without diabetes (group I), 30 eyes without diabetic retinopathy (group II), 66 eyes with non-proliferative diabetic retinopathy (group III), 45 eyes with panretinal photocoagulation (group IV), and 32 eyes with normal tension glaucoma (group V). Sequential images acquired using swept-source optical coherence tomography in three-dimensional mode were used to measure peripapillary retinal nerve fiber layer thickness, neuro-retinal rim thickness, anterior lamina cribrosa depth, prelaminar thickness, and thickness of the lamina cribrosa. The peripapillary retinal nerve fiber layer thickness and lamina cribrosa thickness were significantly thinner in group IV than in group III (p = 0.019 and p < 0.001). However, there was no significant difference in rim thickness, anterior lamina cribrosa depth, or prelaminar thickness between groups III and IV (p = 0.307, p = 0.877, and p = 0.212). Multivariate analysis revealed that time since panretinal photocoagulation and thickness of the lamina cribrosa had a significant effect on peripapillary retinal nerve fiber layer thickness (p < 0.001 and p = 0.014). In group IV, there was a negative correlation between time elapsed since panretinal photocoagulation and peripapillary retinal nerve fiber layer thickness, rim thickness, and thickness of the lamina cribrosa (r = -0.765, r = -0.490, and r = -0.419), but no correlation with prelaminar thickness or anterior lamina cribrosa depth (r = 0.104 and r = -0.171). Panretinal photocoagulation may be related to thinning of the peripapillary retinal nerve fiber layer, rim thickness, and lamina cribrosa, but not prelaminar thickness or anterior lamina cribrosa depth. These features are different from the peripapillary features of eyes with typical normal tension glaucoma.


Assuntos
Retinopatia Diabética/diagnóstico por imagem , Glaucoma de Baixa Tensão/diagnóstico por imagem , Disco Óptico/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Idoso , Retinopatia Diabética/fisiopatologia , Feminino , Humanos , Glaucoma de Baixa Tensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Disco Óptico/fisiopatologia , Retina/diagnóstico por imagem , Retina/fisiopatologia , Células Ganglionares da Retina/patologia
8.
Cytotherapy ; 19(1): 28-35, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27840134

RESUMO

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) offer tremendous potential for therapeutic applications for inflammatory diseases. However, tissue-derived MSCs, such as bone marrow-derived MSCs (BM-MSCs), have considerable donor variations and limited expandability. It was recently demonstrated that MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have less pro-tumor potential and greater expandability of homogenous cell population. In this study, we investigated the anti-inflammatory effects and mechanism of iPSC-MSCs in a murine model of chemical and mechanical injury to the cornea and compared the effects with those of BM-MSCs. METHODS: To create an injury, ethanol was applied to the corneal surface in mice, and the corneal epithelium was removed with a blade. Immediately after injury, mice received an intravenous injection of (i) iPSC-MSCs, (ii) BM-MSCs or (iii) vehicle. Clinical, histological and molecular assays were performed in the cornea to evaluate inflammation. RESULTS: We found that corneal opacity was significantly reduced by iPSC-MSCs or BM-MSCs. Histological examination revealed that the swelling and inflammatory infiltration in the cornea were markedly decreased in mice treated with iPSC-MSCs or BM-MSCs. Corneal levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were lower in iPSC-MSC- and BM-MSC-treated mice, compared with vehicle-treated controls. In contrast, iPSC-MSCs with a knockdown of the TNF-α stimulating gene (TSG)-6 did not suppress the levels of inflammatory cytokines and failed to reduce corneal opacity. CONCLUSIONS: Together these data demonstrate that iPSC-MSCs exert therapeutic effects in the cornea by reducing inflammation in part through the expression of TSG-6, and the effects are similar to those seen with BM-MSCs.


Assuntos
Lesões da Córnea/terapia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Mesenquimais/citologia , Animais , Células da Medula Óssea/citologia , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Lesões da Córnea/metabolismo , Opacidade da Córnea/patologia , Opacidade da Córnea/terapia , Modelos Animais de Doenças , Células-Tronco Pluripotentes Induzidas/transplante , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Ceratite/patologia , Ceratite/terapia , Transplante de Células-Tronco Mesenquimais , Camundongos Endogâmicos BALB C , Fator de Necrose Tumoral alfa/metabolismo
9.
Hepatobiliary Pancreat Dis Int ; 15(5): 480-486, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27733316

RESUMO

BACKGROUND: Although perioperative portal vein (PV) stent implantation is an effective treatment for steno-occlusive disease in adult living donor liver transplantation (LDLT) recipients, we experienced high incidence of biliary anastomotic strictures (BAS) after PV stenting. In this study, we sought to clarify the relation between BAS and PV stenting and to suggest the possible mechanism of BAS and measures to reduce its incidence. METHODS: We retrospectively analyzed 44 LDLT recipients who underwent PV stent implantation across the line of PV anastomosis regardless of the location of steno-occlusion (stent group) and their matched controls (non-stented LDLT recipients, n=131). RESULTS: The incidence of BAS was higher in patients in the stent group than that in the control group (43.2% vs 17.6%, P=0.001). Cumulative 6-month and 1-, 2- and 5-year BAS rates were 31.8%, 34.1%, 41.4% and 43.2%, respectively, in the stent group and 13.0%, 13.8%, 16.1% and 17.8%, respectively, in the control group (P=0.001). Multivariate analysis revealed that PV stenting was an independent risk factor for BAS. CONCLUSIONS: Although PV stent implantation is a reliable treatment modality for steno-occlusive PV in adult LDLT recipients, innovative methods to prevent the PV stent from crossing the line of PV anastomosis may be necessary to reduce the incidence of postoperative BAS.


Assuntos
Colestase/etiologia , Procedimentos Endovasculares/instrumentação , Transplante de Fígado/efeitos adversos , Doadores Vivos , Stents , Doenças Vasculares/terapia , Adulto , Distribuição de Qui-Quadrado , Colestase/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Constrição Patológica , Intervalo Livre de Doença , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Flebografia/métodos , Veia Porta/diagnóstico por imagem , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Doenças Vasculares/diagnóstico
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