The Experts below are selected from a list of 7365 Experts worldwide ranked by ideXlab platform
Alessia Stanzi - One of the best experts on this subject based on the ideXlab platform.
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do we need to cool the lung graft after ex vivo lung perfusion a preliminary study
Journal of Surgical Research, 2014Co-Authors: Alessia Stanzi, Arne Neyrinck, Jana Somers, Hans Cauwenberghs, Eric Verbeken, L Santambrogio, Dirk Van RaemdonckAbstract:Abstract Background After normothermic ex vivo lung perfusion (EVLP), pulmonary grafts are usually flush-cooled and stored on ice until implantation although evidence for this practice lacks. We compared outcomes between 2 post-EVLP preservation strategies in a porcine left single-lung transplantation model. Material and methods After cold flush and 2-h EVLP, donor lungs were prepared and split. In [C], ( n = 5) lungs cooled on device to 15°C were preserved in ice-water; in [W] ( n = 5), lungs were disconnected from EVLP at 37°C and kept at room temperature. The left lung was transplanted in a Recipient Animal. Posttransplant, 6 h-monitoring included hourly assessment of pulmonary vascular resistance, pulmonary artery pressure, plateau airway pressure, compliance, and oxygenation before and after exclusion of the right lung. Lung biopsies and bronchoscopy with bronchoalveolar lavage (BAL) were performed at retrieval, at the end of EVLP (R lung), and 1 and 6 h after reperfusion (L lung). Results Lungs in [W] showed the highest compliance ( P P Conclusions Normothermic preparation after EVLP results in similar graft performances compared with lung cooling after EVLP.
James M Wilson - One of the best experts on this subject based on the ideXlab platform.
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transient immune blockade prevents formation of neutralizing antibody to recombinant adenovirus and allows repeated gene transfer to mouse liver
Gene Therapy, 1996Co-Authors: Yiping Yang, K Greenough, James M WilsonAbstract:The hepatotropic properties of human adenoviruses have been used to develop vectors for in vivo liver-directed gene therapy. Current limitations for this vector system are the associated hepatitis that develops as a result of antigen-specific cellular immune responses and the difficulty in accomplishing repeated gene transfer. This study uses mouse models to define immune responses of the Recipient Animal that have previously been shown to prevent successful re-administration of virus and suggests approaches for preventing the development of these blocking immune responses. Our studies are most consistent with class II MHC-dependent activation ot T helper cells and B cells to capsid proteins of the input virus leading to the production of antiviral neutralizing antibody following a primary exposure to virus; this capsid-specific antibody appears to bind to virus and prevents entry in the context of a second administration of virus. Transient ablation of CD4 function at the time of virus administration prevents the formation of neutralizing antibody thereby allowing efficient gene transfer after at least two subsequent administrations of virus. Experiments in beta(2)m(-) mice and C57BL/6 mice treated with IL-12 suggested a more selective ablation of immune function based on inhibiting the activation of the T(H2) subset of T helper cells. From these studies on immune mechanisms it is hoped that viable strategies can be developed to overcome the problem of humoral immunity that occurs after the initial genetic therapy.
Lidia Ibbamanneschi - One of the best experts on this subject based on the ideXlab platform.
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protection of rat heart from ischaemia reperfusion injury by the 21 aminosteroid u 74389g
Pharmacological Research, 1996Co-Authors: A M Perna, P Liguori, Massimo Bonacchi, G M Laino, Chiara Nediani, Claudia Fiorillo, B Lunghi, Sandra Zecchiorlandini, Lucia Formigli, Lidia IbbamanneschiAbstract:In ischaemia-reperfusion syndromes lipid peroxidation appears an important factor contributing to tissue damage. The 21-aminosteroids (lazaroids) exhibit beneficial effects in various pathological conditions, especially in post-traumatic lesions of the central nervous system, where a peroxidative injury seems to be involved. The aim of our study was to ascertain if one of these compounds, U-74389G, plays a significant role in protecting heart muscle from ischaemia-reperfusion damage. Rat hearts used for heterotopic transplantation represented the experimental model in this investigation. Animals (Wistar rats weighing 200–250g) were divided into five groups: controls, untreated and treated donors, untreated and treated Recipients. Donors were anaesthetized and heparinized, and the heart was excised through a bilateral thoracotomy, arrested with St Thomas solution and stored in cold saline for 2 hours. For the Recipient preparation, a modified Ono's technique was used, and heart reimplantation was performed with a termino-lateral aorto-aortic anasthomosis and a termino-lateral pulmonary-cava anasthomosis. After the anasthomoses were completed hearts were reperfused for 30 min; then hearts were excised and specimens were taken for biochemical and morphological studies. These were conducted on three groups of hearts: (A) hearts reimplanted and reperfused without treatment of the donor or of the Recipient Animal; (B) hearts subjected to the same procedure but in the presence of U-74389G treatment of donors and Recipient rats; (C) control hearts rapidly excised from normal, non-operated Animals. Electron microscopy studies showed, in hearts transplanted without treatment, the typical morphological aspects of lipoperoxidative injury: swollen mitochondria with disrupted cristae, damaged endothelial cells with the nucleous bulging into the lumen and a discontinued endothelial lining with diffuse oedema among the fibers. Lazaroid treatment attenuated most of these damages in hearts of group B. As for the biochemical findings, the hearts transplanted in the presence of U-74389G treatment had significantly higher ATP and creatine phosphate levels (P<0.01) and lower malondialdehyde concentrations (P<0.05) with respect to the hearts transplanted without treatment. Furthermore, serum creatine kinase activity was lower in treated than in untreated Recipient Animals (P<0.05). Taken together, all these results indicate that U-74389G treatment is effective in protecting cardiac muscle from structural and functional ischaemia-reperfusion injuries, at least from those arising during a heart transplantation procedure.
Bergen A.a. - One of the best experts on this subject based on the ideXlab platform.
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A Systematic Review on Transplantation Studies of the Retinal Pigment Epithelium in Animal Models
'MDPI AG', 2020Co-Authors: Koster C., Wever K.e., Hirk K., Hooijmans C.r., Bergen A.a.Abstract:The retinal pigment epithelium (RPE) and the adjacent light-sensitive photoreceptors form a single functional unit lining the back of the eye. Both cell layers are essential for normal vision. RPE degeneration is usually followed by photoreceptor degeneration and vice versa. There are currently almost no effective therapies available for RPE disorders such as Stargardt disease, specific types of retinitis pigmentosa, and age-related macular degeneration. RPE replacement for these disorders, especially in later stages of the disease, may be one of the most promising future therapies. There is, however, no consensus regarding the optimal RPE source, delivery strategy, or the optimal experimental host in which to test RPE replacement therapy. Multiple RPE sources, delivery methods, and Recipient Animal models have been investigated, with variable results. So far, a systematic evaluation of the (variables influencing) efficacy of experimental RPE replacement parameters is lacking. Here we investigate the effect of RPE transplantation on vision and vision-based behavior in Animal models of retinal degenerated diseases. In addition, we aim to explore the effect of RPE source used for transplantation, the method of intervention, and the Animal model which is used. METHODS: In this study, we systematically identified all publications concerning transplantation of RPE in experimental Animal models targeting the improvement of vision (e.g., outcome measurements related to the morphology or function of the eye). A variety of characteristics, such as species, gender, and age of the Animals but also cell type, number of cells, and other intervention characteristics were extracted from all studies. A risk of bias analysis was performed as well. Subsequently, all references describing one of the following outcomes were analyzed in depth in this systematic review: a-, b-, and c-wave amplitudes, vision-based, thickness analyses based on optical coherence tomography (OCT) data, and transplant survival based on scanning laser ophthalmoscopy (SLO) data. Meta-analyses were performed on the a- and b-wave amplitudes from electroretinography (ERG) data as well as data from vision-based behavioral assays. RESULTS: original research articles met the inclusion criteria after two screening rounds. Overall, most studies were categorized as unclear regarding the risk of bias, because many experimental details were poorly reported. Twenty-three studies reporting one or more of the outcome measures of interest were eligible for either descriptive (thickness analyses based on OCT data; n = 2) or meta-analyses. RPE transplantation significantly increased ERG a-wave (Hedges' g 1.181 (0.471-1.892), n = 6) and b-wave (Hedges' g 1.734 (1.295-2.172), n = 42) amplitudes and improved vision-based behavior (Hedges' g 1.018 (0.826-1.209), n = 96). Subgroup analyses revealed a significantly increased effect of the use of young and adolescent Animals compared to adult Animals. Moreover, transplanting more cells (in the range of 10(5) versus in the range of 10(4)) resulted in a significantly increased effect on vision-based behavior as well. The origin of cells mattered as well. A significantly increased effect was found on vision-based behavior when using ARPE-19 and OpRegen(®) RPE. CONCLUSIONS: This systematic review shows that RPE transplantation in Animal models for retinal degeneration significantly increases a- and b- wave amplitudes and improves vision-related behavior. These effects appear to be more pronounced in young Animals, when the number of transplanted cells is larger and when ARPE-19 and OpRegen(®) RPE cells are used. We further emphasize that there is an urgent need for improving the reporting and methodological quality of Animal experiments, to make such studies more comparable
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A Systematic Review on Transplantation Studies of the Retinal Pigment Epithelium in Animal Models
'MDPI AG', 2020Co-Authors: Koster C., Wever K.e., Hirk K., Hooijmans C.r., Bergen A.a.Abstract:Contains fulltext : 220892.pdf (publisher's version ) (Open Access)The retinal pigment epithelium (RPE) and the adjacent light-sensitive photoreceptors form a single functional unit lining the back of the eye. Both cell layers are essential for normal vision. RPE degeneration is usually followed by photoreceptor degeneration and vice versa. There are currently almost no effective therapies available for RPE disorders such as Stargardt disease, specific types of retinitis pigmentosa, and age-related macular degeneration. RPE replacement for these disorders, especially in later stages of the disease, may be one of the most promising future therapies. There is, however, no consensus regarding the optimal RPE source, delivery strategy, or the optimal experimental host in which to test RPE replacement therapy. Multiple RPE sources, delivery methods, and Recipient Animal models have been investigated, with variable results. So far, a systematic evaluation of the (variables influencing) efficacy of experimental RPE replacement parameters is lacking. Here we investigate the effect of RPE transplantation on vision and vision-based behavior in Animal models of retinal degenerated diseases. In addition, we aim to explore the effect of RPE source used for transplantation, the method of intervention, and the Animal model which is used. METHODS: In this study, we systematically identified all publications concerning transplantation of RPE in experimental Animal models targeting the improvement of vision (e.g., outcome measurements related to the morphology or function of the eye). A variety of characteristics, such as species, gender, and age of the Animals but also cell type, number of cells, and other intervention characteristics were extracted from all studies. A risk of bias analysis was performed as well. Subsequently, all references describing one of the following outcomes were analyzed in depth in this systematic review: a-, b-, and c-wave amplitudes, vision-based, thickness analyses based on optical coherence tomography (OCT) data, and transplant survival based on scanning laser ophthalmoscopy (SLO) data. Meta-analyses were performed on the a- and b-wave amplitudes from electroretinography (ERG) data as well as data from vision-based behavioral assays. RESULTS: original research articles met the inclusion criteria after two screening rounds. Overall, most studies were categorized as unclear regarding the risk of bias, because many experimental details were poorly reported. Twenty-three studies reporting one or more of the outcome measures of interest were eligible for either descriptive (thickness analyses based on OCT data; n = 2) or meta-analyses. RPE transplantation significantly increased ERG a-wave (Hedges' g 1.181 (0.471-1.892), n = 6) and b-wave (Hedges' g 1.734 (1.295-2.172), n = 42) amplitudes and improved vision-based behavior (Hedges' g 1.018 (0.826-1.209), n = 96). Subgroup analyses revealed a significantly increased effect of the use of young and adolescent Animals compared to adult Animals. Moreover, transplanting more cells (in the range of 10(5) versus in the range of 10(4)) resulted in a significantly increased effect on vision-based behavior as well. The origin of cells mattered as well. A significantly increased effect was found on vision-based behavior when using ARPE-19 and OpRegen(®) RPE. CONCLUSIONS: This systematic review shows that RPE transplantation in Animal models for retinal degeneration significantly increases a- and b- wave amplitudes and improves vision-related behavior. These effects appear to be more pronounced in young Animals, when the number of transplanted cells is larger and when ARPE-19 and OpRegen(®) RPE cells are used. We further emphasize that there is an urgent need for improving the reporting and methodological quality of Animal experiments, to make such studies more comparable
Dirk Van Raemdonck - One of the best experts on this subject based on the ideXlab platform.
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do we need to cool the lung graft after ex vivo lung perfusion a preliminary study
Journal of Surgical Research, 2014Co-Authors: Alessia Stanzi, Arne Neyrinck, Jana Somers, Hans Cauwenberghs, Eric Verbeken, L Santambrogio, Dirk Van RaemdonckAbstract:Abstract Background After normothermic ex vivo lung perfusion (EVLP), pulmonary grafts are usually flush-cooled and stored on ice until implantation although evidence for this practice lacks. We compared outcomes between 2 post-EVLP preservation strategies in a porcine left single-lung transplantation model. Material and methods After cold flush and 2-h EVLP, donor lungs were prepared and split. In [C], ( n = 5) lungs cooled on device to 15°C were preserved in ice-water; in [W] ( n = 5), lungs were disconnected from EVLP at 37°C and kept at room temperature. The left lung was transplanted in a Recipient Animal. Posttransplant, 6 h-monitoring included hourly assessment of pulmonary vascular resistance, pulmonary artery pressure, plateau airway pressure, compliance, and oxygenation before and after exclusion of the right lung. Lung biopsies and bronchoscopy with bronchoalveolar lavage (BAL) were performed at retrieval, at the end of EVLP (R lung), and 1 and 6 h after reperfusion (L lung). Results Lungs in [W] showed the highest compliance ( P P Conclusions Normothermic preparation after EVLP results in similar graft performances compared with lung cooling after EVLP.