RESUMO
The field of orthobiologics continues to advance at a rapid pace and theoretically holds some promise to augment the biologic healing response in rotator cuff repair (RCR). However, the clinical evidence for use of substances such as platelet-rich plasma (PRP) for RCR remains inconclusive. Atelocollagen, as a synthetic collagen substitute, has been proposed as another alternative to provide more collagen substrate for healing, but outcomes data with this technique is lacking. In contrast, (biologic) PRP has been well studied, does not show adverse outcomes, and has been shown to improve healing of large to massive tears, as well as RCR outcomes. As biologic augmentation options continue to push the envelope on indications, due diligence is required to carefully examine options for safety and efficacy. Evolutions in RCR should also continue to motivate sports medicine surgeons and researchers to seek out further innovations to improve patient outcomes. That said, PRP outcome improvement for RCR is not definitive and requires further study. RCR can humble even the best of surgeons and demands that we continue to look for ways to improve outcomes.
RESUMO
During their development, B lymphocytes undergo V(D)J recombination events and selection processes that, if successfully completed, produce mature B cells expressing a non-self-reactive B-cell receptor (BCR). Primary V(D)J rearrangements yield self-reactive B cells at high frequency, triggering attempts to remove, silence, or reprogramme them through deletion, anergy induction, or secondary V(D)J recombination (receptor editing), respectively. In principle, expressing a catalytically inactive V(D)J recombinase during a developmental stage in which V(D)J rearrangement is initiated may impair this process. To test this idea, we generated transgenic mice expressing a RAG1 active site mutant (dnRAG1 mice); RAG1 transcript was elevated in splenic, but not bone marrow, B cells in dnRAG1 mice relative to wild-type mice. The dnRAG1 mice accumulate splenic B cells with a B1-like phenotype that exhibit defects in B-cell activation, and are clonally diverse, yet repertoire restricted with a bias toward Jκ1 gene segment usage. The dnRAG1 mice show evidence of impaired B-cell development at the immature-to-mature transition, immunoglobulin deficiency, and poorer immune responses to thymus-independent antigens. Interestingly, dnRAG1 mice expressing the anti-dsDNA 3H9H56R heavy chain fail to accumulate splenic B1-like cells, yet retain peritoneal B1 cells. Instead, these mice show an expanded marginal zone compartment, but no difference is detected in the frequency of heavy chain gene replacement. Taken together, these data suggest a model in which dnRAG1 expression impairs secondary V(D)J recombination. As a result, selection and/or differentiation processes are altered in a way that promotes expansion of B1-like B cells in the spleen.
Assuntos
Linfócitos B/imunologia , Genes RAG-1 , Recombinação V(D)J , Animais , Linfócitos B/citologia , Domínio Catalítico , Proliferação de Células , Ativação Enzimática , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/imunologia , Camundongos , Camundongos Transgênicos , Modelos Imunológicos , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/imunologia , Baço/citologia , Baço/imunologia , VDJ Recombinases/genética , VDJ Recombinases/imunologiaRESUMO
OBJECTIVES: Alcohol consumption is a known risk factor for traumatic injuries of all types and has been shown to produce detrimental effects on bone metabolism. Although the mechanisms responsible for these detrimental effects are not well characterized, oxidative stress from alcohol exposure appears to play a central role. This study was designed to examine the effect of a short-term binge alcohol consumption pattern on fracture repair and the effect of an antioxidant, N-acetylcysteine, on fracture healing after binge alcohol consumption. METHODS: One hundred forty-four adult male Sprague-Dawley rats underwent unilateral closed femur fracture after injection of either saline or alcohol to simulate a binge alcohol cycle. Animals in the antioxidant treatment group received daily N-acetylcysteine after fracture. Femurs were harvested at 1, 2, 4, and 6 weeks after injury and underwent biomechanical testing and histologic analysis. RESULTS: Binge alcohol administration was associated with significant decreases in biomechanical strength at 1- and 2-week time points with a trend toward decreased strength at 4- and 6-week time points as well. Alcohol-treated animals had less cartilage component within the fracture callus and healed primarily by intramembranous ossification. Administration of N-acetylcysteine in alcohol-treated animals improved biomechanical strength to levels comparable to the control animals and was associated with increased endochondral ossification. CONCLUSIONS: Our results indicate that binge alcohol alters the quality of fracture healing after a traumatic injury and that concurrent administration of an antioxidant is able to reverse these effects.