Oxidative stress is a pathogenic feature in vitreoretinal disease. However, the ability of the inner retina to manage metabolic waste and oxidative stress is unknown. Proteomic analysis of antioxidants in the human vitreous, the extracellular matrix opposing the inner retina, identified superoxide dismutase-3 (SOD3) that localized to a unique matrix structure in the vitreous base and cortex. To determine the role of SOD3, Sod3−/− mice underwent histological and clinical phenotyping. Although the eyes were structurally normal, at the vitreoretinal interface Sod3−/− mice demonstrated higher levels of 3-nitrotyrosine, a key marker of oxidative stress. Pattern electroretinography also showed physiological signaling abnormalities within the inner retina. Vitreous biopsies and epiretinal membranes collected from patients with diabetic vitreoretinopathy (DVR) and a mouse model of DVR showed significantly higher levels of nitrates and/or 3-nitrotyrosine oxidative stress biomarkers suggestive of SOD3 dysfunction. This study analyzes the molecular pathways that regulate oxidative stress in human vitreous substructures. The absence or dysregulation of the SOD3 antioxidant at the vitreous base and cortex results in increased oxidative stress and tissue damage to the inner retina, which may underlie DVR pathogenesis and other vitreoretinal diseases.
Esophageal perforation is a rare condition that is commonly missed. Male gender and alcohol use are predisposing risk factors. Most of the cases are iatrogenic or traumatic; nonetheless, spontaneous cases are not uncommon. It typically occurs after vomiting or straining as the increased intra-abdominal pressure transmits into the esophagus and results in the tear. One of the main complications is acute bacterial mediastinitis from contamination with esophageal flora. This condition can be life-threatening because it is very frequently misdiagnosed and appropriate management is often delayed.A 49-year-old man presented with worsening sudden-onset interscapular back pain that then changed to chest pain with odynophagia and was found to have fever and leukocytosis.Chest computed tomography revealed signs of mediastinitis with possible esophageal perforation. He reported symptoms started 2 days ago after lifting of heavy objects. Empiric antimicrobial was begun with conservative management and avoidance of oral intake. Barium esophagram and esophagogastroduodenoscopy revealed no signs of perforation or inflammation. His symptoms resolved and he gradually resumed oral intake. Blood cultures grew Methicillin-sensitive Staphylococcus aureus and he was discharged on appropriate antibiotics for 4 weeks. He did well on follow-up 3 months after hospitalization.The case highlights the importance of considering esophageal etiologies of chest pain.
Five bacteriophages that infect the Rhodobacter capsulatus strain YW1 were isolated from stream water near Bloomington, Illinois, USA. Two distinct genome types are represented in the newly isolated bacteriophages. These genomes are different from other bacteriophage genomes previously described.
A major limitation of the use of cellular therapies is the loss of donor-derived cells because of immune incompatibility. While induced pluripotent stem (iPS) cells offer the potential for autologous transplant therapies, questions have been raised using a mouse model that specific antigens mediate the rejection of grafts after syngeneic transplants with iPS, but not embryonic stem (ES) cells. In this study, we examined whether the human homologs of these markers, HORMAD1, ZG16, and Cyp3A, are differentially expressed in human iPS versus ES cells, as well as undifferentiated and in vitro-differentiated cells. Both qRT-PCR and flow cytometric analyses demonstrated similar gene and protein expression profiles for iPS and ES cells regardless of differentiation state. Our data are consistent with a recent study in mice that showed no evidence of rejection of differentiated syngeneic iPS cells. Furthermore, our results suggest that expression of these gene products cannot predict differences in clinical outcomes between human iPS and ES-derived cells.
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