Inhibition of NAD(P)H oxidase reduces apoptosis and avascular retina in an animal model of retinopathy of prematurity

Purpose: To study the mechanisms of action of the antioxidants, n-acetylcysteine (NAC), and the nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase oxidase inhibitor, apocynin, on intravitreous neovascularization (IVNV), and retinal avascularity in a rat model of retinopathy of prematurity (ROP). Methods: Newborn rats exposed to oxygen-induced retinopathy underwent intraperitoneal (IP) injections of NAC (150 mg/kg) at post-natal day (p)2, p6, p10 (early NAC-treated), or p12 through p17 (late NAC-treated), apocynin (10 mg/kg) from p12 through p17, or phosphate buffered saline (PBS; controls). Lipid hydroperoxide (LHP) was measured in early NAC-treated oxygen-induced retinopathy (OIR) at p7, p14 and p18. Pups were placed in room air at p14. At p18, retinal flat mounts were scored for IVNV and avascular/total retinal area, or retinas were assayed for cleaved caspase-3 and vascular endothelial growth factor (VEGF) protein. In non-injected OIR pups, retinas were assayed for gp91phox. Cryosections were stained with isolectin B4, cleaved caspase-3, CD68, CD31, gp91phox, neuron-glial antigen 2 (NG-2), or anti-glial fibrillary acidic protein (GFAP) and visualized with confocal microscopy. Results: LHP increased over time in retinas from OIR exposed pups in association with IVNV. Early NAC-treated retinas had significantly reduced LHP compared to PBS-control at p18 (p<0.012). However, neither early nor late treatment with NAC had an effect on IVNV or retinal avascularity. Although apocynin had no effect on IVNV, it reduced both avascular retina (p=0.017) and retinal cleaved caspase-3 determined by western blot (p=0.021). In cryosections from OIR eyes, cleaved caspase-3 positive cells co-labeled with some lectin-stained vessels, NG2 labeled cells, and with GFAP positive cells in the inner nuclear layer. We found that the intravascular expression of gp91phox co-localized mostly with CD31 and some CD68 positive cells. Conclusions: Our results do not support the antioxidant properties of NAC as effective in reducing IVNV or avascular retina in the 50/10 OIR rat model. Apocynin reduced avascularity and apoptosis in the OIR model perhaps through pathways triggered by ROS generation but upstream from LHP production. Further study and consideration may be given to apocynin or NAD(P)H oxidase inhibitors as adjunctive therapy for ROP to reduce the avascular retina

Activated NAD(P)H Oxidase from Supplemental Oxygen Induces Neovascularization Independent of VEGF in Retinopathy of Prematurity Model

To study NAD(P)H oxidase-dependent outcomes after oxygen stresses that are similar to those experienced by preterm infants today using a rat model of retinopathy of prematurity

Goblet Cell Tumors of the Appendix: Clinical & Molecular Features

View full abstracthttps://openworks.mdanderson.org/leading-edge/1047/thumbnail.jp

Utility of plasma tumor marker levels in management of patients with appendiceal adenocarcinoma

View full abstracthttps://openworks.mdanderson.org/leading-edge/1049/thumbnail.jp

A Prospective Randomized Crossover Trial of Systemic Chemotherapy in Patients with Low-Grade Mucinous Appendiceal Adenocarcinoma

View full abstracthttps://openworks.mdanderson.org/leading-edge/1048/thumbnail.jp

New-Onset Maternal Gestational Hypertension and Risk of Retinopathy of Prematurity

Conditions of new-onset maternal gestational hypertension, such as pre-eclampsia, were associated with lower ROP zone at initial examination, but were not associated with increased severity of ROP at the examinations when the most severe ROP was seen. The prior use of erythropoietin did not have an effect on ROP severity, even when maternal condition was considered

Duodenal GI stromal tumors: Is radical resection necessary?

BACKGROUND AND OBJECTIVES: Duodenal gastrointestinal stromal tumors (GISTs) are rare tumors that pose a surgical challenge, and long-term outcomes after resection have not been detailed outside of small case series. This study uses the National Cancer Database (NCDB) to examine the determinants of radical resection for duodenal GISTs as well as the impact of local vs radical resection on overall survival (OS). METHODS: The NCDB was queried for nonmetastatic duodenal GISTs from 2004 to 2014. Predictors of radical resection were determined using multivariate logistic regression stratified by extent of tumor involvement. Factors associated with OS were identified with Cox proportional regression analysis. RESULTS: Treatment at an academic center, size \u3e5 cm, and extra-duodenal extension were associated with radical resection. On multivariate analysis, radical resection was associated with decreased OS (HR, 1.93; P \u3c .03). Systemic therapy, extra-duodenal extension, grade, stage, mitoses, and receipt of systemic therapy did not impact OS. CONCLUSION: Local resection of duodenal GISTs is associated with improved OS compared to radical resection after controlling for tumor factors and systemic treatment. Traditional indicators of tumor aggressiveness were associated with radical resection, but not OS. When feasible, local resection should be considered for resection of duodenal GISTs