Chondroitin sulfate supplementation improves clinical outcomes in a murine model of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) continues to be a devastating disease in preterm neonates and has a paucity of medical management options. Chondroitin sulfate (CS) is a naturally occurring glycosaminoglycan (GAG) in human breast milk (HM) and has been shown to reduce inflammation. We hypothesized that supplementation with CS in an experimental NEC model would alter microbial diversity, favorably alter the cytokine profile, and (like other sulfur compounds) improve outcomes in experimental NEC via the eNOS pathway.

Hydrogen Sulfide Improves Outcomes in a Murine Model of Necrotizing Enterocolitis via the Cys440 Residue on Endothelial Nitric Oxide Synthase.

Background: Hydrogen sulfide (HS) has been shown to improve outcomes in a murine model of necrotizing enterocolitis (NEC). There is evidence in humans that HS relies on endothelial nitric oxide synthase (eNOS) to exert its protective effects, potentially through the persulfidation of eNOS at the Cysteine 443 residue. We obtained a novel mouse strain with a mutation at this residue (eNOS) and hypothesized that this locus would be critical for GYY4137 (an HS donor) to exert its protective effects.

Age disparities in intestinal stem cell quantities: a possible explanation for preterm infant susceptibility to necrotizing enterocolitis.

Purpose: Preterm infants are more susceptible to necrotizing enterocolitis (NEC) than term Queryinfants. This may be due to a relative paucity of Lgr5 or Bmi1-expressing intestinal stem cells (ISCs) which are responsible for promoting intestinal recovery after injury. We hypothesized that the cellular markers of Lgr5 and Bmi1, which represent the two distinct ISC populations, would be lower in younger mice compared to older mice.

A hydrogen-sulfide derivative of mesalamine reduces the severity of intestinal and lung injury in necrotizing enterocolitis through endothelial nitric oxide synthase.

Necrotizing enterocolitis (NEC) remains a devastating disease that affects preterm infants. Hydrogen sulfide (HS) donors have been shown to reduce the severity of NEC, but the optimal compound has yet to be identified. We hypothesized that oral HS-Mesalamine (ATB-429) would improve outcomes in experimental NEC, and its benefits would be dependent on endothelial nitric oxide synthase (eNOS) pathways.

Sildenafil attenuates intestinal injury in necrotizing enterocolitis independently of endothelial nitric oxide synthase.

Background: Necrotizing enterocolitis (NEC) is a devastating disease that impacts the intestine of premature infants. Sildenafil has shown benefit in colitis and ischemia/reperfusion models but has not been adequately studied in NEC. Sildenafil's best studied mechanism involves augmenting nitric oxide induced vasodilation.

The assessment of microbiome changes and fecal volatile organic compounds during experimental necrotizing enterocolitis.

Introduction: Necrotizing enterocolitis (NEC) remains a devastating disease that affects the gastrointestinal tract of the preterm infant. Volatile organic compounds (VOCs) have emerged as a non-invasive biomarker in many diseases. We hypothesized that fecal VOC profiles would be significantly different between control and NEC pups in a NEC mouse model.

It's all in the milk: chondroitin sulfate as potential preventative therapy for necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a devastating condition affecting up to 5% of neonatal intensive care unit (NICU) admissions. Risk factors include preterm delivery, low birth weight, and antibiotic use. The pathogenesis is characterized by a combination of intestinal ischemia, necrosis of the bowel, reperfusion injury, and sepsis typically resulting in surgical resection of afflicted bowel.

Angiogenesis: A Cellular Response to Traumatic Injury.

The development of new vasculature plays a significant role in a number of chronic disease states, including neoplasm growth, peripheral arterial disease, and coronary artery disease, among many others. Traumatic injury and hemorrhage, however, is an immediate, often dramatic pathophysiologic insult that can also necessitate neovascularization to promote healing. Traditional understanding of angiogenesis involved resident endothelial cells branching outward from localized niches in the periphery.

The Assessment of Fecal Volatile Organic Compounds in Healthy Infants: Electronic Nose Device Predicts Patient Demographics and Microbial Enterotype.

Background: The assessment of fecal volatile organic compounds (VOCs) has emerged as a noninvasive biomarker in many different pathologies. Before assessing whether VOCs can be used to diagnose intestinal diseases, including necrotizing enterocolitis (NEC), it is necessary to measure the impact of variable infant demographic factors on VOC signals.

Materials And Methods: Stool samples were collected from term infants at four hospitals in a large metropolitan area.

Are surgeons behind the scientific eight ball: Delayed acquisition of the NIH K08 mentored career development award.

Background: Surgery residents complete their research training early in residency. Non-surgical trainees typically have research incorporated toward the last two years of their fellowship, conferring an advantage to apply for grants with recent research experience and preliminary data.

Methods: The NIH RePORTER database was queried for K08 awardees trained in medicine, pediatrics, and surgery from 2013 to 2017.

Sildenafil as a Rescue Agent Following Intestinal Ischemia and Reperfusion Injury.

Background: Acute mesenteric ischemia carries a significant morbidity. Measures to improve blood flow parameters to the intestine may ameliorate the disease. Sildenafil, a phosphodiesterase 5 inhibitor, increases cyclic guanosine monophosphate and has been shown to prevent the effects of ischemia when given before injury.

Mesenchymal stem cells promote mesenteric vasodilation through hydrogen sulfide and endothelial nitric oxide.

Mesenteric ischemia is a devastating process that can result in intestinal necrosis. Mesenchymal stem cells (MSCs) are becoming a promising treatment modality. We hypothesized that ) MSCs would promote vasodilation of mesenteric arterioles, ) hydrogen sulfide (HS) would be a critical paracrine factor of stem cell-mediated vasodilation, ) mesenteric vasodilation would be impaired in the absence of endothelial nitric oxide synthase (eNOS) within the host tissue, and ) MSCs would improve the resistin-to-adiponectin ratio in mesenteric vessels.