Abstract
Necrotizing enterocolitis (NEC) is the leading intestinal emergency in premature infants. The underlying etiology of NEC remains elusive, but hypoxic conditions and early enteral feeding are consistently implicated as the main risk factors in the pathogenesis of NEC. We postulate that nitric oxide (NO) plays a key role as a molecular signaling "hub" in the generation of gut barrier failure in NEC. Clinical studies suggest that inflammatory cytokines and excessive NO production may contribute to the pathogenesis of NEC. One of the major challenges in defining the critical signaling pathways that lead to the development of NEC is the lack of specific biochemical markers that consistently delineate the early stages of NEC. Intestinal pathology and molecular markers derived from late-stage NEC represent end-stage findings and thus provide little insight into the early events that led to intestinal inflammation. Such markers may not represent viable therapeutic targets for the treatment or prevention of NEC. Therefore, novel strategies are needed to identify the patients at risk for NEC and define the clinically relevant molecules that characterize the early stages of NEC. This review will examine the mechanisms of NO-mediated gut barrier failure and propose novel genetic-based approaches for elucidating the critical molecular pathways in NEC.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 159-166 |
| Number of pages | 8 |
| Journal | Seminars in Pediatric Surgery |
| Volume | 14 |
| Issue number | 3 |
| DOIs | |
| State | Published - Aug 1 2005 |
| Externally published | Yes |
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Keywords
- Gene polymorphism
- Intestinal inflammation
- Micro array
- Necrotizing enterocolitis
- Nitric oxide
- Sepsis
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
Cite this
Mechanisms of nitric oxide-mediated intestinal barrier failure in necrotizing enterocolitis. / Upperman, Jeffrey S.; Potoka, Douglas; Grishin, Anatoly; Hackam, David; Zamora, Ruben; Ford, Henri.
In: Seminars in Pediatric Surgery, Vol. 14, No. 3, 01.08.2005, p. 159-166.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mechanisms of nitric oxide-mediated intestinal barrier failure in necrotizing enterocolitis
AU - Upperman, Jeffrey S.
AU - Potoka, Douglas
AU - Grishin, Anatoly
AU - Hackam, David
AU - Zamora, Ruben
AU - Ford, Henri
PY - 2005/8/1
Y1 - 2005/8/1
N2 - Necrotizing enterocolitis (NEC) is the leading intestinal emergency in premature infants. The underlying etiology of NEC remains elusive, but hypoxic conditions and early enteral feeding are consistently implicated as the main risk factors in the pathogenesis of NEC. We postulate that nitric oxide (NO) plays a key role as a molecular signaling "hub" in the generation of gut barrier failure in NEC. Clinical studies suggest that inflammatory cytokines and excessive NO production may contribute to the pathogenesis of NEC. One of the major challenges in defining the critical signaling pathways that lead to the development of NEC is the lack of specific biochemical markers that consistently delineate the early stages of NEC. Intestinal pathology and molecular markers derived from late-stage NEC represent end-stage findings and thus provide little insight into the early events that led to intestinal inflammation. Such markers may not represent viable therapeutic targets for the treatment or prevention of NEC. Therefore, novel strategies are needed to identify the patients at risk for NEC and define the clinically relevant molecules that characterize the early stages of NEC. This review will examine the mechanisms of NO-mediated gut barrier failure and propose novel genetic-based approaches for elucidating the critical molecular pathways in NEC.
AB - Necrotizing enterocolitis (NEC) is the leading intestinal emergency in premature infants. The underlying etiology of NEC remains elusive, but hypoxic conditions and early enteral feeding are consistently implicated as the main risk factors in the pathogenesis of NEC. We postulate that nitric oxide (NO) plays a key role as a molecular signaling "hub" in the generation of gut barrier failure in NEC. Clinical studies suggest that inflammatory cytokines and excessive NO production may contribute to the pathogenesis of NEC. One of the major challenges in defining the critical signaling pathways that lead to the development of NEC is the lack of specific biochemical markers that consistently delineate the early stages of NEC. Intestinal pathology and molecular markers derived from late-stage NEC represent end-stage findings and thus provide little insight into the early events that led to intestinal inflammation. Such markers may not represent viable therapeutic targets for the treatment or prevention of NEC. Therefore, novel strategies are needed to identify the patients at risk for NEC and define the clinically relevant molecules that characterize the early stages of NEC. This review will examine the mechanisms of NO-mediated gut barrier failure and propose novel genetic-based approaches for elucidating the critical molecular pathways in NEC.
KW - Gene polymorphism
KW - Intestinal inflammation
KW - Micro array
KW - Necrotizing enterocolitis
KW - Nitric oxide
KW - Sepsis
UR - http://www.scopus.com/inward/record.url?scp=23444452207&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23444452207&partnerID=8YFLogxK
U2 - 10.1053/j.sempedsurg.2005.05.004
DO - 10.1053/j.sempedsurg.2005.05.004
M3 - Article
VL - 14
SP - 159
EP - 166
JO - Seminars in Pediatric Surgery
JF - Seminars in Pediatric Surgery
SN - 1055-8586
IS - 3
ER -