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1.
Abdullah Kumral Kazim Tugyan Huseyin Baskin Isil Tekman Nuray Duman Hasan Ozkan 《Journal of pediatric surgery》2010,45(3):483-489
Background
Necrotizing enterocolitis is a devastating intestinal disease of premature infants. Although activated protein C (APC) is well defined as a physiologic anticoagulant, emerging data suggest that it also has cytoprotective, antiinflammatory, and antiapoptotic properties. There is no study on active protein C administration for necrotizing enterocolitis in animal models.Methods
Twenty-one Wistar albino rat pups were divided into 3 groups: group 1 = control; group 2 = hypoxia-reoxygenation and saline; group 3 = hypoxia-reoxygenation and APC (0.2 mg/kg per day) treatment. On the 15th day, hypoxia was induced by placing the pups in a 100% carbon dioxide chamber for 5 minutes. After the hypoxia period, the pups were reoxygenated for 10 minutes with 100% oxygen and returned to their mothers. All pups were killed 4 hours after the hypoxia-reoxygenation period was over. The abdomen was opened, and representative samples of injured areas were taken for histopathologic examination, nitrite levels, apoptosis, and cytokine levels.Results
On histopathologic examination, injury scores in group 2 animals were found to be significantly higher than in group 3 animals (P = .002). Significantly increased intestinal nitric oxide levels were found in group 2 rats compared with the rats of groups 1 and 3 (P = .001 and P = .001, respectively). The APC treatment was significantly reduced “apoptotic cell death” in the bowel, when compared with vehicle-treated group. The proinflammatory cytokine levels (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, and IL-6) were significantly increased in hypoxia group as compared with control group. The concentration of cytokines, IL-1β, IL-6, and TNF-α was reduced in the APC treatment group.Conclusion
The APC treatment attenuates hypoxia-reoxygenation induced with intestinal injury and decreased apoptotic cell index in this animal model. The protective effect of APC is associated with its ability to reduce the expression of inflammatory cytokines and nitric oxide. 相似文献2.
Jonathan Saul Karpelowsky Stefanie van Mil Ernesto Leva 《Journal of pediatric surgery》2010,45(2):315-318
Aim
The aim of the study was to assess the impact of human immunodeficiency virus (HIV) exposure on survival and extent of disease in necrotizing enterocolitis (NEC).Patients and Methods
All patients with NEC requiring surgery between June 1998 and June 2008 were analyzed. Three groups were identified: those born to HIV-positive (HIV+) mothers, those born to HIV-negative (HIV−) mothers, and those with an unknown HIV status. Primary outcome measure was survival to discharge. Secondary outcome measure was extent of disease.Results
One hundred nine infants (mean gestational age, 31 weeks; birth weight, 1413 g) underwent surgery for NEC. Gestational age, birth weight, and day of presentation were similar in all 3 groups, showing no statistical difference. The HIV+ group consisted of 22 infants, of which 13 (59%) died and 2 (9%) had panintestinal necrosis. The HIV− group consisted of 48 infants, of which 11 (23%) died, with 3(6%) having panintestinal necrosis. The remaining group of HIV (unknown) consisted of 38 infants, of which 14 (37%) died, with 2 (5%) having panintestinal necrosis. The latter group was not included in the analysis; but comparing the HIV+ and HIV− groups, there was a statistically higher chance of death (odds ratio = 4.8, P = .05). There was no difference statistically in the extent of disease.Conclusion
Neonates with NEC born to HIV+ mothers have a higher mortality 相似文献3.
Zani A Eaton S Leon FF Malerba A Hall NJ De Coppi P Smith VV Pierro A 《Journal of pediatric surgery》2008,43(2):308-314
Background/Purpose
Selective mesenteric ischemia may result from activation of the renin-angiotensin system during periods of shock and is implicated in the pathogenesis of neonatal necrotizing enterocolitis (NEC). We investigated the effectiveness of captopril, an angiotensin-converting enzyme inhibitor, in reducing the severity of bowel damage in a neonatal rat model of NEC.Methods
Necrotizing enterocolitis was induced by a combination of gavage feeding of hypertonic formula, hypoxia, and oral lipopolysaccharide (LPS). Rats were randomly divided into 3 groups: group A, control (breast fed; n = 20); group B, NEC (gavage/hypoxia/LPS; n = 31); group C, NEC with captopril 20 mg/kg per dose with the formula for 4 days (gavage/hypoxia/LPS/captopril; n = 35). Pups were killed after 4 days. Incidence of NEC was evaluated microscopically.Results
Severity of bowel damage was higher in the NEC group compared to controls and was reduced by administration of captopril. Dilatation of the intestinal vasculature was observed in the captopril group. There were no cases of NEC in the controls; the incidence increased to 55% in NEC group and reduced to 29% by captopril.Conclusions
In this model of neonatal NEC, captopril supplementation of formula reduces the severity of intestinal damage and the incidence of NEC, presumably by affecting mesenteric blood flow. 相似文献4.
Purpose
We have previously demonstrated that heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potent intestinal cytoprotective agent. The aim of this study was to determine the effect of enterally administered HB-EGF on the incidence of necrotizing enterocolitis (NEC) in neonatal rats.Methods
Necrotizing enterocolitis was induced in neonatal rats delivered by C-section on day 21 of gestation by exposure to repeated cycles of hypoxia and hypothermia plus administration of hypertonic formula feeding (HHHTF) plus enteral administration of lipopolysaccharide (LPS) (2 mg/kg). Neonatal rats were randomly assigned to breast-feeding, hypertonic formula feeding, HHHTF + LPS, and HHHTF + LPS with HB-EGF (600 μg/kg) supplementation in the formula. Animals were monitored until 96 hours of life and assessed for death, histological NEC, and intestinal mucosal permeability.Results
The incidence of NEC in the HHHTF group was higher than that in the breast-feeding or hypertonic formula feeding groups. With administration of HB-EGF, the incidence and severity of NEC were significantly decreased. Administration of HB-EGF also increased rat pup survival rate and extended survival time. In addition, treatment with HB-EGF significantly decreased intestinal permeability to fluorescein isothiocyanate-dextran.Conclusions
We conclude that HB-EGF reduces the incidence and severity of NEC in a neonatal rat model, with simultaneous preservation of gut barrier integrity. These results support our contention that HB-EGF administration may represent a useful therapeutic and prophylactic therapy for the treatment of NEC. 相似文献5.
Natalie A. Drucker Amanda R. Jensen Jan P. te Winkel Michael J. Ferkowicz Troy A. Markel 《Journal of pediatric surgery》2018,53(6):1208-1214
Background
Necrotizing enterocolitis (NEC) continues to be a devastating condition among preterm infants. Nitric oxide, which is synthesized in the intestine by endothelial nitric oxide synthase (eNOS), acts as a potent vasodilator and antioxidant within the mesentery and may play a role in prevention of NEC. We hypothesized that loss of endothelial nitric oxide would worsen both intestinal and associated lung injury and increase local and systemic inflammation during experimental NEC.Methods
NEC was induced in five-day-old wild type (WT) and eNOS-knockout (eNOSKO) mouse pups. Experimental groups (n = 10) were formula fed and subjected to intermittent hypoxic and hypothermic stress, while control groups (n = 10) remained with their mother to breastfeed. Pups were monitored by daily clinical assessment. After sacrifice on day nine, intestine and lung were assessed for injury, and cytokines were measured in tissue homogenates by ELISA. Data were compared with Mann–Whitney, and p < 0.05 was significant.Results
Each NEC group was compared to its respective strain’s breastfed control to facilitate comparisons between the groups. Both NEC groups were significantly sicker than their breastfed controls. eNOSKO NEC animals had a median clinical assessment score of 3 (IQR = 1–5), and the WT NEC animal’s median score was 3 (IQR = 2–5). Despite similar clinical scores, intestinal injury was significantly worse in the eNOSKO NEC groups compared to WT NEC groups (median injury scores of 3.25 (IQR = 2.25–3.625) and 2 (IQR = 1–3), respectively (p = 0.0474). Associated lung injury was significantly worse in the eNOSKO NEC group as compared to the WT NEC group (median scores of 8.5 (IQR = 6.75–11.25) and 6.5 (IQR = 5–7.5), respectively, p = 0.0391). Interestingly, cytokines in both tissues were very different between the two groups, with varying effects noted for each cytokine (IL-6, IL-1β, VEGF, and IL-12) in both tissues.Conclusion
Nitric oxide from eNOS plays a key role in preventing the development of NEC. Without eNOS function, both intestinal and lung injuries are more severe, and the inflammatory cascade is significantly altered. Further studies are needed to determine how eNOS-derived nitric oxide facilitates these beneficial effects. 相似文献6.
The role of diagnostic laparoscopy in micropremmies with suspected necrotizing enterocolitis 总被引：1，自引：0，他引：1
Abstract
Background The timely diagnosis of perforations or dead gut can be extremely difficult in micropremmies with necrotizing enterocolitis.
A negative laparotomy is just as detrimental as failure to recognize early perforation in this group of patients. We have
been exploring the role of microlaparoscopy using a needlescope to determine if this modality is feasible and useful in the
surgical management of these patients. We report our technique and initial experience with needlescopic diagnosis.
Methods Four patients (weight >500 to <1000 g) with abdominal distension and clinical sepsis not responsive to aggressive medical
treatment were included in this study. None had radiologic evidence of pneumatosis or perforation. There was no absolute surgical
indication for laparotomy except for strong suspicion of a surgical cause. Needlescopic diagnosis was performed in all these
patients.
Results There was no evidence of perforation or bile in the abdominal cavity in one patient. This patient improved on medical management,
avoiding a laparotomy. The rest had bile or fibrin in the abdominal fluid with a localized perforation, and in each case we
performed a microlaparotomy directly over the site of perforation to create a stoma.
Conclusions Needlescopic diagnosis is feasible and appears to be safe, even in critically ill micropremmies less than 1000 g. The technique
can provide useful information for surgical decision-making and allows for precise placement of a microlaparotomy incision
over the site of perforation, thus minimizing the trauma from open surgery in this special group of patients. We are currently
expanding its role in patients with overt perforations to determine if we can limit the extent of surgical exploration without
compromising the adequacy of surgical management. 相似文献
7.
Mark A. Underwood 《Journal of pediatric surgery》2019,54(3):405-412
Background
Immaturity of the host immune system and alterations in the intestinal microbiome appear to be key factors in the pathogenesis of necrotizing enterocolitis (NEC). The aim of this paper is to weigh the evidence for the use of probiotics to prevent NEC in premature infants.Methods
Animal studies, randomized controlled trials, observational cohort studies and meta-analyses involving administration of probiotic products for the prevention of NEC were reviewed. This review of the evidence summarizes the available preclinical and clinical data.Results
In animal models probiotic microbes alter the intestinal microbiome, decrease inflammation and intestinal permeability and decrease the incidence and severity of experimental NEC. In randomized, placebo-controlled trials and cohort studies of premature infants, probiotic microbes decrease the risk of NEC, death and sepsis.Conclusion
Evidence is strong for the prevention of NEC with the use of combination probiotics in premature infants who receive breast milk. The potential risks and benefits of probiotic administration to premature infants should be carefully reviewed with parents.Type of study
Therapeutic.Level of evidence
I. 相似文献8.
Natalie A. Drucker Amanda R. Jensen Michael Ferkowicz Troy A. Markel 《Journal of pediatric surgery》2018,53(9):1692-1698
Background
Necrotizing enterocolitis (NEC) continues to be a morbid surgical condition among preterm infants. Novel therapies for this condition are desperately needed. Hydrogen sulfide (H2S) is an endogenous gasotransmitter that has been found to have beneficial properties. We therefore hypothesized that intraperitoneal injection of various H2S donors would improve clinical outcomes, increase intestinal perfusion, and reduce intestinal injury in an experimental mouse model of necrotizing enterocolitis.Methods
NEC was induced in five-day-old mouse C57BL/6 mouse pups through maternal separation, formula feeding, and intermittent hypoxic and hypothermic stress. The control group (n = 10) remained with their mother and breastfed ad lib. Experimental groups (n = 10/group) received intraperitoneal injections of phosphate buffered saline (PBS) vehicle or one of the following H2S donors: (1) GYY4137, 50 mg/kg daily; (2) Sodium sulfide (Na2S), 20 mg/kg three times daily; (3) AP39, 0.16 mg/kg daily. Pups were monitored for weight gain, clinical status, and intestinal perfusion via transcutaneous Laser Doppler Imaging (LDI). After sacrifice on day nine, intestinal appearance and histology were scored and cytokines were measured in tissue homogenates of intestine, liver, and lung. Data were compared with Mann–Whitney and p < 0.05 was considered significant.Results
Clinical score and weight gain were significantly improved in all three H2S-treated groups as compared to vehicle (p < 0.05 for all groups). Intestinal perfusion of the vehicle group was 22% of baseline while the GYY4137 group was 38.7% (p = 0.0103), Na2S was 47.0% (p = 0.0040), and AP39 was 43.0% (p = 0.0018). The vehicle group had a median histology score of 2.5, while the GYY4137 group's was 1 (p = 0.0013), Na2S was 0.5 (p = 0.0004), and AP39 was 0.5 (p = 0.0001). Cytokine analysis of the intestine of the H2S-treated groups revealed levels closer to breastfed pups as compared to vehicle (p < 0.05 for all groups).Conclusion
Intraperitoneal administration of H2S protects against development of NEC by improving mesenteric perfusion, and by limiting mucosal injury and altering the tissue inflammatory response. Further experimentation is necessary to elucidate downstream mechanisms prior to clinical implementation. 相似文献9.
Stefanutti G Lister P Smith VV Peters MJ Klein NJ Pierro A Eaton S 《Journal of pediatric surgery》2005,40(6):942-948
Background/Purpose
P-selectin promotes adherence of leukocytes to the endothelium in inflammatory processes. The aim of this study was to investigate the expression of P-selectin and its role in the development of inflammation in neonates with necrotizing enterocolitis (NEC).Methods
Twenty-nine intestinal specimens from 13 neonates with NEC and 7 control neonates with congenital gastrointestinal abnormalities were studied. Histologic damage, immunohistochemical expression of P-selectin, and polymorphonuclear cell infiltrate were graded blindly. Mann-Whitney U and Spearman rank tests were used to compare grades.Results
Expression of P-selectin was increased in NEC compared with controls in both medium-sized vessels (P = .03) and in the microcirculation (P = .03). P-selectin expression on medium-sized vessels correlated with the degree of histologic injury (P = .02, r = 0.425). P-selectin expression was greatest in areas of active inflammation but markedly lower in necrotic areas. The degree of polymorphonuclear cell infiltration strongly correlated with P-selectin expression on both medium-sized vessels (P = .004, r = 0.513) and the microcirculation (P = .001, r = 0.578).Conclusions
Expression of P-selectin is increased in medium-sized vessels and in the microcirculation in intestinal specimens of neonates with NEC compared with neonatal controls. Expression of P-selectin is associated with the recruitment of polymorphonuclear cells and the severity of histologic injury, although P-selectin expression is lost in necrotic tissue. 相似文献10.
Shogo Seo Hiromu Miyake Mashriq Alganabi Maarten Janssen Lok Joshua S. O&#x;Connell Carol Lee Bo Li Agostino Pierro 《Journal of pediatric surgery》2019,54(12):2520-2523
Background and PurposeExcessive inflammatory cell infiltration and accumulation in the intestinal mucosa are pathological features of necrotizing enterocolitis (NEC) leading to intestinal barrier disruption. Vasoactive intestinal peptide (VIP) is a potent anti-inflammatory agent that regulates intestinal epithelial barrier homeostasis. We previously demonstrated that VIP-ergic neuron expression is decreased in experimental NEC ileum, and this may be associated with inflammation and barrier compromise. We hypothesize that exogenous VIP administration has a beneficial effect in NEC.MethodsNEC was induced in C57BL/6 mice by gavage feeding, hypoxia, and lipopolysaccharide administration between postnatal day (P) 5 and 9. There were four studied groups: Control (n = 6): Breast feeding without stress factors; Control + VIP (n = 5): Breast feeding + intraperitoneal VIP injection once a day from P5 to P9; NEC (n = 9): mice exposed to NEC induction; NEC + VIP (n = 9): NEC induction + intraperitoneal VIP injection. Terminal ileum was harvested on P9. NEC severity, intestinal inflammation, (IL-6 and TNFα), and Tight junctions (Claudin-3) were evaluated.ResultsNEC severity and intestinal inflammation were significantly decreased in NEC + VIP compared to NEC. Tight junction expression was significantly increased in NEC + VIP compared to NEC.ConclusionVIP administration has a beneficial therapeutic effect in NEC by reducing inflammation and tight junction disruption. 相似文献
11.
Purpose
Abdominal radiographs are frequently employed in the surveillance of patients with necrotizing enterocolitis (NEC), with typical findings well described. Clinicians interpret and act upon these films at different intervals, however, and inter-rater agreement has not been evaluated to date.Methods
Thirty abdominal radiographs of premature infants were distributed to attending radiologists (4), pediatric surgeons (4), and trainees (4), who evaluated for findings of NEC from a list of eight potential choices (1 = normal, 8 = perforation). Fleiss’s Kappa (FK) was used to evaluate concordance between multiple raters with 0–0.2 = slight association and 0.8–1 = almost perfect agreement.Results
Practicing surgeons had an FK of 0.77 overall (95% CI: 0.67–0.87), but demonstrated poor agreement when evaluating decubitus films (FK: 0.39, 95% CI:0.12–0.65). Radiologists had excellent inter-rater agreement (FK: 0.81, 95% CI: 0.74–0.88), but had only modest agreement with surgeons (FK: 0.59, 95% CI: 0.56–0.63) and poor agreement for decubitus films (FK: 0.15, 95% CI: 0.47–0.26). Surgical and radiology trainees had fair agreement with their respective attendings (0.60, 95% CI: 0.55–0.65 and 0.64, 95% CI: 0.60–0.69, respectively).Conclusions
While inter-rater agreement was good–excellent among attending staff, it was only moderate between radiologists and surgeons and between trainees and their attendings. This highlights the importance of inter-disciplinary and hierarchical communication to optimize clinical decision-making. Decubitus films may be of limited value in evaluating patients with NEC. 相似文献12.
Anne G.J.F. van Zoonen Christian V. Hulzebos Anneke C. Muller Kobold Elisabeth M.W. Kooi Arend F. Bos Jan B.F. Hulscher 《Journal of pediatric surgery》2019,54(3):455-459
Purpose
To investigate whether serial measurements of fecal calprotectin concentrations enable us to identify infants who will develop NEC prior to development of symptoms.Methods
Prospective matched case–control study including 100 high-risk neonates. High risk includes 1) gestational age (GA) ≤ 30?weeks, 2) birth-weight (BW) ≤ 1000?g, 3) GA 30–32?weeks and BW ≤ 1250?g, 4) born from a mother who received indomethacin for tocolysis. We matched every NEC subject with three controls for birth weight and gestational age. Fecal calprotectin was measured twice a week from day one until five weeks after birth or until NEC development. We analyzed differences in fecal calprotectin between NEC subjects and controls in the week preceding NEC onset and course of fecal calprotectin within subjects who developed NEC.Results
Of 100 included patients, ten (median GA 27.5?weeks [24.6–29.4], BW 1010?g [775–1630]) developed NEC. The median calprotectin concentration in all samples combined was 332?μg/g [< 40–8230] μg/g feces. There were no differences between NEC subjects and controls, with a wide variation in both groups. In NEC subjects, there was no intraindividual rise in calprotectin before clinical symptoms occurred.Conclusions
There are high concentrations and wide interindividual variations in calprotectin in preterm infants during the first weeks of life. Wide intraindividual variation further precludes the serial use of fecal calprotectin in the early detection or prediction of NEC in high risk infants.Level of Evidence
III 相似文献13.
Hiromu Miyake Bo Li Carol Lee Yuhki Koike Yong Chen Shogo Seo Agostino Pierro 《Journal of pediatric surgery》2018,53(5):909-913
Background
Necrotizing enterocolitis (NEC) is a disease known to cause injury to multiple organs including the liver. Liver regeneration is essential for the recovery after NEC-induced liver injury. Our aim was to investigate hepatic proliferation and progenitor cell marker expression in experimental NEC.Methods
Following ethical approval (#32238), NEC was induced in mice by hypoxia, gavage feeding of hyperosmolar formula, and lipopolysaccharide. Breastfed pups were used as control. We analyzed serum ALT level, liver inflammatory cytokines, liver proliferation markers, and progenitor cell marker expression. Comparison was made between NEC and controls.Results
Serum ALT level was higher in NEC (p < 0.05). The mRNA expression of inflammatory cytokines in the liver was also higher in NEC (IL6: p < 0.05, TNF-α: p < 0.01). Conversely, mRNA expression of proliferation markers in the liver was lower in NEC (Ki67; p < 0.01, PCNA: p < 0.01). LGR5 expression was also significantly decreased in NEC as demonstrated by mRNA (p < 0.05) and protein (p < 0.01) levels.Conclusions
Inflammatory injury was present in the liver during experimental NEC. Proliferation and LGR5 expression were impaired in the NEC liver. Modulation of progenitor cell expressing LGR5 may result in stimulation of liver regeneration in NEC-induced liver injury and improved clinical outcome.Level of evidence
Level IV. 相似文献14.
15.
Ergün O Ergün G Oktem G Selvi N Doğan H Tunçyürek M Saydam G Erdener A 《Journal of pediatric surgery》2007,42(10):1687-1694
Background/Purpose
The release of various enzymes including inducible nitric oxide synthase (iNOS) leads to enterocyte apoptosis through free nitrogen radicals, which in turn leads to impaired mucosal barrier and bacterial translocation with resultant sepsis in necrotizing enterocolitis (NEC). Resveratrol, a polyphenol compound from phytoalexins with antioxidant and scavenger properties, also play a critical role in modulating key enzymes in cell cycle including iNOS. We therefore hypothesized that resveratrol would prevent mucosal damage in experimental NEC in rats.Methods
Newborn rats were randomized into 3 groups: group 1 was left to breast-feed (BF), whereas group 2 (NEC) was induced by enteral formula feedings twice daily and by being subjected to hypoxia thrice. The third group (R) received the same treatment as the NEC group but the enteral feeds were supplemented with resveratrol. Rats were killed on day 4, and their terminal ileal samples were harvested for histopathologic analysis. Expression of iNOS was assessed by sodium dodecyl sulfate polyacrylamide-gel electrophoresis analysis and immunohistochemistry. Band densities were quantified by using the software NIH image.Results
The epithelial structure in group BF was normal. In the NEC group, there were marked loss of the brush border, vacuolization, and necrosis. The epithelial structure was found to be preserved in group R. Western blot analysis revealed marked elevation in the expression of iNOS protein at 130 kD molecular weight (band densities in groups BF, NEC, and R were 0.3 ± 3.5, 3.7 ± 2.9, and 0.6 ± 5.1, respectively; P < .01). Immunohistochemical analysis revealed that iNOS staining was significantly increased in the NEC group, whereas it remained minimal for the BF and R groups. Ileal tissue nitrate/nitrite levels for groups BF, NEC, and R were 178.3 ± 7, 191.4 ± 4.1, and 181 ± 3.6 μmol/(L·g), respectively (P < .01).Conclusions
These findings may provide insights for the beneficial effect of enteral resveratrol supplementation on inflammatory conditions of the bowel including NEC through attenuating the release of iNOS and preservation of mucosal integrity. 相似文献16.
Background
Necrotizing enterocolitis (NEC) is a devastating disease of newborns, and despite years of research, there is no known cure. The mortality rate of infants with NEC remains as high as 20%–30%. Babies who survive NEC frequently have long term complications including short gut syndrome, developmental delays and neurological sequelae. Unfortunately, despite much research over the past years, the precise pathogenesis of the disease is still not completely understood.Methods
Our laboratory has focused on identifying novel therapies to prevent the disease, including the use of stem cells (SC), heparin-binding epidermal growth factor-like growth factor (HB-EGF) and recently, stem cell derived-exosomes, a type of nanovesicle, to combat this illness.Results
We have outlined the major SC lines and data suggesting potential benefit as a curative or preventive approach for NEC as well as describing several new therapeutic strategies, including stem cell derived- exosomes and HB-EGF for decreasing the incidence and severity of this disease in rat models in our lab.Conclusion
Overall, our lab has demonstrated that these different types of SC equivalently reduce the incidence and severity of NEC and equally preserve intestinal barrier function during NEC. We have previously demonstrated that AF-MSC can protect the intestines from intestinal injury and may therefore hold strong therapeutic potential for the prevention of NEC. Most recently, our work with stem cell derived-exosomes has shown them to be equivalent to their derived SC lines in decreasing the incidence of this disease. 相似文献17.
Purpose
We have previously demonstrated that enterally administered heparin-binding epidermal growth factor-like growth factor (HB-EGF) decreases the incidence and severity of necrotizing enterocolitis (NEC) in a neonatal rat model. Because apoptosis contributes to gut barrier failure in this model, the aim of this study was to investigate the effect of HB-EGF on apoptosis during the development of NEC.Methods
NEC was induced in neonatal rats by exposure to hypoxia, hypothermia, hypertonic formula feeding (HHHTF) plus enteral administration of lipopolysaccharide (LPS). Fifty-one neonatal rats were randomly divided into the following groups: (1) breast-fed (BF), (2) HHHTF + LPS, and (3) HHHTF + LPS with HB-EGF (600 μg/kg) added to the formula. NEC was evaluated using a standard histological scoring system. Apoptotic cells in intestinal tissues were detected by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) and by active caspase 3 immunohistochemical staining.Results
The incidence of NEC in the HHHTF + LPS group was higher than that in the BF group (65% vs 0%, P < .05). With administration of HB-EGF, the incidence of NEC significantly decreased to 23.8% (P < .05). The median TUNEL and active caspase 3 scores in the HHHTF + LPS group were higher than those in the BF group (1.9 vs 0.9 and 1.75 vs 0.6, respectively, P < .05). The median TUNEL and active caspase 3 scores were significantly decreased in the HHHTF + LPS + HB-EGF group compared with the HHHTF + LPS group (1.24 vs 1.9 and 1.0 vs 1.75, respectively, P < .05).Conclusion
HB-EGF reduces the incidence of NEC in a neonatal rat model in part by decreasing apoptosis. These results support the use of HB-EGF-based clinical regimens for the treatment of NEC. 相似文献18.
Paracentesis and lavage for diagnosis of intestinal gangrene in neonatal necrotizing enterocolitis 总被引：1，自引：0，他引：1
A study to evaluate peritoneal fluid as an index of intestinal gangrene in infants with necrotizing entercolitis (NEC) was begun in 1974. Twenty samples of peritoneal fluid were obtained by paracentesis or lavage from 15 infants with nonperforated NEC. A brown color in the peritoneal fluid was noted in all 8 patients found to have intestinal gangrene at subsequent operation. Gram stain showed bacteria in 6 of these 8 patients and bacterial cultures were confimatory in all but one. In 12 samples of peritoneal fluid in patients without intestinal gangrene, the fluid was straw-colored or pink and Gram stain showed no bacteria. The decision to operate on an infant with intestinal gangrene and impending perforation may be aided by analysis of the peritoneal fluid. 相似文献
19.
Seitz G Warmann SW Guglielmetti A Heitmann H Ruck P Kreis ME Fuchs J 《Journal of pediatric surgery》2005,40(9):1440-1445
Background
Necrotizing enterocolitis (NEC) is a common and devastating disorder of premature infants. Elevated proinflammatory cytokines, especially tumor necrosis factor α (TNF-α), have been implicated in the pathogenesis of NEC. The aim of this study was to evaluate the effects of TNF-α on the inflammatory response in NEC by immunoneutralizing TNF-α with a selective antibody.Methods
Neonatal Sprague-Dawley rats were divided in 3 groups: group 1 (n = 20), a NEC-like enterocolitis was induced by formula feeding, asphyxia, and cold exposure; group 2 (n = 9), animals were treated like in group 1 and additionally received TNF-α antibody intraperitoneally; and group 3 (n = 17), animals were dam-fed (controls). Animals were killed in case of imminent death or after 96 hours. Specimens from small bowel were processed for blinded histologic (H&E) and immunhistologic (myeloperoxidase [MPO]) analysis.Results
In group 1, animals developed severe NEC (mean NEC score, 3.28 ± 0.32; mean MPO, 65.85 ± 9.46). In group 2, animals developed mild NEC (mean NEC score, 1.72 ± 0.41; mean MPO, 34.33 ± 9.69; P < .05). In group 3, no NEC was induced (mean NEC score, 0.0 ± 0; mean MPO, 6 ± 1.32; P < .05).Conclusion
Tumor necrosis factor α antibody may have an attenuating effect on experimental NEC in rats. 相似文献20.