All-Trans-Retinoic Acid Attenuates Intestinal Injury in a Neonatal Rat Model of Necrotizing Enterocolitis

Оздемир, Рамазан; Yurttutan, Sadık; Sarı, Fatma Nur; Öncel, Mehmet Yekta; Erdeve, Ömer; Ünverdǐ, Hatǐce; Uysal, Bülent; Dilmen, Uğur

doi:10.1159/000350510

Cited by 24 publications

(22 citation statements)

References 23 publications

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“…The pathogenesis of NEC is still incompletely understood. Despite all research into possible pathogenic mechanisms and clear advances in neonatal care, NEC-associated morbidity and mortality (up to 50%) have not decreased substantially over the last decades [2,3,4,5,6,7,8,9,10]. …”

Section: Introductionmentioning

confidence: 99%

Clinical Importance of a Fixed Bowel Loop in the Treatment of Necrotizing Enterocolitis

Muller¹,

Schurink²,

Bos

et al. 2013

Neonatology

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Background: The need for surgical treatment in neonates with necrotizing enterocolitis (NEC) is associated with high mortality. Although pneumoperitoneum and progressive disease are generally accepted indications for surgery, it is unclear whether a fixed bowel loop (FBL) should prompt surgery. Objective: To determine the relationship between an FBL, type of treatment, and death in the management of NEC. Methods: Retrospective analysis (January 2000-December 2011) of all neonates with definite NEC in a tertiary neonatal intensive care unit. FBL was defined as a persistent (i.e. >24 h) dilated intestinal segment present on serial abdominal X-rays. Results: NEC was diagnosed in 141 neonates (median gestational age 30 weeks; median birth weight 1,340 g). An FBL was reported in 38 (27%) patients, of whom 18 were treated surgically. Mortality among FBL patients was independent of the type of treatment (surgical versus conservative): 8/18 and 7/20, respectively (p = 0.55). Of the 103 patients without FBL, 37 (36%) were treated surgically, which is comparable to the FBL group. Again, mortality was not related to the type of treatment (surgical versus conservative): 5/37 and 6/66, respectively (p = 0.49). The presence of an FBL was associated with mortality: more patients with an FBL (15/38, 39%) died than without an FBL (11/103, 11%; odds ratio 5.45, 95% confidence interval 2.21-13.45; p < 0.01). Conclusions: In NEC patients, an FBL is associated with increased mortality. On its own it has moderate significance to guide treatment. Nevertheless, because it reflects disease severity, early recognition is important and prompt (surgical) treatment should be considered.

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Section: Introductionmentioning

confidence: 99%

Clinical Importance of a Fixed Bowel Loop in the Treatment of Necrotizing Enterocolitis

Muller¹,

Schurink²,

Bos

et al. 2013

Neonatology

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“…Also as these newer modalities are expensive, the ability to define a population which may be at risk for developing severe disease, these diagnostic and treatment modalities can be used judiciously for at risk population. [27][28][29][30] Our findings are limited by the retrospective nature of our study, although we validated the data extraction from charts, variation in nursing documentation of clinical signs may have altered our findings. Use of this multi-parameter scoring tool to determine whether more aggressive treatment for at risk infants for developing NEC stage 2 and 3, even before radiological confirmation of pneumatosis intestinalis, may result in a less severe course of NEC and improve morbidity and mortality.…”

Section: Discussionmentioning

confidence: 83%

Early prediction of severity of necrotizing enterocolitis in preterm infants: A composite scoring tool

Grino

Miller

Carrasquilla-Lopez

et al. 2016

Clinical Nursing Studies

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Background: Necrotizing enterocolitis (NEC) predominantly affects preterm infants and is associated with high mortality and morbidity. There is no composite scoring tool that predicts the severity of NEC in preterm infants early in the disease process before it is established. Methods: A retrospective chart review was performed on NEC cases (n = 41) defined as infants who developed NEC stage ≥ 2 with pneumatosis intestinalis, and controls (n = 41) defined as infants with NEC stage 1, to develop a scoring tool that utilized the preterm infant's clinical status, feeding practices, radiographic and laboratory findings at set time-points (7 days, 2 days and 24 and 12 hours) before the suspicion of NEC to predict the severity of NEC. Repeated measures analysis along with sensitivity, specificity and area under curve were measured to compare the composite risk score between cases and controls. Results: The composite risk score was higher among the cases at 24 hours (2.73 ± 0.20 vs. 2.20 ± 0.20, p < .05) and 12 hours (4.20 ± 0.22 vs. 2.50 ± 0.22, p < .001) but not on 2 day (2.37 ± 0.17 vs. 2.18 ± 0.17, p = .42) prior to the suspicion of NEC to predict the severity of the disease. Feeding practices, gastric residuals, and laboratory signs of inflammation were main determinants of the final score. The most discriminatory score to differentiate between NEC stage 1 and NEC stage 2 and 3 was ≤ 2. Conclusions: This scoring system is easy to use as it utilizes normally collected data and can predict the severity of the disease enabling the physician to make decisions regarding appropriate timing of correct treatment. Further larger prospective studies are required to validate this pilot study describing NEC severity prediction tool.

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“…Because of high lipophilicity, ATRA is thought to be responsible for the slow dissolution and low bioavailability following oral administration [51] , so ATRA (500 μg/kg body weight) was dosed intraperitoneally. This dose of ATRA was selected on the basis of existing data [52,53] . In vivo, retinol is the major source of RA and RALDH is identified as an RA-generating enzyme [54] .…”

Section: Discussionmentioning

confidence: 99%

Regulation of IgA Class Switch Recombination in Immunoglobulin A Nephropathy: Retinoic Acid Signaling and BATF

Peng²,

Chen³

et al. 2016

Am J Nephrol

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Background: Immunoglobulin (Ig) A nephropathy (IgAN) is the ﬁnding of immune deposits predominantly containing polymeric IgA in the glomerular mesangium on renal biopsy. Increasing evidence suggested that retinoic acid (RA) signaling selectively induces IgA isotype switching and basic leucine zipper transcription factor, ATF-like (BATF) controls the global regulators of class switch recombination (CSR) in lymphocytes. Great effort has been paid to identify whether impaired immune regulation along the ‘mucosa-bone marrow (BM) axis' play an important role in the pathogenesis of IgAN. Methods: The aim of the study was to investigate the expression of all-trans-RA (ATRA) and BATF, and to identify their impact on IgA CSR in IgAN patients and rat animal models. Blood samples and tonsillar tissue specimens were obtained from 22 patients with IgAN and 24 patients with chronic tonsillitis as control. Results: Immunohistochemical, RT-PCR and western blotting examination revealed that RA signaling and BATF productions are activated in IgAN patients compared with controls. Lipopolysaccharide and α-hemolytic streptococcus stimulation upregulated RA receptor (RAR) and BATF expression, promote IgA CSR and ATRA productions in tonsil mononuclear cells. RAR alpha (RARα) or BATF siRNA decreases IgA expression. We also built IgAN rat models and found that RARα, BATF and activation-induced cytidine deaminase were upregulated in the peripheral blood, spleen and BM. With ATRA (500 μg/kg body weight) treatment for 8 weeks, IgA deposition on glomeruli and mesangial cells proliferation increased. It also revealed that ATRA activated BATF and IgA CSR in vivo. Conclusion: These data point toward the role of RA signaling together with BATF in IgA CSR of IgAN, and the data also support the notion that mucosal immunization with neoantigen results in impaired mucosal and systemic IgA responses.

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All-Trans-Retinoic Acid Attenuates Intestinal Injury in a Neonatal Rat Model of Necrotizing Enterocolitis

Cited by 24 publications

References 23 publications

Clinical Importance of a Fixed Bowel Loop in the Treatment of Necrotizing Enterocolitis

Clinical Importance of a Fixed Bowel Loop in the Treatment of Necrotizing Enterocolitis

Early prediction of severity of necrotizing enterocolitis in preterm infants: A composite scoring tool

Regulation of IgA Class Switch Recombination in Immunoglobulin A Nephropathy: Retinoic Acid Signaling and BATF

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