Abstract:OBJECTIVES:Necrotizing enterocolitis is a severe multifactorial intestinal disorder that primarily affects preterm newborns, causing 20-40% mortality and morbidity. Intestinal fatty acid-binding protein has been reported to be a biomarker for the detection of intestinal injuries. Our aim was to assess intestinal tissue injury and the molecular expression of intestinal fatty acid-binding protein over time in a necrotizing enterocolitis model.METHODS:A total of 144 Newborn rats were divided into two groups: 1) C… Show more
“…NEC is characterized by ischemic necrosis of gastrointestinal tract and intestinal perforation. The pathogenesis involves intestinal hypoxia-ischemia, immature intestinal development, microbial reproduction and high immune response of intestinal mucosa ( 13 , 14 ). I-FABP is mainly distributed in villus cells in intestinal mucosa, which can be quickly released when intestinal ischemic injury occurs, enters the blood circulation through the cell membranes, capillaries, lymphatic capillaries and portal veins, and is finally discharged with urine from the body ( 15 ).…”
To study the significance of dynamic evolution of serum tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and intestinal fatty acid-binding protein (I-FABP) levels in neonatal necrotizing enterocolitis (NEC). A total of 45 NEC child patients, 45 non-NEC child patients and 45 healthy newborns were enrolled. After the day age, weight, gestational week and delivery mode were matched, the serum TNF-α, IL-6 and I-FABP levels at 6, 24 and 72 h after admission were measured via ELISA method, and their correlations with prognosis were analyzed. The levels of serum TNF-α and IL-6 in NEC and non-NEC group reached the peak at 24 h and fell at 72 h; there were no differences in each time point between the two groups (P>0.05), but the levels of serum TNF-α and IL-6 were higher than those in the control group (P<0.05). The level of serum I-FABP in NEC and non-NEC group reached the peak at 6 h, and it fell at 72 h in NEC group and 24 h in non-NEC group; the level of I-FABP in each time point in NEC was significantly higher than that in non-NEC group, and the level was the lowest in healthy group; the differences were statistically significant (P<0.05). There were 40 cases of survival and 5 cases of death (11.1%) in NEC group, while there were 43 cases of survival and 2 cases of death (4.4%) in non-NEC group. There were no differences in serum TNF-α and IL-6 levels at different times between surviving child patients and dead child patients in NEC group (P>0.05), but the levels of serum I-FABP in surviving child patients at 6 h and 24 h were significantly lower than those in dead child patients (P<0.05), and there was no difference at 72 h (P>0.05). There were no differences in serum TNF-α, IL-6 and I-FABP levels at different times between surviving and dead child patients in non-NEC group (P>0.05). Serum I-FABP level and its dynamic evolution may be important indexes of early diagnosis and prognosis evaluation of NEC.
“…NEC is characterized by ischemic necrosis of gastrointestinal tract and intestinal perforation. The pathogenesis involves intestinal hypoxia-ischemia, immature intestinal development, microbial reproduction and high immune response of intestinal mucosa ( 13 , 14 ). I-FABP is mainly distributed in villus cells in intestinal mucosa, which can be quickly released when intestinal ischemic injury occurs, enters the blood circulation through the cell membranes, capillaries, lymphatic capillaries and portal veins, and is finally discharged with urine from the body ( 15 ).…”
To study the significance of dynamic evolution of serum tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and intestinal fatty acid-binding protein (I-FABP) levels in neonatal necrotizing enterocolitis (NEC). A total of 45 NEC child patients, 45 non-NEC child patients and 45 healthy newborns were enrolled. After the day age, weight, gestational week and delivery mode were matched, the serum TNF-α, IL-6 and I-FABP levels at 6, 24 and 72 h after admission were measured via ELISA method, and their correlations with prognosis were analyzed. The levels of serum TNF-α and IL-6 in NEC and non-NEC group reached the peak at 24 h and fell at 72 h; there were no differences in each time point between the two groups (P>0.05), but the levels of serum TNF-α and IL-6 were higher than those in the control group (P<0.05). The level of serum I-FABP in NEC and non-NEC group reached the peak at 6 h, and it fell at 72 h in NEC group and 24 h in non-NEC group; the level of I-FABP in each time point in NEC was significantly higher than that in non-NEC group, and the level was the lowest in healthy group; the differences were statistically significant (P<0.05). There were 40 cases of survival and 5 cases of death (11.1%) in NEC group, while there were 43 cases of survival and 2 cases of death (4.4%) in non-NEC group. There were no differences in serum TNF-α and IL-6 levels at different times between surviving child patients and dead child patients in NEC group (P>0.05), but the levels of serum I-FABP in surviving child patients at 6 h and 24 h were significantly lower than those in dead child patients (P<0.05), and there was no difference at 72 h (P>0.05). There were no differences in serum TNF-α, IL-6 and I-FABP levels at different times between surviving and dead child patients in non-NEC group (P>0.05). Serum I-FABP level and its dynamic evolution may be important indexes of early diagnosis and prognosis evaluation of NEC.
“…In this regard, perinatal hypoxia, early feeding with formula milk, and bacterial colonization play a fundamental role in the activation of the inflammatory cascade of NEC. These factors induce intestinal damage, which may progress to coagulative necrosis of the gastrointestinal tract 1,3 .…”
Section: Use Of Sildenafil and L-arginine In An Experimental Rat Mode...mentioning
confidence: 99%
“…2 Pediatric Surgery Department, Federal University of Parana, Curitiba, R. Gen. Carneiro, 181 -Alto da Glória, Curitiba, PR 80060-900, Brazil. 3 Biochemistry Department, Federal University of Parana Campus Polytechnic Center, Curitiba, Jardim das Américas, Curitiba, PR 80050-540, Brazil. 4 www.nature.com/scientificreports/ signaling within the endothelium with reduced blood flow and impaired eNOS function, Yazji et al 4 evaluated the supplementation of the phosphodiesterase-5 inhibitor, sildenafil, in wild-type mice and observed a reduction in the severity of NEC, through vasodilation and maintenance of the intraluminal NO activity promoted by the substance 4 .…”
Section: Use Of Sildenafil and L-arginine In An Experimental Rat Mode...mentioning
Necrotizing enterocolitis (NEC) has a 45% mortality in neonatal intensive care units. This paper aimed to evaluate the isolated and combined effects of sildenafil and l-arginine in the prevention of necrotizing enterocolitis. Neonatal rats were fed formula milk and submitted to hypoxia under a 100% N2 atmosphere for 70 s. Then, animals were subjected to hypothermia (4 °C for 10 min), twice a day for 3 days. Forty neonatal rats were divided into five groups: negative control—not submitted to the protocol (n = 5), sildenafil group—NEC protocol (n = 9), l-arginine group—NEC protocol (n = 9), l-arginine and sildenafil group—NEC protocol (n = 9) and positive control—NEC protocol and intraperitoneal saline solution (n = 8). Jejunum and terminal ileus were removed for histopathologic and immunohistochemical Ki-67 analysis. Kruskal–Wallis test was used to analyze mortality, survival, body weight, intestinal injury score and Ki-67 proliferation index. All animals submitted to the protocol developed enterocolitis. Mortality rate was higher in group that received only l-arginine (p = 0.0293). The Ki-67 analysis showed a higher proliferative index in groups that received interventional drugs (p = 0.017). In conclusion, sildenafil and l-arginine were not effective to reduce intestinal injury.
“…Rat NEC models have also been useful in temporal biomarker studies (e.g. correlation on intestinal fatty acid binding protein with timing of ischemia and severity of tissue injury(23)). Currently, the administration of a protein kinase A inhibitor(24) and milk-derived exosomes(25) are being studied in a rat model with promising results as potential treatments for NEC.…”
Necrotizing enterocolitis (NEC) remains one of the highest causes of mortality and of acute and long-term morbidity in premature infants. Multiple factors are involved in the pathophysiology of NEC including the immaturity of the immune system and the complex changing composition of the intestinal microbiome. This is compounded by the fact that the premature infant should ideally still be a developing fetus and has an immature intestinal tract. Because these complexities are beyond the scope of studies in single-cell cultures, animal models are absolutely essential to understand the mechanisms involved in the pathophysiology of NEC and the effects of inflammation on the immature intestinal tract. To this end, investigators have utilized many different species (e.g., rats, mice, rabbits, quails, piglets, and non-human primates) and conditions to develop models of NEC. Each animal has distinct advantages and drawbacks related to its preterm viability, body size, genetic variability, and cost. The choice of animal model is strongly influenced by the scientific question being addressed. While no model perfectly mimics human NEC, each has greatly improved our understanding of disease. Examples of recent discoveries in NEC pathogenesis and prevention underscore the importance of continued animal research in NEC.
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