Óbitos neonatais por enterocolite necrosante: estudo de coorte retrospectiva / Neonatal deaths from necrotizing enterocolitis: a retrospective cohort study / Muertes neonatales por enterocolitis necrozante: estudio de cohorte retrospectivo

Introdução:A enterocolite necrosante é uma doença que pode afetar o trato gastrointestinal de recém-nascidos,cujas manifestações clínicas podem ser caracterizadas por vômitos biliosos, sangue nas fezes, distensão abdominal, além de alterações nos parâmetros hemodinâmicos e instabilidade térmica. As populações mais vulneráveis a essa enfermidade são recém-nascidos de baixo peso,expostos ao ambiente de terapia intensiva neonatal. Objetivos: Identificar o perfil de recém-nascidos e os fatores maternos e neonatais associados à ocorrência de óbitos por enterocolite necrosante, em maternidade de referência do Ceará-Brasil. Metodologia: Trata-se de coorte retrospectiva, estudo que objetiva a descrição da incidência de determinado evento ao longo do tempo, além do estabelecimento de relações causais entre os fatores associados ao acontecimento. Incluíram-serecém-nascidos que tiveram óbitos por enterocolite necrosante entre 2019 e 2021, comficha de investigação de óbitos neonatais preenchida corretamente, não sendo excluído nenhum recém-nascido, totalizando amostra de 29 óbitos.Resultados: Identificou-se que o perfil dos recém-nascidos foi,em maioria, deprematuros e com baixo peso e fatores de risco para outras doenças associadas,como a sepse, o que acarretourealização de procedimentos invasivos e internação em ambiente de terapia intensiva neonatal.Conclusões: A prematuridade e o baixo peso ao nascer foram as variáveis relevantes no estudo e podem estar associadas à piora das condições clínicas do recém-nascido e ao desenvolvimento de enterocolite necrosante (AU).

Introduction: Necrotizing Enterocolitis is a disease that can affect the gastrointestinal tract of newborns, whose clinical manifestations can be characterized by bilious vomiting, blood in stool, abdominal distension, in addition to changes in hemodynamic parameters and thermal instability. The populations most vulnerable to this disease are low birth weight newborns exposed to the neonatal intensive care environment. Objectives: This study aimed to identify the profile of newborns and maternal and neonatal factors associated with the occurrence of deaths from necrotizing enterocolitis in a reference maternity hospital in Ceará, Brazil. Methodology: This is a retrospective cohort study seeking to describe the incidence ofa particular event over time, as well as establish causal relationships between the factors associated with the event. The study population comprised newborns who died from necrotizing enterocolitis between 2019 and 2021, who had neonatal death investigation forms filled out correctly, with no newborns being excluded, totaling a sample of 29 deaths. Results: It was identified that the profile of newborns was mostly premature, of low birth weight and with risk factors for other associated diseases such as sepsis, leading to invasive procedures and hospitalization in a neonatal intensive care environment. Conclusions: Prematurity and low birth weight were relevant variables in the study and may be associated with worsening of the newborn's clinical conditionsand development of necrotizing enterocolitis (AU).

ntroducción:La Enterocolitis Necrotizante es enfermedad que puede afectar el tracto gastrointestinal del recién nacido, cuyas manifestaciones clínicas pueden caracterizarse por vómitos biliosos, sangre en las heces, distensión abdominal, además de cambios en los parámetros hemodinámicos e inestabilidad térmica.Las poblaciones más vulnerables a esta enfermedad son recién nacidos con bajo peso expuestos al entorno de cuidados intensivos neonatales.Objetivos: Identificar el perfil de recién nacidos y los factores maternos y neonatales asociados a la ocurrencia de muertes por enterocolitis necrotizante, en maternidad de referencia en el Ceará-Brasil.Metodología: Estudio de cohorte retrospectivo, para describir la incidencia de determinado evento a lo largo del tiempo, además de establecer relaciones causales entre los factores asociados al evento.Se incluyeron recién nacidos fallecidos por enterocolitis necrotizante entre 2019 y 2021, quienes tuvieron formulario de investigación de muerte neonatal correctamente diligenciado, no excluyéndose ningún recién nacido, totalizando muestra de 29 defunciones.Resultados:El perfil de los recién nacidos fue mayoritariamente prematuro y de bajo peso al nacer y con factores de riesgo para otras enfermedades asociadas, como sepsis, con procedimientos invasivos y hospitalización en ambiente de cuidados intensivosneonatales.Conclusiones:La prematuridad y el bajo peso al nacer fueron variables relevantes en el estudio y pueden estar asociados con empeoramiento de las condiciones clínicas de recién nacidos y desarrollo de enterocolitis necrotizante (AU).

Use of sildenafil and L-arginine in an experimental rat model for the prevention of neonatal necrotizing enterocolitis.

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.

Necrotizing enterocolitis totalis: High mortality in the absence of an aggressive surgical approach.

BACKGROUND: Necrotizing enterocolitis is the leading case of gastrointestinal-related morbidity in premature infants. Necrotizing enterocolitis totalis is an aggressive form of necrotizing enterocolitis, which has traditionally been managed with comfort care. Recent advances in management of short bowel syndrome have resulted in some reported long-term survival. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, studies that reported outcomes in children with necrotizing enterocolitis totalis were identified. The definition of necrotizing enterocolitis totalis was captured along with length of follow-up, patient demographics, and outcomes. RESULTS: A total of 766 articles were screened, of which 166 were selected for full article review. Of these, 32 articles included data on 414 patients with necrotizing enterocolitis totalis. In the majority of studies (52%), necrotizing enterocolitis totalis was not defined. Aggressive surgical therapy (defined as bowel resection or fecal diversion) was undertaken in 32 patients (7.7%), with a mortality rate of 68.8%. In contrast, nonaggressive surgical therapy was undertaken in 382 patients (92.3%), and the mortality in these patients was 95%. Long-term outcomes for necrotizing enterocolitis totalis survivors, such as length of time on parenteral nutrition, progression to liver and/or small bowel transplant, and quality of life, were not reported. CONCLUSION: We found that there is no accepted definition of necrotizing enterocolitis totalis. Aggressive surgical therapy is rarely pursued, which likely drives the overall high mortality rate. This study underscores the importance of standardizing the definition of necrotizing enterocolitis totalis and capturing short and long-term outcomes prospectively. With more aggressive surgical therapy, more infants are likely to survive this abdominal catastrophe, which was once thought to be uniformly fatal.

There is an association between disease location and gestational age at birth in newborns submitted to surgery due to necrotizing enterocolitis / Existe associação entre a localização da doença e a idade gestacional ao nascimento de recém-nascidos operados por enterocolite necrosante

Abstract Objectives To evaluate if there are differences regarding disease location and mortality of necrotizing enterocolitis, according to the gestational age at birth, in newborns submitted to surgery due to enterocolite. Methods A historical cohort study of 198 newborns submitted to surgery due to necrotizing enterecolitis in a tertiary hospital, from November 1991 to December 2012. The newborns were divided into different categories according to gestational age (<30 weeks, 30-33 weeks and 6 days, 34-36 weeks and 6 days, and ≥37 weeks), and were followed for 60 days after surgery. The inclusion criterion was the presence of histological findings of necrotizing enterocolitis in the pathology. Patients with single intestinal perforation were excluded. Results The jejunum was the most commonly affected site in extremely premature infants (p = 0.01), whereas the ileum was the most commonly affected site in premature infants (p = 0.002), and the colon in infants born at term (p < 0.001). With the increasing gestational age, it was observed that intestinal involvement decreased for the ileum and the jejunum (decreasing from 45% to 0% and from 5% to 0%, respectively), with a progressive increase in colon involvement (0% to 84%). Total mortality rate was 45.5%, and no statistical difference was observed in the mortality at different gestational ages (p = 0.287). Conclusions In newborns submitted to surgery due to necrotizing enterocolitis, the disease in extremely preterm infants was more common in the jejunum, whereas in preterm infants, the most affected site was the ileum, and in newborns born close to term, it was the colon. No difference in mortality was observed according to the gestational age at birth.

Resumo Objetivos Avaliar se há diferença de localização e de mortalidade da enterocolite necrosante de acordo com a idade gestacional ao nascimento, em neonatos operados por enterocolite. Métodos Coorte histórica de 198 neonatos operados por enterocolite necrosante em hospital terciário, de novembro de 1991 a dezembro de 2012. Os recém-nascidos operados foram divididos em diferentes categorias de acordo com a idade gestacional (< 30 semanas, 30 a 33 semanas e seis dias, 34 a 36 semanas e seis dias e ≥ 37 semanas) e foram seguidos por 60 dias depois da cirurgia. O critério de inclusão foi a presença de achados histológicos de enterocolite necrosante no anatomopatológico e o de exclusão foi a presença de perfuração intestinal única. Resultados O jejuno foi mais acometido pela ECN nos prematuros extremos (p = 0,01); o íleo mais afetado nos recém-nascidos prematuros (p = 0,002) e o cólon nos recém-nascidos a termo ou próximos ao termo (p < 0,001). Com o aumento da idade gestacional, observam-se redução do acometimento do jejuno e do íleo (regrediu de 45% para 0% e de 5% para 0%, respectivamente) e aumento progressivo do acometimento do cólon (0% para 84%). A mortalidade total das crianças operadas por ECN foi de 45,5%; não existiu diferença estatística na mortalidade nas diferentes idades gestacionais (p = 0,287). Conclusões Em recém-nascidos operados por enterocolite necrosante, a doença no jejuno foi mais comum no prematuro extremo, no íleo no prematuro, e a doença no cólon nos recém-nascidos próximos ao termo. Não foi observada diferença de mortalidade de acordo com a idade gestacional ao nascimento.

There is an association between disease location and gestational age at birth in newborns submitted to surgery due to necrotizing enterocolitis.

OBJECTIVES: To evaluate if there are differences regarding disease location and mortality of necrotizing enterocolitis, according to the gestational age at birth, in newborns submitted to surgery due to enterocolite. METHODS: A historical cohort study of 198 newborns submitted to surgery due to necrotizing enterecolitis in a tertiary hospital, from November 1991 to December 2012. The newborns were divided into different categories according to gestational age (<30 weeks, 30-33 weeks and 6 days, 34-36 weeks and 6 days, and ≥37 weeks), and were followed for 60 days after surgery. The inclusion criterion was the presence of histological findings of necrotizing enterocolitis in the pathology. Patients with single intestinal perforation were excluded. RESULTS: The jejunum was the most commonly affected site in extremely premature infants (p=0.01), whereas the ileum was the most commonly affected site in premature infants (p=0.002), and the colon in infants born at term (p<0.001). With the increasing gestational age, it was observed that intestinal involvement decreased for the ileum and the jejunum (decreasing from 45% to 0% and from 5% to 0%, respectively), with a progressive increase in colon involvement (0% to 84%). Total mortality rate was 45.5%, and no statistical difference was observed in the mortality at different gestational ages (p=0.287). CONCLUSIONS: In newborns submitted to surgery due to necrotizing enterocolitis, the disease in extremely preterm infants was more common in the jejunum, whereas in preterm infants, the most affected site was the ileum, and in newborns born close to term, it was the colon. No difference in mortality was observed according to the gestational age at birth.

Neonatal necrotizing enterocolitis rat model attenuated by a remote ischemic preconditioning in the pregnant.

PURPOSE:: To evaluate the effect of remote ischemic preconditioning (r-IPC) administered to pregnant rats, in the ileum of newborn rats subjected to hypoxia and reoxygenation. METHODS:: We used three pregnant rats and their newborn rats distributed in three groups: 1) Control (C) - Newborn rats born from a pregnant rat which did not undergo any intervention; 2) Hypoxia-Reoxygenation (H/R) - Newborn rats born from a pregnant rat which did not undergo any intervention, and were subjected to hypoxia-reoxygenation; 3) Remote Ischemic Preconditioning (r-IPC) - newborn rats born from a pregnant rat which was subjected to remote ischemic preconditioning twenty-four hours before giving birth and the newborn rats were subjected to hypoxia-reoxygenation. Segments of ileum were prepared for histological analysis by HE and immunohistochemistry by the Ki67 to evaluate cell proliferation, crypt depth and villus height and evaluation of apoptosis by cleaved caspase-3. RESULTS:: The intensity of the lesions was lower in the r-IPC than in the H/R group, showing significant difference (p<0.01). The r-IPC group showed a higher proliferative activity compared to the H/R group (p<0.01), with deeper crypts (r-IPC > H/R - p < 0.05), and higher villi, showing significant difference (r-IPC > H/R - (p <0.01). The occurrence of apoptosis in the H/R group was lower in comparison to groups C and r-IPC, with significant difference (H/R < r-IPC; p<0.05). CONCLUSION:: The remote ischemic preconditioning applied to the pregnant rat protected the ileum of newborn rats subjected to hypoxia and reoxygenation, with decreased intensity of the lesions in the ileum mucosa and preservation of proliferative activity, keeping the villus height and crypt depth similar to group C.

Neonatal necrotizing enterocolitis rat model attenuated by a remote ischemic preconditioning in the pregnant

Abstract Purpose: To evaluate the effect of remote ischemic preconditioning (r-IPC) administered to pregnant rats, in the ileum of newborn rats subjected to hypoxia and reoxygenation. Methods: We used three pregnant rats and their newborn rats distributed in three groups: 1) Control (C) - Newborn rats born from a pregnant rat which did not undergo any intervention; 2) Hypoxia-Reoxygenation (H/R) - Newborn rats born from a pregnant rat which did not undergo any intervention, and were subjected to hypoxia-reoxygenation; 3) Remote Ischemic Preconditioning (r-IPC) - newborn rats born from a pregnant rat which was subjected to remote ischemic preconditioning twenty-four hours before giving birth and the newborn rats were subjected to hypoxia-reoxygenation. Segments of ileum were prepared for histological analysis by HE and immunohistochemistry by the Ki67 to evaluate cell proliferation, crypt depth and villus height and evaluation of apoptosis by cleaved caspase-3. Results: The intensity of the lesions was lower in the r-IPC than in the H/R group, showing significant difference (p<0.01). The r-IPC group showed a higher proliferative activity compared to the H/R group (p<0.01), with deeper crypts (r-IPC > H/R - p < 0.05), and higher villi, showing significant difference (r-IPC > H/R - (p <0.01). The occurrence of apoptosis in the H/R group was lower in comparison to groups C and r-IPC, with significant difference (H/R < r-IPC; p<0.05). Conclusion: The remote ischemic preconditioning applied to the pregnant rat protected the ileum of newborn rats subjected to hypoxia and reoxygenation, with decreased intensity of the lesions in the ileum mucosa and preservation of proliferative activity, keeping the villus height and crypt depth similar to group C.

Acute necrotizing colitis with pneumatosis intestinalis in an Amazonian manatee calf.

On 25 January 2014, a 1 mo old female Amazonian manatee Trichechus inunguis calf weighing 12 kg was rescued by air transport in Guajará, Brazil, and transferred to Mamirauá Institute's Community-based Amazonian Manatee Rehabilitation Center. The calf presented piercing/cutting lesions on the back, neck, and head, in addition to dehydration and intermittent involuntary buoyancy. X-ray analysis revealed a large amount of gases in the gastrointestinal tract. Daily procedures included wound cleaning and dressing, clinical and laboratory monitoring, treatment for intestinal tympanism, and artificial feeding. Adaptation to the nursing formula included 2 kinds of whole milk. Up to 20 d post-rescue the calf presented appetite, was active, and gained weight progressively. Past this period the calf started losing weight and presented constant involuntary buoyancy and died after 41 d in rehabilitation. The major findings at necropsy were pneumatosis intestinalis in cecum and colon, pulmonary edema, and hepatomegaly. The microscopic examination revealed pyogranulomatous and necrohemohrragic colitis with multinucleated giant cells, acute multifocal lymphadenitis with lymphoid depletion in cortical and paramedullary regions of mesenteric lymph nodes, and diffuse severe acinar atrophy of the pancreas. Anaerobic cultures of fragments of cecum and colon revealed colonies genotyped as Clostridium perfringens type A. We speculate that compromised immunity, thermoregulatory failure, and intolerance to artificial diet may have been contributing factors to the infection, leading to enterotoxemia and death.

Temporal profile of intestinal tissue expression of intestinal fatty acid-binding protein in a rat model of necrotizing enterocolitis.

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) Control, which received breastfeeding (n=72) and 2) Necrotizing Enterocolitis, which received formula feeding and underwent hypoxia and hypothermia (n=72). A total of six time points of ischemia (2 times a day for 3 days; 12 pups for each time point) were examined. Samples were collected for analysis of body weight, morphological and histological characteristics, intestinal weight, intestinal weight/body weight ratio, injury grade, and intestinal fatty acid-binding protein levels. RESULTS: Body and intestinal weights were lower in the Necrotizing Enterocolitis group than in the Control group (p<0.005 and p<0.0005, respectively). The intestinal weight/body weight ratio was higher in the Necrotizing Enterocolitis group than in the Control group (p<0.005) only at the sixth ischemia time point. The Necrotizing Enterocolitis group displayed higher expression of intestinal fatty acid-binding protein (p<0.0005) and showed greater tissue damage than the Control group. CONCLUSION: Intestinal fatty acid-binding protein was an efficient marker of ischemic injury to the intestine and a good correlation was demonstrated between the time of ischemic injury and the grade of intestinal injury.

Temporal profile of intestinal tissue expression of intestinal fatty acid-binding protein in a rat model of necrotizing enterocolitis

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) Control, which received breastfeeding (n=72) and 2) Necrotizing Enterocolitis, which received formula feeding and underwent hypoxia and hypothermia (n=72). A total of six time points of ischemia (2 times a day for 3 days; 12 pups for each time point) were examined. Samples were collected for analysis of body weight, morphological and histological characteristics, intestinal weight, intestinal weight/body weight ratio, injury grade, and intestinal fatty acid-binding protein levels. RESULTS: Body and intestinal weights were lower in the Necrotizing Enterocolitis group than in the Control group (p<0.005 and p<0.0005, respectively). The intestinal weight/body weight ratio was higher in the Necrotizing Enterocolitis group than in the Control group (p<0.005) only at the sixth ischemia time point. The Necrotizing Enterocolitis group displayed higher expression of intestinal fatty acid-binding protein (p<0.0005) and showed greater tissue damage than the Control group. CONCLUSION: Intestinal fatty acid-binding protein was an efficient marker of ischemic injury to the intestine and a good correlation was demonstrated between the time of ischemic injury and the grade of intestinal injury.

Are there gender differences in left ventricular remodeling after myocardial infarction in rats? / Há diferenças entre os gêneros no remodelamento ventricular esquerdo após infarto do miocárdio em ratos?

Objective: An unclear issue is whether gender may influence at cardiac remodeling after myocardial infarction (MI). We evaluated left ventricle remodeling in female and male rats post-MI. Methods: Rats were submitted to anterior descending coronary occlusion. Echocardiographic evaluations were performed on the first and sixth week post-occlusion to determine myocardial infarction size and left ventricle systolic function (FAC, fractional area change). Pulsed Doppler was applied to analyze left ventricle diastolic function using the following parameters: E wave, A wave, E/A ratio. Two-way ANOVA was applied for comparisons, complemented by the Bonferroni test. A P≤=0.05 was considered significant. Results: There were no significant differences between genders for morphometric parameters on first (MI [Female (FE): 44.0±5.0 vs. Male (MA): 42.0±3.0%]; diastolic [FE: 0.04±0.003 vs. MA: 0.037±0.005, mm/g] and systolic [FE: 0.03±0.0004 vs. MA: 0.028±0.005, mm/g] diameters of left ventricle) and sixth (MI [FE: 44.0±5.0 vs. MA: 42.0±3.0, %]; diastolic [FE: 0.043±0.01 vs. MA: 0.034±0.005, mm/g] and systolic [FE: 0.035±0.01 vs. MA: 0.027±0.005, mm/g] of LV) week. Similar findings were reported for left ventricle functional parameters on first (FAC [FE: 34.0±6.0 vs. MA: 32.0±4.0, %]; wave E [FE: 70.0±18.0 vs. MA: 73.0±14.0, cm/s]; wave A [FE: 20.0±12.0 vs. MA: 28.0±13.0, cm/s]; E/A [FE: 4.9±3.4 vs. MA: 3.3±1.8]) and sixth (FAC [FE: 29.0±7.0 vs. MA: 31.0±7.0, %]; wave E [FE: 85.0±18.0 vs. MA: 87.0±20.0, cm/s]; wave A [FE: 20.0±11.0 vs. MA: 28.0±17.0, cm/s]; E/A [FE: 6.2±4.0 vs. MA: 4.6±3.4]) week. Conclusion: Gender does not influence left ventricle remodeling post-MI in rats. .

Objetivo: A influência do gênero no remodelamento cardíaco após o infarto do miocárdio é uma questão em intenso debate. Nós avaliamos o remodelamento ventricular esquerdo em ratos infartados de ambos os gêneros. Métodos: O infarto do miocárdio foi induzido por oclusão da artéria coronária descendente anterior (fêmeas [FM]; machos [MC]). A ecocardiografia foi realizada na primeira e sexta semana pós-oclusão para determinar o tamanho do infarto do miocárdio e a função sistólica do ventricular esquerdo (mudança na área fracional [FAC]). A função diastólica derivou dos seguintes parâmetros: onda E; onda A; razão E/A. ANOVA duas vias com pós-teste de Bonferroni foi aplicado nas comparações (P≤=0,05). Resultados: Todas variáveis morfométricas foram similares (P>0,05) entre os gêneros com uma (infarto do miocárdio [FM: 44,0±5,0 vs. MC: 42,0±3,0, %]; diâmetro diastólico [FM: 0,04±0,003 vs. MC: 0,037±0,005, mm/g] e sistólico [FM: 0,03±0,0004 vs. MC: 0,028±0,005, mm/g] do VE) e seis (IM [FM: 44,0±5,0 vs. MC: 42,0±3,0, %]; diâmetro diastólico [FM: 0,043±0,01 vs. MC: 0,034±0,005, mm/g] e sistólico [FM: 0,035±0,01 vs. MC: 0,027±0,005, mm/g] do ventricular esquerdo) semanas. Achado similar ocorreu para os dados funcionais com uma (FAC [FM: 34,0±6,0 vs. MC: 32,0±4,0, %]; onda E [FM: 70,0±18,0 vs. MC: 73,0±14,0, cm/s]; onda A [FM: 20,0±12,0 vs. MC: 28,0±13,0, cm/s]; E/A [FM: 4,9±3,4 vs. MC: 3,3±1,8]) e seis (FAC [FM: 29,0±7,0 vs. MC: 31,0±7,0, %]; onda E [FM: 85,0±18,0 vs. MC: 87,0±20,0, cm/s]; onda A [FM: 20,0±11,0 vs. MC: 28,0±17,0 cm/s]; E/A [FM: 6,2±4,0 vs. MC: 4,6±3,4]) semanas. Conclusão: O gênero não é determinante para o remodelamento ventricular esquerdo pós-infarto do miocárdio em ratos. .

L-FABP and I-FABP expression in newborn rats changes inversely in the model of necrotizing enterocolitis.

PURPOSE: To determine the expression of hepatic L-FABP and intestinal I-FABP in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats. METHODS: Newborn Sprague-Dawley rats were divided into four groups: Control (C1) - exclusive breastfeeding at the first and sixth procedures (C6), NEC1 - fed formula milk and submitted to hypoxia and hypothermia at the first and sixth procedures (NEC6). The newborn pups were fed twice a day for three days, for a total of six procedures. Samples were collected for morphometric evaluation (body weight, liver weight, liver weight/body weight ratio, intestinal weight and intestinal/body weight ratio) and for immunohistochemical and Western blotting analysis. The values obtained were analyzed statistically, with the level of significance set at p<0.05. RESULTS: Morphometric measurements showed reduction of body and liver weights in the NEC group (p<0.05). Both immunohistochemistry and western blotting revealed that L-FABP expression in the liver was decreased and I-FABP expression in the ileum was increased in the NEC group (p<0.05). CONCLUSION: L-FABP and I-FABP expression changed inversely in the rat NEC model. These findings can contribute to a better diagnosis of NEC in human newborns.

Effects of maternal ischemic preconditioning in the colon of newborn rats submitted to hypoxia-reoxygenation insult.

PURPOSE: To evaluate the effects of maternal remote ischemic preconditioning (IPCr) in the colonic mucosa of newborn rats subjected to hypoxia and reoxygenation. METHODS: Newborn Wistar rats were divided into three groups. Control Group (CG), Hypoxia and Reoxygenation Group (HRG) and Remote Ischemic Preconditioning Group (IPCrG). Hypoxia and reoxygenation was performed 2x per day, with an interval of 6 hours, on the 1st, 2nd and 3rd days of life, with 10 minutes of CO2 at 100%, followed by 10 minutes O2 at 100%(HRG/IPCrG). The maternal IPCr was performed 24 hours before delivery by applying a rubber band tourniquet to the left hind limb (IPCrG). Segments of the colon underwent histological (HE) and immunohistochemical analysis for caspase-3 and COX - 2. RESULTS: The histological findings showed no intestinal mucosal damage in the CG group and severe lesions in HRG that was attenuated in the IPCrG (p<0.05). The expression of the apoptotic cells was lower in the HRG group than in the CG and IPCrG. The COX-2 expression was intense in HRG and attenuated in the IPCrG (p<0.05). CONCLUSIONS: Maternal IPCr protected the colonic mucosa of newborn rats subjected to hypoxia and reoxygenation, reducing the morphological alterations and inflammatory response. It ameliorates the occurrence of apoptosis, keeping the physiological process of renewal and regeneration in the epithelial lining of the colonic mucosa.

Effects of maternal ischemic preconditioning in the colon of newborn rats submitted to hypoxia-reoxygenation insult

PURPOSE: To evaluate the effects of maternal remote ischemic preconditioning (IPCr) in the colonic mucosa of newborn rats subjected to hypoxia and reoxygenation. METHODS: Newborn Wistar rats were divided into three groups. Control Group (CG), Hypoxia and Reoxygenation Group (HRG) and Remote Ischemic Preconditioning Group (IPCrG). Hypoxia and reoxygenation was performed 2x per day, with an interval of 6 hours, on the 1st, 2nd and 3rd days of life, with 10 minutes of CO2 at 100%, followed by 10 minutes O2 at 100%(HRG/IPCrG). The maternal IPCr was performed 24 hours before delivery by applying a rubber band tourniquet to the left hind limb (IPCrG). Segments of the colon underwent histological (HE) and immunohistochemical analysis for caspase-3 and COX - 2. RESULTS: The histological findings showed no intestinal mucosal damage in the CG group and severe lesions in HRG that was attenuated in the IPCrG (p<0.05). The expression of the apoptotic cells was lower in the HRG group than in the CG and IPCrG. The COX-2 expression was intense in HRG and attenuated in the IPCrG (p<0.05). CONCLUSIONS: Maternal IPCr protected the colonic mucosa of newborn rats subjected to hypoxia and reoxygenation, reducing the morphological alterations and inflammatory response. It ameliorates the occurrence of apoptosis, keeping the physiological process of renewal and regeneration in the epithelial lining of the colonic mucosa. .

L-FABP and I-FABP expression in newborn rats changes inversely in the model of necrotizing enterocolitis

PURPOSE: To determine the expression of hepatic L-FABP and intestinal I-FABP in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats. METHODS: Newborn Sprague-Dawley rats were divided into four groups: Control (C1) - exclusive breastfeeding at the first and sixth procedures (C6), NEC1 - fed formula milk and submitted to hypoxia and hypothermia at the first and sixth procedures (NEC6). The newborn pups were fed twice a day for three days, for a total of six procedures. Samples were collected for morphometric evaluation (body weight, liver weight, liver weight/body weight ratio, intestinal weight and intestinal/body weight ratio) and for immunohistochemical and Western blotting analysis. The values obtained were analyzed statistically, with the level of significance set at p<0.05. RESULTS: Morphometric measurements showed reduction of body and liver weights in the NEC group (p<0.05). Both immunohistochemistry and western blotting revealed that L-FABP expression in the liver was decreased and I-FABP expression in the ileum was increased in the NEC group (p<0.05). CONCLUSION: L-FABP and I-FABP expression changed inversely in the rat NEC model. These findings can contribute to a better diagnosis of NEC in human newborns. .

Spontaneous and experimental intoxication of cattle by Simarouba versicolor A. St.-Hill (Simaroubaceae).

This study describes an outbreak of Simarouba versicolor intoxication in cattle from Mato Grosso do Sul, Brazil, and reproduces it experimentally. Clinical signs of the affected animals were weakness, tremors, hind limbs incoordination, reluctance to move, sternal and lateral recumbency and death. The main necropsy findings, observed in the abomasum and in segments of the small and large intestines, were diffuse redness and mucosal and serosal swelling. Histological examination revealed necrosis of lymphoid tissues and necrotizing enterocolitis. One experiment was carried out using 3 male calves to test the toxicity of a single dose of S. versicolor leaves at 15 g/kg, 5 g/kg and 2.5 g/kg. Clinical signs, necropsy findings and histological examination of calves receiving 15 g/kg and 5 g/kg leaves were similar to those of cattle from the intoxication outbreak. The calf fed 2.5 g/kg leaves developed clinical symptoms of poisoning and recovered naturally. In a second experiment, two male calves received daily administration of S. versicolor leaves at 1.5 g/kg and 2.5 g/kg for 10 days. They developed clinical signs of intoxication within 24 h and recovered eight to nine days after the leaves were administered. These findings suggest that S. versicolor was responsible for the outbreak studied, although this plant does not have cumulative intoxication effects on cattle.

Ischemia-reperfusion and neonatal intestinal injury.

We review research relating ischemia/reperfusion to injury in the neonatal intestine. Epidemiologic evidence suggests that the most common form of necrotizing enterocolitis is not triggered by a primary hypoxic-ischemic event. Its late occurrence, lack of preceding ischemic events, and evidence for microbial and inflammatory processes preclude a major role for primary hypoxic ischemia as the sentinel pathogenic event. However, term infants, especially those with congenital heart disease who have development of intestinal necrosis, and those preterm infants with spontaneous intestinal perforations, are more likely to have intestinal ischemia as a primary component of their disease pathogenesis.

Tetrahydrobiopterin is present in high quantity in human milk and has a vasorelaxing effect on newborn rat mesenteric arteries.

Breast milk reduces the incidence of necrotizing enterocolitis (NEC). BH4 is a cofactor for endothelial NOS (eNOS). Reduced BH4 levels, or its oxidation to dihydrobiopterin (BH2), uncouple eNOS resulting in formation of reactive oxygen species (ROS) that have been implicated in the pathogenesis of NEC. We evaluated colostrum and mature breast milk, as well as infant formula, BH4 and BH2 content. In addition, we tested the BH4 effect on the newborn rat mesenteric arterial vascular tone. BH4 and BH2 content increased 3-fold in mature breast milk, when compared with colostrum (p < 0.01), without a change in their ratio. Infant formula had a negligible BH4 content and lower biopterins ratio, when compared with breast milk. eNOS is the predominant synthase isoform in newborn rat mesenteric arteries. In the presence of BH4, mesenteric arteries contracted less to thromboxane A2 analog U46619 (p < 0.01) and this effect was abolished following eNOS inhibition. BH4 (10⁻6 M) vasorelaxed the newborn rat mesenteric arteries. We conclude that when compared with infant formula, breast milk has a high BH4 content that increases as breastfeeding continues. Given its mesenteric arterial vasorelaxing effect, BH4 may play an important role in the reduced NEC incidence among breast fed infants.

[Evaluation of the risk of the clinical-surgical and pathology study findings in newborns with necrotizing enterocolitis who have received surgical treatment]. / Valoración de riesgo de los hallazgos clínico-quirúrgicos y de anatomía patológica en neonatos con enterocolitis necrotizante que han recibido tratamiento quirúrgico.

INTRODUCTION: Despite advances in neonatal care between 20% and 63% of children with necrotizing enterocolitis (NEC) require surgery. The aim was correlation the risk factors of infants with NEC "IIB / IIIA / IIIB" Bell and the clinical, surgical and pathological findings. METHOD: In the children with diagnosis of NEC surgically treated, were analyzed of variables: clinical, surgical and pathological findings. We studied two groups: control (n=5) and NEC group (n=12). Comparisons were made between groups using the Mann-Whitney U- and the Spearman coefficient (r). To assess the risk of morbidity / mortality associated with the extent of intestinal resection we applied the Cox regression. RESULT: We found differences (p < 0.05) between control group and the NEC group regarding Bell, the mean height of villi, Chiu and the number of goblet cells. In the NEC group we find correlations (p < 0.05) from Bell, regarding Chiu (r = 0.761), resection of the colon (r = 0.687), pneumatosis / perforation (r = 1) and the mean height of villi (r = -0.878). The gut reseccion was at 26 cm (3-107). We observed a risk of 1.04 in the neonatal period (p > 0.05) of mortality or consequence post-enterocolitis associated with the extent of bowel resection. CONCLUSION: The decrease in the average height of villi, the highest level of microscopic intestinal injury and reduced goblet cell population contributes to a greater extent of intestinal resection, which favors the risk of death or developing consequence post-enterocolitis.

Enterocolitis necrotizante: caracterización del recién nacido con enterocolitis necrotizante en neonatología del Hospital Roosevelt durante el 2006 / Necrotizing enterocolitis in newborns

Objetivo: Caracterizar la Enterocolitis Necrotizante (ENC) en los recién nacidos de la Unidad de Neonatología del Hospital Roosevelt en el 2006. Resultados: se estudiaron 81 recién nacidos con ENC, mediante un estudio descriptivo, encontrando 47 masculinos y 34 femeninos, que representó una incidencia de 10.2x1000 nacidos vivos(nv), de los cuales 4.9 por ciento fueron a término y 95.1 por ciento fueron pretérmino...