Heat shock pretreatment reduces intestinal injury in a neonatal rat model of early necrotizing enterocolitis.

BACKGROUND: Increased pro-inflammatory cytokines are suggested in the pathogenesis of necrotizing enterocolitis (NEC). The transcription factor, nuclear factor-ĸB (NF-ĸB), is a central regulator of inflammatory and immune responses, and recent rodent NEC models have shown that NF-ĸB may have a critical role in the disease processes that underlie NEC. Heat shock proteins have important functions in response to stress-related events in a variety of systems, including digestive organs. OBJECTIVES: We investigated whether heat shock pretreatment protects intestinal epithelial damage in the early NEC rat model. METHODS: We generated human NEC-like lesions in neonatal rat ileum by administering oral endotoxin (10 mg/kg), intermittent 8% hypoxia, and hypertonic formula. Heat shock was administered by raising the chamber temperature to 42°C for 20 min, 3 h prior to endotoxin ingestion. RESULTS: Heat shock pretreatment increased the expression of HSP70 in the ileal tissue and attenuated histological severity of early experimental NEC. NF-ĸB was activated in the ileal tissue of the NEC group and this activation was attenuated by heat shock pretreatment, which was determined by electrophoretic mobility shift assay and Western blot analysis of p50 in subcellular fractionated samples. CONCLUSIONS: Heat shock pretreatment reduced the incidence and severity of early experimental NEC in rats. A possible mechanism underlying this protective effect includes inhibition of NF-ĸB activation through increased HSP70 expression.

A case of mucolipidosis II presenting with prenatal skeletal dysplasia and severe secondary hyperparathyroidism at birth.

Mucolipidosis II (ML II) or inclusion cell disease (I-cell disease) is a rarely occurring autosomal recessive lysosomal enzyme-targeting disease. This disease is usually found to occur in individuals aged between 6 and 12 months, with a clinical phenotype resembling that of Hurler syndrome and radiological findings resembling those of dysostosis multiplex. However, we encountered a rare case of an infant with ML II who presented with prenatal skeletal dysplasia and typical clinical features of severe secondary hyperparathyroidism at birth. A female infant was born at 37(+1) weeks of gestation with a birth weight of 1,690 g (<3rd percentile). Prenatal ultrasonographic findings revealed intrauterine growth retardation and skeletal dysplasia. At birth, the patient had characteristic features of ML II, and skeletal radiographs revealed dysostosis multiplex, similar to rickets. In addition, the patient had high levels of alkaline phosphatase and parathyroid hormone, consistent with severe secondary neonatal hyperparathyroidism. The activities of ß-D-hexosaminidase and α-N-acetylglucosaminidase were moderately decreased in the leukocytes but were 5- to 10-fold higher in the plasma. Examination of a placental biopsy specimen showed foamy vacuolar changes in trophoblasts and syncytiotrophoblasts. The diagnosis of ML II was confirmed via GNPTAB genetic testing, which revealed compound heterozygosity of c.3091C>T (p.Arg1031X) and c.3456_3459dupCAAC (p.Ile1154GlnfsX3), the latter being a novel mutation. The infant was treated with vitamin D supplements but expired because of asphyxia at the age of 2 months.

Induction of early meconium evacuation promotes feeding tolerance in very low birth weight infants.

BACKGROUND: A delay in reaching full enteral feeding is linked to poorer outcome in preterm neonates. Meconium retention has been viewed as a cause of bowel dysfunction in very low birth weight infants (VLBWI). Thus, adequate evacuation of meconium could help to promote feeding tolerance. OBJECTIVES: Our goal was to determine the effect of the induction of early meconium evacuation on feeding tolerance in VLBWI. METHODS: An observational study involving two subsequent periods was performed in inborn infants with birth weights of <1,500 g, before (control) and after (study) the induction of early meconium evacuation by routine glycerin enema. The total duration of these periods was from January 2003 to December 2005. To evaluate feeding tolerance, we measured time to achieve full enteral feeding. Complications such as sepsis and necrotizing enterocolitis were compared. RESULTS: The study group achieved full enteral feeding significantly faster than the control group (hazard ratio (HR) = 2.9; 95% confidence interval (CI) = 1.8-4.8), and this effect was more definite in infants with a birth weight of <1,000 g (HR = 4.6; 95% CI = 1.9-11.1). The study group passed first meconium faster than the control group (median = 1.4 vs. 3.7 days; p < 0.001). Sepsis, especially as determined by positive culture in central venouscatheter, was significantly reduced in the study group (7.7 vs. 27.8%; p = 0.02). CONCLUSIONS: The induction of early meconium evacuation had a significantly positive effect on feeding tolerance and sepsis prevention in VLBWI.