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Liver disease after intensive care of premature baboons: histopathologic observations.

ABSTRACT: Cholestasis affects 50% of extremely low-birth-weight infants. Its etiology remains poorly understood and the extent of liver injury in these infants is unclear. The premature baboon model provides an opportunity to study neonatal liver disease. We characterize hepatic histopathologic changes in this model.Archival tissue and data were obtained from the Southwest Foundation for Biomedical Research Primate Center, San Antonio, TX. Animals were selected based on history of antenatal steroid therapy and absence of sepsis or necrotizing enterocolitis with a protocol duration of at least 21 days and no early death (n?=?45). Baboons had been treated per protocol in the neonatal intensive care unit (NICU). At necropsy, liver tissue was harvested and stored. Tissues from fetal gestational controls at similar ages were used for comparison (n?=?28). Histologic changes were scored by consensus of 2 pathologists blinded to treatment group. Descriptive and comparative statistics were performed.Control fetal livers had extramedullary hematopoiesis (EMH) that decreased across the gestational range. There was evidence of hepatocyte iron storage and ongoing portal tract development. Livers of NICU-treated baboons had increased Kupffer cell hypertrophy and hemosiderosis. There was a shift away from erythroid EMH toward increased myeloid EMH. There was increased cholestasis, ductular proliferation, portal tract fibrosis, and steatosis in treated animals.We found pathologic changes in NICU-treated baboons comparable with findings reported in human infants. The baboon model of prematurity may be a useful tool to explore cholestasis and liver dysfunction in extremely low-birth-weight infants.

SUBMITTER: Kerecman J

PROVIDER: S-EPMC3738296 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Liver disease after intensive care of premature baboons: histopathologic observations.

Kerecman Jay J Mehrotra Anupamjit A Goodman Zachary Z

Journal of pediatric gastroenterology and nutrition 20130801 2

<h4>Background and objectives</h4>Cholestasis affects 50% of extremely low-birth-weight infants. Its etiology remains poorly understood and the extent of liver injury in these infants is unclear. The premature baboon model provides an opportunity to study neonatal liver disease. We characterize hepatic histopathologic changes in this model.<h4>Methods</h4>Archival tissue and data were obtained from the Southwest Foundation for Biomedical Research Primate Center, San Antonio, TX. Animals were sel ...[more]

PMID: 23880624

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Project description:BACKGROUND: The source inoculum of gastrointestinal tract (GIT) microbes is largely influenced by delivery mode in full-term infants, but these influences may be decoupled in very low birth weight (VLBW, <1,500 g) neonates via conventional broad-spectrum antibiotic treatment. We hypothesize the built environment (BE), specifically room surfaces frequently touched by humans, is a predominant source of colonizing microbes in the gut of premature VLBW infants. Here, we present the first matched fecal-BE time series analysis of two preterm VLBW neonates housed in a neonatal intensive care unit (NICU) over the first month of life. RESULTS: Fresh fecal samples were collected every 3 days and metagenomes sequenced on an Illumina HiSeq2000 device. For each fecal sample, approximately 33 swabs were collected from each NICU room from 6 specified areas: sink, feeding and intubation tubing, hands of healthcare providers and parents, general surfaces, and nurse station electronics (keyboard, mouse, and cell phone). Swabs were processed using a recently developed 'expectation maximization iterative reconstruction of genes from the environment' (EMIRGE) amplicon pipeline in which full-length 16S rRNA amplicons were sheared and sequenced using an Illumina platform, and short reads reassembled into full-length genes. Over 24,000 full-length 16S rRNA sequences were produced, generating an average of approximately 12,000 operational taxonomic units (OTUs) (clustered at 97% nucleotide identity) per room-infant pair. Dominant gut taxa, including Staphylococcus epidermidis, Klebsiella pneumoniae, Bacteroides fragilis, and Escherichia coli, were widely distributed throughout the room environment with many gut colonizers detected in more than half of samples. Reconstructed genomes from infant gut colonizers revealed a suite of genes that confer resistance to antibiotics (for example, tetracycline, fluoroquinolone, and aminoglycoside) and sterilizing agents, which likely offer a competitive advantage in the NICU environment. CONCLUSIONS: We have developed a high-throughput culture-independent approach that integrates room surveys based on full-length 16S rRNA gene sequences with metagenomic analysis of fecal samples collected from infants in the room. The approach enabled identification of discrete ICU reservoirs of microbes that also colonized the infant gut and provided evidence for the presence of certain organisms in the room prior to their detection in the gut.

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Liver disease after intensive care of premature baboons: histopathologic observations.

Publications

Liver disease after intensive care of premature baboons: histopathologic observations.

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