A novel noninvasive approach for evaluating work of breathing indices in a developmental rat model using respiratory inductance plethysmography.

Pulmonary function testing (PFT) is an important component for evaluating the outcome of experimental rodent models of respiratory diseases. Respiratory inductance plethysmography (RIP) provides a noninvasive method of PFT requiring minimal cooperation. RIP measures work of breathing (WOB) indices including phase angle (Ф), percent rib cage (RC %), breaths per minute (BPM), and labored breathing index (LBI) on an iPad. The aim of this study was to evaluate the utility of a recently developed research instrument, pneuRIP, for evaluation of WOB indices in a developmental rat model. Sprague Dawley rats (2 months old) were commercially acquired and anaesthetised with isoflurane. The pneuRIP system uses two elastic bands: one band (RC) placed around the rib cage under the upper armpit and another band (AB) around the abdomen. The typical thoracoabdominal motion (TAM) plot showed the abdomen and rib cage motion in synchrony. The plots of phase angle and LBI as a function of data point number showed that values were within the range. The distribution for phase angle and LBI was within a narrow range. pneuRIP testing provided instantaneous PFT results. This study demonstrated the utility of RIP as a rapid, noninvasive approach for evaluating treatment interventions in the rodent model.

DNA Methylation Profile in Human Cord Blood Mononuclear Leukocytes From Term Neonates: Effects of Histological Chorioamnionitis.

Background: Histological chorioamnionitis (HCA) is an infection/inflammation of fetal membranes and complicates 5.2-28.5% of all live births. Exposure to HCA can have long-term consequences including abnormal neurodevelopment and an increased risk for allergic disorders and asthma later in childhood. HCA may incite epigenetic changes, which have the potential to modulate both the immune and neurological systems as well as increase the risk of related disorders later in life. However, there is limited data on the impact of HCA on epigenetics, in particular DNA methylation, and changes to immune and neurological systems in full-term human neonates. Objective: To determine differential DNA methylation in cord blood mononuclear leukocytes from neonates exposed to HCA. Methods: Cord blood was collected from 10 term neonates (5 with HCA and 5 controls without HCA) and mononuclear leukocytes were isolated. Genome-wide DNA methylation screening was performed on Genomic DNA extracted from mononuclear leukocytes. Results: Mononuclear leukocytes from cord blood of HCA-exposed neonates showed differential DNA methylation of 68 probe sets compared to the control group (44 hypermethylated, 24 hypomethylated) with a p ≤ 0.0001. Several genes involved in immune modulation and nervous system development were found to be differentially methylated. Important canonical pathways as revealed by Ingenuity Pathway Analysis (IPA) were CREB Signaling in Neurons, FcγRIIB Signaling in B Lymphocytes, Cell Cycle: G1/S Checkpoint Regulation, Interleukin-1, 2, 3, 6, 8, 10, 17, and 17A signaling, p53 signaling, dopamine degradation, and serotonin degradation. The diseases and disorders picked up by IPA were nervous system development and function, neurological disease, respiratory disease, immune cell trafficking, inflammatory response, and immunological disease. Conclusions: HCA induces differential DNA methylation in cord blood mononuclear leukocytes. The differentially methylated genes may contribute to inflammatory, immunological and neurodevelopmental disorders in neonates exposed to HCA.

Histological Chorioamnionitis Induces Differential Gene Expression in Human Cord Blood Mononuclear Leukocytes from Term Neonates.

Histological chorioamnionitis (HCA) is an infection of fetal membranes and complicates 5.2% to 28.5% of all live births. HCA is associated with increased mortality and morbidity in both premature and term neonates. Exposure to HCA may have long-term consequences, including an increased risk for allergic disorders and asthma later in childhood, the mechanism(s) of which are still not yet well understood. The objective of this study was to determine the mRNA transcriptome of cord blood mononuclear leukocytes from term neonates to identify key genes and pathways involved in HCA. We found 366 differentially expressed probe IDs with exposure to HCA (198 upregulated, 168 downregulated). These transcriptomes included novel genes and pathways associated with exposure to HCA. The differential gene expression included key genes regulating inflammatory, immune, respiratory and neurological pathways, which may contribute to disorders in those pathways in neonates exposed to HCA. Our data may lead to understanding of the role of key genes and pathways identified on the long-term sequelae related to exposure to HCA, as well as to identifying potential markers and therapies to prevent HCA-associated complications.