Detection of acute ventilatory problems via magnetic induction in a newborn animal model

Background Magnetic induction measurement (MIM) is a noninvasive method for the contactless registration of respiration in newborn piglets by using measurement coils positioned at the bottom of an incubator. Acute pulmonary problems may be determinants of poor neurological and psychomotor outcomes in preterm infants. The current study tested the detection of pulmonary ventilation disorders via MIM in 11 newborn piglets. Methods Six measurement coils determined changes in magnetic induction, depending on the ventilation of the lung, in comparison with flow resistance. Contactless registration of induced acute pulmonary ventilation disorders (apnea, atelectasis, pneumothorax, and aspiration) was detected by MIM. Results All pathologies except aspiration were detected by MIM. Significant changes occurred after induction of apnea (three coils), malposition of the tube (one coil), and pneumothorax (three coils) (p ≤ 0.05). No significant changes occurred after induction of aspiration (p = 0.12). Conclusions MIM seems to have some potential to detect acute ventilation disorders in newborn piglets. The location of the measurement coil related to the animal’s position plays a critical role in this process. In addition to an early detection of acute pulmonary problems, potential information pointing to a therapeutic intervention, for example, inhalations or medical respiratory analepsis, may be conceivable with MIM in the future. Impact MIM seems to be a method in which noncontact ventilation disorders of premature and mature infants can be detected. This study is an extension of the experimental setup to obtain preliminary evidence for detection of respiratory activity in neonatal piglets. For the first time, MIM is used to register acute ventilation problems of neonates. The possibility of an early detection of acute ventilation problems via MIM may provide an opportunity to receive patient-side information for therapeutical interventions like inhalations or medical respiratory analepsis.

A Recombinant BCG Vaccine Is Safe and Immunogenic in Neonatal Calves and Reduces the Clinical Disease Caused by the Respiratory Syncytial Virus

The human respiratory syncytial virus (hRSV) constitutes a major health burden, causing millions of hospitalizations in children under five years old worldwide due to acute lower respiratory tract infections. Despite decades of research, licensed vaccines to prevent hRSV are not available. Development of vaccines against hRSV targeting young infants requires ruling out potential vaccine-enhanced disease presentations. To achieve this goal, vaccine testing in proper animal models is essential. A recombinant BCG vaccine that expresses the Nucleoprotein of hRSV (rBCG-N-hRSV) protects mice against hRSV infection, eliciting humoral and cellular immune protection. Further, this vaccine was shown to be safe and immunogenic in human adult volunteers. Here, we evaluated the safety, immunogenicity, and protective efficacy of the rBCG-N-hRSV vaccine in a neonatal bovine RSV calf infection model. Newborn, colostrum-replete Holstein calves were either vaccinated with rBCG-N-hRSV, WT-BCG, or left unvaccinated, and then inoculated via aerosol challenge with bRSV strain 375. Vaccination with rBCG-N-hRSV was safe and well-tolerated, with no systemic adverse effects. There was no evidence of vaccine-enhanced disease following bRSV challenge of rBCG-N-hRSV vaccinated animals, suggesting that the vaccine is safe for use in neonates. Vaccination increased virus-specific IgA and virus-neutralization activity in nasal fluid and increased the proliferation of virus- and BCG-specific CD4+ and CD8+ T cells in PBMCs and lymph nodes at 7dpi. Furthermore, rBCG-N-hRSV vaccinated calves developed reduced clinical disease as compared to unvaccinated control calves, although neither pathology nor viral burden were significantly reduced in the lungs. These results suggest that the rBCG-N-hRSV vaccine is safe in neonatal calves and induces protective humoral and cellular immunity against this respiratory virus. These data from a newborn animal model provide further support to the notion that this vaccine approach could be considered as a candidate for infant immunization against RSV.

Review article: key aspects of mammal microbiome development

This review article summarizes current understanding of the microbiota development in neonatal mammals based on the results of modern experimental studies in animals focusing on three aspects: initial colonization, microbiota effect on the immune function of the developing newborn animal intestine and external factors influencing the microbiome shaping during the juvenile period. The presented study results confirm that the microbial landscape correction is the most important factor for animal health improvement since healthy microflora contributes to the intestinal infection frequency and intensity reduction, and this, in turn, minimizes the use of antibiotics. The microbiome is known to have an impact on the immune system development, metabolic processes and even on the ethology, so an atypical microbial population can cause immune and metabolic disorders. The active interaction between microorganisms and the host organism begins already at birth. Even different modes of delivery (caesarean or vaginal delivery) may determine the initial colonization of the newborn. The animal genetics, nutrition and environment also influence the intestinal microbiota development. In this regard, further studies of probiotics are important to understand their efficacy for diarrhea prevention and treatment, their use as an alternative to antibiotics as well as for enhancement of the animal resistance to stress factors.

A Systematic Review of the Influence of Continuous Positive Airway Pressure on Fetal and Newborn Animal Models: Suggestions to Improve Neonatal Respiratory Care

<b><i>Introduction:</i></b> Prematurely born infants regularly develop respiratory distress syndrome and require assisted ventilation. Ventilation may injure the premature lung and increase the risk of bronchopulmonary dysplasia. Continuous positive airway pressure (CPAP), a form of noninvasive ventilation, is commonly used in modern neonatology. Limited clinical data are available on the acute and long-term effect of neonatal exposure to CPAP on the lung. Given the restricted clinical data, newborn animal models have been used to study the influence of CPAP on lung structure and function. The findings of animal studies can guide neonatal care and improve the use of CPAP. <b><i>Methods:</i></b> A systematic review of electronic databases (Medline, Embase, and Cinahl) was performed using the medical subject heading terms, “CPAP” or “continuous positive airway pressure” and “animals” and “newborn.” Abstracts were screened for inclusion using predetermined eligibility criteria. <b><i>Results:</i></b> In total, 235 abstracts were identified and screened for inclusion. Of these, 21 papers were included. Large (<i>N</i> = 18) and small (<i>N</i> = 3) animal models investigated the effects of CPAP. Pulmonary outcomes included gas exchange, lung structure and function, surfactant metabolism, lung inflammation and injury, and the effect of intrapulmonary therapy. Compared to mechanical ventilation, CPAP improves lung function, evokes less lung injury, and does not disrupt alveolar development. Surfactant administration combined with CPAP further improves respiratory outcomes. Of concern are findings that CPAP may increase airway reactivity. <b><i>Discussion/Conclusion:</i></b> CPAP offers numerous advantages over mechanical ventilation for the immature lung. The combination of CPAP and exogenous surfactant administration offers further pulmonary benefit.

The Importance of Correlation of T-helper and T-supressor Limfocitary Subpopulations – Indicators of Animals Immune Status

The scientific investigations reflected in this study present the research in dynamics of the activity of correlating T-helper and T-suppressor immunocompetent cells at the newborn calves in different age periods. In the scientific research is presented the main effector role of these indicators, regarding the importance of the immune system through the ability to synthesize lymphokines, etc. The researches reveal T-helper and T-suppressor level of lymphocytes at all research ages. Thus at 10 days the concentration of T-helper lymphocytes was 7.85±0.001 and 8.30±0.08; 7.57 ± 0.008 at the age of 20 and 30 days, compared to T-suppressor lymphocytes, which in these age groups was equal to 6.0 ± 0.08; 6.33 ± 0.08 and 6.0±0.08. The results of the investigations offer the possibility to understand that the correlation of some lymphocytary subpopulations of the newborn animal organism provides the possibility of installing a strong immunity and ensures the maintenance of the biochemical homeostasis of the organism.

Animal models of bronchopulmonary dysplasia. The preterm and term rabbit models

Bronchopulmonary dysplasia (BPD) is an important lung developmental pathophysiology that affects many premature infants each year. Newborn animal models employing both premature and term animals have been used over the years to study various components of BPD. This review describes some of the neonatal rabbit studies that have contributed to the understanding of BPD, including those using term newborn hyperoxia exposure models, premature hyperoxia models, and a term newborn hyperoxia model with recovery in moderate hyperoxia, all designed to emulate aspects of BPD in human infants. Some investigators perturbed these models to include exposure to neonatal infection/inflammation or postnatal malnutrition. The similarities to lung injury in human premature infants include an acute inflammatory response with the production of cytokines, chemokines, and growth factors that have been implicated in human disease, abnormal pulmonary function, disordered lung architecture, and alveolar simplification, development of fibrosis, and abnormal vascular growth factor expression. Neonatal rabbit models have the drawback of limited access to reagents as well as the lack of readily available transgenic models but, unlike smaller rodent models, are able to be manipulated easily and are significantly less expensive than larger animal models.