Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Non-pulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and ten deletions, we have identified an additional thirty eight novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, twenty missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic whereas four familial cases with three showing maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA binding domain, indicating its plausible role in gene regulation. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.

This study was undertaken to evaluate the role of IL-5 in eosinophil migration and in the maintenance of eosinophilia in a guinea-pig model of visceral larva migrans syndrome. The results show that the infection of animals with Toxocara canis induced an early increase in serum IL-5 levels that might be essential for eosinophil differentiation and proliferation and for the development of eosinophilia. When infected guinea-pigs were treated with mAb anti-IL-5 (TRFK-5) given at the same time or 1 or 3 days after infection, there was a high percentage of reduction of eosinophil counts 18 days after infection. However, when the mAb was administered during the peak of eosinophilia, there was high inhibition in blood, no inhibition in bronchoalveolar lavage fluid (BALF) or peritoneum and an increase in eosinophil numbers in bone marrow. Thus, a basic level of IL-5 may be essential to drive eosinophils from bone marrow to blood and tissues, and for the maintenance of eosinophilia in infected animals. We may also conclude that when eosinophils have already migrated to the lungs, TRFK-5 has no power to inhibit eosinophilia, which is also under control of local lung cells producing IL-5. In this way, only one later TRFK-5 treatment may not be sufficient to modify the lung parenchyma microenvironment, since T. canis antigens had already stimulated some cell populations to produce IL-5.

Parenchymal lung diseases are the main cause of persistent pulmonary hypertension of the newborn (PPHN). We aimed to assess the non cardiac conditions associated to PPHN in the newborn and the survival rate over the last 15 years, at our center. A retrospective chart review of the neonates admitted for PPHN from 1996 to 2010 was performed. New therapies were introduced in 2003, and the survival rates between two periods (1996–2002 and 2003–2010) were compared. Out of 6750 newborns, 78 (1.1%) had the diagnosis of PPHN of non cardiac cause. The most prevalent causes were associated to pulmonary hypoplasia (30.7%), infection (24.3%), and aspiration syndromes (15.3%). Many other causes were identified in 33.3%. The overall survival rate was 68%. There was a significant difference on survival rates between the two periods (1996–2002 = 63.8% and 2003–2010 = 71.4%, P = 0.04). Our study showed a myriad of non cardiac aetiologies for PPHN of the newborn, most of them related to lung disease or lung hypoplasia. We observed an improvement in survival rate since 2003, which was associated to the use of new therapies.

Big defensins are antimicrobial polypeptides believed to be the ancestors of β-defensins, the most evolutionary conserved family of host defense peptides (HDPs) in vertebrates. Nevertheless, big defensins underwent several independent gene loss events during animal evolution, being only retained in a limited number of phylogenetically distant invertebrates. Here, we explore the evolutionary history of this fascinating HDP family and investigate its patchy distribution in extant metazoans. We highlight the presence of big defensins in various classes of lophotrochozoans, as well as in a few arthropods and basal chordates (amphioxus), mostly adapted to life in marine environments. Bivalve mollusks often display an expanded repertoire of big defensin sequences, which appear to be the product of independent lineage-specific gene tandem duplications, followed by a rapid molecular diversification of newly acquired gene copies. This ongoing evolutionary process could underpin the simultaneous presence of canonical big defensins and non-canonical (β-defensin-like) sequences in some species. The big defensin genes of mussels and oysters, two species target of in-depth studies, are subjected to gene presence/absence variation (PAV), i.e., they can be present or absent in the genomes of different individuals. Moreover, big defensins follow different patterns of gene expression within a given species and respond differently to microbial challenges, suggesting functional divergence. Consistently, current structural data show that big defensin sequence diversity affects the 3D structure and biophysical properties of these polypeptides. We discuss here the role of the N-terminal hydrophobic domain, lost during evolution toward β-defensins, in the big defensin stability to high salt concentrations and its mechanism of action. Finally, we discuss the potential of big defensins as markers for animal health and for the nature-based design of novel therapeutics active at high salt concentrations.

Bronchopulmonary dysplasia (BPD) remains the most common severe complication of preterm birth, and nutrition plays a crucial role in lung growth and repair. A practical nutritional approach for infants at risk of BPD or with established BPD is provided based on a comprehensive literature review. Ideally, infants with BPD should receive a fluid intake of not more than 135‒150 mL/kg/day and an energy intake of 120‒150 kcal/kg/day. Providing high energy in low volume remains a challenge and is the main cause of growth restriction in these infants. They need a nutritional strategy that encompasses early aggressive parenteral nutrition and the initiation of concentrated feedings of energy and nutrients. The order of priority is fortified mother’s own milk, followed by fortified donor milk and preterm enriched formulas. Functional nutrient supplements with a potential protective role against BPD are revisited, despite the limited evidence of their efficacy. Specialized nutritional strategies may be necessary to overcome difficulties common in BPD infants, such as gastroesophageal reflux and poorly coordinated feeding. Planning nutrition support after discharge requires a multidisciplinary approach to deal with multiple potential problems. Regular monitoring based on anthropometry and biochemical markers is needed to guide the nutritional intervention.

Our survival rate for infants with CDH has improved over the last ten years, and this improvement is associated with the use of new therapies such as HFOV, inhaled nitric oxide and sildenafil.

We conclude that, when controlling for gestational age, maternal PE results in higher incidence of only BPD among preterm Portuguese infants.

Based on this clinical report, megalocornea, partial callosal agenesis and mild bilateral occipital lobe hypoplasia should perhaps be included in the list of anomalies associated with partial trisomy 16q.