Selective activation of rat vomeronasal amygdala by pheromones

Pisa, Ital

First-in-class thyrotropin-releasing hormone (TRH)-based compound binds to a pharmacologically distinct TRH receptor subtype in human brain and is effective in neurodegenerative models

JAK4D, a first-in-class thyrotropin-releasing hormone (TRH)-based compound, is a prospective therapeutic candidate offering a multifaceted approach to treating neurodegeneration and other CNS conditions. The purpose of these studies was to determine the ability of JAK4D to bind to TRH receptors in human brain and to evaluate its neuropharmacological effects in neurodegenerative animal models. Additionally, JAK4D brain permeation was examined in mouse, and initial toxicology was assessed in vivo and in vitro. We report that JAK4D bound selectively with nanomolar affinity to native TRH receptors in human hippocampal tissue and showed for the first time that these receptors are pharmacologically distinct from TRH receptors in human pituitary, thus revealing a new TRH receptor subtype which represents a promising neurotherapeutic target in human brain. Systemic administration of JAK4D elicited statistically significant and clinically-relevant neuroprotective effects in three established neurodegenerative animal models: JAK4D reduced cognitive deficits when administered post-insult in a kainate (KA)-induced rat model of neurodegeneration; it protected against free radical release and neuronal damage evoked by intrastriatal microdialysis of KA in rat; and it reduced motor decline, weight loss, and lumbar spinal cord neuronal loss in G93A-SOD1 transgenic Amyotrophic Lateral Sclerosis mice. Ability to cross the blood–brain barrier and a clean initial toxicology profile were also shown. In light of these findings, JAK4D is an important tool for investigating the hitherto-unidentified central TRH receptor subtype reported herein and an attractive therapeutic candidate for neurodegenerative disorders. •First-in-class TRH-based compound JAK4D detects new receptor subtype in human brain.•JAK4D elicits statistically significant effects in neurodegenerative animal models.•JAK4D crosses the blood–brain barrier and has a clean initial toxicology profile.•JAK4D is a tool to study central pharmacologically-distinct TRH receptor subtype.•JAK4D is an attractive therapeutic candidate for neurodegenerative diseases

Survey of neonatal respiratory care and surfactant administration in very preterm infants in the Italian neonatal network

Introduction: Variation of respiratory care is described between centers around the world.The Italian Neonatal Network (INN), as a national group of the Vermont-Oxford Network (VON) allows to perform a wide analysis of respiratory care in very low birth weight infants. Methods:We analyzed the dataset of infants enrolled in the INN in 2009 and 2010 and, for surfactant administration only, from 2006 to 2010 from 83 participating centers. All definitions are those of the (VON). A questionnaire analysis was also performed with a questionnaire on centers practices. Results: We report data for 8297 infants. Data on ventilator practices and outcomes are outlined. Variation for both practices and outcome is found. Trend in surfactant administration is also analyzed. Conclusions. The great variation across hospitals in all the surveyed techniques points to the possibility of implementing potentially better practices with the aim of reducing unwanted variation. These data also show the power of large neonatal networks in identifying areas for potential improvement. \ua9 Mattioli 1885

Survey of neonatal respiratory care and surfactant administration in very preterm infants in the Italian neonatal network

Introduction: Variation of respiratory care is described between centers around the world.The Italian Neonatal Network (INN), as a national group of the Vermont-Oxford Network (VON) allows to perform a wide analysis of respiratory care in very low birth weight infants. Methods:We analyzed the dataset of infants enrolled in the INN in 2009 and 2010 and, for surfactant administration only, from 2006 to 2010 from 83 participating centers. All definitions are those of the (VON). A questionnaire analysis was also performed with a questionnaire on centers practices. Results: We report data for 8297 infants. Data on ventilator practices and outcomes are outlined. Variation for both practices and outcome is found. Trend in surfactant administration is also analyzed. Conclusions. The great variation across hospitals in all the surveyed techniques points to the possibility of implementing potentially better practices with the aim of reducing unwanted variation. These data also show the power of large neonatal networks in identifying areas for potential improvement. © Mattioli 1885

Association of maternal hypertension and chorioamnionitis with preterm outcomes

OBJECTIVES: We compared the relative effect of hypertensive disorders of pregnancy and chorioamnionitis on adverse neonatal outcomes in very preterm neonates, and studied whether gestational age (GA) modulates these effects. METHODS: A cohort of neonates 23 to 30 weeks' GA, born in 2008 to 2011 in 82 hospitals adhering to the Italian Neonatal Network, was analyzed. Infants born from mothers who had hypertensive disorders (N = 2096) were compared with those born after chorioamnionitis (N = 1510). Statistical analysis employed logistic models, adjusting for GA, hospital, and potential confounders. RESULTS: Overall mortality was higher after hypertension than after chorioamnionitis (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.08-1.80), but this relationship changed across GA weeks; the OR for hypertension was highest at low GA, whereas from 28 weeks' GA onward, mortality was higher for chorioamnionitis. For other outcomes, the relative risks were constant across GA; infants born after hypertension had an increased risk for bronchopulmonary dysplasia (OR, 2.20; 95% CI, 1.68-2.88) and severe retinopathy of prematurity (OR, 1.48; 95% CI, 1.02-2.15), whereas there was a lower risk for early-onset sepsis (OR, 0.25; 95% CI, 0.19-0.34), severe intraventricular hemorrhage (OR, 0.65; 95% CI, 0.48-0.88), periventricular leukomalacia (OR, 0.70; 95% CI, 0.48-1.01), and surgical necrotizing enterocolitis or gastrointestinal perforation (OR, 0.47; 95% CI, 0.31-0.72). CONCLUSIONS: Mortality and other adverse outcomes in very preterm infants depend on antecedents of preterm birth. Hypertension and chorioamnionitis are associated with different patterns of outcomes; for mortality, the effect changes across GA weeks. Copyright \uc2\ua9 2014 by the American Academy of Pediatrics