Health Economic Studies of Surfactant Replacement Therapy in Neonates with Respiratory Distress Syndrome: A Systematic Literature Review.

Background: Neonatal respiratory distress syndrome (RDS) is one of the most common problems for preterm infants, and symptoms include tachypnoea, grunting, retractions and cyanosis, which occur immediately after birth. Treatment with surfactants has reduced morbidity and mortality rates associated with neonatal RDS.

Objective: The objective of this review is to describe the treatment costs, healthcare resource utilization (HCRU) and economic evaluations of surfactant use in the treatment of neonates with RDS.

Small Molecule Inhibitor Adjuvant Surfactant Therapy Attenuates Ventilator- and Hyperoxia-Induced Lung Injury in Preterm Rabbits.

Background: Invasive mechanical ventilation (IMV) has become one of the mainstays of therapy in NICUs worldwide, as a result of which premature babies with extremely low birth weight have been able to survive. Although lifesaving, IMV can result in lung inflammation and injury. Surfactant therapy is considered a standard of care in preterm infants with immature lungs.

Melatonin as an adjunct to therapeutic hypothermia in a piglet model of neonatal encephalopathy: A translational study.

Therapeutic hypothermia is only partially protective for neonatal encephalopathy; there is an urgent need to develop treatments that augment cooling. Our objective was to assess safety, efficacy and pharmacokinetics of 5 and 15 mg/kg/24 h melatonin (proprietary formulation) administered at 2 h and 26 h after hypoxia-ischemia (HI) with cooling in a piglet model. Following moderate cerebral HI, 30 piglets were eligible and randomized to: i) Hypothermia (33.

Melatonin Acts in Synergy with Hypothermia to Reduce Oxygen-Glucose Deprivation-Induced Cell Death in Rat Hippocampus Organotypic Slice Cultures.

Background: Hypoxic-ischemic encephalopathy is a major cause of neonatal morbidity. Therapeutic hypothermia, while beneficial, still leaves many treated infants with lifelong disabilities. Thus, adjunctive therapies, such as melatonin, are needed to provide additional neuroprotection.

Metabolism of a synthetic compared with a natural therapeutic pulmonary surfactant in adult mice.

Secreted pulmonary surfactant phosphatidylcholine (PC) has a complex intra-alveolar metabolism that involves uptake and recycling by alveolar type II epithelial cells, catabolism by alveolar macrophages, and loss up the bronchial tree. We compared the in vivo metabolism of animal-derived poractant alfa (Curosurf) and a synthetic surfactant (CHF5633) in adult male C57BL/6 mice. The mice were dosed intranasally with either surfactant (80 mg/kg body weight) containing universally C-labeled dipalmitoyl PC (DPPC) as a tracer.

Cerebral and lung effects of a new generation synthetic surfactant with SP-B and SP-C analogs in preterm lambs.

Background: Though natural surfactants (SF) are clinically superior to protein-free synthetic preparations, CHF-5633, a synthetic SF containing SP-B and SP-C analog peptides is a potential alternative to natural SF for treating neonatal respiratory distress syndrome (RDS). Nevertheless, information is lacking regarding the safety of this new treatment for the neonatal brain. We sought to compare the cerebral and pulmonary effects of this new synthetic surfactant (CHF5633) with those of natural porcine surfactant (Cursosurf) in premature lambs with RDS.

In vitro and in vivo comparison between poractant alfa and the new generation synthetic surfactant CHF5633.

Background: CHF5633 is a new generation synthetic surfactant containing both SP-B and SP-C analogues developed for the treatment of respiratory distress syndrome. Here, the optimal dose and its performance in comparison to the animal-derived surfactant poractant alfa were investigated.

Methods: In vitro surfactant activity was determined by means of the Wilhelmy balance and the capillary surfactometer.

Phospholipid Composition in Synthetic Surfactants Is Important for Tidal Volumes and Alveolar Stability in Surfactant-Treated Preterm Newborn Rabbits.

Background: The development of synthetic surfactants for the treatment of lung pulmonary diseases has been going on for many years.

Objectives: To investigate the effects of phospholipid mixtures combined with SP-B and SP-C analogues on lung functions in an animal model of respiratory distress syndrome.

Methods: Natural and synthetic phospholipid mixtures with/without SP-B and/or SP-C analogues were instilled in ventilated premature newborn rabbits.

Characterization of Ganstigmine metabolites in hepatocytes by low- and high-resolution mass spectrometry coupled with liquid chromatography.

In order to deepen the understanding of the metabolism of Ganstigmine, a new acetylcholinesterase inhibitor under evaluation for the treatment of Alzheimer's disease, samples obtained by incubating the drug with female rat hepatocytes were investigated by low-resolution liquid chromatography/tandem mass spectrometry (LC/MS/MS). The results confirmed the formation of most of the phase I metabolites already demonstrated, but also three new species. The combination of high-resolution quadrupole time-of-flight (Q-TOF) LC/MS and LC/MS/MS measurements, and the evaluation of the more reasonable metabolic routes, allowed the identification of the new metabolites as Geneseroline-glucuronide and oxidized and rearranged Ganstigmine.

Different electrospray tandem mass spectrometric approaches for rapid characterization of phospholipid classes of Curosurf, a natural pulmonary surfactant.

Curosurf is a pulmonary surfactant used in the treatment or prophylaxis of neonatal respiratory distress syndrome. It contains low molecular weight hydrophobic apoproteins and a series of lipids including phosphatidylcholines, lisophosphatidylcholines, phosphatidylethanolamines, sphingomyelins, phosphatidylinositols, phosphatidylglycerols and phosphatidylserines. In the present work, a rapid method to qualitatively map the Curosurf phospholipid classes without prior derivatization or chromatographic separations is described.

On the detailed mechanisms of collision-induced dissociation experiments performed by electrospray ion trap.

The product ion spectra obtained by electrospray ionization (ESI) ion trap instruments exhibit a higher number of fragment ions than those achieved by other ion-trap-based systems, indicating the presence of more effective energy deposition mechanisms. This behavior can be attributed to several different reasons, among which different initial internal energy of the precursor ions, pre-activation due to collisions taking place outside the trap, different target gas mixtures inside the trap, and different ion trap geometry were considered. Data obtained from experiments using a triple quadrupole instrument, CI-ion trap, and ESI-ion trap have been compared.

Phase I metabolism of ganstigmine. Rat, dog, monkey and human liver microsomal extracts investigated by liquid chromatography electrospray tandem mass spectrometry.

Ganstigmine, a new acetylcholinesterase inhibitor, was incubated with rat liver microsomes and the resulting metabolites were identified by high-performance liquid chromatographic/mass spectrometric (HPLC/MS) and HPLC/MS/MS analyses. The results showed the formation of eight main metabolites, among which geneseroline and molecules corresponding to mono-hydroxylated, demethylated and reduced ganstigmine. The metabolic profile drawn for humans, dog and monkey showed a pattern very similar to that of rat: only in the case of liver dog microsomes higher amounts of geneseroline and of a metabolite identified as demethylated and reduced drug were detected.