Thymulin inhibits monocrotaline-induced pulmonary hypertension modulating interleukin-6 expression and suppressing p38 pathway

The pathogenesis of pulmonary hypertension (PH) includes an inflammatory response. Thymulin, a zinc-dependent thymic hormone, has important immunobiological effects by inhibiting various proinflammatory cytokines and chemokines. We investigated morphological and hemodynamic effects of thymulin administration in a rat model of monocrotaline (MCT)-induced PH, as well as the pattern of proinflammatory cytokine gene expression and the intracellular pathways involved. Adult Wistar rats received an injection of MCT (60 mg/kg, sc) or an equal volume of saline. One day after, the animals randomly received during 3 wk an injection of saline, vehicle (zinc plus carboxymethyl cellulose), or thymulin (100 ng/kg, sc, daily). At d 23-25, the animals were anesthetized for hemodynamic recordings, whereas heart and lungs were collected for morphometric and molecular analysis. Thymulin prevented morphological, hemodynamic, and inflammatory cardiopulmonary profile characteristic of MCT-induced PH, whereas part of these effects were also observed in MCT-treated animals injected with the thymulin's vehicle containing zinc. The pulmonary thymulin effect was likely mediated through suppression of p38 pathway.Portuguese Foundation for Science and Technology (No. POCI/SAVFCF/60803/2004; POCTI/SAV-MMO/61547/2004 and PTDC/SAV-FCF/65793/2006) through Cardiovascular R&D Unit (FCT No. 51/94). R.S.M. was supported by Fundação para a Ciência e a Tecnologia (reference SFRH/BPD/15408/2005

PDA management in VLBW infants: experience of a level III NICU

Introduction: Hemodynamically significant patent ductus arteriosus (PDA) is a common condition in very low birth weight infants. Therapeutic options include medical therapy and surgical ligation. Medical treatment is based on non-selective inhibitors of cyclooxygenases 1 and 2 (indomethacin and ibuprofen). The debate on the most appropriate treatment for the closure of the PDA is far from being closed, in the light of the currently available evidence. Aim: The objective of this study was to compare efficacy and safety of indomethacin and ibuprofen. Methods: All infants < 32 weeks of gestational age or ≤ 1,500 g of birth weight born in “Centro Hospitalar São João” between January 2005 and December 2014 were included. Those with major malformations or genetic disorders, congenital TORCH infections, transferred or deceased before 72 hours of life, outborns, and those with severe pathologies at birth were excluded. The cohort of neonates treated with indomethacin from January 2005 to December 2009 was compared to those treated with ibuprofen from January 2010 to December 2014. Results: 328 newborns were included in the study: 99 (30.2%) with PDA and 229 (69.8%) without. The median gestational age was 30 weeks and the median birth weight was 1,231 grams. Among the 99 patients with PDA, 21 were treated with indomethacin and 41 received ibuprofen. There was no statistically significant difference in efficacy between groups. There was a higher incidence of thrombocytopenia in the indomethacin group compared to the ibuprofen group, but there was no significant difference in any other PDA-associated comorbidities between groups. Conclusion: Our study showed that indomethacin and ibuprofen have a similar effect in closing PDA in < 32 weeks preterm infants. We found no significant differences in safety, except for thrombocytopenia. Further studies are necessary to compare both efficacy and adverse events of ibuprofen and indomethacin to identify the optimal pharmacological agent for PDA