Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide

Inhaled nitric oxide (iNO) is approved for use in persistent pulmonary hypertension of the newborn (PPHN) but does not lead to sustained improvement in oxygenation in a third of patients with PPHN. Inhaled NO is less effective in the management of PPHN secondary to congenital diaphragmatic hernia (CDH), extreme prematurity and bronchopulmonary dysplasia (BPD). Intravenous pulmonary vasodilators such as prostacyclin, alprostadil, sildenafil and milrinone have been successfully used in PPHN resistant to iNO. Oral pulmonary vasodilators such as endothelin-receptor antagonist bosentan and phosphodiesterase-5 inhibitors such as sildenafil and tadalafil are used both during acute and chronic phase of PPHN. In the absence of infection, glucocorticoids may also be effective in PPHN. Many of these pharmacologic agents are not approved for use in PPHN and our knowledge is based on case reports and small trials. Large multicenter randomized controlled trials with long-term follow-up are required to evaluate pharmacologic strategies in PPHN

sp3 C–H Bond Functionalization with Ruthenium Catalysts

International audienceThe selective formation of carbon–carbon bond by functionalization of an sp3C–H bond is still a challenge in organic synthesis. There are already examples involving transition metal catalysis. In this chapter we review the use of ruthenium(0) and ruthenium(II) catalysts for the formation of carbon–carbon bonds based on creation of reactive sites by sp3C–H bond activation. We show that in most cases, regioselective sp3C–H bond activation is induced either from functional substrates bearing a directing group, which strongly coordinates the metal centre, or by selective C–H bond activation at the α-carbon of a heteroatom accompanied by hydrogen transfer processes and transient creation of reactive functional group