Babies with brain damage who can not swallow: surgical management

BACKGROUND: Neonates with severe neurological impairment are often unable to swallow, necessitating gastrostomy for feeding. Because of the risk of developing severe reflux, this procedure is often associated with fundoplication. OBJECTIVE: To assess the safety and efficacy of gastrostomy and Nissen fundoplication in 22 neonates with swallowing difficulties due to serious neurological impairment. METHOD: All children underwent an initial period of nasogastric feeding and after informed consent underwent gastrostomy and Nissen fundoplication. RESULTS: There were no significant intraoperative complications. There were two cases of postoperative periostomy leakage. Of the 22 neonates 16 were alive four months after surgery. Six neonates died of complications due to underlying disease. CONCLUSION: We concluded that gastrostomy and Nissen fundoplication are safe procedures and help parents give a better care to these children.INTRODUÇÃO: Neonatos com dano neurológico são freqüentemente incapazes de deglutir necessitando de gastrostomia para alimentação. Devido ao risco de refluxo grave, esse procedimento é associado à fundoplicatura. OBJETIVO: Avaliar a segurança e eficácia da gastrostomia com fundoplicatura Nissen em 22 neonatos com dificuldades de deglutição devido à lesão neurológica grave. MÉTODO: Todos os neonatos foram submetidos a um período inicial de alimentação por sonda nasogástrica e, após consentimento informado, foram submetidos a gastrostomia com fundoplicatura Nissen. RESULTADOS: Não houve complicações intra-operatórias significativas. Houve dois casos de vazamento pós-operatório da ostomia. Dos 22 neonatos, 16 estavam vivos 4 meses após a cirurgia. Seis neonatos morreram por complicações devido à doença de base. CONCLUSÃO: A gastrostomia com fundoplicatura Nissen é procedimento seguro e ajuda os pais a darem melhor cuidado a crianças com lesão neurológica

Carbohydrate Amphiphiles Enable Peptide Delivery to the CNS

Non peer reviewe

Nose to brain delivery

The global prevalence of neurological disorders is rising and yet we are still unable to deliver most drug molecules, in therapeutic quantities, to the brain. The blood brain barrier, consists of a tight layer of endothelial cells surrounded by astrocyte foot processes and these anatomical features constitute a significant barrier to drug transport from the blood to the brain. One way to bypass the BBB and thus treat diseases of the brain is to use the nasal route of administration and deposit drugs at the olfactory region of the nares; from where they travel to the brain via mechanisms that are still not clearly understood; with travel across nerve fibres and travel via a perivascular pathway both being hypothesized. The nose to brain route has been demonstrated repeatedly in preclinical models, with both solution and particulate formulations. The nose to brain route has also been demonstrated in human studies with solution and particle formulations. The entry of device manufacturers into the arena will enable the benefits of this delivery route to become translated into approved products. The key factors which determine the efficacy of delivery via this route include: delivery to the olfactory area of the nares as opposed to the respiratory region, a longer retention time at the nasal mucosal surface, penetration enhancement of the active through the nasal epithelia and a reduction in drug metabolism in the nasal cavity. Indications where nose to brain products are likely to emerge first include: neurodegeneration, post-traumatic stress disorder, pain and glioblastoma

Oral polymeric nanomedicines for peptide delivery to the brain : Polymer molecular weight effect

Poster T3058 at the AAPS Annual Meeting and ExpositionNon peer reviewe

Polyelectrolyte nanoparticles with high drug loading enhance the oral uptake of hydrophobic compounds

In the pharmaceutical industry, orally active compounds are required to have sufficient water solubility to enable dissolution within the gastrointestinal tract prior to absorption. Limited dissolution within the gastrointestinal tract often reduces the bioavailability of hydrophobic drugs. To improve gastrointestinal tract dissolution, nonaqueous solvents are often used in the form of emulsions and microemulsions. Here, we show that oil-free polyelectrolyte nanosystems (micellar dispersions and 100 - 300 nm particles) prepared from poly(ethylenimines) derivatized with cetyl chains and quaternary ammonium groups are able to encapsulate high levels of hydrophobic drug (0.20 g of drug per g of polymer) for over 9 months, as demonstrated using cyclosporine A (log P = 4.3). The polyelectrolytes facilitate the absorption of hydrophobic drugs within the gastrointestinal tract by promoting drug dissolution and by a hypothesized mechanism involving paracellular drug transport. Polyelectrolyte nanoparticle drug blood levels are similar to those obtained with commercial microemulsion formulations. The polyelectrolytes do not promote absorption by inhibition of the P-glycoprotein efflux pump.Peer reviewe