A rare polymorphism affects a mitogen-activated protein kinase site in synapsin III: possible relationship to schizophrenia.

BACKGROUND: Synapsin III plays a role in neuronal plasticity and maps to chromosome 22q12-13, a region suggested to be linked to schizophrenia. To determine if synapsin III plays a role in this disease, we searched for polymorphisms in this gene in patients with schizophrenia and controls. METHODS: The synapsin III gene was initially sequenced from 10 individuals with schizophrenia to identify polymorphisms. Association analysis was then performed using 118 individuals with schizophrenia and 330 population controls. Synapsin III expression was studied by immunoblot analyses, and phosphorylation sites were mapped by sequencing trypsin-digested synapsin III fragments phosphorylated with phosphorus-32. RESULTS: A rare, missense polymorphism, S470N, was identified in the synapsin III gene and appeared more frequently in individuals with schizophrenia than in controls (p =.0048). The site affected by the polymorphism, Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action. Phosphorylation at Ser470 was increased during neonatal development and in response to neurotrophin-3 in cultured hippocampal neurons. CONCLUSIONS: Our observations suggest an association of a rare polymorphism in synapsin III with schizophrenia, but further studies will be required to clarify its role in this disease.     

High-dose infliximab prophylaxis in endotoxin-induced uveitis.

PURPOSE: The aim of this study to analyze the preventive effect of high-dose infliximab in endotoxin-induced uveitis (EIU) in rabbits. METHODS: An experimental study was conducted on 64 rabbits. Salmonella typhimurium lipopolysaccharide endotoxin was intravitreally injected. Infliximab was intravenously (i.v.) injected 24 h before the intravitreal injection (20 mg/kg). The animals were randomly assigned to five groups: group A, saline intravitreal injection; group B, Infliximab i.v. group C, infliximab + saline; group D, intravitreal endotoxin and group E, infliximab i.v. + intravitreal endotoxin. With two masked observers, a microscopic examination of aqueous humor (cells, tumor necrosis factor [TNF] alpha) and aqueous protein level were performed 24 h after an endotoxin injection and 48 h after an infliximab infusion. RESULTS: Infliximab treatment, at a dose of 20 mg/kg, significantly improved all the parameters. Inflammatory cell infiltration was significantly reduced in the iris, ciliary body, and anterior chamber (U Mann-Whitney test, P = 0.01). Associated with a lower level of TNF-alpha and protein exudate in aqueous humor (U Mann-Whitney test, P = 0.01). CONCLUSIONS: Infliximab, at a dose of 20 mg/kg, is effective in the prophylaxis of the EIU.     

Copper deficiency during parenteral nutrition: a report of four pediatric cases.

The standard of care for patients with cholestasis (direct bilirubin >or=2 mg/dL) while receiving parenteral nutrition (PN) solutions is to reduce or discontinue the copper and manganese. The repercussions of this action have not been studied. Two adult case reports document low serum copper levels associated with clinical symptoms of copper deficiency after the removal of copper from their PN solutions. We now describe the first known series of pediatric patients to develop copper deficiency after copper was removed from their PN solutions.