The purpose of this study was to determine whether inhibition of CaMKIV would improve disease pathology.\n\nMethods. We treated MRL/lpr mice with KN-93, a CaMKIV inhibitor, starting at week 8 or week 12 of age and continuing through week
16 and evaluated skin lesions, proteinuria, kidney histopathology, proinflammatory cytokine production, and costimulatory molecule expression. We also determined the effect of silencing of CAMK4 on interferon-gamma (IFN gamma) expression by human SLE T cells.\n\nResults. CaMKIV inhibition in MRL/lpr mice resulted in significant suppression of nephritis and skin disease, decreased expression of the costimulatory molecules CD86 and CD80 on B cells, and suppression of IFN gamma and tumor necrosis factor alpha production. In human SLE T cells, silencing of CAMK4 resulted in suppression of IFN gamma production.\n\nConclusion. PLX3397 mouse We conclude that suppression of CaMKIV mitigates disease development in lupus-prone mice by suppressing cytokine production and costimulatory molecule expression. Specific silencing of CAMK4 in human
T cells results in similar suppression of IFN gamma production. Our data justify the development of small-molecule CaMKIV inhibitors for the treatment of patients with SLE.”
“Objective: Acute encephalitis with refractory repetitive partial seizure (AERRPS) is a peculiar type of post-encephalitic/encephalopathic epilepsy. Here we report all AZD6094 cell line analysis of AERRPS in a series of children and propose an effective treatment option for seizure control in these children. Methods: We retrospectively reviewed cases of AERRPS treated in a pediatric intensive care unit., between February 2002 and June 2006. Clinical characteristics were systemically assessed. Burst Suppression coma was induced by high-dose suppressive therapy; 24-h electroencephalogram (EEG) monitoring was performed oil each patient. The goal of treatment was to achieve complete clinical seizure control or burst-suppression pattern on EEG, aiming for all interburst interval of >5 s. Brain imaging was done for each patient. Results: There were nine
patients click here (seven boys), aged 5-15 years. Clinical symptoms included fever (100%), upper respiratory symptoms (66.7%) and altered consciousness (66.7%). All patients received multiple high-dose suppressive drugs and were intubated with/without inotropic agents. Seizures in three patients were stopped after high-dose lidocaine infusion (6-8 mg/kg/h) in the acute stage and three patients were stopped after high dose phenobarbital (serum level 60-80 ug/mL) combined with high-dose oral topiramate (15-20 mg/kg/day). Follow-up for this study was 16-61 months. Two subjects died while seven developed epilepsy and/or neurologic deficits; none returned to baseline. All survivors were discharged and Continued multiple antiepileptic medications. Conclusions: Our data indicates that children with AERRPS have high mortality and morbidity rates.