Prevalence of Macular Atrophy in the MARINA Study of Ranibizumab versus Sham for Neovascular Age-Related Macular Degeneration.

Objective: Determine prevalence, progression rates, and associations of newly detectable macular atrophy (MA) in patients with choroidal neovascularization (CNV) secondary to neovascular age-related macular degeneration (nAMD) with/without ranibizumab treatment.

Design: Post hoc analysis of MA in patients with occult/minimally classic nAMD who received monthly intravitreal ranibizumab (0.3 or 0.

Efficacy of Every Four Monthly and Quarterly Dosing of Faricimab vs Ranibizumab in Neovascular Age-Related Macular Degeneration: The STAIRWAY Phase 2 Randomized Clinical Trial.

Importance: Faricimab neutralizes angiopoietin-2 and vascular endothelial growth factor A via both simultaneous and independent binding.

Objective: To evaluate extended dosing with faricimab, the first bispecific antibody designed for intraocular use, in patients with neovascular age-related macular degeneration.

Design, Setting, And Participants: This phase 2 randomized clinical trial was a 52-week multicenter, active comparator-controlled, parallel-group study.

Systemic Safety in Ranibizumab-Treated Patients with Neovascular Age-Related Macular Degeneration: A Patient-Level Pooled Analysis.

Topic: This study evaluated the cardiovascular/cerebrovascular safety profile of ranibizumab 0.5 mg versus sham ± verteporfin in patients with neovascular age-related macular degeneration (nAMD). In addition, comparisons of ranibizumab 0.

The Systemic Safety of Ranibizumab in Patients 85 Years and Older with Neovascular Age-Related Macular Degeneration.

Objective: Ranibizumab safety is well established for treatment of neovascular age-related macular degeneration (nAMD), but less is known about the risk of systemic serious adverse events (SAEs), specifically among patients with heightened baseline risk due to age (≥85 years). This analysis examines whether patients ≥85 years of age versus those <85 years experience an increased risk of key systemic SAEs during intravitreal ranibizumab treatment for nAMD.

Design: Retrospective, pooled analysis of safety data from 5 phase III/IIIb multicenter randomized clinical trials in patients with nAMD: ANCHOR, MARINA, PIER, SAILOR, and HARBOR.

Safety and efficacy of ocrelizumab in combination with methotrexate in MTX-naive subjects with rheumatoid arthritis: the phase III FILM trial.

Objective: To determine the efficacy and safety of ocrelizumab (OCR) with methotrexate (MTX) in MTX-naive rheumatoid arthritis (RA) patients.

Methods: In a randomised, double-blind, controlled trial, patients received placebo+MTX (MTX; n=210), OCR 200 mg×2+MTX (OCR 200; n=200) or OCR 500 mg×2+MTX (OCR 500; n=203). OCR/placebo (two intravenous infusions) was given on days 1 and 15, with fixed re-treatment scheduled at weeks 24/26, 52/54 and 76/78.

Hydroxyurea enhances SMN2 gene expression through nitric oxide release.

Small molecules that increase full-length survivor motor neuron (SMN) gene transcript are promising therapeutic candidates for spinal muscular atrophy (SMA). Hydroxyurea (HU) has recently been shown to increase full-length SMN transcript in cultured lymphocytes from patients with SMA. We investigate the mechanism by which HU enhances full-length SMN2 gene expression in SMA lymphocytes.

A 2-week, polysomnographic, safety study of sodium oxybate in obstructive sleep apnea syndrome.

Purpose: Sodium oxybate (SXB) is approved for cataplexy and excessive daytime sleepiness in narcolepsy. Obstructive sleep apnea syndrome (OSAS) affects ∼9-50% of narcoleptics. Effects of 2-week SXB administration on apnea-hypopnea index (AHI), oxygen saturation (SaO(2)), and sleep architecture were investigated in OSAS patients.

A safety trial of sodium oxybate in patients with obstructive sleep apnea: Acute effects on sleep-disordered breathing.

Objective: Sodium oxybate (SXB) is an approved drug for the treatment of excessive daytime sleepiness (EDS) and cataplexy in narcolepsy. Obstructive sleep apnea syndrome (OSAS) is a condition that frequently co-occurs with narcolepsy. Given the known central nervous system (CNS) depressant effects of SXB, this study aimed to examine its effects on sleep-disordered breathing (SDB) and sleep architecture in patients with OSAS.

Hydroxyurea enhances SMN2 gene expression in spinal muscular atrophy cells.

Spinal muscular atrophy (SMA) is a motor neuron disease caused by dysfunction of the survival motor neuron (SMN) gene. Human SMN gene is present in duplicated copies: SMN1 and SMN2. More than 95% of patients with SMA lack a functional SMN1 but retain at least one copy of SMN2.

Oleic acid causes apoptosis and dephosphorylates Bad.

There is increasing evidence showing the involvement of unsaturated free fatty acids in cell death pathways, particularly in the context of apoptotic signalling. Our previous in vitro study has demonstrated that oleic acid, a monounsaturated fatty acid, reduces phosphorylation of proapoptotic Bad through activation of protein phosphatase type 2Cbeta. In the present study, we attempted to investigate the role of oleic acid in neuronal apoptosis using different types of cell cultures, and, furthermore, to explore the underlying mechanism with regard to its effect on Bad expression.

Neurodegeneration in striatum induced by the mitochondrial toxin 3-nitropropionic acid: role of matrix metalloproteinase-9 in early blood-brain barrier disruption?

Blood-brain barrier (BBB) dysfunction is a potential mechanism involved in progressive striatal damage induced by the mitochondrial excitotoxin, 3-nitropropionic acid (3-NP). After activation by proteases and free radicals, matrix metalloproteinases (MMPs), particularly MMP-9 and -2, can digest the endothelial basal lamina leading to BBB opening. Using CD-1 mice, we show that MMP-9 expression by zymography is increased in the injured striatum compared with the contralateral striatum 2 hr after 3-NP injection [133.

Effects of cold injury-induced trauma in manganese superoxide dismutase-deficient mice.

Manganese superoxide dismutase (Mn-SOD, SOD2) is an inducible antioxidant localized to the mitochondria, which have been shown to be both the sites of superoxide anion (O(2)*-)) production and the target of free radical attacks. Knock-out mice with targeted disruption of Sod2 (SOD2-KO) are more susceptible to ischemic damage than their wild-type (WT) counterparts, showing increased loss of mitochondrial cytochrome c after trauma, but less apoptotic cell death in the first 24 h following controlled cortical injury. In this study, we sought to investigate whether oxidative stress plays a significant role in the development of secondary brain damage following cold injury-induced brain trauma (CIBT), a model of vasogenic edema.