Infliximab for the treatment of plaque psoriasis

Infliximab is a monoclonal antibody that targets tumor necrosis factor-α (TNFα). It is used in the treatment of a number of inflammatory disorders including severe plaque psoriasis. TNFα is thought to have a major role in psoriasis by promoting an inflammatory infiltrate into the skin and inducing keratinocyte proliferation and preventing keratinocyte apoptosis, which directly contributes to the characteristic plaque skin lesions. Based on four randomized, placebo-controlled, double-blind clinical trials and nine open-label uncontrolled trials of the use of infliximab in plaque psoriasis, it was found that infliximab is a highly efficacious, rapid, sustainable, and relatively safe therapy. Yet as with any biologic, caution is recommended in its use as infusion reactions, lupus-like syndromes, infections, malignancies including lymphomas, as well as other rare events have been reported

Ustekinumab in the therapy of chronic plaque psoriasis

Psoriasis is a chronic inflammatory disorder characterized by T cell dysregulation and a chronic inflammatory infiltrate within the epidermis. Several cytokines play an important role in the pathogenesis of psoriasis, including interleukin-12 (IL-12) and IL-23. These cytokines act via induction of pro-inflammatory cytokines which promote chronic inflammation and auto-reactivity. Ustekinumab is a fully human monoclonal antibody against the common p40 subunit of IL-12 and IL-23. Two randomized, double-blind, placebo-controlled trials of ustekinumab have demonstrated significant and prolonged efficacy in the treatment of plaque psoriasis. Adverse events were generally similar across treatment and control groups. Studies are ongoing to assess the long term safety and efficacy profiles of ustekinumab

NASA's Black Marble Product Suite: Validation Strategy

NASA's Black Marble nighttime lights product suite (VNP46) is available at 500m resolution since January 2012 with data fro the Visible Infrared Imaging Radiometer Suite (VIIRS) Day/Night Band (DNB) onboard the Suomi National Polar-orbiting Platform (SNPP). The retrieval algorithm, developed and implemented for routine global processing at NASA's Land Science Investigator-led Processing System (SIPS), utilizes all high-quality, cloud-free, atmospheric-terrain, vegetation, snow, lunar and stray light corrected radiances to estimate daily nighttime lights (NTL) and other intrinsic surface optical properties. Extensive benchmark tests at representative spatial and temporal scales were conducted on the VNP46 time series record to characterize the uncertainties stemming from upstream data sources. Current and planned validation activities under the Group on Earth Observations (GEO) Human Planet Initiative are aimed at evaluating the products at difference geographic locations and time periods representing the full range of retrieval conditions

Biosimilars for the treatment of patients with psoriasis : A consensus statement from the Biosimilar Working Group of the International Psoriasis Council

As biosimilars have become available in various parts of the world, the International Psoriasis Council has reviewed aspects of their use. To provide consensus statements from the Biosimilar Working Group about the use of biosimilars in patients with psoriasis. A semiqualitative structured process was employed to approve the consensus statements on biosimilars using the nominal group technique. The final statements were validated by a survey of the paricipants. The approval of the consensus statements was predefined as >80% positive opinions. A consensus was reached in 36/38 statements regarding regulatory considerations, extrapolation of indication, interchangeability, substitution at the pharmacy level, pharmacovigilance, traceability, naming, biosimilar policy, education, and cost of biosimilars. Example statements include "Switching a stable patient from a reference product to a biosimilar product is appropriate if the patient and physician agree to do so" and "Patients and patients' organisations should be involved in all decision making and policy development about the use of biosimilars." The International Psoriasis Council Biosimilar Working Group provides consensus statements for the use of biosimilars in the treatment of patients with psoriasis. We suggest that these statements provide global guidance to clinicians, healthcare organizations, pharmaceutical companies, regulators, and patients regarding the development and use of biosimilars in patients with psoriasis

Neuropeptide signaling regulates the susceptibility of developing C. elegans to anoxia

Inadequate delivery of oxygen to organisms during development can lead to cell dysfunction/death and life-long disabilities. Although the susceptibility of developing cells to low oxygen conditions changes with maturation, the cellular and molecular pathways that govern responses to low oxygen are incompletely understood. Here we show that developing Caenorhabditis elegans are substantially more sensitive to anoxia than adult animals and that this sensitivity is controlled by nervous system generated hormones (e.g., neuropeptides). A screen of neuropeptide genes identified and validated nlp-40 and its receptor aex-2 as a key regulator of anoxic survival in developing worms. The survival-promoting action of impaired neuropeptide signaling does not rely on five known stress resistance pathways and is specific to anoxic insult. Together, these data highlight a novel cell non-autonomous pathway that regulates the susceptibility of developing organisms to anoxia

Comparative effectiveness of less commonly used systemic monotherapies and common combination therapies for moderate to severe psoriasis in the clinical setting.

BACKGROUND: The effectiveness of psoriasis therapies in real-world settings remains relatively unknown. OBJECTIVE: We sought to compare the effectiveness of less commonly used systemic therapies and commonly used combination therapies for psoriasis. METHODS: This was a multicenter cross-sectional study of 203 patients with plaque psoriasis receiving less common systemic monotherapy (acitretin, cyclosporine, or infliximab) or common combination therapies (adalimumab, etanercept, or infliximab and methotrexate) compared with 168 patients receiving methotrexate evaluated at 1 of 10 US outpatient dermatology sites participating in the Dermatology Clinical Effectiveness Research Network. RESULTS: In adjusted analyses, patients on acitretin (relative response rate 2.01; 95% confidence interval [CI] 1.18-3.41), infliximab (relative response rate 1.93; 95% CI 1.26-2.98), adalimumab and methotrexate (relative response rate 3.04; 95% CI 2.12-4.36), etanercept and methotrexate (relative response rate 2.22; 95% CI 1.25-3.94), and infliximab and methotrexate (relative response rate 1.72; 95% CI 1.10-2.70) were more likely to have clear or almost clear skin compared with patients on methotrexate. There were no differences among treatments when response rate was defined by health-related quality of life. LIMITATIONS: Single time point assessment may result in overestimation of effectiveness. CONCLUSIONS: The efficacy of therapies in clinical trials may overestimate their effectiveness as used in clinical practice. Although physician-reported relative response rates were different among therapies, absolute differences were small and did not correspond to differences in patient-reported outcomes

Daf-2 Signaling Modifies Mutant SOD1 Toxicity in C. elegans

The DAF-2 Insulin/IGF-1 signaling (IIS) pathway is a strong modifier of Caenorhabditis elegans longevity and healthspan. As aging is the greatest risk factor for developing neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), we were interested in determining if DAF-2 signaling modifies disease pathology in mutant superoxide dismutase 1 (SOD1) expressing C. elegans. Worms with pan-neuronal G85R SOD1 expression demonstrate significantly impaired locomotion as compared to WT SOD1 expressing controls and they develop insoluble SOD1 aggregates. Reductions in DAF-2 signaling, either through a hypomorphic allele or neuronally targeted RNAi, decreases the abundance of aggregated SOD1 and results in improved locomotion in a DAF-16 dependant manner. These results suggest that manipulation of the DAF-2 Insulin/IGF-1 signaling pathway may have therapeutic potential for the treatment of ALS

Tracking Membrane Protein Association in Model Membranes

Membrane proteins are essential in the exchange processes of cells. In spite of great breakthrough in soluble proteins studies, membrane proteins structures, functions and interactions are still a challenge because of the difficulties related to their hydrophobic properties. Most of the experiments are performed with detergent-solubilized membrane proteins. However widely used micellar systems are far from the biological two-dimensions membrane. The development of new biomimetic membrane systems is fundamental to tackle this issue

Repeated PTZ Treatment at 25-Day Intervals Leads to a Highly Efficient Accumulation of Doublecortin in the Dorsal Hippocampus of Rats

BACKGROUND: Neurogenesis persists throughout life in the adult mammalian brain. Because neurogenesis can only be assessed in postmortem tissue, its functional significance remains undetermined, and identifying an in vivo correlate of neurogenesis has become an important goal. By studying pentylenetetrazole-induced brain stimulation in a rat model of kindling we accidentally discovered that 25±1 days periodic stimulation of Sprague-Dawley rats led to a highly efficient increase in seizure susceptibility. METHODOLOGY/PRINCIPAL FINDINGS: By EEG, RT-PCR, western blotting and immunohistochemistry, we show that repeated convulsive seizures with a periodicity of 25±1 days led to an enrichment of newly generated neurons, that were BrdU-positive in the dentate gyrus at day 25±1 post-seizure. At the same time, there was a massive increase in the number of neurons expressing the migratory marker, doublecortin, at the boundary between the granule cell layer and the polymorphic layer in the dorsal hippocampus. Some of these migrating neurons were also positive for NeuN, a marker for adult neurons. CONCLUSION/SIGNIFICANCE: Our results suggest that the increased susceptibility to seizure at day 25±1 post-treatment is coincident with a critical time required for newborn neurons to differentiate and integrate into the existing hippocampal network, and outlines the importance of the dorsal hippocampus for seizure-related neurogenesis. This model can be used as an in vivo correlate of neurogenesis to study basic questions related to neurogenesis and to the neurogenic mechanisms that contribute to the development of epilepsy