(interferon beta 1a) articles in PubMed
- Dietary vitamin C deficiency depressed the gill physical barriers and immune barriers referring to Nrf2, apoptosis, MLCK, NF-κB and TOR signaling in grass carp (Ctenopharyngodon idella) under infection of Flavobacterium columnare. [Journal Article]
- Fish Shellfish Immunol 2016 Sep 15FS
- This study explored the effects of vitamin C on the physical barriers and immune barriers, and relative mRNA levels of signaling molecules in the gill of grass carp (Ctenopharyngodon idella) under in...
This study explored the effects of vitamin C on the physical barriers and immune barriers, and relative mRNA levels of signaling molecules in the gill of grass carp (Ctenopharyngodon idella) under infection of Flavobacterium columnare. The results indicated that compared with optimal vitamin C supplementation, vitamin C deficiency (2.9 mg/kg diet) (1) increased reactive oxygen species, malondialdehyde and protein carbonyl (PC) contents (P < 0.05), decreased the copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities and mRNA levels (P < 0.05), and glutathione and vitamin C contents (P < 0.05), down-regulated NF-E2-related factor 2 mRNA level (P < 0.05), and up-regulated Kelch-like ECH-associating protein (Keap) 1a (rather than Keap1b) mRNA level (P < 0.05) in the gill of grass carp under infection of F. columnare, suggesting that vitamin C deficiency induced oxidative injury in fish gill; (2) up-regulated caspase-3, -7, -8, -9, Fas ligand, B-cell lymphoma protein 2 associated X protein, apoptotic protease activating factor-1 mRNA levels (P < 0.05), and down-regulated inhibitor of apoptosis protein and B-cell lymphoma-2 (rather than myeloid cell leukemia-1) mRNA level (P < 0.05) in the gill of grass carp under infection of F. columnare, suggesting that vitamin C deficiency aggravated cell apoptosis in fish gill; (3) up-regulated pore-forming TJs Claudin-12, 15a, -15b, and related signaling molecules myosin light chain kinase, p38 mitogen-activated protein kinase (rather than c-Jun N-terminal kinases) mRNA levels (P < 0.05), and down-regulated barrier-forming TJs Occludin, zonula occludens (ZO) 1, ZO-2, Claudin-c, -3c, -7a, -7b mRNA levels (P < 0.05) in the gill of grass carp under infection of F. columnare, suggesting that vitamin C deficiency disrupted tight junctional complexes in fish gill; (4) decreased lysozyme and acid phosphatase (ACP) activities, and complement 3 (C3), C4 and IgM contents (P < 0.05), down-regulated the mRNA levels of antimicrobial peptides liver expressed antimicrobial peptide (LEAP) 2A, LEAP-2B, Hepcidin, β-defensin mRNA levels (P < 0.05) in the gill of grass carp under infection of F. columnare, suggesting that vitamin C deficiency decrease fish gill immune function; (5) down-regulated the mRNA levels of anti-inflammatory cytokines-related factors interleukin 10 (IL-10), IL-11, transforming growth factor (TGF) β1, TGF-β2, inhibitor of κBa and eIF4E-binding protein 1 (4E-BP1) (rather than 4E-BP2) (P < 0.05), and up-regulated pro-inflammatory cytokines-related factors interferon γ2, IL-1β, IL-6, IL-8, IL-12 P35, IL-12 P40, nuclear factor κB (NF-κB) p65 (rather than NF-κB p52), IκB kinases (IKK) (only IKKα and IKKγ), target of rapamycin and ribosomal protein S6 kinase 1 mRNA levels (P < 0.05) in the gill of grass carp under infection of F. columnare, suggesting that vitamin C deficiency aggravated fish gill inflammation. In conclusion, vitamin C deficiency disrupted physical barriers and immune barriers, and regulated relative mRNA levels of signaling molecules in fish gill. The vitamin C requirement for against gill rot morbidity of grass carp (264-1031 g) was estimated to be 156.0 mg/kg diet. In addition, based on the gill biochemical indices (antioxidant indices MDA, PC and vitamin C contents, and immune indices LA and ACP activity) the vitamin C requirements for grass carp (264-1031 g) were estimated to be 116.8, 156.6, 110.8, 57.8 and 134.9 mg/kg diet, respectively.
- Multiple Sclerosis in Pediatrics: Current Concepts and Treatment Options. [Review]
- Neurol Ther 2016 Sep 17NT
- Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory, demyelinating disease of the central nervous system. MS is increasingly recognized in the pediatric population, and it is usually diagn...
Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory, demyelinating disease of the central nervous system. MS is increasingly recognized in the pediatric population, and it is usually diagnosed around 15 years of age. The exact etiology of MS is still not known, although autoimmune, genetic, and environmental factors play important roles in its development, making it a multifactorial disease. The disease in children almost always presents in the relapsing-remittent form. The therapy involves treatment of relapses, and immunomodulatory and symptomatic treatment. The treatment of children with MS has to be multidisciplinary and include pediatric neurologists, ophthalmologists, psychologists, physiotherapists, and if necessary, pediatric psychiatrists and pharmacologists. The basis of MS therapy should rely on drugs that are able to modify the course of the disease, i.e. immunomodulatory drugs. These drugs can be subdivided into two general categories: first-line immunomodulatory therapy (interferon beta-1a, interferon beta-1b, glatiramer acetate) and second-line immunomodulatory therapy (natalizumab, mitoxantrone, fingolimod, teriflunomide, azathioprine, rituximab, dimethyl fumarate, daclizumab). Treatment of relapses involves the use of high intravenous doses of corticosteroids, administration of intravenous immunoglobulins, and plasmapheresis. We summarize here the current available information related to the etiology and treatment options in MS. Early administration of immunomodulatory therapy is beneficial in adults, while more studies are needed to prove their effectiveness in pediatric populations. Therefore, pediatric MS still represents a great challenge for both, the early and correct diagnosis, as well as its treatment.
- Toll-like receptor (TLR)7 and TLR9 agonists enhance interferon (IFN) beta-1a's immunoregulatory effects on B cells in patients with relapsing-remitting multiple sclerosis (RRMS). [Journal Article]
- J Neuroimmunol 2016 Sep 15; 298:181-8JN
- We report that B cells from patients with RRMS have decreased endogenous IFN-β secretion and deficient IFN receptor (IFNAR)1/2 and TLR7 gene expression in comparison to healthy controls (HCs), which ...
We report that B cells from patients with RRMS have decreased endogenous IFN-β secretion and deficient IFN receptor (IFNAR)1/2 and TLR7 gene expression in comparison to healthy controls (HCs), which may contribute to disregulation of cytokine secretion by B cells. We propose that TLR7 and TLR9 stimulation with loxorubin (LOX) and CpG, in combination with exogenous IFN-β may effectively reconstitute endogenous IFN-β production deficit and induce the secretion of immunoregulatory cytokines by B cells. Both LOX/IFN-β and CpG/IFN-β in-vitro treatments of B cells from RRMS patients induced higher endogenous IFN-β gene expression in comparison to the exogenous IFN-β alone. CpG/IFN-β combination induced higher secretion of IL-10, TGF-β, and IL-27 in comparison to stimulation with IFN-β. Our study provides a basis for future clinical studies employing IFN-β and TLR7/9 agonists, which may enhance the resolution of the inflammatory response in RRMS.
- Superior MRI outcomes with alemtuzumab compared with subcutaneous interferon β-1a in MS. [Journal Article]
- Neurology 2016 Sep 2Neur
- CONCLUSIONS: Alemtuzumab demonstrated greater efficacy than SC IFN-β-1a on MRI endpoints in active RRMS. The superiority of alemtuzumab was more prominent during the second year of both studies. These findings complement the superior clinical efficacy of alemtuzumab over SC IFN-β-1a in RRMS.
- Rapid Conformational Analysis of Protein Drugs in Formulation by Hydrogen/Deuterium Exchange Mass Spectrometry. [Journal Article]
- J Pharm Sci 2016 Aug 28JP
- Hydrogen deuterium exchange coupled to mass spectrometry (HDX-MS) has become an established method for analysis of protein higher order structure. Here, we use HDX-MS methodology based on manual soli...
Hydrogen deuterium exchange coupled to mass spectrometry (HDX-MS) has become an established method for analysis of protein higher order structure. Here, we use HDX-MS methodology based on manual solid-phase extraction (SPE) to allow fast and simplified conformational analysis of proteins under pharmaceutically relevant formulation conditions. Of significant practical utility, the methodology allows global HDX-MS analyses to be performed without refrigeration or external cooling of the setup. In mode 1, we used dimethyl sulphoxide-containing solvents for SPE, allowing the HDX-MS analysis to be performed at acceptable back-exchange levels (<30%) without the need for cooling any components of the setup. In mode 2, SPE and chromatography were performed using fast isocratic elution at 0°C resulting in a back-exchange of 10%-30%. Real-world applicability was demonstrated by HDX-MS analyses of interferon-β-1a in formulation, using an internal HDX reference peptide (P7I) to control for any sample-to-sample variations in back-exchange. Advantages of the methodology include low sample use, optimized excipient removal using multiple solvents, and fast data acquisition. Our results indicate that HDX-MS can provide a reliable approach for fast conformation analysis of proteins in their intended formulations, which could facilitate an increased use of the technique in pharmaceutical development research.
- EVASEP: A Noninterventional Study Describing the Perception of Neurologists, Patients, and Caregivers on Caregivers' Role in the Support of Patients Suffering from Multiple Sclerosis Treated with Subcutaneous Interferon Beta 1a. [Journal Article]
- Mult Scler Int 2016; 2016:4986073MS
- CONCLUSIONS: There are many unmet needs in the perception of the role of caregivers for people with MS which need to be addressed to deliver the most effective care package for patients and to support the needs of the support provider.
- [Clinical and demographic characteristics of patients with multiple sclerosis]. [Journal Article]
- Rev Med Inst Mex Seguro Soc 2016; 54 Suppl 2:S186-90RM
- CONCLUSIONS: Clinical and demographic characteristics are similar to those reported in international literature. More studies would be needed to typify Mexican population with MS.
- Management Strategies for Flu-Like Symptoms and Injection-Site Reactions Associated with Peginterferon Beta-1a: Obtaining Recommendations Using the Delphi Technique. [Journal Article]
- Int J MS Care 2016 Jul-Aug; 18(4):211-8IJ
- CONCLUSIONS: Delphi responders agreed on the management strategies for FLSs/ISRs and agreed that patient education is critical to set treatment expectations and promote adherence.
- Retinal measures correlate with cognitive and physical disability in early multiple sclerosis. [Journal Article]
- J Neurol 2016 Aug 20JN
- Further studies are needed to determine the role of retinal optical coherence tomography (OCT) in non-optic neuritis (ON) eyes of patients with early MS. The objective of this study is to explore the...
Further studies are needed to determine the role of retinal optical coherence tomography (OCT) in non-optic neuritis (ON) eyes of patients with early MS. The objective of this study is to explore the relationship between retinal layers' thickness and cognitive as well as physical disability in patients with the early RRMS. Participants in this cross-sectional study were adults with early RRMS, stable on interferon beta-1a, or fingolimod therapy, and without a history of ON in one or both eyes. Patients were evaluated clinically, underwent a battery of cognitive tests, and a retinal OCT scan which was also performed on a group of healthy age- and gender-matched controls. We studied 47 patients with RRMS, on interferon beta-1a (N = 32) or fingolimod (N = 15), and 18 healthy controls. Multivariate analyses controlling for age, disease duration, treatment, and education when exploring cognitive function, showed that pRNFL thickness correlated negatively with 9HPT (standardized Beta -0.4, p < 0.0001), and positively with SDMT (standardized Beta 0.72, p = 0.007). In patients with early RRMS without optic neuropathy, retinal thickness measures correlated with physical disability and cognitive disability, supporting their potential as biomarkers of axonal loss.
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- Predictors of first-line treatment persistence in a Portuguese cohort of relapsing-remitting multiple sclerosis. [Journal Article]
- J Clin Neurosci 2016 Aug 16JC
- Treatment persistence in first-line injectable disease-modifying therapies (DMT) for relapsing-remitting multiple sclerosis (RRMS) is an important indicator of effectiveness. Identifying predictors o...
Treatment persistence in first-line injectable disease-modifying therapies (DMT) for relapsing-remitting multiple sclerosis (RRMS) is an important indicator of effectiveness. Identifying predictors of treatment discontinuation is important as there are other therapies currently available and a growing range of emerging drugs. We report a retrospective study of RRMS and clinically isolated syndrome patients followed in a University Hospital during a 13-year period with the objective of identifying predictors of treatment persistence. An evaluation of persistence on the first DMT, rates of DMT discontinuation, and reasons and predictors of discontinuation was performed. A total of 410 patients were included, 69% female, with mean disease duration of 37.8months, mean age of 34.2years and mean follow-up time of 6.1years. The first DMT was glatiramer acetate (GA) in 27.56% of patients, interferon (IFN) β-1a intramuscular in 26.34%, IFNβ-1b in 26.10%, IFNβ-1a22 in 13.66% and IFNβ-1a44 in 6.34%. Treatment was discontinued in 16.34% of patients after 1year of treatment and in 50.24% of patients in the total follow-up time, with a mean time for discontinuation of 39.80months. Higher baseline Expanded Disability Status Scale score was an independent predictor of treatment discontinuation (hazard ratio 1.35, p=0.002). After the first year, treatment persistence was 90.74% for IFNβ-1a-IM, 88.46% for IFNβ-1a44, 83.18% for IFNβ-1b, 83.19% for GA and 69.64% for IFNβ-1a22 (p=0.014). Lower frequency of administration was associated with higher persistence rates. The most common reason for treatment discontinuation was lack of efficacy in all DMT subgroups.