scholarly journals Re-Examining the Role of TNF in MS Pathogenesis and Therapy

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2290 ◽  
Author(s):  
Diego Fresegna ◽  
Silvia Bullitta ◽  
Alessandra Musella ◽  
Francesca Romana Rizzo ◽  
Francesca De Vito ◽  
...  
Keyword(s):  
Neurological Disorder ◽  
Experimental Studies ◽  
Convincing Evidence ◽  
Special Focus ◽  
Pathophysiological Role ◽  
The Central Nervous System ◽  
Ms Pathogenesis

Multiple sclerosis (MS) is a common neurological disorder of putative autoimmune origin. Clinical and experimental studies delineate abnormal expression of specific cytokines over the course of the disease. One major cytokine that has been shown to play a pivotal role in MS is tumor necrosis factor (TNF). TNF is a pleiotropic cytokine regulating many physiological and pathological functions of both the immune system and the central nervous system (CNS). Convincing evidence from studies in human and experimental MS have demonstrated the involvement of TNF in various pathological hallmarks of MS, including immune dysregulation, demyelination, synaptopathy and neuroinflammation. However, due to the complexity of TNF signaling, which includes two-ligands (soluble and transmembrane TNF) and two receptors, namely TNF receptor type-1 (TNFR1) and type-2 (TNFR2), and due to its cell- and context-differential expression, targeting the TNF system in MS is an ongoing challenge. This review summarizes the evidence on the pathophysiological role of TNF in MS and in different MS animal models, with a special focus on pharmacological treatment aimed at controlling the dysregulated TNF signaling in this neurological disorder.

scholarly journals Polarização de macrófagos e as complicações da Obesidade: o que podemos aprender com os modelos experimentais

2016 ◽  
Vol 95 (2) ◽  
pp. 103
Author(s):  
Brendha Cação ◽  
Ávaro Simões ◽  
Cícero Mendes ◽  
Heraldo P. Souza
Keyword(s):  
Adipose Tissue ◽  
Macrophage Polarization ◽  
Experimental Studies ◽  
Experimental Models ◽  
Lifestyle Changes ◽  
Pubmed Database ◽  
Open Question

Clinical and experimental evidences pointed to the role of immune cells and inflammatory mediators on the development of diseases in obese patients. Therefore, it is our objective to explore experimental studies that approach the relationship between the different types of inflammatory reaction inside the adipose tissue, particularly the macrophage polarization and the development of obesity complications. Further, we intend to speculate how to translate this knowledge, obtained from experimental studies, to treatments applicable to the human diseases. PubMed database was sought using the terms “obesity”, “macrophage” and “polarization”. After applying the filters “Language - English” and “Species - Animals”, we arrived to 90 references. Sixty-two were excluded for being reviews or not related to the main subject. Results in experimental models of obesity pointed a relevant correlation between the macrophage polarization to a type 1 response (M1) inside white adipose tissue and the development of insulin resistance, diabetes and other complications of obesity. Several articles report strategies to shift to a type 2 phenotype (M2), using drugs or lifestyle changes. How these findings could be translated to new human treatments is still an open question that only well designed researches could answer.

scholarly journals Differences in use and function of verbal irony between real and fictional discourse: (mis)interpretation and irony blindness

2014 ◽  
Vol 27 (4) ◽  
Author(s):  
Eleni Kapogianni
Keyword(s):  
At Risk ◽  
Special Focus ◽  
Intended Meaning ◽  
Verbal Irony ◽  
Natural Discourse ◽  
And Function ◽  
The Relationship

AbstractThis paper presents a contrastive approach to the presence of two distinct types of verbal irony in real (natural, unscripted) versus fictional (scripted) discourse, with a special focus on irony blindness, i.e. the inability to recognize ironic utterances. Irony strategies are categorized into two general types, based on the relationship between the expressed and the intended meaning (Type 1: meaning reversal and Type 2: meaning replacement). First, the differences between these two types are discussed in terms of use, interpretation, and misinterpretation. It is found that the first type of irony strongly prevails in natural discourse, while the second type is considerably more present in fictional discourse than it is in natural discourse. At the same time, the first type of irony appears to be more at risk of misinterpretation in natural discourse, as opposed to the second type, which seems to be a safer (even though less frequently selected) option. These findings are then further analyzed in light of the discussion concerning fictional (comedic, in particular) irony blindness and the construction and role of the irony-blind characters. Interestingly, the causes of fictional irony blindness are found to correlate more strongly with the (more humorous) misinterpretation of the second type of irony.

The Role of Angiotensin-(1-7)/Mas Axis and Angiotensin Type 2 Receptors in the Central Nervous System in Cardiovascular Disease and Therapeutics: A Riddle to be Solved

2019 ◽  
Vol 17 (4) ◽  
pp. 319-325 ◽  
Author(s):  
Vasiliki Katsi ◽  
Spyridon Maragkoudakis ◽  
Maria Marketou ◽  
Costas Tsioufis ◽  
Fragkiskos Parthenakis ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Experimental Studies ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Pressure Lowering ◽  
The Central Nervous System ◽  
Novel Therapeutic Strategies ◽  
Angiotensin Type

: In recent years, the Angiotensin-(1-7)/Mas receptor [Ang-(1-7)/Mas] sub-branch of the Renin-Angiotensin System (RAS) in the brain, and Angiotensin Type 2 Receptors (AT2R), have attracted scientific interest, as there is evidence that they constitute an essential pathway in cardiovascular regulation, in health and in disease. By acting centrally, the Ang-(1-7)/Mas axis - that has been termed ‘the axis of good’- can exert blood pressure-lowering effects, while also favourably altering baroreflex sensitivity and noradrenergic neurotransmission. Thus, research has focused on the possible neuro- and cardioprotective effects of this pathway in the setting of cardiovascular disease, ultimately aiming to evaluate the potential for development of novel therapeutic strategies based on its modulation. : We summarize the available evidence from experimental studies in this context, aiming to assess current limits of scientific knowledge relevant to this newly-described ‘player’ in haemodynamic regulation, that may become a potential therapeutic target.

scholarly journals Elaborations on the role of project owner: introducing project owners type 1 and 2

2018 ◽  
Vol 11 (3) ◽  
pp. 827-844 ◽  
Author(s):  
Nils O.E. Olsson
Keyword(s):  
Close Relation ◽  
Business Case ◽  
Project Manager ◽  
Project Delivery ◽  
Special Focus ◽  
Information Technology Projects ◽  
Content Type

Purpose The purpose of this paper is to study how the project owner role is described in the literature, and how the role is carried out in practice. In particular, the author studies the project owner role in relation to project execution and benefit realization. Design/methodology/approach Based on a literature review, the author proposes a model for the relationships between the project owner, project manager and the operation of project delivery. The author then uses the model to describe the empirical results derived from a mapping of project owner responsibilities in a set of Norwegian information technology projects. Findings The author defines a project owner type 1 as a project owner that is focused on the business case and has responsibility for both project delivery and benefit realization. This project owner is the type described in most of the literature. The author further defines a project owner type 2 as a project owner that is mainly concerned with supporting the project manager and enabling project delivery. This is the type of project owner found in the empirical study. Research limitations/implications The author identified a mismatch between the project management literature and observed practice. Practical implications There is a need to clarify the type of project owner role referred to in different contexts. Different project owners will have a different set of incentives and priorities. It is important to make sure that both investment costs and benefits (i.e., the complete business case), are seen in close relation to each other and not as separate undertakings. Originality/value There is a need for a distinction between two types of project owners. This study proposes a framework for the description, analysis and implementation of project governance, with a special focus on the project owner role.

scholarly journals Role of Oral Antioxidant Supplementation in the Current Management of Diabetic Retinopathy

2021 ◽  
Vol 22 (8) ◽  
pp. 4020
Author(s):  
Enrique Antonio Alfonso-Muñoz ◽  
Raquel Burggraaf-Sánchez de las Matas ◽  
Jorge Mataix Boronat ◽  
Julio César Molina Martín ◽  
Carmen Desco
Keyword(s):  
Diabetic Retinopathy ◽  
Diabetic Macular Oedema ◽  
Complementary Therapy ◽  
Antioxidant Supplementation ◽  
Current Management ◽  
Adult Type ◽  
Aged People

Oxidative stress has been postulated as an underlying pathophysiologic mechanism of diabetic retinopathy (DR), the main cause of avoidable blindness in working-aged people. This review addressed the current daily clinical practice of DR and the role of antioxidants in this practice. A systematic review of the studies on antioxidant supplementation in DR patients was presented. Fifteen studies accomplished the inclusion criteria. The analysis of these studies concluded that antioxidant supplementation has a IIB level of recommendation in adult Type 1 and Type 2 diabetes mellitus subjects without retinopathy or mild-to-moderate nonproliferative DR without diabetic macular oedema as a complementary therapy together with standard medical care.

scholarly journals EXPRESS: Pulmonary Hypertension Associated With Neurofibromatosis Type 2

2021 ◽  
pp. 204589402110295
Author(s):  
Hirohisa Taniguchi ◽  
Tomoya Takashima ◽  
Ly Tu ◽  
Raphaël Thuillet ◽  
Asuka Furukawa ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Neurofibromatosis Type ◽  
Pulmonary Vascular Remodeling ◽  
Life Threatening ◽  
History Of ◽  
Pulmonary Arterial ◽  
First Time

Although precapillary pulmonary hypertension (PH) is a rare but severe complication of patients with neurofibromatosis type 1 (NF1), its association with NF2 remains unknown. Herein, we report a case of a 44-year-old woman who was initially diagnosed with idiopathic pulmonary arterial hypertension (IPAH) and treated with PAH-specific combination therapy. However, a careful assessment for a relevant family history of the disease and genetic testing reveal that this patient had a mutation in the NF2 gene. Using immunofluorescence and Western blotting, we demonstrated a decrease in endothelial NF2 protein in lungs from IPAH patients compared to control lungs, suggesting a potential role of NF2 in PAH development. To our knowledge, this is the first time that precapillary PH has been described in a patient with NF2. The altered endothelial NF2 expression pattern in PAH lungs should stimulate work to better understand how NF2 is contributing to the pulmonary vascular remodeling associated to these severe life-threatening conditions.

The role of modifiable pre-pregnancy risk factors in preventing adverse fetal outcomes among women with type 1 and type 2 diabetes

2009 ◽  
Vol 88 (10) ◽  
pp. 1153-1157 ◽  
Author(s):  
Melanie E. Inkster ◽  
Tom P. Fahey ◽  
Peter T. Donnan ◽  
Graham P. Leese ◽  
Gary J. Mires ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Fetal Outcomes ◽  
Pregnancy Risk

scholarly journals NEUROPROTECTIVE ROLE OF ASCORBIC ACID: ANTIOXIDANT AND NON-ANTIOXIDANT FUNCTIONS

2018 ◽  
Vol 11 (10) ◽  
pp. 30 ◽  
Author(s):  
Arun Kumar ◽  
Reena V Saini ◽  
Adesh K Saini
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glutamate Toxicity ◽  
Cellular Functions ◽  
Dietary Antioxidant ◽  
The Central Nervous System

Ascorbic acid (AA) or Vitamin C is an important antioxidant which participates in numerous cellular functions. Although in human plasma its concentration is in micromolars but it reaches millimolar concentrations in most of the human tissues. The high ascorbate cellular concentrations are generated and maintained by a specific sodium-dependent Vitamin C transporter type 2 (SVCT2, member of Slc23 family). Metabolic processes recycle Vitamin C from its oxidized forms (ascorbate) inside the cells. AA concentration is highest in the neurons of the central nervous system (CNS) of mammals, and deletion of its transporter affects mice brain and overall survival. In the CNS, intracellular ascorbate serves several functions including antioxidant protection, peptide amidation, myelin formation, synaptic potentiation, and protection against glutamate toxicity. SVCT2 maintains neuronal ascorbate content in CNS which has relevance for neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease. As ascorbate supplements decrease infarct size in ischemia-reperfusion injury and protect neurons from oxidative damage, it is a vital dietary antioxidant. The aim of this review is to assess the role of the SVCT2 in regulating neuronal ascorbate homeostasis in CNS and the extent to which ascorbate affects brain function as an antioxidant.

Keratoprostheses in silicone oil-filled eyes: long-term outcomes

2018 ◽  
Vol 103 (6) ◽  
pp. 781-788 ◽  
Author(s):  
Geetha Iyer ◽  
Bhaskar Srinivasan ◽  
Shweta Agarwal ◽  
Ruchika Pattanaik ◽  
Ekta Rishi ◽  
...  
Keyword(s):  
Silicone Oil ◽  
Vitreoretinal Surgery ◽  
Retrospective Chart Review ◽  
Protective Role ◽  
Visual Rehabilitation ◽  
Two Factors

PurposeTo analyse the functional and anatomical outcomes of different types of keratoprostheses in eyes with retained silicone oil following vitreoretinal surgery.MethodsRetrospective chart review of patients operated with any type of permanent keratoprosthesis (Kpro) in silicone oil-filled eyes between March 2003 and June 2017 were analysed.Results40 silicone oil-filled eyes underwent keratoprostheses, of which 22 were type 1 and 18 were type 2 Kpros (Lucia variant—nine, modified osteo odonto kerato prosthesis (MOOKP)—four, Boston type 2—three and osteoKpro—two) with a mean follow-up of 61.54 , 42.77, 45.25 , 25 and 37 months, respectively. Anatomic retention of the primary Kpro was noted in 33 eyes (82.5%). A best-corrected visual acuity of better than 20/200 and 20/400 was achieved in 26 (65%)+32 (80%) eyes. Retroprosthetic membrane (RPM) was the most common complication noted in 17 eyes (42.5%). Perioptic graft melt was noted in 4 of 22 eyes of the type 1 Kpro (2 (10.5%) without associated ocular surface disorder (OSD)) and in 1 eye each of Boston and Lucia type 2 Kpro. Laminar resorption occurred in one eye each of the MOOKP and OKP groups. Endophthalmitis and glaucoma did not occur in any eye.ConclusionAppropriately chosen keratoprosthesis is a viable option for visual rehabilitation in eyes post vitreoretinal surgery with retained silicone oil-induced keratopathy not amenable to conventional penetrating keratoplasty. Kpro melt among type 1 Kpro did not occur in 89.5% eyes without associated OSD (19 of 22 eyes), despite the lack of aqueous humour and presence of RPM (4 eyes), two factors considered to play a significant role in the causation of sterile melts. Of interest to note was the absence of infection in any of these eyes. The possible protective role of oil from endophthalmitis is interesting, though yet to be ascertained.

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