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systemic sclerosis update

Matteo Gastaldi, Elisabetta Zardini, Diego Franciotta
Intrathecal B-lymphocyte activation is a hallmark of multiple sclerosis (MS), a multi-factorial inflammatory-demyelinating disease of the central nervous system. Such activation has a counterpart in the cerebrospinal fluid (CSF) oligoclonal IgG bands (OCB), whose diagnostic role in MS has been downgraded within the current McDonald's criteria. With a theoretico-practical approach, the authors review the physiopathological basis of the CSF dynamics, and the state-of-the-art of routine CSF analysis and CSF biomarkers in MS...
December 2, 2016: Expert Review of Molecular Diagnostics
Paolo Poggio, Gianluca Folesani, Giuseppe M Raffa, Paola Songia, Vincenzo Valenti, Veronika Myasoedova, Alessandro Parolari
Systemic hypertension and aortic valve stenosis (AVS) are both age-related diseases. Severe aortic stenosis affects ≈2% to 5% of adults age > 65 years. Systemic hypertension (HTN) is a frequent comorbidity in patients with AVS and is coexistent for a longer period of time before AVS is treated. Essential systemic hypertension, per se, plays an important role in the creation of lesions on the aortic side of the valve, the region of higher exposure to tension stress. The subsequent endothelial defect represents the principal site of inflammatory process and oxidative stress, leading to aortic sclerosis and calcification...
November 23, 2016: Current Pharmaceutical Design
H Agut, P Bonnafous, A Gautheret-Dejean
Human herpesviruses 6A, 6B, and 7 (HHV-6A, HHV-6B, HHV-7) are genetically related to cytomegalovirus. They belong to the Roseolovirus genus and to the Betaherpesvirinae subfamily. They infect T cells, monocytes-macrophages, epithelial cells, and central nervous system cells. These viruses are ubiquitous and are responsible for lifelong chronic infections, most often asymptomatic, in the vast majority of the general adult population. HHV-6B is responsible for exanthema subitum, which is a benign disease of infants...
October 20, 2016: Médecine et Maladies Infectieuses
Gordon D Ko, Sara L Bober, Sean Mindra, Jason M Moreau
Cannabis has been widely used as a medicinal agent in Eastern medicine with earliest evidence in ancient Chinese practice dating back to 2700 BC. Over time, the use of medical cannabis has been increasingly adopted by Western medicine and is thus a rapidly emerging field that all pain physicians need to be aware of. Several randomized controlled trials have shown a significant and dose-dependent relationship between neuropathic pain relief and tetrahydrocannabinol - the principal psychoactive component of cannabis...
2016: Journal of Pain Research
Md Asiful Islam, Fahmida Alam, Mohammad Amjad Kamal, Kah Keng Wong, Teguh Haryo Sasongko, Siew Hua Gan
Neurological manifestations or disorders associated with central nervous system (CNS) are one of the most common as well as important clinical characteristics of antiphospholipid syndrome (APS). Although in the last updated (2006) classification criteria of APS its neurological manifestations encompassed only transient ischemic attack (TIA) and stroke, diverse 'non-criteria' neurological disorders or manifestations (headache, migraine, bipolar disorder, transverse myelitis, dementia, chorea, epileptic seizures, multiple sclerosis, psychosis, cognitive impairment, Tourette's syndrome, parkinsonism, dystonia, transient global amnesia, obsessive compulsive disorder and leukoencephalopathy) have been observed in APS patients...
September 20, 2016: CNS & Neurological Disorders Drug Targets
Jinlong Jian, Guangfei Li, Aubryanna Hettinghouse, Chuanju Liu
Autoimmune disease encompasses an array of conditions with a variety of presentations and the involvement of multiple organs. Though the etiologies of many autoimmune conditions are unclear, uncontrolled inflammatory immune response is believed to be a major cause of disease development and progression. Progranulin (PGRN), an anti-inflammatory molecule with therapeutic effect in inflammatory arthritis, was identified as an endogenous antagonist of TNFα by competitively binding to TNFR. PGRN exerts its anti-inflammatory activity through multiple pathways, including induction of Treg differentiation and IL-10 expression and inhibition of chemokine release from macrophages...
August 12, 2016: Cytokine
Jiu-Hua Zhao, Yu Duan, Yu-Jie Wang, Xiao-Lei Huang, Guo-Jun Yang, Jing Wang
BACKGROUND: Several studies have collected detailed data to examine which specific solvents account for the association between solvents and risk of systemic sclerosis (SSc). These studies generally reported elevated risks associated with many of the specific solvents examined, such as toluene, xylene, and trichloroethylene. The previous meta-analysis was not able to conduct separate analyses for specific solvent subtypes. OBJECTIVE: The aims of the new meta-analysis were to investigate a more comprehensive estimate and to consider the effect of different solvents on SSc...
August 2016: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
Massimo Filippi, Paolo Preziosa, Maria A Rocca
Due to its sensitivity to the different multiple sclerosis (MS)-related abnormalities, magnetic resonance imaging (MRI) has become an established tool to diagnose MS and to monitor its evolution. MRI has been included in the diagnostic workup of patients with clinically isolated syndromes suggestive of MS, and ad hoc criteria have been proposed and are regularly updated. In patients with definite MS, the ability of conventional MRI techniques to explain patients' clinical status and progression of disability is still suboptimal...
2016: Handbook of Clinical Neurology
Abdulla Watad, Shana G Neumann, Alessandra Soriano, Howard Amital, Yehuda Shoenfeld
There is growing interest in the contribution of vitamin D deficiency to autoimmunity. Several studies have shown an association between low levels of vitamin D and autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, type 1 diabetes, autoimmune thyroid diseases, celiac disease, and systemic lupus erythematosus (SLE). Vitamin D receptor ligands can mediate immunosuppressive effects. It has been suggested that low levels of this hormone contribute to the immune activation in lupus and other autoimmune diseases...
March 2016: Israel Medical Association Journal: IMAJ
Meng-Chen Lu, Jian-Ai Ji, Zheng-Yu Jiang, Qi-Dong You
The Keap1-Nrf2-ARE ((Kelch-like ECH-Associating protein 1) nuclear factor erythroid 2 related factor 2-antioxidant response element) pathway is one of the most important defense mechanisms against oxidative and/or electrophilic stresses, and it is closely associated with inflammatory diseases, including cancer, neurodegenerative diseases, cardiovascular diseases, and aging. In recent years, progress has been made in strategies aimed at modulating the Keap1-Nrf2-ARE pathway. The Nrf2 activator DMF (Dimethylfumarates) has been approved by the FDA as a new first-line oral drug to treat patients with relapsing forms of multiple sclerosis, while a phase 3 study of another promising candidate, CDDO-Me, was terminated for safety reasons...
September 2016: Medicinal Research Reviews
Alexandra Maria Giovanna Brunasso, Cesare Massone
In systemic sclerosis (SSc), the development of fibrosis seems to be a consequence of the initial ischemic process related to an endothelial injury. The initial trigger event in SSc is still unknown, but circulating progenitor cells (CPCs) might play a key role. Such cells have the ability to traffic into injury sites, exhibiting inflammatory features of macrophages, tissue remodeling properties of fibroblasts, and vasculogenesis functions of endothelial cells. The different subsets of CPCs described thus far in SSc arise from a pool of circulating monocyte precursors (CD14 (+) cells) and probably correspond to a different degree of differentiation of a single cell of origin...
2016: F1000Research
Jessica K Gordon, Robyn T Domsic
Systemic sclerosis (scleroderma, SSc) is a multisystem disease characterized by vasculopathy, autoimmunity, and fibrosis. SSc has the highest disease-related mortality rate among the rheumatologic illnesses. In the USA, there remains no FDA-approved therapy. As our understanding of SSc pathogenesis improves, targeted therapies interrupting key pathways and mediators will be studied in clinical trials. However, clinical trials in SSc are fraught with challenges. Validated clinical outcome measures do not exist for all disease manifestations...
June 2016: Current Rheumatology Reports
Álvaro Danza, Guillermo Ruiz-Irastorza, Munther Khamashta
Systemic autoimmune diseases especially affect young women during childbearing age. The aim of this review is to update systemic lupus erythematosus, antiphospholipid syndrome and systemic sclerosis management during pregnancy. These diseases present variable maternal and fetal risks. Studies show that an appropriate disease control and a reasonable remission period prior to pregnancy are associated with satisfactory obstetric outcomes. Antiphospholipid autoantibodies profile, anti-Ro/anti-La antibodies, pulmonary pressure and activity evaluation are crucial to assess the pregnancy risk...
October 7, 2016: Medicina Clínica
P Guillaume-Jugnot, A Daumas, J Magalon, N Sautereau, J Veran, G Magalon, F Sabatier, B Granel
Systemic sclerosis is an autoimmune disease characterized by sclerosis (hardening) of the skin and deep viscera associated with microvascular functional and structural alteration, which leads to chronic ischemia. In the hands of patients, ischemic and fibrotic damages lead to both pain and functional impairment. Hand disability creates a large burden in professional and daily activities, with social and psychological consequences. Currently, the proposed therapeutic options for hands rely mainly on hygienic measures, vasodilatator drugs and physiotherapy, but have many constraints and limited effects...
January 2016: Current Research in Translational Medicine
Joo Young Kim, Seung-Mo Hong
CONTEXT: -Gastrointestinal (GI) and pancreatobiliary tracts contain a variety of neuroendocrine cells that constitute a diffuse endocrine system. Neuroendocrine tumors (NETs) from these organs are heterogeneous tumors with diverse clinical behaviors. Recent improvements in the understanding of NETs from the GI and pancreatobiliary tracts have led to more-refined definitions of the clinicopathologic characteristics of these tumors. Under the 2010 World Health Organization classification scheme, NETs are classified as grade (G) 1 NETs, G2 NETs, neuroendocrine carcinomas, and mixed adenoneuroendocrine carcinomas...
May 2016: Archives of Pathology & Laboratory Medicine
Tobias Pflugshaupt, Olivia Geisseler, Thomas Nyffeler, Michael Linnebank
Cognitive impairment is found in up to 70% of patients with multiple sclerosis (MS). Once thought of as a variant of subcortical dementia with a characteristic set of deficits, we now know that MS-related cognitive impairment can have many faces. This conceptual change in neuropsychology is embedded in a paradigm shift in the neuroscientific understanding of MS over the past 25 years: Partly based on modern neuroimaging techniques, the classical view of MS as an inflammatory demyelinating disease affecting the white matter of the central nervous system has been extended...
April 2016: Seminars in Neurology
Cheong-Meng Chong, Nana Ai, Simon Ming-Yuen Lee
Rho-associated protein kinase (ROCK) is a serine-threonine kinase originally identified as a crucial regulator of actin cytoskeleton. Recent studies have defined new functions of ROCK as a critical component of diverse signaling pathways in neurons. In addition, inhibition of ROCK causes several biological events such as increase of neurite outgrowth, axonal regeneration, and activation of pro-survival Akt. Thus, it has attracted scientist's strong attentions and considered ROCK as a promising therapeutic target for treatment of neurodegenerative disorders including Alzheimer disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis...
April 1, 2016: Current Drug Targets
Roberta A Berard, Ronald M Laxer
Pediatric-onset mixed connective tissue disease is among the rare disease entities in pediatric rheumatology and includes features of arthritis, polymyositis/dermatomyositis, systemic lupus erythematosus, and systemic sclerosis. Accurate recognition and diagnosis of the disease is paramount to prevent long-term morbidity. Advances in the genetic and immunologic understanding of the factors involved in the etiopathogenesis provide an opportunity for improvements in prognostication and targeted therapy. The development of a multinational cohort of patients with mixed connective tissue disease would be invaluable to provide more updated data regarding the clinical presentation, to develop a standardized treatment approach, disease activity and outcome tools, and to provide data on long-term outcomes and comorbidities...
May 2016: Current Rheumatology Reports
Dian He, Chao Zhang, Xia Zhao, Yifan Zhang, Qingqing Dai, Yuan Li, Lan Chu
BACKGROUND: This is an update of the Cochrane review "Teriflunomide for multiple sclerosis" (first published in The Cochrane Library 2012, Issue 12).Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system. It is clinically characterized by recurrent relapses or progression, or both, often leading to severe neurological disability and a serious decline in quality of life. Disease-modifying therapies (DMTs) for MS aim to prevent occurrence of relapses and disability progression...
March 22, 2016: Cochrane Database of Systematic Reviews
Cécile M Yelnik, Elizabeth Kozora, Simone Appenzeller
Thrombotic manifestations of antiphospholipid syndrome (APS) are well known, and various non-stroke neuro-psychiatric manifestations (NPMs) have also been consistently described, but their place in APS remains unclear. Some syndromes, such as migraine or cognitive dysfunction, are frequently described in APS, whereas others, like seizure, multiple sclerosis-like symptoms, transverse myelitis, movement disorders, or psychiatric symptoms, are rarely found. Overlap with other autoimmune diseases, in particular with systemic lupus erythematosus, the lack of large sample size prospective studies, and discrepancies in antiphospholipid antibody (aPL) determinations complicate the study of the relationship between those disorders and aPL/APS...
February 2016: Current Rheumatology Reports
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