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Cytokine storm

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https://www.readbyqxmd.com/read/28206702/statistical-issues-in-first-in-human-studies-on-bia-10-2474-neglected-comparison-of-protocol-against-practice
#1
Sheila M Bird, Rosemary A Bailey, Andrew P Grieve, Stephen Senn
By setting the regulatory-approved protocol for a suite of first-in-human studies on BIA 10-2474 against the subsequent French investigations, we highlight 6 key design and statistical issues, which reinforce recommendations by a Royal Statistical Society Working Party, which were made in the aftermath of cytokine release storm in 6 healthy volunteers in the United Kingdom in 2006. The 6 issues are dose determination, availability of pharmacokinetic results, dosing interval, stopping rules, appraisal by safety committee, and clear algorithm required if combining approvals for single and multiple ascending dose studies...
February 16, 2017: Pharmaceutical Statistics
https://www.readbyqxmd.com/read/28198028/proinflammatory-chemokines-are-major-mediators-of-exuberant-immune-response-associated-with-influenza-a-h1n1-pdm09-virus-infection
#2
Maria Thomas, Reeta Subramaniam Mani, Mariamma Philip, Ranjeeta Adhikary, Sangeeta Joshi, Srigiri S Revadi, Shashidhar Buggi, Anita Desai, Ravi Vasanthapuram
In India, the case fatality ratio of the pandemic A (H1N1) pdm09 influenza was relatively higher when compared to seasonal influenza A infection. Hypercytokinemia or "cytokine storm" has been previously implicated in the pathogenesis of other influenza viruses. The present study was undertaken to compare the cytokine profiles of A (H1N1) pdm09 influenza and seasonal H3 infection in Indian population and to correlate the findings with disease severity. Plasma levels of 18 cytokines/chemokines were measured by flow-cytometry using a bead based assay in patients infected with A (H1N1) pdm09 virus (n = 96) and Influenza A seasonal H3 virus (n = 30) categorised into mild, moderate and severe groups along with healthy controls (n = 36)...
February 15, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28197626/kdm6a-and-kdm6b-altered-expression-in-malignant-pleural-mesothelioma
#3
Sian Cregan, Maeve Breslin, Gerard Roche, Sigrid Wennstedt, Lauren MacDonagh, Cinaria Albadri, Yun Gao, Kenneth J O'Byrne, Sinead Cuffe, Stephen P Finn, Steven G Gray
Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura primarily associated with prior exposure to asbestos. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Inflammation is thought to be a key element in the pathogenesis of MPM, and recently Kdm6 family members (Kdm6a and Kdm6b) have been identified as playing important roles in inflammatory processes...
February 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28135567/tafro-syndrome-new-subtype-of-idiopathic-multicentric-castleman-disease
#4
REVIEW
Gordan Srkalovic, Inga Marijanovic, Maya B Srkalovic, David C Fajgenbaum
Castleman disease (CD) describes a group of three rare and poorly understood lymphoproliferative disorders that have heterogeneous clinical symptoms and common lymph node histopathological features. Unicentric CD (UCD) involves a single region of enlarged nodes. Multicentric CD (MCD) involves multiple regions of enlarged lymph nodes, constitutional symptoms, and organ dysfunction due to a cytokine storm often including interleukin 6. MCD is further divided into Human Herpes Virus-8 (HHV-8)-associated MCD, which occurs in immunocompromised individuals, and HHV-8-negative/idiopathic MCD (iMCD)...
January 26, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28133873/the-future-of-immunotherapy-for-canine-atopic-dermatitis-a-review
#5
REVIEW
Douglas J DeBoer
Allergen specific immunotherapy (ASIT) is a foundation treatment for canine atopic dermatitis (CAD), though few critical studies have documented its effectiveness as a disease-modifying treatment in dogs. The mechanisms by which ASIT works in dogs have not been elucidated, although they are likely to parallel those known for humans. Current ASIT approaches in CAD focus on either subcutaneous or sublingual administration. Greater knowledge of major allergens in dogs, ideal dosage regimes and details of allergen admixture are likely to lead to better efficacy in CAD...
February 2017: Veterinary Dermatology
https://www.readbyqxmd.com/read/28128003/current-and-future-developments-in-the-treatment-of-virus-induced-hypercytokinemia
#6
Jonathan P Wong, Satya Viswanathan, Ming Wang, Lun-Quan Sun, Graeme C Clark, Riccardo V D'Elia
Emerging pathogenic viruses such as Ebola and Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) can cause acute infections through the evasion of the host's antiviral immune responses and by inducing the upregulation of inflammatory cytokines. This immune dysregulation, termed a cytokine storm or hypercytokinemia, is potentially fatal and is a significant underlying factor in increased mortality of infected patients. The prevalence of global outbreaks in recent years has offered opportunities to study the progression of various viral infections and have provided an improved understanding of hypercytokinemia associated with these diseases...
January 27, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28127437/effect-of-extracorporeal-cytokine-removal-on-vascular-barrier-function-in-a-septic-shock-patient
#7
Sascha David, Kristina Thamm, Bernhard M W Schmidt, Christine S Falk, Jan T Kielstein
BACKGROUND: Sepsis and septic shock are major healthcare problems, affecting millions of individuals around the world each year. Pathophysiologically, septic multiple organ dysfunction (MOD) is a life-threatening condition caused by an overwhelming systemic inflammatory response of the host's organism to an infection. We experimentally tested if high circulating cytokine levels might increase vascular permeability-a critical hallmark of the disease-and if this phenomenon can be reversed by therapeutic cytokine removal (CytoSorb®) in an exemplary patient...
2017: Journal of Intensive Care
https://www.readbyqxmd.com/read/28116826/mechanistic-perspective-of-the-oxido-immunopathologic-resolution-property-of-kolaviron-in-mice-influenza-pneumonitis
#8
Ifeoluwa O Awogbindin, David O Olaleye, Ebenezer O Farombi
Implicated in influenza-associated pathology are innate defence overzealousness and unabated secretion of oxidative tissue-sensitive antimicrobial agents. At different time points, mice were pre-treated with kolaviron (400 mg/kg), a natural antioxidant and anti-inflammatory agent, and subsequently challenged with 2 LD50 influenza A/H3N2/Perth/16/09 virus. After euthanasia at day 6, blood, lungs, liver and spleen were collected and processed for biochemical, immunohistochemical and flow cytometric assessment of redo-inflammatory imbalance, cytokine storm indices and T helper 1 host response...
January 23, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28106157/tlr4-antagonist-fp7-inhibits-lps-induced-cytokine-production-and-glycolytic-reprogramming-in-dendritic-cells-and-protects-mice-from-lethal-influenza-infection
#9
Laure Perrin-Cocon, Anne Aublin-Gex, Stefania E Sestito, Kari Ann Shirey, Mira C Patel, Patrice André, Jorge C Blanco, Stefanie N Vogel, Francesco Peri, Vincent Lotteau
Dysregulated Toll-like receptor (TLR)-4 activation is involved in acute systemic sepsis, chronic inflammatory diseases, such as atherosclerosis and diabetes, and in viral infections, such as influenza infection. Thus, therapeutic control of the TLR4 signalling pathway is of major interest. Here we tested the activity of the small-molecule synthetic TLR4 antagonist, FP7, in vitro on human monocytes and monocyte-derived dendritic cells (DCs) and in vivo during influenza virus infection of mice. Our results indicate that FP7 antagonized the secretion of proinflammatory cytokines (IL-6, IL-8, and MIP-1β) by monocytes and DCs (IC50 < 1 μM) and prevented DC maturation upon TLR4 activation by ultrapure lipopolysaccharide (LPS)...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089834/recent-clinical-trials-utilizing-chimeric-antigen-receptor-t-cells-therapies-against-solid-tumors
#10
Shuanglin Han, Olivier Latchoumanin, Guang Wu, Gang Zhou, Lionel Hebbard, Jacob George, Liang Qiao
Chimeric antigen receptors (CARs) are a series of manufactured receptors that have the capacity of binding to specific antigens expressed on surface of tumor cells. A CAR normally has an extracellular antigen recognition domain derived from single variable chain of a monoclonal antibody, a transmembrane domain and an intracellular T cell activation domain. During the last decade, CAR-T cells were demonstrated to possess great therapeutic effects on hematological malignancies. However, strategies using CAR-T cells to treat solid tumors have been hindered by considerable obstacles including "on tissue off target" effects and cytokine storm syndrome...
April 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28088477/selected-scorpion-toxin-exposures-induce-cytokine-release-in-human-peripheral-blood-mononuclear-cells
#11
Gerardo Corzo, Gerardo Pavel Espino-Solis
A cytokine screening on human peripheral blood mononuclear cells (PBMCs) stimulated with selected scorpion toxins (ScTx's) was performed in order to evaluate their effect on human immune cells. The ScTx's chosen for this report were three typical buthid scorpion venom peptides, one with lethal effects on mammals Centruroides suffussus suffusus toxin II (CssII), another, with lethal effects on insects and crustaceans Centruroides noxius toxin 5 (Cn5), and one more without lethal effects Tityus discrepans toxin (Discrepin)...
January 11, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28087540/international-evidence-based-consensus-diagnostic-criteria-for-hhv-8-negative-idiopathic-multicentric-castleman-disease
#12
David C Fajgenbaum, Thomas S Uldrick, Adam Bagg, Dale Frank, David Wu, Gordan Srkalovic, David Simpson, Amy Y Liu, David Menke, Shanmuganathan Chandrakasan, Mary Jo Lechowicz, Raymond S M Wong, Sheila Pierson, Michele Paessler, Jean-François Rossi, Makoto Ide, Jason Ruth, Michael Croglio, Alexander Suarez, Vera Krymskaya, Amy Chadburn, Gisele Colleoni, Sunita Nasta, Raj Jayanthan, Christopher S Nabel, Corey Casper, Angela Dispenzieri, Alexander Fosså, Dermot Kelleher, Razelle Kurzrock, Peter Voorhees, Ahmet Dogan, Kazuyuki Yoshizaki, Frits van Rhee, Eric Oksenhendler, Elaine S Jaffe, Kojo S J Elenitoba-Johnson, Megan S Lim
Human Herpesvirus-8(HHV-8)-negative, idiopathic multicentric Castleman disease (iMCD) is a rare and life-threatening disorder involving systemic inflammatory symptoms, polyclonal lymphoproliferation, cytopenias, and multiple organ system dysfunction due to a cytokine storm often including interleukin-6. iMCD accounts for one-third to one-half of all cases of MCD and can occur in individuals of any age. Accurate diagnosis is challenging, as no standard diagnostic criteria or diagnostic biomarkers currently exist, and there is significant overlap with malignant, autoimmune, and infectious disorders...
January 13, 2017: Blood
https://www.readbyqxmd.com/read/28086978/correlation-of-cytokine-level-with-the-severity-of-severe-fever-with-thrombocytopenia-syndrome
#13
Miao-Miao Liu, Xiao-Ying Lei, Hao Yu, Jian-Zhi Zhang, Xue-Jie Yu
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) was an emerging hemorrhagic fever that was caused by a tick-borne bunyavirus, SFTSV. Although SFTSV nonstructural protein can inhibit type I interferon (IFN-I) production Ex Vivo and IFN-I played key role in resistance SFTSV infection in animal model, the role of IFN-I in patients is not investigated. METHODS: We have assayed the concentration of IFN-α, a subtype of IFN-I as well as other cytokines in the sera of SFTS patients and the healthy population with CBA (Cytometric bead array) assay...
January 13, 2017: Virology Journal
https://www.readbyqxmd.com/read/28077582/severity-of-plasma-leakage-is-associated-with-high-levels-of-interferon-%C3%AE-inducible-protein-10-hepatocyte-growth-factor-matrix-metalloproteinase-2-mmp-2-and-mmp-9-during-dengue-virus-infection
#14
Zhisheng Her, Yiu-Wing Kam, Victor C Gan, Bernett Lee, Tun-Linn Thein, Jeslin J L Tan, Linda K Lee, Katja Fink, David C Lye, Laurent Rénia, Yee-Sin Leo, Lisa F P Ng
BACKGROUND:  Dengue virus infection typically causes mild dengue fever, but, in severe cases, life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) occur. The pathophysiological hallmark of DHF and DSS is plasma leakage that leads to enhanced vascular permeability, likely due to a cytokine storm. METHODS:  Ninety patients with dengue during 2010-2012 in Singapore were prospectively recruited and stratified according to their disease phase, primary and secondary infection status, and disease severity, measured by plasma leakage...
January 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28067630/novel-swine-model-of-ricin-induced-acute-respiratory-distress-syndrome
#15
Shahaf Katalan, Reut Falach, Amir Rosner, Michael Goldvaser, Tal Brosh-Nissimov, Ayana Dvir, Avi Mizrachi, Orr Goren, Barak Cohen, Yoav Gal, Anita Sapoznikov, Sharon Ehrlich, Tamar Sabo, Chanoch Kronman
Pulmonary exposure to the plant toxin ricin, leads to respiratory insufficiency and death. To date, in-depth study of the functional disorders ensuing pulmonary intoxication, a prerequisite for establishing a clinically-relevant therapeutic protocol, is hampered by the lack of an appropriate animal model. To this end, we set up the pig, as a large animal model for the comprehensive study of the multifarious clinical manifestations of pulmonary ricinosis.Here we report for the first time, the monitoring of barometric whole body plethysmography for pulmonary function tests in non-anesthetized ricin-intoxicated pigs...
January 6, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28062701/widespread-virus-replication-in-alveoli-drives-acute-respiratory-distress-syndrome-in-aerosolized-h5n1-influenza-infection-of-macaques
#16
Elizabeth R Wonderlich, Zachary D Swan, Stephanie J Bissel, Amy L Hartman, Jonathan P Carney, Katherine J O'Malley, Adebimpe O Obadan, Jefferson Santos, Reagan Walker, Timothy J Sturgeon, Lonnie J Frye, Pauline Maiello, Charles A Scanga, Jennifer D Bowling, Anthea L Bouwer, Parichat A Duangkhae, Clayton A Wiley, JoAnne L Flynn, Jieru Wang, Kelly S Cole, Daniel R Perez, Douglas S Reed, Simon M Barratt-Boyes
Human infections with highly pathogenic avian influenza A (H5N1) virus are frequently fatal but the mechanisms of disease remain ill-defined. H5N1 infection is associated with intense production of proinflammatory cytokines, but whether this cytokine storm is the main cause of fatality or is a consequence of extensive virus replication that itself drives disease remains controversial. Conventional intratracheal inoculation of a liquid suspension of H5N1 influenza virus in nonhuman primates likely results in efficient clearance of virus within the upper respiratory tract and rarely produces severe disease...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28057212/regulation-of-cellular-immune-responses-in-sepsis-by-histone-modifications
#17
W F Carson, S L Kunkel
Severe sepsis, septic shock, and related inflammatory syndromes are driven by the aberrant expression of proinflammatory mediators by immune cells. During the acute phase of sepsis, overexpression of chemokines and cytokines drives physiological stress leading to organ failure and mortality. Following recovery from sepsis, the immune system exhibits profound immunosuppression, evidenced by an inability to produce the same proinflammatory mediators that are required for normal responses to infectious microorganisms...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28038465/viral-host-interaction-in-kidney-reveals-strategies-to-escape-host-immunity-and-persistently-shed-virus-to-the-urine
#18
Xumin Ou, Sai Mao, Yifan Jiang, Shengyong Zhang, Chen Ke, Guangpeng Ma, Anchun Cheng, Mingshu Wang, Dekang Zhu, Shun Chen, Renyong Jia, Mafeng Liu, Kunfeng Sun, Qiao Yang, Ying Wu, Xiaoyue Chen
Hepatitis A virus is one of five types of hepatotropic viruses that cause human liver disease. A similar liver disease is also identified in ducks caused by Duck Hepatitis A virus (DHAV). Notably, many types of hepatotropic viruses can be detected in urine. However, how those viruses enter into the urine is largely unexplored. To elucidate the potential mechanism, we used the avian hepatotropic virus to investigate replication strategies and immune responses in kidney until 280 days after infection. Immunohistochemistry and qPCR were used to detect viral distribution and copies in the kidney...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28035011/invariant-nkt-cells-are-pathogenic-in-the-hla-dr4-transgenic-humanized-mouse-model-of-toxic-shock-syndrome-and-can-be-targeted-to-reduce-morbidity
#19
Peter A Szabo, Patrick T Rudak, Joshua Choi, Stacey X Xu, Robert Schaub, Bhagirath Singh, John K McCormick, S M Mansour Haeryfar
During toxic shock syndrome (TSS), bacterial superantigens trigger a polyclonal T cell response leading to a potentially catastrophic 'cytokine storm'. Whether innate-like invariant natural killer T(iNKT) cells, with remarkable immunomodulatory properties, participate in TSS is unclear. Using genetic and cell depletion approaches, we generated iNKT cell-deficient, superantigen-sensitive HLA-DR4-transgenic (DR4tg) mice, which were compared with their iNKT-sufficient counterparts for responsiveness to staphylococcal enterotoxin B(SEB)...
December 29, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28006034/peripheral-organs-of-dengue-fatal-cases-present-strong-pro-inflammatory-response-with-participation-of-ifn-gamma-tnf-alpha-and-rantes-producing-cells
#20
Tiago F Póvoa, Edson R A Oliveira, Carlos A Basílio-de-Oliveira, Gerard J Nuovo, Vera L A Chagas, Natália G Salomão, Ester M Mota, Marciano V Paes
Dengue disease is an acute viral illness caused by dengue virus (DENV) that can progress to hemorrhagic stages leading to about 20000 deaths every year worldwide. Despite many clinical investigations regarding dengue, the immunopathogenic process by which infected patients evolve to the severe forms is not fully understood. Apart from differences in virulence and the antibody cross reactivity that can potentially augment virus replication, imbalanced cellular immunity is also seen as a major concern in the establishment of severe dengue...
2016: PloS One
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