Dorsay Sadeghian, Farid Azmoudeh-Ardalan, Simin Dashti-Khavidaki, Nasir Fakhar
Occurrence of hepatotoxicity following prescription of etanercept, a tumor necrosis factor-alpha (TNF-α) antagonist, is a relatively well-known issue. On the other hand, acute hepatic failure which could lead to liver transplantation is extremely rare to the best of our knowledge, and there is no previously published case in the literature. In this article, we presented a case of acute liver failure followed by liver transplantaion, in a 32- year old man with a previous history of ankylosing spondylitis after etanercept usage...
2020: Iranian Journal of Pathology
L M S Elisei, T R Moraes, I H Malta, I Charlie-Silva, I M O Sousa, F P Veras, M A Foglio, L F Fraceto, G Galdino
Artemisinin (ART) was initially described for the control of inflammation and pain. However, the mechanisms involved with its antinociceptive effect are still poorly understood. Thus, this present study aimed to investigate the effect of ART in both free and nanocapsulated form on postoperative pain, as well as the participation of the spinal Toll-like receptor 4 (TLR4) in this process. Postoperative pain was induced using the skin/muscle incision retraction (SMIR) model in male Swiss mice. After 3 and 28 days of SMIR, the animals received an intrathecal injection of free or nanocapsulated ART, and the nociceptive threshold was evaluated by von Frey filament test...
September 16, 2020: Inflammopharmacology
Yukie Murata, Kana Sugimoto, Chihpin Yang, Kazuo Harada, Rina Gono, Teiji Harada, Yohei Miyashita, Kazuma Higashisaka, Ryuichi Katada, Junya Tanaka, Hiroshi Matsumoto
Brain edema following brain infarction affects mobility and mortality. The mechanisms underlying this process remain to be elucidated. Animal studies have shown that aquaporin-4 (AQP4) expression in astrocytes increases after stroke, and its deletion significantly reduces brain swelling. Recently, two kinds of cells, resident microglia-derived macrophage-like cells (MG-MΦ) and bone marrow-derived macrophages (BM-MΦ), have been reported to accumulate in the ischemic core and stimulate adjacent astrocytes. Therefore, we hypothesized that these cells play crucial roles in the expression of AQP4 and ultimately lead to exacerbated brain edema...
September 10, 2020: Neurochemistry International
Huahui Lu, Huijun Zhang, Ying Cong, Wenjun Li, Juan Zhou, Chuang Wu, Fulong Liang, Ying Li
Our previous study showed that propane-2-sulfonic acid octadec-9-enyl-amide (N15), a novel peroxisome proliferator-activated receptor α and γ (PPARα/γ) dual agonist, inhibits inflammatory responses in tumor necrosis factor alpha (TNFα)-induced vascular endothelial cells or lipopolysaccharide (LPS)-induced human myeloid leukemia mononuclear cells-1. However, little is known about whether N15 applies to other pathological or neuroinflammatory conditions. In the present study, we detected the effect of N15 on the LPS-induced neuroinflammatory response in mice and further investigated whether the effect of N15 on neuroinflammation and neuronal cells survival was related to PPARα/γ dual pathways...
August 31, 2020: Neuroreport
John P Hussman
With the objective of linking early findings relating to the novel SARS-CoV-2 coronavirus with potentially informative findings from prior research literature and to promote investigation toward therapeutic response, a coherent cellular and molecular pathway is proposed for COVID-19. The pathway is consistent with a broad range of observed clinical features and biological markers and captures key mediators of pathophysiology. In this proposed pathway, membrane fusion and cytoplasmic entry of SARS-CoV-2 virus via ACE2 and TMPRSS2-expressing respiratory epithelial cells, including pulmonary type-II pneumocytes, provoke an initial immune response featuring inflammatory cytokine production coupled with a weak interferon response, particularly in IFN-λ-dependent epithelial defense...
2020: Frontiers in Pharmacology
Erzsébet Fehér, Károly Altdorfer
Neuropeptides synthetised in the enteric nervous system can change the function of the immunocells and play a role in inflammatory processes. In our review the effects of inflammation on the neuropeptide content of nerves and immune cells were compared. Inflamed tissue samples (human gastritis and animal models with experimental colitis and streptozotocin-induced diabetes mellitus) were examined. The number and contacts of neuropeptide-containing nerves and immune cells were studied using immunohistochemistry, confocal laser microscopy and electronmicroscopy...
August 2020: Orvosi Hetilap
K Tuomisto, P Jousilahti, A S Havulinna, K Borodulin, S Männistö, V Salomaa
Background and aims: There is a growing body of literature confirming the association between inflammation and obesity. Recent research suggests that inflammation may play a role in weight gain. The aim of the study was to analyse whether serum inflammatory markers predict weight gain or development of obesity in a prospective study design. Methods and results: The baseline study (DILGOM 2007) consists of a population-based sample of 5024 Finnish men and women aged 25-75 years, of whom 3735 participated in the follow-up study in 2014...
September 2019: Metabolism open
Suoyi Feng, Longzhu Ju, Ziqi Shao, Mark Grzanna, Lu Jia, Ming Liu
Objective and Design: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated inflammatory respiratory hypersensitivity characterized by elevated Th2 cytokines and infiltration of inflammatory cells to nasal tissues. BX471 is a small-molecule C-C chemokine receptor type 1 (CCR1) antagonist involved in suppression of inflammation via blocking of primary ligands. In this study, we examined the anti-inflammatory effect of BX471 on ovalbumin (OVA)-induced AR mice model. Materials and Methods: Levels of OVA-specific IgE and Th1 cytokines were determined by enzyme-linked immunosorbent assay (ELISA)...
2020: Journal of Inflammation Research
Sho Hayashida, Shunsuke Sato, Yuji Shimada, Hironori Tsuzura, Yuji Ikeda, Sho Takahashi, Sho Sato, Nozomi Amano, Ayato Murata, Akihito Nagahara, Takuya Genda
A 45-year-old man with steroid-dependent ulcerative pancolitis was hospitalized with frequent diarrhea, abdominal pain and distension 3 months after induction of golimumab, a tumor necrosis factor-alpha antagonist. Computed tomography showed wall thickening from the stomach to the colon and massive ascites. Peripheral blood test revealed eosinophilia. A large number of eosinophils were observed in the ascites fluid. Although esophagogastroduodenoscopy showed no abnormal findings and colonoscopy showed ulcerative colitis with a Mayo endoscopic subscore of 1, eosinophil infiltration was histologically observed...
2020: Internal Medicine
Changhwan Jang, Jungjin Kim, Youngsun Kwon, Sangmee A Jo
Telmisartan is an angiotensin-II receptor blocker and acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPARγ). Several studies have demonstrated that telmisartan ameliorates depression and memory dysfunction and reduces brain inflammation. We hypothesized that the beneficial effects of telmisartan on brain could be due to modulation of the blood-brain barrier (BBB) function. Here, we examined the effect of telmisartan on tumor necrosis factor alpha (TNF-α)-induced expression of intercellular adhesion molecule 1 (ICAM-1) which plays an important role in leukocyte transcytosis through the BBB...
August 12, 2020: Biomolecules & Therapeutics
Loral Showalter, Brian J Czerniecki, Gary K Koski
Targeted drug approaches have been a major focus for developing new anticancer therapies. Although many such agents approved in the last 20 years have improved outcomes, almost all have underperformed expectations. The full potential of such agents may yet be obtained through novel combinations. Previously, we showed that anti-estrogen drugs combined with a dendritic cell-based anti-HER-2 vaccine known to induce strong Th1-polarized immunity dramatically improved clinical response rates in patients with HER-2pos /ERpos early breast cancer...
July 28, 2020: Oncotarget
G G Resende, C R L Machado, M A Rocha, R B V Macedo, J S S Bueno Filho, A M Kakehasi, M V Andrade
Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) are inflammatory diseases with different bone remodeling patterns. Fibroblast-like synoviocytes (FLS) are cells involved in the transition from an acute and reparable phase to a chronic and persistent stage in these diseases. The distinction of joint phenotypes involves inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-17, and IL-22 directly or through key signaling pathways such as Wnt...
2020: Brazilian Journal of Medical and Biological Research
Rustem Anil Ugan, Harun Un, Duygu Kose, Elif Cadirci, Tugba Bal Tastan, Muhammed Yayla, Zekai Halici
Aprepitant is a selective SP/NK-1 receptor antagonist and used in postoperative and chemotherapeutics induced emesis and vomiting. The aim of our study is to show aprepitant may have beneficial effects on gastrointestinal complaints in cancer patients undergoing chemotherapeutics by indomethacin-induced gastric ulcer model. A total of 48 rats were fasted 24 h for ulcer experiment. Aprepitant doses of 5, 10, 20, and 40 mg/kg were evaluated for their antiulcer activity. Omeprazole (20 mg/kg) was used as a positive control group...
August 3, 2020: Naunyn-Schmiedeberg's Archives of Pharmacology
Marianne Vulliemoz, Stephan Brand, Pascal Juillerat, Christian Mottet, Shomron Ben-Horin, Pierre Michetti
BACKGROUND: Anti-tumour necrosis factor-alpha (anti-TNF) antagonists have been the mainstay in the treatment of inflammatory bowel diseases (IBDs) for over 20 years. SUMMARY: This review article aimed to provide an update on recent advances in TNF antagonist therapy for IBDs. Key Messages: Their position in the treatment algorithm has evolved to "rapid step-up therapy" or "top-down therapy" according to disease severity and patients' characteristics...
July 31, 2020: Digestion
Rustem Anil Ugan, Harun Un, Muhammed Ali Gurbuz, Gokce Kaya, Aysenur Kahramanlar, Zeynep Berna Aksakalli-Magden, Zekai Halici, Elif Cadirci
AIM: Omapatrilat is an antagonist of angiotensin-converting (ACE) and neprilysin-neuropeptidase (NEP) enzymes. The aim of our study is to show that omapatrilat may have beneficial effects as a treatment for polymicrobial sepsis. MAIN METHODS: A cecal ligation and puncture (CLP) sepsis model was used to evaluate 10 and 20 mg/kg doses of omapatrilat in mice (n = 30) fasted for 12 h. The lungs were removed 12 h after CLP, and lung levels of cytokines (tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6], NF-κB), iNOS and eNOS mRNA expression, GSH and MDA levels, and ACE and NEP activities were determined...
July 29, 2020: Life Sciences
Maiju Rinne, Kert Mätlik, Tiina Ahonen, Fabio Vedovi, Giovanni Zappia, Vânia M Moreira, Jari Yli-Kauhaluoma, Sakari Leino, Outi Salminen, Eija Kalso, Mikko Airavaara, Henri Xhaard
Toll-like receptor 4 (TLR4) recognizes various endogenous and microbial ligands and is an essential part in the innate immune system. TLR4 signaling initiates transcription factor NF-κB and production of proinflammatory cytokines. TLR4 contributes to the development or progression of various diseases including stroke, neuropathic pain, multiple sclerosis, rheumatoid arthritis and cancer, and better therapeutics are currently sought for these conditions. In this study, a library of 140 000 compounds was virtually screened and a resulting hit-list of 1000 compounds was tested using a cellular reporter system...
July 27, 2020: European Journal of Pharmaceutical Sciences
Neda Roshanravan, Farhad Seif, Alireza Ostadrahimi, Mahboub Pouraghaei, Samad Ghaffari
Corona Virus Disease 2019 (COVID-19) pandemic is rapidly spreading all over the world. Excessive immune responses trigger life-threatening cytokine release syndrome (CRS) which can result in overproduction of pro-inflammatory cytokines including tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1β with different pro-inflammatory roles. Anecdotal evidence suggests that the modulation of systemic immune responses may have a potential role in the treatment of patients with COVID-19. Given the importance of the issue and the lack of therapeutic treatment or vaccine; anti-cytokine therapy such as IL-6, TNFα and IL-1 antagonists have been suggested for the alleviation of hyper-inflammation status in these patients...
June 19, 2020: Archives of Medical Research
Zhukai Cong, Dan Li, Xiangpeng Lv, Cui Yang, Qiang Zhang, Changyi Wu, Zongyu Wang, Xi Zhu
Acute respiratory distress syndrome (ARDS) is a severe condition with high morbidity and mortality and few interventions. The role of sympathetic stress in the pathogenesis of ARDS has attracted recent research attention. Blockade of alpha-2- or alpha2A-adrenoceptor (α2A-AR) has been shown to attenuate lung injury induced by lipopolysaccharide in rats. However, the mechanism is unclear. We confirmed the role of α2A-AR in ARDS using knockout mice and alveolar macrophages following lipopolysaccharide stimulation to assess the underlying mechanisms...
July 9, 2020: Clinical Science (1979-)
Thibaut Renouprez, Liana Veresezan, Franck Dujardin, Fabrice Jardin, Thierry Lequerré, Olivier Vittecoq
Castleman's disease is a rare lymphoproliferative syndrome involving several anatomical and clinical entities. We report two cases of Castleman's disease in patients with spondyloarthritis (with and without psoriasis) treated with Tumor Necrosis Factor-alpha blockers. During follow-up, imaging examinations, carried out for disease assessment, fortuitously revealed a pelvic mass close to the psoas or an atypical cervical adenopathy. Both lesions were in moderate hypermetabolism on Positron emission tomography-computed tomography...
July 1, 2020: Joint, Bone, Spine: Revue du Rhumatisme
Gerhard Eichhoff
With a prevalence of up to 20%, eczematous lesions are the most common skin adverse events of tumor necrosis factor alpha inhibitors. Eczematous lesions triggered by more modern biologics such as the IL17A antagonist secukinumab have been rarely reported. Herein, a case of secukinumab-induced pompholyx in a psoriasis patient is presented.
April 15, 2020: Dermatology Online Journal
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