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
Sanami Takada, Megumu K Saito, Naotomo Kambe
Blau syndrome, or early-onset sarcoidosis, is hereditary juvenile-onset systemic granulomatosis. Clinical symptoms appear before the age of 4 years and mainly affect the skin, joints, and eyes. The symptoms are progressive and cause severe complications, such as joint destruction and blindness. Although tumor necrosis factor alpha (TNFα) antagonists are effective for controlling some of the symptoms of Blau syndrome, there is no specific curative treatment. Heterozygous mutations in nucleotide-binding oligomerization domain 2 (NOD2) were identified as the cause of Blau syndrome onset...
July 2, 2020: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
Rodrigo B Mansur, Mehala Subramaniapillai, Yena Lee, Zihang Pan, Nicole E Carmona, Margarita Shekotikhina, Michelle Iacobucci, Nelson Rodrigues, Flora Nasri, Houman Rashidian, Joshua D Rosenblat, Elisa Brietzke, Victoria E Cosgrove, Nicole E Kramer, Trisha Suppes, Roger S McIntyre
A potential role for leptin in the pathophysiology of bipolar disorder (BD) has been proposed. We recently investigated the effects of the tumor necrosis factor-alpha (TNF-α) antagonist infliximab in individuals with bipolar depression. Leptin is known to interact with the TNF-α system. Herein, we aimed to explore infliximab's effects on leptin and its relationship with brain structure and function. Sixty adults with bipolar depression were enrolled in this randomized, double-blind, 12-week clinical trial of adjunctive infliximab (n = 29) and saline control (n = 31), which were administered intravenously at weeks 0, 2, and 6...
June 20, 2020: Psychoneuroendocrinology
Jan Kempski, Anastasios D Giannou, Kristoffer Riecken, Lilan Zhao, Babett Steglich, Jöran Lücke, Laura Garcia-Perez, Karl-Frederick Karstens, Anna Wöstemeier, Mikolaj Nawrocki, Penelope Pelczar, Mario Witkowski, Sven Nilsson, Leonie Konczalla, Ahmad Mustafa Shiri, Joanna Kempska, Ramez Wahib, Leonie Brockmann, Philipp Huber, Ann-Christin Gnirck, Jan-Eric Turner, Dimitra E Zazara, Petra C Arck, Alexander Stein, Ronald Simon, Anne Daubmann, Jan Meiners, Daniel Perez, Till Strowig, Pandelakis Koni, Andrey A Kruglov, Guido Sauter, Jakob R Izbicki, Andreas H Guse, Thomas Roesch, Ansgar W Lohse, Richard A Flavell, Nicola Gagliani, Samuel Huber
BACKGROUND & AIMS: Unregulated activity of interleukin 22 (IL22) promotes intestinal tumorigenesis in mice. IL22 binds the antagonist IL22 subunit alpha 2 (IL22RA2, also called IL22BP). We studied if alterations in IL22BP contribute to colorectal carcinogenesis in humans and mice. METHODS: We obtained tumor and non-tumor tissues from patients with colorectal cancer (CRC) and measured levels of cytokines by quantitative PCR, flow cytometry, and immunohistochemistry...
June 18, 2020: Gastroenterology
Sundas Hira, Uzma Saleem, Fareeha Anwar, Zohaib Raza, Atta Ur Rehman, Bashir Ahmad
Alzheimer's disease (AD) is the neurodegenerative disorder characterized by impairment of higher intellectual dysfunctions associated with changes in the cognitive, behavioral, and social activities. AIM OF THE STUDY: The current study was designed to evaluate the potential of aldosterone antagonist in the treatment of AD. METHODOLOGY: The study was conducted on albino mice of either sex ( n = 60). Mice were subcategorized into six groups, each group having 10 mice...
June 16, 2020: ACS Omega
Weifeng Jiang, Xiaoying Wang, Wei Wang, Fang Hua, Zunsheng Zhang, Zuohui Zhang, Jie Xiang, Xinxin Yang
Microglia, the resident immune cells in the central nervous system, play a critical role under physiological conditions, but they may be activated and exaggerate the pathological development of Parkinson's disease (PD). Recent reports have suggested that neurokinin 1 receptor (NK1R) is involved in various inflammatory diseases, including PD. However, whether neurokinin 1 (NK1) is involved in the activation of microglial cells remains unclear. In the present study, we found that (1) NK1R is located in microglial cells and upregulated in lipopolysaccharide (LPS)-activated BV2 microglia...
June 12, 2020: Brain Research Bulletin
Marliese Dion Nist, Rita H Pickler, Tondi M Harrison, Deborah K Steward, Abigail B Shoben
BACKGROUND: Preterm infants are at risk for impaired neurodevelopment. Inflammation may be an important modifiable mediator of preterm birth and neurodevelopmental impairment, but few studies have examined longitudinal measures of inflammation. OBJECTIVE: To determine the relationship between longitudinal measures of inflammation and neurobehavior in very preterm infants. STUDY DESIGN: Non-experimental, repeated measures cohort study. METHODS: Very preterm infants were enrolled between October 2017 and December 2018...
May 22, 2020: Early Human Development
Xiao-Yan Luo, An-Wei Chen, Jin-Hua Cai, Jin Fang, Hua Wang
Chronic infantile neurological, cutaneous and articular (CINCA) syndrome is a rare autoinflammatory disease caused by monogenic defects in the NLRP3 gene. Pro-inflammatory cytokines such as interleukin (IL)-1β play a crucial role in the pathogenesis, and IL-1 receptor antagonists have been regarded as the mainstay therapy. Endogenous tumor necrosis factor (TNF)-α was found recently to be involved in the onset of the disease. Here, we report two Chinese children with CINCA syndrome who had elevated serum levels of TNF-α, with one carrying a novel mutation of c...
June 3, 2020: Journal of Dermatology
Mohamad Goldust, Jeffrey M Weinberg, Leon H Kircik, Sidharth Sonthalia, Vito Di Lernia, Dipali Rathod
BACKGROUND: Pityriasis lichenoides chronica, a papulosquamous disorder often considered a subtype of pityriasis lichenoides. It is considered a clonal T-cell disorder, which may be associated with cutaneous T-cell lymphoma that may develops in response to foreign antigens. CASE PRESENTATION: We present a 38-year-old male patient with ankylosing spondylitis who was on treatment with etanercept. After 8 weeks of treatment, the patient presented with scaly erythematous papules, on the back and arms...
May 1, 2020: Journal of Drugs in Dermatology: JDD
Danny D Dinh, Darcy Lidington, Jeffrey T Kroetsch, Chloe Ng, Hangjun Zhang, Sergei A Nedospasov, Scott P Heximer, Steffen-Sebastian Bolz
Subarachnoid hemorrhage (SAH) is a devastating cerebral event caused by an aneurysmal rupture. In addition to neurological injury, SAH has significant effects on cardiac function and the peripheral microcirculation. Since these peripheral complications may exacerbate brain injury, the prevention and management of these peripheral effects are important for improving the overall clinical outcome after SAH. In this investigation, we examined the effects of SAH on cardiac function and vascular reactivity in a well-characterized blood injection model of SAH...
2020: Frontiers in Physiology
James Ryan, Andrew I Bayliffe, Daniel F McAuley, Joyce Yeung, David R Thickett, Phillip A Howells, Ciara O'Donnell, Arlette M Vassallo, Tracey J Wright, Elizabeth McKie, Kelly Hardes, Charlotte Summers, Martin O Shields, William Powley, Robert Wilson, Aili L Lazaar, Andrew Fowler, Gavin D Perkins
BACKGROUND: Tumour necrosis factor receptor 1 (TNFR1) signalling mediates the cell death and inflammatory effects of TNF-α. OBJECTIVE: The current clinical trial investigated the effects of a nebulised TNFR1 antagonist (GSK2862277) on signs of lung injury in patients undergoing oesophagectomy. DESIGN: Randomised double-blind (sponsor unblind), placebo-controlled, parallel group study. SETTING: Eight secondary care centres, the United Kingdom between April 2015 and June 2017...
May 27, 2020: European Journal of Anaesthesiology
Sedigheh Amiresmaili, Mohammad Khaksari, Nader Shahrokhi, Moslem Abolhassani
Several studies have shown that 17β-estradiol (E2) exerted beneficial effects on liver disease, and it has a protective impact on brain damage after traumatic brain injury (TBI). TBI-induced liver injury is associated with the activation of TLR4. However, it remains unknown whether E2 can modulate TBI-induced liver injury through TLR4. The objective of this study was to determine the role of TLR4 in hepatoprotective mechanisms of E2 after TBI. Diffuse TBI induced by the Marmarou model in male rats. TAK-242 as a selective antagonist of TLR4 (3mg/kg) and E2 (33...
May 20, 2020: Biochemical Pharmacology
Mousumi Dutta, Prafulla Dutta, Subhash Medhi, Biswajyoti Borkakoty, Dipankar Biswas
Introduction: The pathogenicity of influenza virus infection is modulated by the cytokine expressions in patients. The present study was aimed to measure some important pro- and anti-inflammatory cytokines in influenza-infected population of Assam, Northeast India. Materials and Methods: Influenza viruses consisting of subtypes influenza A(H1N1)pdm09, H3N2 and influenza-B were detected in patients with symptoms of influenza-like-illness by Real-time reverse transcriptase polymerase chain reaction (RT-PCR) method...
October 2019: Indian Journal of Medical Microbiology
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