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https://www.readbyqxmd.com/read/29457989/propylthiouracil-induced-anti-neutrophil-cytoplasmic-antibody-associated-vasculitis-mimicking-kawasaki-disease
#1
Yoshihiro Aoki, Katsuhiko Kitazawa, Hironobu Kobayashi
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is rare in children and is characterised as necrotising vasculitis predominantly affecting small and medium-sized vessels. Propylthiouracil (PTU), an antithyroid drug, has been implicated in drug-induced AAV. In contrast, Kawasaki disease (KD) is a common systemic vasculitis, typically observed in children, which affects the medium-sized vessels, including the coronary arteries. An 11-year-old girl who developed AAV while receiving PTU therapy for Graves' disease is described...
February 19, 2018: Paediatrics and International Child Health
https://www.readbyqxmd.com/read/29457828/dihydrodiosgenin-protects-against-experimental-acute-pancreatitis-and-associated-lung-injury-through-mitochondrial-protection-and-pi3k%C3%AE-akt-inhibition
#2
Yan Shen, Li Wen, Rui Zhang, Zeliang Wei, Na Shi, Qiuyang Xiong, Qing Xia, Zhihua Xing, Zhi Zeng, Hai Niu, Wen Huang
BACKGROUND AND PURPOSE: Acute pancreatitis (AP) is a painful and burdensome exocrine pancreatic disorder with no specific drug treatment. Diosgenyl saponin extracts from Dioscorea zingiberensis C. H. Wright were reported to protect against experimental models of AP and diosgenin or its derivatives have anti-inflammatory effects in various diseases. However, the effects of diosgenin and its spiroacetal ring opened analog dihydrodiosgenin (Dydio) have not yet been determined in AP. EXPERIMENTAL APPROACH: Various concentrations of diosgenin and Dydio were tested for sodium taurocholate hydrate (Tauro)-induced necrosis in freshly isolated murine pancreatic acinar cells...
February 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29457309/severe-intestinal-malabsorption-associated-with-ace-inhibitor-or-angiotensin-receptor-blocker-treatment-an-observational-cohort-study-in-germany-and-italy
#3
Peter Malfertheiner, Claudio Ripellino, Nazarena Cataldo
PURPOSE: The angiotensin II receptor blocker (ARB) olmesartan has been recently associated with sprue-like enteropathy (SLE), a gastrointestinal condition characterized by intestinal malabsorption (IM) and severe diarrhea. Whether the increased risk of SLE is substance-specific or a class effect involving all ARBs is uncertain. The aim of this study is to assess the risk of enteropathy associated with ARBs and angiotensin converting enzyme inhibitors (ACE-i) by using data from large administrative and claim databases...
February 19, 2018: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/29457278/zwitterionic-nanocages-overcome-the-efficacy-loss-of-biologic-drugs
#4
Bowen Li, Zhefan Yuan, Peng Zhang, Andrew Sinclair, Priyesh Jain, Kan Wu, Caroline Tsao, Jingyi Xie, Hsiang-Chieh Hung, Xiaojie Lin, Tao Bai, Shaoyi Jiang
For biotherapeutics that require multiple administrations to fully cure diseases, the induction of undesirable immune response is one common cause for the failure of their treatment. Covalent binding of hydrophilic polymers to proteins is commonly employed to mitigate potential immune responses. However, while this technique is proved to partially reduce the antibodies (Abs) reactive to proteins, it may induce Abs toward their associated polymers and thus result in the loss of efficacy. Zwitterionic poly(carboxybetaine) (PCB) is recently shown to improve the immunologic properties of proteins without inducing any antipolymer Abs against itself...
February 19, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29456831/early-afterdepolarisation-tendency-as-a-simulated-pro-arrhythmic-risk-indicator
#5
Beth McMillan, David J Gavaghan, Gary R Mirams
Drug-induced Torsades de Pointes (TdP) arrhythmia is of major interest in predictive toxicology. Drugs which cause TdP block the hERG cardiac potassium channel. However, not all drugs that block hERG cause TdP. As such, further understanding of the mechanistic route to TdP is needed. Early afterdepolarisations (EADs) are a cell-level phenomenon in which the membrane of a cardiac cell depolarises a second time before repolarisation, and EADs are seen in hearts during TdP. Therefore, we propose a method of predicting TdP using induced EADs combined with multiple ion channel block in simulations using biophysically-based mathematical models of human ventricular cell electrophysiology...
November 1, 2017: Toxicology Research
https://www.readbyqxmd.com/read/29456508/the-molecular-determinants-of-small-molecule-ligand-binding-at-p2x-receptors
#6
Gaia Pasqualetto, Andrea Brancale, Mark T Young
P2X receptors are trimeric eukaryotic ATP-gated cation channels. Extracellular ATP-their physiological ligand-is released as a neurotransmitter and in conditions of cell damage such as inflammation, and substantial evidence implicates P2X receptors in diseases including neuropathic pain, cancer, and arthritis. In 2009, the first P2X crystal structure, Danio rerio P2X4 in the apo - state, was published, and this was followed in 2012 by the ATP-bound structure. These structures transformed our understanding of the conformational changes induced by ATP binding and the mechanism of ligand specificity, and enabled homology modeling of mammalian P2X receptors for ligand docking and rational design of receptor modulators...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29456473/adverse-events-of-trastuzumab-emtansine-t-dm1-in-the-treatment-of-her2-positive-breast-cancer-patients
#7
REVIEW
Lidia Kowalczyk, Rupert Bartsch, Christian F Singer, Alex Farr
The human epidermal growth factor receptor 2 (HER2) is commonly associated with poor prognosis and is overexpressed in approximately 15-20% of all breast cancers. The introduction of HER2-targeted therapies led to significant improvement in the prognosis of patients with HER2-positive breast cancer, for both early and advanced disease. These targeted therapies include the antibodies trastzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib, and the antibody-drug conjugate trastuzumab emtansine (T-DM1)...
December 2017: Breast Care
https://www.readbyqxmd.com/read/29455987/design-and-biological-response-of-doxycycline-loaded-chitosan-microparticles-for-periodontal-disease-treatment
#8
Silvana Gjoseva, Nikola Geskovski, Simona Dimchevska Sazdovska, Riste Popeski-Dimovski, Gjorgji Petruševski, Kristina Mladenovska, Katerina Goracinova
The aim of this study was to develop chitosan (CS) microparticulated mucoadhesive drug delivery system (DDS) with improved therapeutic performance and biological responce. Ionotropic gelation/spray drying process was used for preparation of doxycycline hyclate (DOXY) loaded low and medium molecular weight (LMw and MMw) CS/sodium tripolyphosphate microparticles (CS/TPP MPs), further coated with ethyl cellulose (EC) using coacervation/solvent displacement technique. The relevant physico-chemical and biopharmaceutical properties were optimized using experimental design approach...
April 15, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29455070/oral-engineered-bifidobacterium-longum-expressing-rhmnsod-to-suppress-experimental-colitis
#9
Mengge Liu, Shiyu Li, Qian Zhang, Zhenrui Xu, Jiajia Wang, Hanxiao Sun
In recent years, using genetic engineering and bioengineering techniques, Bifidobacterium as a carrier to express specific functions of the protein or polypeptide, has become a new treatment for disease. Ulcerative colitis (UC) is a type of inflammatory bowel diseases (IBD). Although the cause of this inflammatory disorder is still unknown, a large amount of evidence suggests that ulcerative colitis is associated with increased activity of reactive oxygen species (ROS), manganese superoxide dismutase (MnSOD) is a kind of superoxide dismutase (SOD) has been demonstrated to play a key role in the pathophysiology of colitis...
February 14, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29454857/distinct-cd40l-receptors-mediate-inflammasome-activation-and-secretion-of-il-1%C3%AE-and-mcp-1-in-cultured-human-retinal-pigment-epithelial-cells
#10
Zong-Mei Bian, Matthew G Field, Susan G Elner, J Michelle Kahlenberg, Victor M Elner
CD40L signaling occurs in several diseases with inflammatory components, including ocular and retinal diseases. However, it has never been evaluated as a pathogenic mechanism in age-related macular degeneration (AMD) or as an inducer of inflammasome formation in any cell type. mRNA and protein levels of CD40, IL-1β, NALP1, NALP3, caspase-1, and caspase-5 were determined by RT-PCR, qPCR, and Western blot. CD40L receptor (CD40, α5β1, and CD11b) expression was determined by Western and immunofluorescent staining...
February 15, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29453977/amelioration-of-progressive-autoimmune-encephalomyelitis-by-epigenetic-regulation-involves-selective-repression-of-mature-neutrophils-during-the-preclinical-phase
#11
Arathi Jayaraman, Monica Sharma, Bellur Prabhakar, Mark Holterman, Sundararajan Jayaraman
We have recently demonstrated that treatment of NOD mice with the epigenetic drug Trichostatin A (TSA) ameliorated myelin peptide induced progressive experimental autoimmune encephalomyelitis (P-EAE). Protection was accompanied by induction of antigen-specific T-cell tolerance in the periphery and reduced the influx of T cells into the spinal cord. In this investigation, we examined whether the epigenetic drug could impact the innate immune system as well. Whereas the mature (MHC class II + ) CD11b + Ly-6G + neutrophils expanded substantially in the peripheral lymphoid compartment during the preclinical phase, the MHC class II + , CD11b + Ly-6C + mature monocytes increased modestly throughout the disease course...
February 14, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29451848/mr-imaging-of-atraumatic-muscle-disorders
#12
Edward Smitaman, Dyan V Flores, Catalina Mejía Gómez, Mini N Pathria
Atraumatic disorders of skeletal muscles include congenital variants; inherited myopathies; acquired inflammatory, infectious, or ischemic disorders; neoplastic diseases; and conditions leading to muscle atrophy. These have overlapping appearances at magnetic resonance (MR) imaging and are challenging for the radiologist to differentiate. The authors organize muscle disorders into four MR imaging patterns: (a) abnormal anatomy with normal signal intensity, (b) edema/inflammation, (c) mass, and (d) atrophy, highlighting each of their key clinical and imaging findings...
February 16, 2018: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/29451352/chronic-exposure-of-mice-to-low-doses-of-imazalil-induces-hepatotoxicity-at-the-physiological-biochemical-and-transcriptomic-levels
#13
Cuiyuan Jin, Ting Luo, Zhengwei Fu, Yuanxiang Jin
Imazalil (IMZ), which is a widely used fungicide, can accumulate in the body and threaten an animal's health. However, this fungicide has adverse effects on aquatic organisms and ultimately affects human health when it leaches into the environment. Our research tried to determine that if IMZ might cause liver damage and its potential to cause-related diseases. In this study, male adult C57BL/6 mice were exposed to 0.1, 0.5, or 2.5 mg/kg body weight IMZ in drinking water for 15 weeks. Then, we evaluated the liver damage at the physiological, biochemical, and transcriptome levels in mice after chronic IMZ exposure...
February 16, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29450547/aflibercept-action-in-a-rabbit-model-of-chronic-retinal-neovascularization-reversible-inhibition-of-pathologic-leakage-with-dose-dependent-duration
#14
Jingtai Cao, Thomas C MacPherson, Bibiana V Iglesias, Yang Liu, Natasha Tirko, George D Yancopoulos, Stanley J Wiegand, Carmelo Romano
Purpose: We establish and characterize the chronic retinal neovascularization (RNV) induced by intravitreal (IVT) injection of DL-α-aminoadipic acid (AAA) in a rabbit model and investigate the extent and duration of inhibitory actions induced by IVT aflibercept on the RNV. Methods: Rabbits received a single IVT injection of AAA, with weekly follow-up fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT). After 10 weeks, they received a single IVT aflibercept or control injection...
February 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29449830/screening-for-ppar-non-agonist-ligands-followed-by-characterization-of-a-hit-am-879-with-additional-no-adipogenic-and-cdk5-mediated-phosphorylation-inhibition-properties
#15
Helder Veras Ribeiro Filho, Natália Bernardi Videira, Aline Villanova Bridi, Thais Helena Tittanegro, Fernanda Aparecida Helena Batista, José Geraldo de Carvalho Pereira, Paulo Sérgio Lopes de Oliveira, Marcio Chaim Bajgelman, Albane Le Maire, Ana Carolina Migliorini Figueira
Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of a nuclear receptor superfamily and acts as a ligand-dependent transcription factor, playing key roles in maintenance of adipose tissue and in regulation of glucose and lipid homeostasis. This receptor is the target of thiazolidinediones, a class of antidiabetic drugs, which improve insulin sensitization and regulate glycemia in type 2 diabetes. Despite the beneficial effects of drugs, such as rosiglitazone and pioglitazone, their use is associated with several side effects, including weight gain, heart failure, and liver disease, since these drugs induce full activation of the receptor...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29449707/modulation-of-cardiac-stem-cell-characteristics-by-metoprolol-in-hypertensive-heart-disease
#16
Sherin Saheera, Ajay Godwin Potnuri, Renuka R Nair
Cardiac stem cells (CSCs) play a vital role in cardiac remodeling. Uncontrolled hypertension leads to cardiac hypertrophy, followed by cardiac failure. Pathological remodeling is associated with enhanced oxidative stress. Decreased cardiac stem cell efficiency is speculated in heart diseases. Maintaining a healthy stem cell population is essential for preventing progressive cardiac remodeling. Some anti-hypertensive drugs are cardioprotective. However, the effect of these drugs on CSCs has not been investigated...
February 15, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/29449600/glucocorticoids-promote-apoptosis-of-proinflammatory-monocytes-by-inhibiting-erk-activity
#17
Adrian Achuthan, Ahmad S M Aslam, Quyen Nguyen, Pui-Yeng Lam, Andrew J Fleetwood, Ashlee T Frye, Cynthia Louis, Ming-Chin Lee, Julia E Smith, Andrew D Cook, Moshe Olshansky, Stephen J Turner, John A Hamilton
Glucocorticoids (GCs) are potent anti-inflammatory drugs whose mode of action is complex and still debatable. One likely cellular target of GCs are monocytes/macrophages. The role of GCs in monocyte survival is also debated. Although both granulocyte macrophage-colony stimulating factor (GM-CSF) and macrophage-CSF (M-CSF) are important regulators of macrophage lineage functions including their survival, the former is often associated with proinflammatory functions while the latter is important in lineage homeostasis...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29448848/development-and-characterization-of-morin-hydrate-loaded-micellar-nanocarriers-for-the-effective-management-of-alzheimer-s-disease
#18
Manpreet Singh, Vandana Thakur, Rahul Deshmukh, Amit Sharma, M S Rathore, Ajay Kumar, Neeraj Mishra
The aim of this study was to prepare and characterize oral delivery of Morin hydrate loaded micellar nanocarriers using Pluronic P127 & Pluronic F123 for the effective management of Alzheimer's disease. After administration of formulation brain and blood drug concentration were found to be highest for optimized morin hydrate loaded micellar nanocarriers as compared to plain morin hydrate. Significant (P < 0.05) reduction in assessed pharmacodynamic parameters was observed after administration of morin hydrate loaded micellar nanocarriers as compared to disease control group...
February 16, 2018: Journal of Microencapsulation
https://www.readbyqxmd.com/read/29448253/lycorine-suppresses-endplate-chondrocyte-degeneration-and-prevents-intervertebral-disc-degeneration-by-inhibiting-nf-%C3%AE%C2%BAb-signalling-pathway
#19
Gangliang Wang, Kangmao Huang, Yangxin Dong, Shuai Chen, Jianfeng Zhang, Jiying Wang, Ziang Xie, Xianfeng Lin, Xiangqiang Fang, Shunwu Fan
BACKGROUND/AIMS: Cartilaginous endplate (CEP) degeneration is an important cause for intervertebral disc (IVD) degeneration that leads to low-back pain. The identification of compounds that may prevent CEP degeneration is of interest for the prevention of IVD degeneration. METHODS: Catabolic protease expression in the CEP of disc degeneration patients was first assessed. The toxicity, function and underlying mechanism of lycorine (LY) on CEP-derived chondrocytes degeneration were assessed in vitro by flow cytometry analysis and western blotting...
February 9, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29448038/molecular-and-biological-characterization-of-a-highly-pathogenic-trypanosoma-cruzi-strain-isolated-from-a-patient-with-congenital-infection
#20
Julián Ernesto Nicolás Gulin, Margarita Bisio, Daniela Marisa Rocco, Jaime Altcheh, María Elisa Solana, Facundo García-Bournissen
Although many Trypanosoma cruzi (T. cruzi) strains isolated from a wide range of hosts have been characterized, there is a lack of information about biological features from vertically transmitted strains. We describe the molecular and biological characteristics of the T. cruzi VD strain isolated from a congenital Chagas disease patient. The VD strain was typified as DTU TcVI; in vitro sensitivity to nifurtimox (NFX) and beznidazole (BZ) were 2.88 μM and 6.19 μM respectively, while inhibitory concentrations for intracellular amastigotes were 0...
February 12, 2018: Experimental Parasitology
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