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https://www.readbyqxmd.com/read/29352570/the-nlrp3-inflammasome-and-the-emerging-role-of-colchicine-to-inhibit-atherosclerosis-associated-inflammation
#1
REVIEW
Gonzalo J Martínez, David S Celermajer, Sanjay Patel
Atherosclerosis is considered a chronic inflammatory disease of the arterial wall. Recently, compelling evidence has arisen for the role of monocytes and neutrophils and a particular protein complex that resides within these cells - the NLRP3 inflammasome - in atherosclerosis-associated inflammation. It is now also known that cholesterol crystals are present through all stages of atherosclerosis and can activate the NLRP3 inflammasome within these inflammatory cells to produce interleukin 1β and interleukin 18 - key mediators in the inflammatory cascade that drive plaque progression and instability...
December 25, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29349493/biotic-elicitation-of-ginsenoside-metabolism-of-mutant-adventitious-root-culture-in-panax-ginseng
#2
Kim-Cuong Le, Wan-Taek Im, Kee-Yoeup Paek, So-Young Park
Biotic elicitation is an important biotechnological strategy for triggering the accumulation of secondary metabolites in adventitious root cultures. These biotic elicitors can be obtained from safe, economically important strains of bacteria found in the rhizosphere and fermented foods. Here, we assayed the effects of filtered cultures of five nitrogen-fixing bacteria and four types of fermentation bacteria on mutant adventitious Panax ginseng root cultures induced in a previous study by colchicine treatment...
January 18, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29348557/sensitizing-tumor-cells-to-conventional-drugs-hsp70-chaperone-inhibitors-their-selection-and-application-in-cancer-models
#3
Vladimir F Lazarev, Dmitry V Sverchinsky, Elena R Mikhaylova, Pavel I Semenyuk, Elena Y Komarova, Sergey A Niskanen, Alina D Nikotina, Anton V Burakov, Viktor G Kartsev, Irina V Guzhova, Boris A Margulis
Hsp70 chaperone controls proteostasis and anti-stress responses in rapidly renewing cancer cells, making it an important target for therapeutic compounds. To date several Hsp70 inhibitors are presented with remarkable anticancer activity, however their clinical application is limited by the high toxicity towards normal cells. This study aimed to develop assays to search for the substances that reduce the chaperone activity of Hsp70 and diminish its protective function in cancer cells. On our mind the resulting compounds alone should be safe and function in combination with drugs widely employed in oncology...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29345845/atypical-familial-mediterranean-fever-developed-in-a-long-term-hemodialysis-patient
#4
Toshiyuki Makino, Yoshitatsu Ohara, Namiko Kobayashi, Yohei Kono, Ayumu Nomizu, Mariko Ichijo, Yutaro Mori, Noriaki Matsui, Dai Kishida, Takayuki Toda
Familial Mediterranean Fever (FMF) is usually an autosomal recessive autoinflammatory disease characterized by recurrent attacks of fever and serositis. FMF develops before the age of 20 years in 90% of patients. It has intervals of 1 week to several years between attacks, which leads to renal dysfunction-amyloidosis. We report a case of atypical FMF that developed in a long-term hemodialysis patient. A 65-year-old Japanese female undergoing hemodialysis for 32 years was referred to our hospital with a fever of unknown origin (FUO) following cervical laminoplasty...
January 18, 2018: Hemodialysis International
https://www.readbyqxmd.com/read/29340075/extracting-microtentacle-dynamics-of-tumor-cells-in-a-non-adherent-environment
#5
Eleanor C Ory, Desu Chen, Kristi R Chakrabarti, Peipei Zhang, James I Andorko, Christopher M Jewell, Wolfgang Losert, Stuart S Martin
During metastasis, tumor cells dynamically change their cytoskeleton to traverse through a variety of non-adherent microenvironments, including the vasculature or lymphatics. Due to the challenges of imaging drift in non-adhered tumor cells, the dynamic cytoskeletal phenotypes are poorly understood. We present a new approach to analyze the dynamic cytoskeletal phenotypes of non-adhered cells that support microtentacles (McTNs), which are cell surface projections implicated in metastatic reattachment. Combining a recently-developed cell tethering method with a novel image analysis framework allowed McTN attribute extraction...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29336254/colchicine-in-neurosurgery
#6
Drosos Evangelos, Giakoumettis Dimitrios, Themistocleous S Marios
BACKGROUND: Colchicine is an ancient drug. Many uses have been reported in medical books and reports through the centuries. Currently the understanding of its mechanism of action has opened new horizons to its use. OBJECTIVE: This article aims to discuss the use of colchicine in various neurosurgical conditions. METHODS: A pubmed database and clinical trials search was performed, using the key words "colchicine", "Neurosurgery", "low back pain", "stroke" and glioma"...
January 14, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29336253/colchicine-in-post-operative-atrial-fibrillation-a-review
#7
Dimitrios A Vrachatis, Charalampos Kossyvakis, Christos Angelidis, Vasiliki Panagopoulou, Eleni K Sarri, Sotiria Giotaki, Gerasimos Siasos, Manolis Vavuranakis, Spyridon G Deftereos
Post-operative atrial fibrillation (POAF) is a frequent entity increasing hospitalization duration, stroke and mortality. In the recent years, a few studies have sought to investigate the potential effect of colchicine in POAF prevention after cardiac surgery or catheter pulmonary vein isolation for AF. In the present review article, we intend to provide a synopsis of clinical practice guidelines, summarize and critically approach current evidence for or against colchicine as a means of POAF prevention.
January 14, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29336252/colchicine-in-gout-an-update
#8
Tristan Pascart, Pascal Richette
Despite the fact that colchicine is by far the most ancient treatment for gout, new data are still being gathered. In gout, colchicine's ability to block polymerization of tubulin prevents the activation of the inflammasome. Efficacy of colchicine for the treatment of gout flares has been demonstrated only recently by a randomized-controlled trial, but it still has not been compared to other drugs. Use of colchicine is impaired by the impact of underlying comorbid conditions and drug interactions that can considerably modify its pharmacokinetics and pharmacodynamics...
January 14, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29336251/isolating-colchicine-in-19th-century-an-old-drug-revisited
#9
Marianna Karamanou, Gregory Tsoucalas, Konstantinos Pantos, George Androutsos
Colchicine is a tricyclic alkaloid extracted from the herbaceous plant Colchicum autumnale. Known since antiquity for its therapeutic efficacy in the treatment of gout, colchicine was reintroduced in 19th century pharmacopeia, thanks to the work of the French chemists and pharmacists Pierre-Joseph Pelletier (1788-1842) and Joseph Bienaime Caventou (1795-1877) who in 1819, isolated a peculiar substance in the roots of Colchicum autumnale. In 1833, the substance was further analyzed by the German pharmacist and chemist Philipp Lorenz Geiger (1785-1836), who coined the name colchicine...
January 14, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29336247/the-role-of-colchicine-in-the-treatment-of-autoinflammatory-diseases
#10
Georgia Liantinioti, Antonios A Argyris, Athanase D Protogerou, Panayiotis Vlachoyiannopoulos
Colchicine has been longstanding and widely used for the treatment of acute gout flares and prevention of gout relapses. Its use has been extended to a series of autoinflammatory diseases, such as familial Mediterranean fever and more recently to periodic fever with aphthous stomatitis, pharyngitis and adenitis, Behcet's disease and idiopathic recurrent acute pericarditis. In this review, we summarize current indications of colchicine use, discuss its pharmacokinetics and mechanism of action and examine its use in the treatment of autoinflammatory diseases...
January 15, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29336246/the-role-of-colchicine-in-the-prevention-of-cerebrovascular-ischemia
#11
Georgios Tsivgoulis, Aristeidis H Katsanos, Georgios Giannopoulos, Vasiliki Panagopoulou, Dalius Jatuzis, Robin Lemnens, Spyridon Deftereos, Peter J Kelly
INTRODUCTION: Despite the proven efficacy of anti-thrombotic, lipid-lowering, anti-hypertensive therapies and lifestyle modification changes for secondary ischemic stroke prevention, the risk of recurrent stroke, coronary events and vascular death remains substantial even for patients treated with high rates of established secondary preventive medications. METHODS: In the present review, we summarize available literature data on the association between systemic inflammation and symptomatic atherosclerosis including recurrent cerebral ischemia...
January 15, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29336245/the-role-of-colchicine-in-pericardial-syndromes
#12
George Lazaros, Massimo Imazio, Antonio Brucato, Charalambos Vlachopoulos, Emilia Lazarou, Dimitrios Vassilopoulos, Dimitris Tousoulis
BACKGROUND: Colchicine is an old drug originally employed for the treatment of inflammatory disorders such as acute gout and familiar Mediterranean fever. METHODS: In the past few decades, colchicine has been at the forefront of the pharmacotherapy of several cardiac diseases, including acute and recurrent pericarditis, coronary artery disease, prevention of atrial fibrillation and heart failure. In this review, we have summarized the current evidence based medicine and guidelines recommendations in the specific context of pericardial syndromes...
January 15, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29334816/anti-colchicine-fab-fragments-prevent-lethal-colchicine-toxicity-in-a-porcine-model-a-pharmacokinetic-and-clinical-study
#13
Michael Eddleston, Nicolas Fabresse, Adrian Thompson, Ibrahim Al Abdulla, Rachael Gregson, Tim King, Alain Astier, Frederic J Baud, R Eddie Clutton, Jean-Claude Alvarez
BACKGROUND: Colchicine poisoning is commonly lethal. Colchicine-specific Fab fragments increase rat urinary colchicine clearance and have been associated with a good outcome in one patient. We aimed to develop a porcine model of colchicine toxicity to study the pharmacokinetics and efficacy of ovine Fab. METHODS: A Göttingen minipig critical care model was established and serial blood samples taken for colchicine and Fab pharmacokinetics, clinical chemistry, and haematology...
January 15, 2018: Clinical Toxicology
https://www.readbyqxmd.com/read/29332658/an-extremely-rare-association-of-sweet-s-syndrome-with-active-pulmonary-tuberculosis
#14
Sandhya Chauhan
Sweet's syndrome is a skin manifestation of various systemic infections, drugs, malignancies and autoimmune disorders. There are very few case reports describing the relationship between Sweet's syndrome and non-tubercular mycobacterium infection. Further development of Sweet's syndrome secondary to mycobacterium tuberculosis (active pulmonary tuberculosis) is extremely uncommon and this is the second well established case reported from India. Here we report a forty eight year old man who presented with multiple erythematous and tender plaques over neck, palms and sides of soles...
January 2018: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/29332199/analysis-of-the-data-on-pregnancy-and-lactation-provided-by-patient-information-leaflets-of-anti-rheumatic-drugs-in-argentina
#15
Miguel Ormaza Sabando, Maira Arias Saavedra, Gabriel Sequeira, Eduardo Kerzberg
To analyse the level of consistency and updating of the information on pregnancy and lactation provided by patient information leaflets (PILs) of the antirheumatic drugs approved in Argentina. Inconsistencies between the 2016 EULAR Task Force recommendations on the use of anti-rheumatic drugs during pregnancy and lactation and the information provided by PILs of the same drugs approved in Argentina were analysed along with inconsistencies within the PILs of different registered trademarks of these drugs. Eighty-eight PILs of 32 drugs were analysed...
January 13, 2018: Rheumatology International
https://www.readbyqxmd.com/read/29317407/a20-haploinsufficiency-ha20-clinical-phenotypes-and-disease-course-of-patients-with-a-newly-recognised-nf-kb-mediated-autoinflammatory-disease
#16
Florence A Aeschlimann, Ezgi D Batu, Scott W Canna, Ellen Go, Ahmet Gül, Patrycja Hoffmann, Helen L Leavis, Seza Ozen, Daniella M Schwartz, Deborah L Stone, Annet van Royen-Kerkof, Daniel L Kastner, Ivona Aksentijevich, Ronald M Laxer
OBJECTIVES: The association between mutations in TNFAIP3, encoding the NF-kB regulatory protein A20, and a new autoinflammatory disease has recently been recognised. This study aims at describing the clinical phenotypes and disease course of patients with A20 haploinsufficiency (HA20). METHODS: Data for all cases from the initial publication, and additional cases identified through collaborations since, were collected using standardised data collection forms. RESULTS: A total of 16 patients (13 female) from seven families with a genetic diagnosis of HA20 were included...
January 9, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29311752/computational-design-and-synthesis-of-novel-fluoro-analogs-of-combretastatins-a-4-and-a-1
#17
Yao Zong, Christie Shea, Katherine Maffucci, Iwao Ojima
Combretastatin A-1 (CA-1) and combretastatin A-4 (CA-4) isolated from the African bush willow Combretum caffrum are highly potent tubulin polymerization inhibitors, possessing strong antitumor activities because of their vascular disrupting properties. Extensive SAR studies have been done for CA-4 analogs. Because of poor solubility, water-soluble prodrugs of CA-4 and CA-1 have been developed, which are currently in human clinical trials. Fluorine plays an important role in the current drug discovery and development due to its unique properties...
November 2017: Journal of Fluorine Chemistry
https://www.readbyqxmd.com/read/29310804/the-cytoskeletal-network-regulates-expression-of-the-profibrotic-genes-pai-1-and-ctgf-in-vascular-smooth-muscle-cells
#18
Rohan Samarakoon, Paul J Higgins
Vascular smooth muscle cells (VSMCs) are subject to changing hemodynamic stimuli that alter cytoskeletal dynamics, cellular architecture, and structure-associated signal transduction. Tensional stress, force application, and structural perturbations are sensed by VSMCs and impact the physiological as well as pathophysiological responses of the vasculature. Microtubule-targeting drugs provide useful tools to analyze cytoskeletal-associated signaling pathways and their linkages to pathological outcomes. Architecture-based controls on a subset of profibrotic genes commonly expressed in vascular disease are highlighted by their frequent induction in mechanically manipulated cells and with associated changes in cytoskeletal dynamics...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29306206/design-synthesis-biological-evaluation-and-cocrystal-structures-with-tubulin-of-chiral-%C3%AE-lactam-bridged-combretastatin-a-4-analogues-as-potent-antitumor-agents
#19
Pengfei Zhou, Yuru Liang, Hao Zhang, Hao Jiang, Kechang Feng, Pan Xu, Jie Wang, Xiaoming Wang, Kuiling Ding, Cheng Luo, Mingming Liu, Yang Wang
A diverse of chiral β-lactam bridged analogues of combretastatin A-4 (CA-4), 3-substituted 1,4-diaryl-2-azetidinones, were asymmetrically synthesized and biologically evaluated, leading to identify a number of potent anti-proliferative compounds represented by 14b and 14c with IC50 values of 0.001-0.021 μM, against four human cancer cell lines (A2780, Hela, SKOV-3 and MDA-MB-231). Structure-activity relationship (SAR) studies on all stereoisomers of 14b and 14c revealed that the absolute configurations of the chiral centers at 3- and 4-position were critically important for the activity and generally a trans configuration between the "A" and "B" rings is optimal...
December 7, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29299132/saikosaponins-a-c-and-d-enhance-liver-targeting-effects-of-anticancer-drugs-by-modulating-drug-transporters
#20
Limin Feng, Lijuan Liu, Ya Zhao, Ruizhi Zhao
Vinegar-baked Radix Bupleuri (VBRB) is clinically used to enhance the pharmacological activity of drugs used to treat liver diseases. Our previous study demonstrated that this effect is dependent on increased drug accumulation in the liver; however, the underlying mechanism remains unclear. We hypothesize that VBRB mediated its effects by altering drug transporters. Thus, the present study was designed to determine the effects of VBRB's main components, saikosaponin A, C, and D, on drug transporters. Transporter activity was determined by measuring the intracellular concentration of transporter substrates...
December 15, 2017: Oncotarget
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