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Jeroen Brijs, Grant W Hennig, Anna-Maria Kellermann, Michael Axelsson, Catharina Olsson
Rhythmic contractions of the mammalian gastrointestinal tract can occur in the absence of neuronal or hormonal stimulation due to the generation of spontaneous electrical activity by interstitial cells of Cajal (ICC) that are electrically coupled to smooth muscle cells. The myogenically-driven component of gastrointestinal motility patterns in fish likely also involves ICC, however, little is known of their presence, distribution and function in any fish species. In the present study, we combined immunohistochemistry and in vivo recordings of intestinal motility to investigate the involvement of ICC in the motility of the proximal intestine in adult shorthorn sculpin (Myoxocephalus scorpius)...
November 10, 2016: Journal of Experimental Biology
Yuko Ohta, Azusa Ishizuka, Hisatomi Arima, Shinichiro Hayashi, Yoshio Iwashima, Masatsugu Kishida, Fumiki Yoshihara, Satoko Nakamura, Yuhei Kawano
Uric acid (UA) has been associated with hypertension, renal disease and cardiovascular disease. The aim of the present study was to compare the UA-lowering effects of a standard dose of the UA synthesis inhibitor febuxostat to a standard dose of the uricosuric agent benzbromarone, and to investigate the effects of a low-dose combination of both agents in hypertensive patients with hyperuricemia. Twenty hypertensive patients with inadequate UA control were administered febuxostat 40 mg (Feb), benzbromarone 50 mg (Ben) and febuxostat 20 mg and benzbromarone 25 mg (feb/ben) for 3 months each in a randomized modified crossover manner...
October 20, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Jeffrey Miner, Philip K Tan, David Hyndman, Sha Liu, Cory Iverson, Payal Nanavati, David T Hagerty, Kimberly Manhard, Zancong Shen, Jean-Luc Girardet, Li-Tain Yeh, Robert Terkeltaub, Barry Quart
BACKGROUND: Excess body burden of uric acid promotes gout. Diminished renal clearance of uric acid causes hyperuricemia in most patients with gout, and the renal urate transporter (URAT)1 is important for regulation of serum uric acid (sUA) levels. The URAT1 inhibitors probenecid and benzbromarone are used as gout therapies; however, their use is limited by drug-drug interactions and off-target toxicity, respectively. Here, we define the mechanism of action of lesinurad (Zurampic®; RDEA594), a novel URAT1 inhibitor, recently approved in the USA and Europe for treatment of chronic gout...
October 3, 2016: Arthritis Research & Therapy
Sunao Kojima, Shinobu Kojima, Atsuko Hifumi, Hirofumi Soejima, Hisao Ogawa
No abstract text is available yet for this article.
September 24, 2016: International Journal of Cardiology
Shu Li, Hongxi Yang, Yanan Guo, Fengjiang Wei, Xilin Yang, Daiqing Li, Mingzhen Li, Weili Xu, Weidong Li, Li Sun, Ying Gao, Yaogang Wang
The prevalence of hyperuricemia and gout has been increasing, but the comparative effectiveness and safety of different treatments remain uncertain. We aimed to compare the effectiveness and safety of different treatments for hyperuricemia using network meta-analysis methodology. We systematically reviewed fifteen randomized controlled trials (involving 7,246 patients through January 2016) that compared the effects of different urate-lowering drugs (allopurinol, benzbromarone, febuxostat, pegloticase and probenecid) on hyperuricemia...
2016: Scientific Reports
Huey-En Tzeng, Che-Chen Lin, I-Kuan Wang, Po-Hao Huang, Chun-Hao Tsai
There is still debate on whether high uric acid increases bone mineral density (BMD) against osteoporotic fracture or bone resorption caused by gout inflammation. This study aimed to evaluate whether gout offers a protective effect on bone health or not. We conducted a nationwide population-based retrospective cohort study to evaluate the association between gout history and risk factors of fracture.A retrospective cohort study was designed using the claim data from Longitudinal Health Insurance Database (LHID)...
August 2016: Medicine (Baltimore)
Tae Sik Sung, Kate O'Driscoll, Haifeng Zheng, Nicholas J Yapp, Normand Leblanc, Sang Don Koh, Kenton M Sanders
Anoctamin-1 (ANO1) is a Ca(2+)-activated Cl(-) channel expressed in many types of cells. Splice variants of ANO1 have been shown to influence the biophysical properties of conductance. It has been suggested that several new antagonists of ANO1 with relatively high affinity and selectivity might be useful for experimental and, potentially, therapeutic purposes. We investigated the effects of intracellular Ca(2+) concentration ([Ca(2+)]i) at 100-1,000 nM, a concentration range that might be achieved in cells during physiological activation of ANO1 channels, on blockade of ANO1 channels expressed in HEK-293 cells...
September 1, 2016: American Journal of Physiology. Cell Physiology
Yuki Haga, Shin Yasui, Tatsuo Kanda, Noriyuki Hattori, Toru Wakamatsu, Masato Nakamura, Reina Sasaki, Shuang Wu, Shingo Nakamoto, Makoto Arai, Hitoshi Maruyama, Masayuki Ohtsuka, Shigeto Oda, Masaru Miyazaki, Osamu Yokosuka
On-line hemodiafiltration (OLHDF) is one of the treatment options in the management of acute liver failure (ALF) in Japan. It is essential to avoid infection in the management of ALF. In fact, infection is one of the prognostic factors in ALF. In this report, we present a middle-aged Japanese man with ALF associated with benzbromarone use. He was successfully managed without infection until liver transplantation by creating an arteriovenous fistula for OLHDF. Utilizing an arteriovenous fistula for OLHDF, rather than inserting a vascular access catheter, is a beneficial option to avoid infectious diseases in the management of ALF...
January 2016: Case Reports in Gastroenterology
L K Stamp, J Haslett, C Frampton, D White, D Gardner, S Stebbings, G Taylor, R Grainger, R Kumar, S Kumar, T Kain, D Porter, M Corkill, A Cathro, S Metcalfe, J Wyeth, N Dalbeth
BACKGROUND: Benzbromarone is a potent uricosuric but is not widely available due to concerns about hepatotoxicity. In Aotearoa New Zealand, benzbromarone has been available since April 2013, subject to funding restrictions, for patients with inadequate urate-lowering response or intolerance to allopurinol and probenecid. AIM: To assess the safety and efficacy of benzbromarone in a real-life setting. METHODS: All patients who received funding for benzbromarone from 1 April 2013 to 30 September 2014 were identified...
September 2016: Internal Medicine Journal
Laura C López, Olga Varea, Susanna Navarro, José A Carrodeguas, Natalia Sanchez de Groot, Salvador Ventura, Javier Sancho
Human Amylin, or islet amyloid polypeptide (hIAPP), is a small hormone secreted by pancreatic β-cells that forms aggregates under insulin deficiency metabolic conditions, and it constitutes a pathological hallmark of type II diabetes mellitus. In type II diabetes patients, amylin is abnormally increased, self-assembled into amyloid aggregates, and ultimately contributes to the apoptotic death of β-cells by mechanisms that are not completely understood. We have screened a library of approved drugs in order to identify inhibitors of amylin aggregation that could be used as tools to investigate the role of amylin aggregation in type II diabetes or as therapeutics in order to reduce β-cell damage...
June 18, 2016: International Journal of Molecular Sciences
Nikolaos Pagonas, Samad Kor, Felix S Seibert, Arnd Giese, Walter Zidek, Petra Reinke, Nina Babel, Frederic Bauer, Timm H Westhoff
BACKGROUND Hyperuricemia is very common after renal transplantation. It is associated with an increased risk of cardiovascular events and graft loss. To date, however, treatment is only recommended in symptomatic disease. MATERIAL AND METHODS We included 503 adult patients who underwent kidney transplantation at the Charité-Universitätsmedizin Berlin in this retrospective study. Patients were followed up for up to 120 months. All-cause mortality, graft survival, changes in level of serum uric acid (SUA), and estimated glomerular filtration rate (eGFR) were analyzed...
June 7, 2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Gang Chen, Ping Jia
BACKGROUND: High fructose consumption is considered to be related to the increasing prevalence of hyperuricemia (HUA). Glucose transporters (GLUT) 2 and 5 are crucial for fructose absorption and transporter. Effects of anti-HUA drugs, allopurinol (API) and benzbromarone (BBR), on expressions of GLUT5 and GLUT2 are not evaluated. METHOD: Wistar rats were given 10% fructose in drinking water for 60 days to induce HUA, and 5mg/kg API and 10mg/kg BBR were intragastricly treated for 30 days...
August 2016: Pharmacological Reports: PR
Xi Lan, Chunyan Fan, Wei Ji, Fuyun Tian, Tao Xu, Zhaobing Gao
A classical voltage-gated ion channel consists of four voltage-sensing domains (VSDs). However, the roles of each VSD in the channels remain elusive. We developed a GVTDT (Graft VSD To Dimeric TASK3 channels that lack endogenous VSDs) strategy to produce voltage-gated channels with a reduced number of VSDs. TASK3 channels exhibit a high host tolerance to VSDs of various voltage-gated ion channels without interfering with the intrinsic properties of the TASK3 selectivity filter. The constructed channels, exemplified by the channels grafted with one or two VSDs from Kv7...
August 2016: Cell Research
Junichiro Kumagai, Tatsuo Kanda, Shin Yasui, Yuki Haga, Reina Sasaki, Masato Nakamura, Shuang Wu, Shingo Nakamoto, Makoto Arai, Yotaro Iino, Osamu Yokosuka
We describe a case of autoimmune hepatitis (AIH) that may have occurred following drug-induced liver injury with camostat mesilate and/or benzbromarone in an elderly patient. The patient's liver biopsy showed chronic active hepatitis and autoimmune hepatitis. Stopping the use of these drugs did not lead to complete remission, but the use of a low dose of corticosteroids completely cured his liver dysfunction. In the present case, liver dysfunction was caused by an autoimmune mechanism. Special attention should be paid to idiopathic AIH and drug-induced AIH in elderly patients...
June 2016: Clinical Journal of Gastroenterology
Tsung-Ming Lee, Shinn-Zong Lin, Nen-Chung Chang
Hyperuricemia has been shown to be associated with ventricular arrhythmias. However, the mechanisms remained unknown. We assessed whether different urate-lowering agents can attenuate arrhythmias through lowering urate itself or inhibiting xanthenes oxidize (XO) activity in infarcted rats. Male Wistar rats after ligating coronary artery were randomized to either allopurinol, or febuxostat, chemically unrelated inhibitors of XO, benzbromarone or vehicle for 4 weeks. Post-infarction was associated with increased oxidant stress, as measured by myocardial superoxide, isoprostane, XO activity and dihydroethidine fluorescence staining...
May 2016: Journal of Pharmacological Sciences
C Borghi, F Perez-Ruiz
OBJECTIVE: In patients with gout, serum uric acid (sUA) concentrations should be lowered at least below the target of 6 mg/dL (even below 5 mg/dL in patients with severe gout). To achieve this goal, urate lowering medications (ULMs) should be considered. Currently-used ULMs include xanthine-oxidase inhibitors such as allopurinol, febuxostat, as well as available uricosuric agents. However, evidence comparing these agents remains scant. We have conducted a systematic review and meta-analysis to retrieve evidence on the clinical trials on the above-mentioned drugs in the treatment of gout...
March 2016: European Review for Medical and Pharmacological Sciences
H S Füeßl, P Stiefelhagen
No abstract text is available yet for this article.
November 19, 2015: MMW Fortschritte der Medizin
Naoki Tanimizu, Kota Kaneko, Tohru Itoh, Norihisa Ichinohe, Masayuki Ishii, Toru Mizuguchi, Koichi Hirata, Atsushi Miyajima, Toshihiro Mitaka
UNLABELLED: The intrahepatic bile duct (IHBD) is a highly organized tubular structure consisting of cholangiocytes, biliary epithelial cells, which drains bile produced by hepatocytes into the duodenum. Although several models have been proposed, it remains unclear how the three-dimensional (3D) IHBD network develops during liver organogenesis. Using 3D imaging techniques, we demonstrate that the continuous luminal network of IHBDs is established by 1 week after birth. Beyond this stage, the IHBD network consists of large ducts running along portal veins (PVs) and small ductules forming a mesh-like network around PVs...
July 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
M Mishima, T Hamada, N Maharani, N Ikeda, T Onohara, T Notsu, H Ninomiya, S Miyazaki, E Mizuta, S Sugihara, M Kato, K Ogino, M Kuwabara, Y Hirota, A Yoshida, N Otani, N Anzai, I Hisatome
BACKGROUND: Although urate impaired the endothelial function, its underlying mechanism remains unknown. We hypothesized that urate impaired nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) via activation of uric acid transporters (UATs). PURPOSE AND METHOD: In the present study, we studied effects of urate on NO production and eNOS protein expression in HUVEC cells in the presence and absence of urate lowering agents using molecular biological and biochemical assays...
May 2016: Drug Research
Sung Oh Ahn, Shuichi Ohtomo, Jumpei Kiyokawa, Toshito Nakagawa, Mizuki Yamane, Kyoung June Lee, Ki Hwan Kim, Byung Ho Kim, Jo Tanaka, Yoshiki Kawabe, Naoshi Horiba
Urate-lowering therapy is indispensable for the treatment of gout, but available drugs do not control serum urate levels tightly enough. Although the uricosurics benzbromarone and probenecid inhibit a urate reabsorption transporter known as renal urate transporter 1 (URAT1) and thus lower serum urate levels, they also inhibit other transporters responsible for secretion of urate into urine, which suggests that inhibiting URAT1 selectively would lower serum urate more effectively. We identified a novel potent and selective URAT1 inhibitor, UR-1102, and compared its efficacy with benzbromarone in vitro and in vivo...
April 2016: Journal of Pharmacology and Experimental Therapeutics
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