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https://www.readbyqxmd.com/read/28346103/discovery-of-novel-gq-biased-lpa1-negative-allosteric-modulators
#1
Yuji Shimizu, Masaharu Nakayama
Lysophosphatidic acid (LPA) activates the G-protein-coupled receptor LPA1, which regulates various cellular processes, including cell proliferation and migration. Although LPA1 transduces cellular responses via Gq, Gi, and G12/13, associations between these signaling molecules and cellular phenotypes remain poorly characterized due to the lack of signal-specific pharmacological tools. Here, we characterized novel signal-biased modulators using multiple assays, including label-free impedance assays. LPA caused dramatic changes in cellular impedance in LPA1-expressing recombinant cells, which were susceptible to G-protein and protein kinase inhibitors...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345829/high-fluoroquinolone-resistant-strains-of-helicobacter-pylori-in-the-golden-triangle
#2
Ratha Korn Vilaichone, Thawee Ratanachu ek, Pornpen Gamnarai, Phawinee Subsomwong, Tomahisa Uchida, Yoshio Yamaoka, Varocha Mahachai
Background and aims: Helicobacter pylori (H. pylori) infections, associated with fatal GI diseases such as gastric cancer and MALT lymphoma, remain a major health problem in ASEAN countries. The Golden triangle has long been known as one of Asia’s main opium-producing areas. There have been no prior studies of H. pylori infection in this area. The major objectives of this project were therefore to establish prevalence, antibiotic resistance patterns and associated predictive in the Golden triangle. Methods: We recruited dyspeptic patients in Chiang khong and Chiang saen districts, Chiangrai province of Thailand...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28345660/zinc-deficiency-and-low-enterocyte-zinc-transporter-expression-in-human-patients-with-autism-related-mutations-in-shank3
#3
Stefanie Pfaender, Ann Katrin Sauer, Simone Hagmeyer, Katharina Mangus, Leonhard Linta, Stefan Liebau, Juergen Bockmann, Guillaume Huguet, Thomas Bourgeron, Tobias M Boeckers, Andreas M Grabrucker
Phelan McDermid Syndrome (PMDS) is a genetic disorder characterized by features of Autism spectrum disorders. Similar to reports of Zn deficiency in autistic children, we have previously reported high incidence of Zn deficiency in PMDS. However, the underlying mechanisms are currently not well understood. Here, using inductively coupled plasma mass-spectrometry to measure the concentration of Zinc (Zn) and Copper (Cu) in hair samples from individuals with PMDS with 22q13.3 deletion including SHANK3 (SH3 and multiple ankyrin repeat domains 3), we report a high rate of abnormally low Zn/Cu ratios...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345443/economic-burden-of-irritable-bowel-syndrome-with-diarrhea-retrospective-analysis-of-a-u-s-commercially-insured-population
#4
Jessica L Buono, Kush Mathur, Amelia J Averitt, David A Andrae
BACKGROUND: The economic burden associated with irritable bowel syndrome with diarrhea (IBS-D) is not well understood. OBJECTIVES: To (a) evaluate total annual all-cause, gastrointestinal (GI)-related, and symptom-related (i.e., IBS, diarrhea, abdominal pain) health care resource use and costs among IBS-D patients in a U.S. commercially insured population and (b) estimate incremental all-cause health care costs of IBS-D patients versus matched controls. METHODS: Patients aged ≥ 18 years with 12 months of continuous medical and pharmacy benefit eligibility in 2013 were identified from the Truven Health MarketScan research database...
April 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28344961/recurrence-factors-and-reproductive-outcomes-of-laparoscopic-myomectomy-and-minilaparotomic-myomectomy-for-uterine-leiomyomas
#5
Dong Gi Shin, Heon Jong Yoo, Yeon Ah Lee, In Sun Kwon, Ki Hwan Lee
OBJECTIVE: The aim of this study was to determine recurrence factors and reproductive outcomes of laparoscopic myomectomy (LM) and minilaparotomic myomectomy (MM) for treating uterine leiomyomas. METHODS: Between 2007 and 2013, 160 patients underwent myomectomy, including 122 who underwent LM and 38 who underwent MM. Patients were followed up for recurrence based on pelvic ultrasound exams. Only patients who were followed up for a minimum of two years were selected for this retrospective study...
March 2017: Obstetrics & Gynecology Science
https://www.readbyqxmd.com/read/28344945/an-evaluation-of-the-possible-relationship-between-chronic-periodontitis-and-hypertension
#6
M O Arowojolu, O Oladapo, O I Opeodu, S O Nwhator
BACKGROUND: Periodontal diseases have been reported to have a form of reciprocal relationship with the general systemic health, in which case those with some systemic diseases such as hypertension have poorer periodontal health and vice versa. The issue of causal or casual relationship is however yet to be finally resolved. AIM: The aim of this study was to determine any possible relationship between chronic periodontitis and cardiovascular risk factors. METHODOLOGY: A cross-sectional assessment of cardiovascular risk factors such as blood pressure, body mass index, waist circumference and the carotid artery intima media thickness (CIMT) was done among 100 consecutive subjects in the echocardiogram unit of the University College Hospital, Ibadan, Nigeria over a period of six months...
April 2016: Journal of the West African College of Surgeons
https://www.readbyqxmd.com/read/28344842/effectiveness-of-direct-safety-regulations-on-manufacturers-and-users-of-industrial-machines-its-implications-on-industrial-safety-policies-in-republic-of-korea
#7
Gi Heung Choi
BACKGROUND: Despite considerable efforts made in recent years, the industrial accident rate and the fatality rate in the Republic of Korea are much higher than those in most developed countries in Europe and North America. Industrial safety policies and safety regulations are also known to be ineffective and inefficient in some cases. METHODS: This study focuses on the quantitative evaluation of the effectiveness of direct safety regulations such as safety certification, self-declaration of conformity, and safety inspection of industrial machines in the Republic of Korea...
March 2017: Safety and Health At Work
https://www.readbyqxmd.com/read/28344687/disseminated-pancreatic-neuroendocrine-neoplasm-nen-with-an-uncommon-localisation-in-the-central-nervous-system-a-case-report
#8
Joanna Białkowska, Agnieszka Kolasińska-Ćwikła, Dorota Mroczkowska, Mariusz Sowa, Łukasz Grabarczyk, Wojciech Maksymowicz, Andrzej Cichocki, Jarosław B Ćwikła
BACKGROUND: Neuroendocrine neoplasms (NEN) are rare neoplasms that originate from neuroendocrine cells and are characterized by the potential of hormonal activity. Approximately 70% of these tumours are located in the gastrointestinal system (GI), followed by the bronchi, endocrine glands-like C cells of the thyroid (medullary carcinoma), the parasympathetic and sympathetic system (paragangliomas, pheochromocytoma) and other very rare locations. The prevalence of cerebral metastases in neuroendocrine tumours is estimated by various authors to be approximately 1...
2017: Polish Journal of Radiology
https://www.readbyqxmd.com/read/28344444/distribution-of-platelet-rich-plasma-after-ultrasound-guided-injection-for-chronic-elbow-tendinopathies
#9
Gi-Young Park, Dong Rak Kwon, Hee Kyung Cho, Jinyoung Park, Jung Hyun Park
Characteristics of the spreads of platelet-rich plasma (PRP) are not widely known despite commonly use. This study aims to evaluate whether PRP stays within the injected area by using ultrasonography, to improve understanding of the spreads of intratendinous injected PRP. Thirty-nine patients (15 males, 24 females; mean age, 49.3 years), who had symptoms on their elbows (> 6 months) and diagnosed as lateral (25 elbows) or medial (14 elbows) tendinopathies of elbow, were included. The severity of tendon pathology was assessed by ultrasonography as tear or no tear...
March 2017: Journal of Sports Science & Medicine
https://www.readbyqxmd.com/read/28344416/one-year-outcomes-of-acute-decompensated-systolic-heart-failure-in-taiwan-lessons-from-tsoc-hfref-registry
#10
Hung-Yu Chang, Chun-Chieh Wang, Yen-Wen Wu, Pao-Hsien Chu, Chih-Cheng Wu, Chih-Hsin Hsu, Ming-Shien Wen, Wen-Chol Voon, Wei-Shiang Lin, Jin-Long Huang, Shyh-Ming Chen, Ning-I Yang, Heng-Chia Chang, Kuan-Cheng Chang, Shih-Hsien Sung, Kou-Gi Shyu, Jiunn-Lee Lin, Guang-Yuan Mar, Kuei-Chuan Chan, Jen-Yuan Kuo, Ji-Hung Wang, Zhih-Cherng Chen, Wei-Kung Tseng, Wen-Jin Cherng, Wei-Hsian Yin
BACKGROUND: Heart failure (HF) is a global health problem. The Taiwan Society of Cardiology-Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry was a multicenter, observational survey of patients admitted with HFrEF in Taiwan. The aim of this study was to report the one-year outcome in this large-cohort of hospitalized patients presenting with acute decompensated HFrEF. METHODS: Patients hospitalized for acute HFrEF were recruited in 21 hospitals in Taiwan...
March 2017: Acta Cardiologica Sinica
https://www.readbyqxmd.com/read/28343151/gastric-outlet-obstruction-an-unusual-case-of-primary-duodenal-tuberculosis
#11
Sanket Kalpande, Jayashri Sanjay Pandya, Ajeet Tiwari, Devbrata Adhikari
BACKGROUND: Tuberculosis is a major health problem worldwide. Gastrointestinal tuberculosis presenting as isolated involvement of the duodenum is a rare case. CASE PRESENTATION: A 13 year male, presented with features of gastric outlet obstruction. CT enterography scan showed circumferential mural thickening in first and second part of duodenal junction causing luminal narrowing. Upper GI endoscopy confirmed the narrowing of D1-D2 junction. Duodenal biopsy showed duodenitis with negative result for AFB stain, Helicobacter Pylori...
March 24, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28342779/suppression-of-calpain-expression-by-nsaids-is-associated-with-inhibition-of-cell-migration-in-rat-duodenum
#12
Kristopher Silver, A Littlejohn, Laurel Thomas, Bhupinder Bawa, James D Lillich
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the alleviation of pain and inflammation, but these drugs are also associated with a suite of negative side effects. Gastrointestinal (GI) toxicity is particularly concerning since it affects an estimated 70% of individuals taking NSAIDs routinely, and evidence suggests the majority of toxicity is occurring in the small intestine. Traditionally, NSAID-induced GI toxicity has been associated with indiscriminate inhibition of cyclooxygenase isoforms, but other mechanisms, including inhibition of cell migration, intestinal restitution, and wound healing, are likely to contribute to toxicity...
March 22, 2017: Toxicology
https://www.readbyqxmd.com/read/28342683/white-grape-juice-elicits-a-lower-breath-hydrogen-response-compared-with-apple-juice-in-healthy-human-subjects-a-randomized-controlled-trial
#13
Jennifer Erickson, Qi Wang, Joanne Slavin
BACKGROUND: Diets low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPS) are used to manage symptoms in individuals with irritable bowel syndrome. Although effective at reducing symptoms, the diet can be complex and restrictive. In addition, there are still large gaps in the literature and many foods with unclear effects in the gastrointestinal (GI) tract, like fruit juice. Although many fruits are allowable on a low-FODMAP diet, consumption of all fruit juice is generally cautioned due to the large fructose load contained in juice, regardless of the glucose concentration...
March 22, 2017: Journal of the Academy of Nutrition and Dietetics
https://www.readbyqxmd.com/read/28341844/relevance-of-the-dietary-glycemic-index-glycemic-load-and-genetic-predisposition-for-the-glucose-homeostasis-of-chinese-adults-without-diabetes
#14
Guo Cheng, Hongmei Xue, Jiao Luo, Hong Jia, Lishi Zhang, Junbiao Dai, Anette E Buyken
Type 2 diabetes (T2DM) and pre-diabetes have become a major public health problem in China. We examined whether a higher dietary glycemic index (GI) or glycemic load (GL) was associated with a less favorable glucose homeostasis among Chinese adults and whether these associations were modified by their genetic predisposition or whether combined effects exist with their cereal fiber intake. Multivariable regression analyses were performed in 3918 adults aged 23-69 years for whom three 24-hour dietary recalls and information on glucose homeostasis, genetic background and potential confounders was available...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28341475/genotypic-and-phenotypic-characteristics-of-crb1-associated-retinal-dystrophies-a-long-term-follow-up-study
#15
Mays Talib, Mary J van Schooneveld, Maria M van Genderen, Jan Wijnholds, Ralph J Florijn, Jacoline B Ten Brink, Nicoline E Schalij-Delfos, Gislin Dagnelie, Frans P M Cremers, Ron Wolterbeek, Marta Fiocco, Alberta A Thiadens, Carel B Hoyng, Caroline C Klaver, Arthur A Bergen, Camiel J F Boon
PURPOSE: To describe the phenotype, long-term clinical course, clinical variability, and genotype of patients with CRB1-associated retinal dystrophies. DESIGN: Retrospective cohort study. PARTICIPANTS: Fifty-five patients with CRB1-associated retinal dystrophies from 16 families. METHODS: A medical record review of 55 patients for age at onset, medical history, initial symptoms, best-corrected visual acuity, ophthalmoscopy, fundus photography, full-field electroretinography (ffERG), Goldmann visual fields (VFs), and spectral-domain optical coherence tomography...
March 13, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28341345/the-signaling-signature-of-the-neurotensin-type-1-receptor-with-endogenous-ligands
#16
Élie Besserer-Offroy, Rebecca L Brouillette, Sandrine Lavenus, Ulrike Froehlich, Andrea Brumwell, Alexandre Murza, Jean-Michel Longpré, Éric Marsault, Michel Grandbois, Philippe Sarret, Richard Leduc
The human neurotensin 1 receptor (hNTS1) is a G protein-coupled receptor involved in many physiological functions, including analgesia, hypothermia, and hypotension. To gain a better understanding of which signaling pathways or combination of pathways are linked to NTS1 activation and function, we investigated the ability of activated hNTS1, which was stably expressed by CHO-K1 cells, to directly engage G proteins, activate second messenger cascades and recruit β-arrestins. Using BRET-based biosensors, we found that neurotensin (NT), NT(8-13) and neuromedin N (NN) activated the Gαq-, Gαi1-, GαoA-, and Gα13-protein signaling pathways as well as the recruitment of β-arrestins 1 and 2...
March 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28341152/identification-of-genotoxic-compounds-in-crude-oil-using-fractionation-according-to-distillation-polarity-and-kow
#17
Shin Yeong Park, Hyo Jin Lee, Jong Seong Khim, Gi Beum Kim
We examined the degree of DNA damage caused by fractions of crude oil in accordance with the boiling points, polarity and log Kow. Relatively high DNA damage was observed in the aromatic fraction (290-330°C) and resin and polar fraction (350-400°C). The resin and polar fraction showed relatively high genotoxicity compared with the aliphatic and aromatic fraction at the 1-4 log Kow range. At the 6-7 log Kow range, the aromatic fraction showed relatively high DNA damage compared with the aliphatic and resin and polar fraction...
January 30, 2017: Marine Pollution Bulletin
https://www.readbyqxmd.com/read/28339881/genetic-aspects-and-environmental-sources-of-microsporidia-that-infect-the-human-gastrointestinal-tract
#18
Martin F Heyworth
Enterocytozoon bieneusi and Encephalitozoon intestinalis are microsporidia that infect the human gastrointestinal (GI) tract. Each of these microsporidia has been shown to infect various non-human hosts (mammalian and avian), raising the possibility of inter-species transmission, for example, from such hosts to human subjects via waterborne dispersal of microsporidian spores. During the past two decades, genome sequencing has delineated more than 90 genotypes of Ent. bieneusi, and has led to the conclusion that not all the genotypes of this organism infect human subjects...
February 27, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28339199/structure-based-discovery-of-new-antagonist-and-biased-agonist-chemotypes-for-the-kappa-opioid-receptor
#19
Zhong Zheng, Xi-Ping Huang, Thomas J Mangano, Rodger Zou, Xin Chen, Saheem Zaidi, Bryan L Roth, Raymond C Stevens, Vsevolod Katritch
The ongoing epidemics of opioid overdose raises an urgent need for effective anti-addiction therapies and addiction-free painkillers. The κ-opioid receptor (KOR) has emerged as a promising target for both indications, raising demand for new chemotypes of KOR antagonists, as well as G-protein-biased agonists. We employed the crystal structure of the KOR-JDTic complex and ligand-optimized structural templates to perform virtual screening of available compound libraries for new KOR ligands. The prospective virtual screening campaign yielded a high 32% hit rate, identifying novel fragment-like and lead-like chemotypes of KOR ligands...
March 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28339142/selective-effects-of-oral-anti-angiogenic-tyrosine-kinase-inhibitors-on-an-animal-model-of-hereditary-hemorrhagic-telangiectasia
#20
Yong Hwan Kim, Mi-Jung Kim, Se-Woon Choe, Dennis Sprecher, Young Jae Lee, S Paul Oh
BACKGROUND: Epistaxis and gastrointestinal (GI) tract hemorrhages are common symptoms of aged hereditary hemorrhagic telangiectasia (HHT) patients that result in anemia. Clinical as well as animal studies have suggested that vascular endothelial growth factor (VEGF) neutralizing antibodies lessen hemorrhage associated with adult onset arteriovenous malformations (AVMs). OBJECTIVES: The goal of this study is to evaluate potential therapeutic effects of oral delivery of four anti-angiogenic tyrosine-kinase inhibitors (TKIs) in the development of adult onset AVMs in a murine model of HHT...
March 24, 2017: Journal of Thrombosis and Haemostasis: JTH
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