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https://www.readbyqxmd.com/read/28445961/azilsartan-ameliorates-apoptosis-of-dopaminergic%C3%A2-neurons-and-rescues-characteristic-parkinsonian-behaviors-in-a-rat-model-of-parkinson-s-disease
#1
Qing Gao, Zhou Ou, Teng Jiang, You-Yong Tian, Jun-Shan Zhou, Liang Wu, Jian-Quan Shi, Ying-Dong Zhang
Loss of dopaminergic neurons within the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD), which leads to the onset of motor symptoms. Previously, our in vitro studies revealed that Angiotensin II (Ang II) induced apoptosis of dopaminergic neurons through its type 1 receptor (AT1R), but these findings needed to be confirmed via animal experiments. Here, using a rotenone-induced rat model of PD, we observed an overactivation of Ang II/AT1R axis in the SN, since Ang II level and AT1R expression were markedly increased...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445927/vaccines-targeting-pres1-domain-overcome-immune-tolerance-in-hbv-carrier-mice
#2
Yingjie Bian, Zheng Zhang, Zhichen Sun, Juanjuan Zhao, Danming Zhu, Yang Wang, Sherry Fu, Jingya Guo, Longchao Liu, Lishan Su, Fu-Sheng Wang, Yang-Xin Fu, Hua Peng
Strong tolerance to HBV surface antigens limits the therapeutic effect of the conventional HBsAg vaccination in both preclinical animal models and patients with chronic hepatitis B (CHB) infection. In contrast, we observed that clinical CHB patients presented less immune tolerance to the preS1 domain of HBV large surface antigen. To study whether targeting the weak tolerance of preS1 region could improve therapy gain, we explored vaccination with the long peptide of preS1 domain for HBV virions clearance. Our study showed that this preS1-polypeptide rather than HBsAg vaccination induced robust immune responses in the HBV carrier mice...
April 26, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28445900/central-and-peripheral-glucagon-reduces-hyperlipidemia-in-rats-and-hamsters
#3
Vishal Patel, Amit Joharapurkar, Samadhan Kshirsagar, Hiren M Patel, Dheerendra Pandey, Dipam Patel, Kiran Shah, Rajesh Bahekar, Gaurang B Shah, Mukul R Jain
Increased lipid levels in blood contribute to increasing the risk of diabetic complications. Glucagon exerts lipid lowering effects in diabetic state. However, the mechanism behind the lipid reduction by glucagon independent of glucose homeostasis is not well understood. We assessed the actions of glucagon on lipid modulation in blood and markers in liver in hyperlipidemic hamsters and rats. Male Sprague Dawley rats and Golden Syrian hamsters on a hyperlipidemic diet for 2 weeks were administered a single dose of glucagon by subcutaneous (SC, 150 and 300 µg/kg) or intracerebroventricular (ICV, 15 and 30 µg/animal) route...
April 26, 2017: Drug Research
https://www.readbyqxmd.com/read/28445852/sensitive-analysis-and-pharmacokinetic-study-of-epalrestat-in-c57bl-6j-mice
#4
Jingqiu Huang, Runbin Sun, Siqi Feng, Jun He, Fei Fei, Haoxue Gao, Yuqing Zhao, Yue Zhang, Huilin Gu, Jiye Aa, Guangji Wang
Epalrestat is clinically applied for the management of diabetic peripheral neuropathy, yet its pharmacokinetic properties are not well understood. In this study, a rapid and sensitive LC-MS/MS method was established for assaying epalrestat in bio-samples of mice. The method was validated and it showed a good linearity over the range of 2-5000ng/mL, a precision of less than 12.3%, and recovery and matrix effects of 112.5-123.6% and 87.9-89.5%, respectively. After administration of a single dose of epalrestat administered, the exposure level of AUC0-∞ was positively dose-dependent and the mean Cmax, AUC0-12h, T1/2, and MRT were 36...
April 7, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28445846/a-sharp-robust-and-quantitative-method-by-liquid-chromatography-tandem-mass-spectrometry-for-the-measurement-of-ead-for-acute-radiation-syndrome-and-its-application
#5
Yiwei Zhang, Jian Li, Zhiyun Meng, Xiaoxia Zhu, Hui Gan, Ruolan Gu, Zhuona Wu, Ying Zheng, Jinbin Wei, Guifang Dou
17-Ethinyl-3,17-dihydroxyandrost-5-ene (EAD) is an agent designed for the treatment of acute radiation syndrome (ARS). Given its vital role played in the prevention and mitigation of ARS, the development of a sharp, sensitive and robust liquid chromatography tandem mass spectrometry (LC-MS/MS) method to monitor the metabolism of EAD in vivo was crucial. A new method was constructed and validated for the determination of EAD with the internal standard of androst-5-ene-3β,17β-diol (5-AED). The blood samples were precipitated with methanol, centrifuged, from which the supernatant was separated on UPLC with C18 column and eluted in gradient with acetonitrile and Milli-Q water both containing 0...
April 15, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28445830/overexpression-of-heme-oxygenase-1-in-bone-marrow-stromal-cells-promotes-microenvironment-mediated-imatinib-resistance-in-chronic-myeloid-leukemia
#6
Ping Liu, Dan Ma, Zhengyu Yu, Nana Zhe, Mei Ren, Ping Wang, Meisheng Yu, Jun Huang, Qin Fang, Jishi Wang
Neoplasm cells from patients with chronic myeloid leukemia (CML) interact with stromal cells of the surrounding microenvironment. Bone marrow stromal cells (BMSCs) represent the main population in CML marrow stroma, which may play a key role in disease support and progression. Heme oxygenase-1 (HO-1) is a key enzyme of antioxidative metabolism that is associated with cell proliferation and resistance to apoptosis. We herein up-regulated HO-1 expression of BMSCs and evaluated whether BMSCs influenced K562 cells survival...
April 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28445809/inhibition-of-14q32-microrna-mir-495-reduces-lesion-formation-intimal-hyperplasia-and-plasma-cholesterol-levels-in-experimental-restenosis
#7
Sabine M J Welten, Rob C M de Jong, Anouk Wezel, Margreet R de Vries, Martin C Boonstra, Laura Parma, J Wouter Jukema, Tetje C van der Sluis, Ramon Arens, Ilze Bot, Sudhir Agrawal, Paul H A Quax, A Yaël Nossent
BACKGROUND AND AIMS: We aimed at investigating the role of 14q32 microRNAs in intimal hyperplasia and accelerated atherosclerosis; two major contributors to restenosis. Restenosis occurs regularly in patients treated for coronary artery disease and peripheral arterial disease. We have previously shown that inhibition of 14q32 microRNAs leads to increased post-ischemic neovascularization, and microRNA miR-494 also decreased atherosclerosis, while increasing plaque stability. We hypothesized that 14q32 microRNA inhibition has beneficial effects on intimal hyperplasia, as well as accelerated atherosclerosis...
April 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28445779/the-acute-cardiorespiratory-effects-of-centrally-injected-arachidonic-acid-the-mediation-of-prostaglandin-e-d-and-f2%C3%AE
#8
Leman Gizem Erkan, Burcin Altinbas, Gokcen Guvenc, Begum Aydin, Nasir Niaz, Murat Yalcin
Arachidonic acid (AA), which is released from synaptic membrane phospholipid by neuroreceptor-initiated activation of phospholipase A2, is abundant in the brain and works as a neurotransmitter and/or neuromodulator in the central nervous system. Recently we reported that centrally injected AA generated pressor and hyperventilation effects by activating thromboxane A2 (TXA2) signaling pathway. The present study was designed to investigate the mediation of other metabolites of AA such as prostaglandin (PG) D, PGE and PGF2α alongside TXA2 in the AA-evoked cardiorespiratory effects in anaesthetized rats...
April 23, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28445778/the-impact-of-bilateral-vagotomy-on-the-physostigmine-induced-airway-constriction-in-ferrets
#9
Burim Neziri, Armond Daci, Shaip Krasniqi, Ramadan Sopi, Musa A Haxhiu
Vagal innervations have a great role in the respiratory function and are the main route of signal transmission from respiratory neural centers into the trachea and others conducting airways. We have investigated the role of central mechanisms related to vagal neural pathways and the cholinergic outflow in tracheobronchial smooth muscle tone and lung mechanics parameters. Parameters of lung mechanics such as lung resistance (RL), dynamic compliance (Cdyn) and pressure in bypassed tracheal segment (Ptseg) were measured before and after vagotomy and asphyxia test...
April 23, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28445776/antimicrobial-resistance-in-the-bacteroides-fragilis-group-in-faecal-samples-from-patients-receiving-broad-spectrum-antibiotics
#10
Kia Cirkeline Møller Hansen, Simon A F Schwensen, Daniel Pilsgaard Henriksen, Ulrik Stenz Justesen, Thomas Vognbjerg Sydenham
Members of the Bacteroides fragilis group are opportunistic pathogens and cause severe infections including bacteraemia. As increased levels of antimicrobial resistance in B. fragilis group bacteria can be detected years after administration of specific antibiotics, monitoring antimicrobial susceptibility in the gut microbiota could be important. The objectives of this study were to 1) investigate the distribution of species and the occurrence of reduced antimicrobial susceptibility in the B. fragilis group from patients treated at departments with a high level of antibiotic use, 2) to determine the prevalence of the carbapenem resistance gene cfiA in B...
April 23, 2017: Anaerobe
https://www.readbyqxmd.com/read/28445621/calm-to-chaos-engaging-undergraduate-nursing-students-with-the-complex-nature-of-interruptions-during-medication-administration
#11
Carolyn Hayes, Debra Jackson, Patricia M Davidson, John Daly, Tamara Power
AIMS AND OBJECTIVES: This paper describes undergraduate student nurse responses to a simulated role-play experience focussing on managing interruptions during medication administration. BACKGROUND: Improving patient safety requires that we find creative and innovative methods of teaching medication administration to undergraduate nurses in real-world conditions. Nurses are responsible for the majority of medication administrations in health care. Incidents and errors associated with medications are a significant patient safety issue and often occur as a result of interruptions...
April 26, 2017: Journal of Clinical Nursing
https://www.readbyqxmd.com/read/28445611/equivalence-of-complex-drug-products-advances-in-and-challenges-for-current-regulatory-frameworks
#12
Leonie Hussaarts, Stefan Mühlebach, Vinod P Shah, Scott McNeil, Gerrit Borchard, Beat Flühmann, Vera Weinstein, Sesha Neervannan, Elwyn Griffiths, Wenlei Jiang, Elena Wolff-Holz, Daan J A Crommelin, Jon S B de Vlieger
Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U...
April 26, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28445592/polo-like-kinase-1-is-a-proviral-host-factor-for-hepatitis-b-virus-replication
#13
Ahmed M Diab, Adrien Foca, Floriane Fusil, Thomas Lahlali, Pascal Jalaguier, Fouzia Amirache, Lia N'Guyen, Nathalie Isorce, François-Loïc Cosset, Fabien Zoulim, Ourania M Andrisani, David Durantel
Chronic Hepatitis B Virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) and current treatments for CHB and HCC are perfectible. Herein, we identified cellular Serine/Threonine Polo-like-kinase 1 (PLK1) as a positive effector of HBV replication. The aim of this study was to demonstrate the proviral role of PLK1 in HBV biosynthesis and validate PLK1 inhibition a potential antiviral strategy. To this end, we employed physiologically relevant HBV infection models of Primary Human Hepatocytes (PHH) and differentiated HepaRG cells, in conjunction with pharmacologic PLK1 inhibitors, siRNA-mediated knockdown, and overexpression of constitutively active PLK1 (PLK1(CA) )...
April 26, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28445529/ductular-reaction-correlates-with-fibrogenesis-but-does-not-contribute-to-liver-regeneration-in-experimental-fibrosis-models
#14
András Rókusz, Dániel Veres, Armanda Szücs, Edina Bugyik, Miklós Mózes, Sándor Paku, Péter Nagy, Katalin Dezső
BACKGROUND AND AIMS: Ductular reaction is a standard component of fibrotic liver tissue but its function is largely unknown. It is supposed to interact with the matrix producing myofibroblasts and compensate the declining regenerative capacity of hepatocytes. The relationship between the extent of fibrosis-ductular reaction, proliferative activity of hepatocytes and ductular reaction were studied sequentially in experimental hepatic fibrosis models. METHODS: Liver fibrosis/cirrhosis was induced in wild type and TGFβ overproducing transgenic mice by carbon tetrachloride and thioacetamide administration...
2017: PloS One
https://www.readbyqxmd.com/read/28445523/preventive-child-health-care-at-elementary-school-age-the-costs-of-routine-assessments-with-a-triage-approach
#15
Janine Bezem, Catharina van der Ploeg, Mattijs Numans, Simone Buitendijk, Paul Kocken, Elske van den Akker
BACKGROUND: Triage in Preventive Child Health Care (PCH) assessments could further the efficient use of human resources and budgets and therefore make extra care possible for children with specific needs. We assessed the costs of routine PCH assessments with and without triage for children aged 5/6 years and 10/11 years. In a triage approach, PCH assistants conduct pre-assessments to identify children requiring follow-up assessments by a physician or nurse. In the usual approach, all children are assessed by a physician and an assistant (children aged 5/6 years) or a nurse (children aged 10/11 years)...
2017: PloS One
https://www.readbyqxmd.com/read/28445495/pharmacokinetic-and-pharmacodynamic-modelling-after-subcutaneous-intravenous-and-buccal-administration-of-a-high-concentration-formulation-of-buprenorphine-in-conscious-cats
#16
Graeme M Doodnaught, Beatriz P Monteiro, Javier Benito, Daniel Edge, Francis Beaudry, Ludovic Pelligand, Paulo Steagall
BACKGROUND: The aim of this study was to describe the joint pharmacokinetic-pharmacodynamic model and evaluate thermal antinociception of a high-concentration formulation of buprenorphine (Simbadol™) in cats. METHODS: Six healthy cats (4.9 ± 0.7 kg) were included in a prospective, randomized, blinded, crossover study. Simbadol™ (1.8 mg mL-1) was administered by the subcutaneous (SC; 0.24 mg kg-1), intravenous (IV; 0.12 mg kg-1) or buccal (OTM; 0.12 mg kg-1) route of administration and thermal thresholds (TT) were compared with a saline group (SAL)...
2017: PloS One
https://www.readbyqxmd.com/read/28445472/unsuspected-osteochondroma-like-outgrowths-in-the-cranial-base-of-hereditary-multiple-exostoses-patients-and-modeling-and-treatment-with-a-bmp-antagonist-in-mice
#17
Sayantani Sinha, Christina Mundy, Till Bechtold, Federica Sgariglia, Mazen M Ibrahim, Paul C Billings, Kristen Carroll, Eiki Koyama, Kevin B Jones, Maurizio Pacifici
Hereditary Multiple Exostoses (HME) is a rare pediatric disorder caused by loss-of-function mutations in the genes encoding the heparan sulfate (HS)-synthesizing enzymes EXT1 or EXT2. HME is characterized by formation of cartilaginous outgrowths-called osteochondromas- next to the growth plates of many axial and appendicular skeletal elements. Surprisingly, it is not known whether such tumors also form in endochondral elements of the craniofacial skeleton. Here, we carried out a retrospective analysis of cervical spine MRI and CT scans from 50 consecutive HME patients that included cranial skeletal images...
April 26, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28445409/quantification-of-a-novel-photosensitizer-of-chlorin-e6-c15-monomethyl-ester-in-beagle-dog-plasma-using-hplc-application-to-pharmacokinetic-studies
#18
Xiuxiu Li, Jun Wen, Jingjing Jiang, Xin Zhao, Tingting Zhou, Guorong Fan
Chlorin e6-C15-monomethyl ester (CMME) is a novel photosensitizer, which is synthetized from the degradation products of silkworm excrement. Preclinical studies on the promising photosensitizer CMME are necessary to determine its therapeutic efficacy and druglikeness. A high-performance liquid chromatography with UV detection (HPLC-UV) method was established for the determination of CMME in beagle dog plasma. The sample preparation involved a protein-precipitation method with acetonitrile after the addition of tanshinone IIA as an internal standard (IS)...
April 26, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28445381/regulatory-advocacy-update-american-society-of-plastic-surgeons-comments-in-response-to-the-u-s-food-and-drug-administration-draft-guidance-documents-on-human-cell-and-tissue-products
#19
J Peter Rubin, Richard A D'Amico, Ricardo Rodriguez, Sydney R Coleman, Paul Cederna, Scot Glasberg, Michael Neumeister, David H Song, Charles Butler, Keith M Hume
The U.S. Food and Drug Administration released draft guidance documents on human cells, tissues, and cellular and tissue-based products regulations. These proposed guidance documents can impact the practice of plastic surgery in the area of tissue grafting procedures. This article describes the relevant issues in these draft guidance documents, and presents the comments provided to the U.S. Food and Drug Administration by the American Society of Plastic Surgeons.
May 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28445306/the-efficacy-and-safety-of-epinephrine-for-postoperative-bleeding-in-total-joint-arthroplasty-a-prisma-compliant-meta-analysis
#20
Yanbin Teng, Jianxiong Ma, Xinlong Ma, Ying Wang, Bin Lu, Chaowei Guo
BACKGROUND: Total joint arthroplasty (TJA) usually results in postoperative bleeding. Some randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs) have been performed to evaluate the effects of epinephrine on postoperative bleeding after TJA. However, this remained controversial about the efficacy and safety of epinephrine for postoperative bleeding in TJA. The objective of our meta-analysis was to compare the overall effect and safety of epinephrine and placebo for postoperative bleeding in TJA...
April 2017: Medicine (Baltimore)
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