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Jan M Klenk, Max-Philipp Fischer, Paulina Dubiel, Mahima Sharma, Benjamin Rowlinson, Gideon Grogan, Bernhard Hauer
Cytochrome P450 monooxygenases (P450s) play crucial roles in the cell metabolism and provide an unsurpassed diversity of catalyzed reactions. Here, we report the identification and biochemical characterization of two P450s from Arthrobacter sp., a gram-positive organism known to degrade the opium alkaloid papaverine. Combining phylogenetic and genomic analysis suggested physiological roles for P450s in metabolism, and revealed potential gene clusters with redox partners facilitating the reconstitution of the P450 activities in vitro...
February 13, 2019: Journal of Biochemistry
Ran Marciano, Manu Prasad, Tal Ievy, Sapir Tzadok, Gabriel Leprivier, Moshe Elkabets, Barak Rotblat
Tumor cells utilize glucose to fuel their anabolic needs, including rapid proliferation. However, due to defective vasculature and increased glucose uptake, tumor cells must overcome glucose deprivation. Accordingly, tumor cells depend on cellular pathways promoting survival under such conditions. Targeting these survival mechanisms can thus serve as a new therapeutic strategy in oncology. As such, we sought to identify small-molecule inhibitors which sensitize tumor cells to glucose starvation by high-throughput drug screening in vitro...
January 30, 2019: Cancers
Antonella Riva, Luca Giacomelli, Stefano Togni, Federico Franceschi, Roberto Eggenhoffner, Maria Chiara Zuccarini, Gianni Belcaro
BACKGROUND: The purpose of this study was to evaluate the long-term efficacy and the safety of a lecithin-based delivery form of boswellic acids from Boswellia serrata (Casperome®) for the prevention of symptoms in otherwise healthy subjects with mild irritable bowel syndrome (IBS). METHODS: The study included 69 otherwise healthy participants with a mild form of IBS who completed a 6-month follow-up period. In total, 34 subjects were assigned to the standard management (SM) group: diet and, if needed, hyoscine butylbromide (Buscopan®) or papaverine hydrochloride + 10 mg of Atropa belladonna extract; 35 subjects were assigned to supplementation with the Boswellia serrata lecithin-based delivery form (one tablet/day; Casperome®)...
March 2019: Minerva Gastroenterologica e Dietologica
Reza Salemmilani, Rustin Y Mirsafavi, Augustus W Fountain, Martin Moskovits, Carl D Meinhart
Direct detection, or inferring the presence of illicit substances, is of great forensic and toxicological value. Surface-enhanced Raman spectroscopy (SERS) has been shown capable of detecting such molecules in a quick and sensitive manner. Herein we describe an analysis strategy for quantitation of low concentrations of three analytes (methamphetamine, cocaine, and papaverine) by SERS analysis using the citrate capping agent that initially saturates the silver nanoparticles' surface as an in situ standard. The citrate is subsequently displaced by the analyte to an extent dependent on the analyte's concentration in the analyte solution...
January 23, 2019: Analyst
Omer Tanyeli, Ipek Duman, Yuksel Dereli, Niyazi Gormus, Hatice Toy, Ayse Saide Sahin
BACKGROUND: Radial artery (RA) is widely used in coronary artery bypass (CABG) surgery and the prevention of spasm is crucial for graft patency. Botulinum toxin A (BTX-A) and B are commonly used for aesthetic reasons and neuromuscular disorders. They are proven to raise blood flow and increase survival of ischemic skin flaps. In this study we evaluated and compared the vasodilator effects of BTX-A and papaverine on human RA grafts. METHODS: After resting 60 min in isolated organ baths, human RA grafts were examined...
January 21, 2019: Journal of Cardiothoracic Surgery
Piotr Węgrzyn, Grzegorz Lis, Paweł Rudzinski, Jacek Piatek, Grazyna Pyka-Fosciak, Ryszard Korbut, Boguslaw Kapelak, Krzysztof Bartus, Radoslaw Litwinowicz
OBJECTIVE: The aim of this study was to compare the efficacy of two different papaverine concentrations (0.5 mg/ml and 2 mg/ml) for vasospasm prevention and their impact on endothelium integrity. METHODS: We have studied distal segments of radial arteries obtained by no-touch technique from coronary artery bypass graft (CABG) patients (n=10). The vasodilatory effect of papaverine (concentrations of 0.5 mg/ml and 2 mg/ml) was assessed in vitro, in isometric tension studies using ex vivo myography (organ bath technique) and arterial rings precontracted with potassium chloride (KCl) and phenylephrine...
November 2018: Brazilian Journal of Cardiovascular Surgery
Ricardo Jorge Dinis-Oliveira
Opium poppy has important medical, socioeconomic, forensic and political implications. More than 80 benzylisoquinoline alkaloids have been described, many of them with relevant therapeutic properties such as morphine, codeine, papaverine and noscapine. Heroin, a semi-synthetic drug produced from morphine is a worldwide serious cause of morbidity and mortality. Heroin dependence is complex phenomenon with environmental and genetic influence, and several biomarkers of exposure have been proposed. This work aims to review the metabolism and metabolomics of opiates with particular interest on their relevance as potential clinical and forensic antemortem and postmortem biomarkers...
February 2019: Journal of Forensic and Legal Medicine
Shogo Itabashi, Rina Bito, Maika Nishina, Maki Fukumoto, Midori Soda, Mitsunori Doi, Shigeyuki Usui, Kiyoyuki Kitaichi
AIM: Lamotrigine (LTG) is a widely used anti-epileptic drug that is administered to avoid seizures and to maintain seizure-free status. However, several factors reportedly cause individual differences of plasma LTG levels, and the therapeutic target range of LTG varies between individuals. Thus, to optimize effective doses of LTG, we developed a rapid and simple method for determining plasma LTG concentrations. METHODS: Lamotrigine and the internal standard papaverine were extracted from human plasma using solid-phase extraction...
January 2, 2019: Neuropsychopharmacology reports
Miloš Dvořák, Pavel Kubáň
Planar polyamide 6 nanofibrous membrane was for the first time used in direct coupling of supported liquid membrane (SLM) extraction to CE analysis. Disposable microextraction device with the nanofibrous membrane was preassembled and stored for immediate use. The membrane in the device was impregnated with 1 μL of 1-ethyl-2-nitrobenzene and the device was subsequently filled with 10 μL of acceptor solution (10 mM HCl) and 15 μL of donor solution (sample). The device was in-line coupled to CE system for selective extraction and direct injection, separation and quantification of model basic drugs (nortriptyline, haloperidol, loperamide and papaverine) from standard saline solutions (150 mM NaCl) and from undiluted human body fluids (urine and blood plasma)...
December 23, 2018: Electrophoresis
Chen Shen, Wanli Zhao, Xuming Liu, Jihua Liu
OBJECTIVES: To investigate the regio-selective demethylation of papaverine by CYP105D1 and develop a whole-cell biocatalytic system for the preparative synthesis of 6-O-demethyl-papaverine. RESULTS: CYP105D1 from Streptomyces griseus ATCC 13273 was used for the regioselective demethylation of papaverine at C-6 using putidaredoxin reductase (PDR) and putidaredoxin (Pdx) as the electron transport system. The Km value of CYP105D1 towards papaverine was estimated to be 92...
November 21, 2018: Biotechnology Letters
(no author information available yet)
No abstract text is available yet for this article.
November 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jong Soo Han, Su Jin Kim, Yoonjin Nam, Hak Yeong Lee, Geon Min Kim, Dong Min Kim, Uy Dong Sohn
Most diabetic patients experience diabetic mellitus (DM) urinary bladder dysfunction. A number of studies evaluate bladder smooth muscle contraction in DM. In this study, we evaluated the change of bladder smooth muscle contraction between normal rats and DM rats. Furthermore, we used pharmacological inhibitors to determine the differences in the signaling pathways between normal and DM rats. Rats in the DM group received an intraperitoneal injection of 65 mg/kg streptozotocin and measured blood glucose level after 14 days to confirm DM...
November 12, 2018: Biomolecules & Therapeutics
Jian-Lin Hu, Hui-Xing Chen, Hui-Rong Chen, Yu Wu, Xiao-Wen Sun, Zheng Li, Jin-Fang Xing
Structural alterations in fibroelastic components of the penile corpus cavernousum (CC) may impair its compliance, resulting in venous leakage and erectile dysfunction (ED). Our study evaluated the effectiveness of noninvasive two-dimensional shear-wave elastography (2-D SWE) in quantifying penile CC lesions in rabbits with hyperlipidemia-induced ED. A total of 12 New Zealand white rabbits were randomly divided into two groups. Six were fed a high-cholesterol diet containing 2% cholesterol and 8.5% lard for 10 weeks and the other six were fed normal diet as controls...
November 2, 2018: Asian Journal of Andrology
Ying Cheng, Zhi-Meng Wang, Weiqi Tan, Xiaona Wang, Yujing Li, Bing Bai, Yuxin Li, Shuang-Feng Zhang, Hai-Liang Yan, Zuo-Lun Chen, Chang-Mei Liu, Ting-Wei Mi, Shuting Xia, Zikai Zhou, An Liu, Gang-Bin Tang, Cong Liu, Zhi-Jie Dai, Ying-Ying Wang, Hong Wang, Xusheng Wang, Yunhee Kang, Li Lin, Zhenping Chen, Nina Xie, Qinmiao Sun, Wei Xie, Junmin Peng, Dahua Chen, Zhao-Qian Teng, Peng Jin
Genetic analyses have linked microRNA-137 (MIR137) to neuropsychiatric disorders, including schizophrenia and autism spectrum disorder. miR-137 plays important roles in neurogenesis and neuronal maturation, but the impact of miR-137 loss-of-function in vivo remains unclear. Here we show the complete loss of miR-137 in the mouse germline knockout or nervous system knockout (cKO) leads to postnatal lethality, while heterozygous germline knockout and cKO mice remain viable. Partial loss of miR-137 in heterozygous cKO mice results in dysregulated synaptic plasticity, repetitive behavior, and impaired learning and social behavior...
December 2018: Nature Neuroscience
Victor Curvello, Philip Pastor, Hugh Hekierski, William M Armstead
OBJECTIVE: Traumatic brain injury (TBI) is an important contributor to morbidity and mortality. Cerebral autoregulation is impaired after TBI, contributing to poor outcome. Extracellular signal-related kinase (ERK) mitogen activated protein kinase (MAPK) and ET-1 are upregulated and contribute to impairment of cerebral autoregulation and histopathology after porcine fluid percussion brain injury (FPI). Recent studies show that inhaled nitric oxide (iNO) prevents impairment of cerebral autoregulation and histopathology after FPI in pigs...
November 1, 2018: Neurocritical Care
Shuhei Yoshida, Isao Koshima, Ayano Sasaki, Yumio Fujioka, Shogo Nagamatsu, Kazunori Yokota, Shuji Yamashita, Mitsunobu Harima
Despite advances in supermicrosurgical techniques, the ability to anastomose vessels with a diameter of less than 0.2 mm remains limited. One of the reasons for this limitation is that the dilation methods currently available, such as inserting the tip of a microforceps into the lumen or topical application of a vasodilator such as papaverine hydrochloride or xylocaine spray, are not effective in very small vessels. To overcome this problem, we have developed a method whereby nylon monofilaments are placed inside the vessel lumen to act as a dilator...
October 9, 2018: Annals of Plastic Surgery
Sik Namgoong, Jong-Phil Yang, Seong Ho Jeong, Seung Kyu Han, Woo Kyung Kim, Eun Sang Dhong
Microvascular free flap transfer has become a prevailing surgery with a failure rate of <5%. However, pedicle thrombosis occurs more frequently than indicated by the failure rate. This difference is due to the successful salvage of failing flaps. During exploration, thrombi are often encountered at anastomotic sites, whereas these causes could not explain vascular compromise in other patients. Thus, we hypothesized that thrombogenic processes might occur at remote sites, specifically within microvessels of the transferred flap...
October 4, 2018: Journal of Plastic Surgery and Hand Surgery
Rachel K Smith, Rebecca J Stacey, Ed Bergström, Jane Thomas-Oates
A method has been developed for extracting poppy alkaloids from oily matrices, specifically lipid residues associated with archaeological ceramics. The protocol has been applied to fresh and artificially aged poppyseed oil and to residue from a Late Bronze Age Cypriot juglet in the collections of the British Museum. The juglet is of a type that has been linked with ancient trade in opium due to its poppy-head shape and wide distribution; it is a rare example of an intact vessel with contents sealed inside. Bulk analysis of the residue by GC-EI-MS and pyGC-EI-MS indicated a degraded plant oil and possible presence of papaverine...
October 3, 2018: Analyst
Szilvia Berkó, Stella Zsikó, Gábor Deák, Attila Gácsi, Anita Kovács, Mária Budai-Szűcs, László Pajor, Zoltán Bajory, Erzsébet Csányi
Purpose: Papaverine hydrochloride (PaHCl) is an old, well-known drug with spasmolytic activity but it has therapeutic effect in erectile dysfunction, too. As an intracavernous injection, it is not used in urologic clinics today because the side effects of the injection are pain, scarring or priapism. Our aim was to develop and test a topical semi-solid preparation containing PaHCl that would provide an alternative administration option by eliminating the undesirable side effects of the injection...
2018: Drug Design, Development and Therapy
Jonathan Hédouin, Cédric Schneider, Isabelle Gillaizeau, Christophe Hoarau
Palladium-catalyzed intramolecular carbopalladation onto allenamides completed by direct C-H allylation of heterocycles is studied. The domino construction/heteroarylation of isoquinolone process is first achieved. A general three-step one-pot strategy, involving in situ generation of allenamide, π-allyl-Pd complex generation, and interception with heteroarenes, has been subsequently set up. This methodology has been extended to the construction/heteroarylation of indoles, dihydroquinolines, isoquinolin(on)es, and medium-sized nitrogen heterocycles, which are known to be key challenging structural motifs with pharmaceutical significance...
October 5, 2018: Organic Letters
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