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https://www.readbyqxmd.com/read/29329031/development-of-a-new-ex-vivo-model-for-evaluation-of-endoscopic-submucosal-injection-materials-performance
#1
Ryohei Hirose, Takaaki Nakaya, Yuji Naito, Tomo Daidoji, Hiroaki Yasuda, Hideyuki Konishi, Yoshito Itoh
BACKGROUND AND AIMS: Development of high-performance submucosal injection materials (SIMs) contribute to the advancement of endoscopic therapy for early-stage gastrointestinal neoplasms. This study aimed to develop a new ex vivo model that mimics the human gastrointestinal tract to evaluate the performance (the height and duration of the submucosal elevation) of various SIMs in detail. METHODS: A new ex vivo model that applies a constant tension to the tested specimen (the porcine gastric specimen) was developed...
January 5, 2018: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/29325946/skip-hemilaminectomy-for-large-multilevel-spinal-epidural-haematomas-report-of-a-series-of-11-patients
#2
Alessandro Di Rienzo, Denise Brunozzi, Mauro Dobran, Maurizio Iacoangeli, Roberto Colasanti, Rikin Trivedi, Massimo Scerrati
OBJECTIVE: We present our experience with a modification of the conventional techniques for the removal of large Spinal Epidural Haematomas (SEHs), based on multilevel "skip hemilaminectomies". METHODS: Eleven patients with SEHs extending over 5 or more spinal segments were treated at our institution using a modified hemilaminectomy technique from 2008 to 2014. This procedure, that we called "skip hemilaminectomy" consists in performing consecutive, alternating, unilateral laminar decompressions at two to three levels, followed by sublaminar undercutting, ipsi- and contralateral flavectomy, plus haematoma removal...
January 8, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29315230/maternal-high-fructose-intake-increases-the-vulnerability-to-post-weaning-high-fat-diet-induced-programmed-hypertension-in-male-offspring
#3
You-Lin Tain, Wei-Chia Lee, Kay L H Wu, Steve Leu, Julie Y H Chan
Widespread consumption of high-fructose and high-fat diets relates to the global epidemic of hypertension. Hypertension may originate from early life by a combination of prenatal and postnatal nutritional insults. We examined whether maternal high-fructose diet increases vulnerability to post-weaning high-fructose or high-fat diets induced hypertension in adult offspring and determined the underlying mechanisms. Pregnant Sprague-Dawley rats received regular chow (ND) or chow supplemented with 60% fructose (HFR) during the entire pregnancy and lactation periods...
January 9, 2018: Nutrients
https://www.readbyqxmd.com/read/29311641/blockade-of-soluble-epoxide-hydrolase-attenuates-post-ischemic-neuronal-hyperexcitation-and-confers-resilience-against-stroke-with-trkb-activation
#4
Li-Hsin Chang, Hui-Ching Lin, Shiang-Suo Huang, I-Chih Chen, Kai-Wen Chu, Chun-Lien Chih, Yao-Wen Liang, Yi-Chung Lee, You-Yin Chen, Yi-Hsuan Lee, I-Hui Lee
Inhibition and deletion of soluble epoxide hydrolase (sEH) has been suggested to ameliorate infarction in experimental ischemic stroke possibly via vasoactive epoxyeicosatrienoic acids. However, it is unknown whether the neuroprotective mechanisms involve alteration of post-ischemic neuronal transmission and neurotrophic signaling. We used a permanent middle cerebral artery occlusion (MCAO) model in adult wild-type mice with the sEH inhibitor 12-(3-adamantan-1-yl-ureido)dodecanoic acid (AUDA) post-treatment and in sEH knockout (sEH KO) mice...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29310082/effects-of-adamantane-alterations-on-soluble-epoxide-hydrolase-inhibition-potency-physical-properties-and-metabolic-stability
#5
Vladimir Burmistrov, Christophe Morisseau, Todd R Harris, Gennady Butov, Bruce D Hammock
Adamantyl groups are widely used in medicinal chemistry. However, metabolism limits their usage. Herein, we report the first systematic study of adamantyl ureas and diureas bearing substituents in bridgehead positions of adamantane and/or spacers between urea groups and adamantane group, and tested their effects on soluble epoxide hydrolase inhibitor potency and metabolic stability. Interestingly, the effect on activity against human and murine sEH varied in opposite ways with each new methyl group introduced into the molecule...
December 30, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29303257/unbiased-molecular-dynamics-of-11-min-timescale-drug-unbinding-reveals-transition-state-stabilizing-interactions
#6
Samuel D Lotz, Alex Dickson
Ligand (un)binding kinetics is being recognized as a determinant of drug specificity and efficacy in an increasing number of systems. However, the calculation of kinetics and the simulation of drug unbinding is more difficult than computing thermodynamic quantities, such as binding free energies. Here we present the first full simulations of an unbinding process at pharmacologically relevant time scales (11 min), without the use of biasing forces, detailed prior knowledge, or specialized processors using the weighted ensemble based algorithm, WExplore...
January 5, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29295935/estrogen-dependent-epigenetic-regulation-of-soluble-epoxide-hydrolase-via-dna-methylation
#7
Yang-Ming Yang, Dong Sun, Sharath Kandhi, Ghezal Froogh, Jian Zhuge, Weihua Huang, Bruce D Hammock, An Huang
To elucidate molecular mechanisms responsible for the sexually dimorphic phenotype of soluble epoxide hydrolase (sEH) expression, we tested the hypothesis that female-specific down-regulation of sEH expression is driven by estrogen-dependent methylation of the Ephx2 gene. Mesenteric arteries isolated from male, female, ovariectomized female (OV), and OV with estrogen replacement (OVE) mice, as well as the human cell line (HEK293T) were used. Methylation-specific PCR and bisulfite genomic sequencing analysis indicate significant increases in DNA/CG methylation in vessels of female and OVE compared with those of male and OV mice...
January 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29285425/active-maintenance-of-endothelial-cells-prevents-kidney-fibrosis
#8
Seung Hee Yang, Yong Chul Kim, Jung Nam An, Jin Hyuk Kim, Juhoh Lee, Hee-Yoon Lee, Joo-Youn Cho, Jin Ho Paik, Yun Kyu Oh, Chun Soo Lim, Yon Su Kim, Jung Pyo Lee
Background: Soluble epoxide hydrolase (sEH) expressed by endothelial cells catalyzes the metabolism of epoxyeicosatrienoic acids (EETs), which are vasoactive agents. Methods: We used a unilateral ureteral obstruction mouse model of kidney fibrosis to determine whether inhibition of sEH activity reduces fibrosis, the final common pathway for chronic kidney disease. Results: sEH activity was inhibited by continuous release of the inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA) for 1 or 2 weeks...
December 2017: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/29284644/cox-2-seh-dual-inhibitor-ptupb-potentiates-the-anti-tumor-efficacy-of-cisplatin
#9
Fuli Wang, Hongyong Zhang, Ai-Hong Ma, Weimin Yu, Maike Zimmermann, Jun Yang, Sung Hee Hwang, Daniel Zhu, Tzu-Yin Lin, Michael Malfatti, Kenneth W Turteltaub, Paul T Henderson, Susan Airhart, Bruce D Hammock, Jianlin Yuan, Ralph W de Vere White, Chong-Xian Pan
Cisplatin-based therapy is highly toxic, but moderately effective in most cancers. Concurrent inhibition of cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) results in anti-tumor activity, and has organ protective effects. The goal of this study was to determine the anti-tumor activity of PTUPB, an orally bioavailable COX-2/sEH dual inhibitor, in combination with cisplatin and gemcitabine (GC) therapy. NSG mice bearing bladder cancer patient-derived xenografts were treated with vehicle, PTUPB, cisplatin, GC or combinations thereof...
December 28, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29232926/differential-effects-of-seh-inhibitors-on-the-proliferation-and-migration-of-vascular-smooth-muscle-cells
#10
Hyo Seon Kim, Sang Kyum Kim, Keon Wook Kang
Epoxyeicosatrienoic acid (EET) is a cardioprotective metabolite of arachidonic acid. It is known that soluble epoxide hydrolase (sEH) is involved in the metabolic degradation of EET. The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in the pathogenesis of atherosclerosis and restenosis. Thus, the present study investigated the effects of the sEH inhibitor 12-(((tricyclo(3.3.1.13,7)dec-1-ylamino)carbonyl)amino)-dodecanoic acid (AUDA) on platelet-derived growth factor (PDGF)-induced proliferation and migration in rat VSMCs...
December 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29212229/solid-formulation-of-a-supersaturable-self-microemulsifying-drug-delivery-system-for-valsartan-with-improved-dissolution-and-bioavailability
#11
Dong Woo Yeom, Bo Ram Chae, Jin Han Kim, Jun Soo Chae, Dong Jun Shin, Chang Hyun Kim, Sung Rae Kim, Ji Ho Choi, Seh Hyon Song, Dongho Oh, Se Il Sohn, Young Wook Choi
In order to improve the dissolution and oral bioavailability of valsartan (VST), and reduce the required volume for treatment, we previously formulated a supersaturable self-microemulsifying drug delivery system (SuSMEDDS) composed of VST (80 mg), Capmul® MCM (13.2 mg), Tween® 80 (59.2 mg), Transcutol® P (59.2 mg), and Poloxamer 407 (13.2 mg). In the present study, by using Florite® PS-10 (119.1 mg) and Vivapur® 105 (105.6 mg) as solid carriers, VST-loaded solidified SuSMEDDS (S-SuSMEDDS) granules were successfully developed, which possessed good flow properties and rapid drug dissolution...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29211719/inhibition-of-soluble-epoxide-hydrolase-prevents-diabetic-retinopathy
#12
Jiong Hu, Sarah Dziumbla, Jihong Lin, Sofia-Iris Bibli, Sven Zukunft, Julian de Mos, Khader Awwad, Timo Frömel, Andreas Jungmann, Kavi Devraj, Zhixing Cheng, Liya Wang, Sascha Fauser, Charles G Eberhart, Akrit Sodhi, Bruce D Hammock, Stefan Liebner, Oliver J Müller, Clemens Glaubitz, Hans-Peter Hammes, Rüdiger Popp, Ingrid Fleming
Diabetic retinopathy is an important cause of blindness in adults, and is characterized by progressive loss of vascular cells and slow dissolution of inter-vascular junctions, which result in vascular leakage and retinal oedema. Later stages of the disease are characterized by inflammatory cell infiltration, tissue destruction and neovascularization. Here we identify soluble epoxide hydrolase (sEH) as a key enzyme that initiates pericyte loss and breakdown of endothelial barrier function by generating the diol 19,20-dihydroxydocosapentaenoic acid, derived from docosahexaenoic acid...
December 6, 2017: Nature
https://www.readbyqxmd.com/read/29206762/soluble-epoxide-hydrolase-plays-a-vital-role-in-angiotensin-ii-induced-lung-injury-in-mice
#13
Wei Tao, Ping-Song Li, Gang Xu, Yi Luo, Yu-Sheng Shu, Yong-Zhong Tao, Liu-Qing Yang
BACKGROUND: Angiotensin II plays a vital role in the pathogenesis of acute respiratory distress syndrome (ARDS). However, its mechanism is not well defined. Angiotensin II up-regulates the expression of soluble epoxide hydrolase (sEH; Ephx2). sEH is suggested as a potential pharmacologic target for ARDS. The present study investigates whether the sEH is involved in the angiotensin II triggered pulmonary inflammation and edema using an angiotensin II-induced lung injury animal model. METHODS: Lung injury was induced by angiotensin II intratracheally instillation in wild-type or Ephx2 deficient mice...
December 4, 2017: Shock
https://www.readbyqxmd.com/read/29200772/sclerema-neonatorum-in-a-full-term-infant-showing-favorable-prognosis
#14
Seh Hyun Park, Soo-Chan Kim
Sclerema neonatorum (SN) is a rare disease characterized by firm, indurated, waxy skin lesions extending throughout the body, sparing the fat-free soles, palms, and genitalia. The prognosis of SN is generally very poor, with a high fatality rate. We report the case of a full-term infant with delayed onset of SN showing good prognosis. A 4-month-old Korean male infant presented with diffuse waxy, sclerotic skin lesions on the whole body, sparing the face, nipples, and genital area, which began developing at 2 months of age...
December 2017: Annals of Dermatology
https://www.readbyqxmd.com/read/29196978/the-role-of-soluble-epoxide-hydrolase-enzyme-on-daunorubicin-mediated-cardiotoxicity
#15
Zaid H Maayah, Ghada Abdelhamid, Osama H Elshenawy, Ahmed A El-Sherbeni, Hassan N Althurwi, Erica McGinn, Doaa Dawood, Ahmad H Alammari, Ayman O S El-Kadi
Several studies have demonstrated the role of cytochrome P450 (CYP) and its associated arachidonic acid (AA) metabolites in the anthracyclines-induced cardiac toxicity. However, the ability of daunorubicin (DNR) to induce cardiotoxicity through the modulation of CYP and its associated AA metabolites has not been investigated yet. Therefore, we hypothesized that DNR-induced cardiotoxicity is mediated through the induction of cardiotoxic hydroxyeicosatetraenoic acids and/or the inhibition of cardioprotctive epoxyeicosatrienoic acids (EETs)...
December 1, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29193961/chemical-proteomics-reveals-soluble-epoxide-hydrolase-as-a-therapeutic-target-for-ocular-neovascularization
#16
Rania S Sulaiman, Bomina Park, Sardar Pasha Sheik Pran Babu, Yubing Si, Rakshin Kharwadkar, Sayak K Mitter, Bit Lee, Wei Sun, Xiaoping Qi, Michael E Boulton, Samy O Meroueh, Xiang Fei, Seung-Yong Seo, Timothy W Corson
The standard-of-care therapeutics for the treatment of ocular neovascular diseases like wet age-related macular degeneration (AMD) are biologics targeting vascular endothelial growth factor signaling. There are currently no FDA approved small molecules for treating these blinding eye diseases. Therefore, therapeutic agents with novel mechanisms are critical to complement or combine with existing approaches. Here, we identified soluble epoxide hydrolase (sEH), a key enzyme for epoxy fatty acid metabolism, as a target of an antiangiogenic homoisoflavonoid, SH-11037...
December 1, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29178914/genetic-deletion-or-pharmacological-inhibition-of-soluble-epoxide-hydrolase-reduces-brain-damage-and-attenuates-neuroinflammation-after-intracerebral-hemorrhage
#17
Chun-Hu Wu, Song-Kun Shyue, Tai-Ho Hung, Shin Wen, Chao-Chang Lin, Che-Feng Chang, Szu-Fu Chen
BACKGROUND: Inflammatory responses significantly contribute to neuronal damage and poor functional outcomes following intracerebral hemorrhage (ICH). Soluble epoxide hydrolase (sEH) is known to induce neuroinflammatory responses via degradation of anti-inflammatory epoxyeicosatrienoic acids (EET), and sEH is upregulated in response to brain injury. The present study investigated the involvement of sEH in ICH-induced neuroinflammation, brain damage, and functional deficits using a mouse ICH model and microglial cultures...
November 25, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29178873/prevalence-and-molecular-characterization-of-staphylococcus-aureus-isolated-from-goats-in-chongqing-china
#18
Zuoyong Zhou, Mengsi Zhang, Hexian Li, Haoyue Yang, Xiaoxia Li, Xinyue Song, Zhiying Wang
BACKGROUND: Staphylococcus aureus is an important zoonotic pathogen which not only causes significant economic loss in livestock production but also poses a potential threat to public health. Compared with bovine and swine, the information on the colonization of S. aureus in goats is very limited. To understand the prevalence and characteristics of S. aureus in goats, we used the nasal swabs collected from apparently healthy goats to isolate S. aureus, and tested their antimicrobial susceptibility, virulence gene carrying levels, and multilocus sequence typing (MLST)...
November 25, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29178307/influence-of-postoperative-hypertension-on-the-development-of-spinal-epidural-hematoma
#19
Tetsuro Ohba, Shigeto Ebata, Hirotaka Haro
Spinal epidural hematoma (SEH) is a rare postoperative complication but can result in catastrophic neurological deficits requiring immediate surgical evacuation of the hematoma. Knowing the risk factors for postoperative SEH can help surgeons stratify patients. Therefore, to identify possible risk factors for postoperative SEH, we reviewed 6 clinical cases and examined the relation between postoperative hypertension and the risk of developing SEH. A retrospective review was conducted of 1282 consecutive patients who underwent spinal surgery at a single institution between 2010 and 2015...
November 2017: Orthopaedic Surgery
https://www.readbyqxmd.com/read/29169114/evaluation-of-antiparkinson-activity-of-ptupb-by-measuring-dopamine-and-its-metabolites-in-drosophila-melanogaster-lc-ms-ms-method-development
#20
Navya Lakkappa, Praveen T Krishnamurthy, Karthik Yamjala, Sung Hee Hwang, Bruce D Hammock, B Babu
Soluble epoxide hydrolase (sEH) inhibition is reported to elevate endogenous epoxyeicosatrienoic acids (EET's), which are known to play an important role in neuroprotection by inhibiting oxidative stress and neuroinflammation. In the present study, PTUPB, a dual inhibitor of sEH and COX-2, has been tested for its antiparkinson activity against rotenone (ROT) induced neurodegeneration in Drosophila model of Parkinson's disease (PD). To determine the efficacy and brain bioavailability of PTUPB a simple, rapid and sensitive LC-MS/MS method was developed and validated for the estimation of PTUPB (Method-I), dopamine (DA) and its metabolites (Method-II) in fly head...
November 16, 2017: Journal of Pharmaceutical and Biomedical Analysis
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