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Yong Zhou, Tian Liu, Jia-Xi Duan, Ping Li, Guo-Ying Sun, Yong-Ping Liu, Jun Zhang, Liang Dong, Kin Sing Stephen Lee, Bruce D Hammcok, Jian-Xin Jiang, Cha-Xiang Guan
Acute lung injury (ALI) is characterized by rapid alveolar injury, vascular leakage, lung inflammation, neutrophil accumulation, and induced cytokines production leading to lung edema. The mortality rate of patients suffering from ALI remains high. Epoxyeicosatrienoic acids (EETs) are cytochrome P450-dependent derivatives of polyunsaturated fatty acid (PUFA) with anti-hypertensive, profibrinolytic and anti-inflammatory functions. EETs are rapidly hydrated by soluble epoxide hydrolase (sEH) to their less potent diols...
October 6, 2016: Shock
V A Byval'tsev, A E Budaev, V A Sorokovikov, E G Belykh, A A Kalinin, G S Zhdanovich, A O Asantsev, V V Shepelev
Hemorrhages into the structures of the central nervous system are the most life threatening among warfarin-associated complications. There are extremely few reports about spontaneous spinal epidural hematomas (SEH) associated with warfarin, methods of their timely diagnosis, treatment approaches. The authors present the first in the domestic literature case-report of warfarin-associated spontaneous SEH and the literature review.
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
You-Lin Tain, Wei-Chia Lee, Kay L H Wu, Steve Leu, Julie Y H Chan
Hypertension can be programmed in response to nutritional insults in early life. Maternal high-fructose (HF) intake induced programmed hypertension in adult male offspring, which is associated with renal programming and arachidonic acid metabolism pathway. We examined whether early treatment with a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-Deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) can prevent HF-induced programmed hypertension. Pregnant Sprague Dawley rats received regular chow or chow supplemented with fructose (60% diet by weight) during the whole period of pregnancy and lactation...
September 7, 2016: Journal of Nutritional Biochemistry
Ji Hye Jun, Jong Ho Choi, Si Hyun Bae, Seh Hoon Oh, Gi Jin Kim
BACKGROUND/AIMS: Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL)...
September 2016: Clinical and Molecular Hepatology
Zhipeng Li, André-Denis G Wright, Huazhe Si, Xiaoxu Wang, Wenxi Qian, Zhigang Zhang, Guangyu Li
The rumen microbiota plays important roles in nutrient metabolism and absorption of the host. However, it is poorly understood how host genetic variation shapes the community structure of the rumen microbiota and its metabolic phenotype. Here, we used sika deer (Cervus nippon) and elk (Cervus elaphus) to produce the following two types of hybrid offspring: sika deer ♀ × elk ♂ (SEH) and elk ♀ × sika deer ♂ (ESH). Then, we examined the rumen microbiome and metabolites in the parents and their hybrid offspring...
October 7, 2016: Environmental Microbiology Reports
José Guilherme Prado Martin, Gabriela de Oliveira E Silva, Carolina Rodrigues da Fonseca, Caio Baptista Morales, Caroline Souza Pamplona Silva, Daniel Lima Miquelluti, Ernani Porto
Staphylococci are considered a major concern in dairy plants mainly due to the intensive production flow, automation of processing plants and increased demand in the microbiological quality of dairy products. This study aimed to identify S. aureus strains isolated from three Brazilian dairy plants, evaluate the influence of time, temperature and contact surface on the bacterial adhesion process, as well as the efficiency of simulated hygiene and sanitation protocol in removing adhered cells. For genotypic analyses, the presence of icaA and icaD in strains was evaluated...
December 5, 2016: International Journal of Food Microbiology
Jun-Yan Liu, Christophe Morisseau, Huazhang Huang, Bruce D Hammock
ETHNOPHARMACOLOGICAL RELEVANCE: Inhibition of soluble epoxide hydrolase (sEH) has been extensively reported to be anti-inflammatory in multiple animal models. Some anti-inflammatory traditional Chinese medicines (TCMs) and a few natural compounds were also found to be inhibitory to sEH in vitro. AIM OF THE STUDY: To determine whether the active intergradient (AI) against sEH of anti-inflammatory TCMs in vitro is anti-inflammatory in vivo and the sEH inhibitory action of the AI contributes to its anti-inflammatory effect in vivo...
October 1, 2016: Journal of Ethnopharmacology
Liang Dong, Yong Zhou, Zhao-Qiong Zhu, Tian Liu, Jia-Xi Duan, Jun Zhang, Ping Li, Bruce D Hammcok, Cha-Xiang Guan
Triggering receptors expressed on myeloid cell-1 (TREM-1) is a superimmunoglobulin receptor expressed on myeloid cells. TREM-1 amplifies the inflammatory response. Epoxyeicosatrienoic acids (EETs), the metabolites of arachidonic acid derived from the cytochrome P450 enzyme, have anti-inflammatory properties. However, the effects of EETs on TREM-1 expression under inflammatory stimulation remain unclear. Therefore, inhibition of soluble epoxide hydrolase (sEH) with a highly selective inhibitor [1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea, TPPU] was used to stabilize EETs...
October 1, 2016: Inflammation
Christin Boldt, Tom Roeschel, Nina Himmerkus, Allein Plain, Markus Bleich, Robert Labes, Maximilian Blum, Hans Krause, Ahmed Magheli, Torsten Giesecke, Kerim Mutig, Michael Rothe, Steven M Weldon, Duska Dragun, Wolf-Hagen Schunck, Sebastian Bachmann, Alexander Paliege
Activation of the thick ascending limb (TAL) Na+-K+-2Cl--cotransporter (NKCC2) by the antidiuretic hormone arginine-vasopressin (AVP) is an essential mechanism of renal urine concentration and contributes to extracellular fluid and electrolyte homeostasis. AVP effects in the kidney are modulated by locally and/or by systemically produced epoxyeicosatrienoic acid derivates (EET). The relation between AVP and EET metabolism has not been determined. Here we show that chronic treatment of AVP-deficient Brattleboro rats with the AVP V2 receptor analog desmopressin (dDAVP; 5ng/h, 3d) significantly lowered renal EET levels (-56 ± 3% for 5,6-EET, -50 ± 3...
September 28, 2016: American Journal of Physiology. Renal Physiology
K Wagner, K S S Lee, J Yang, B D Hammock
BACKGROUND: Neuropathic pain is a debilitating condition with no adequate therapy. The health benefits of omega-3 fatty acids are established, however, the role of docosahexaenoic acid (DHA) in limiting pain has only recently been described and the mechanisms of this action remain unknown. DHA is metabolized into epoxydocosapentanoic acids (EDPs) via cytochrome P450 (CYP450) enzymes which are substrates for the soluble epoxide hydrolase (sEH) enzyme. Here, we tested several hypotheses; first, that the antinociceptive action of DHA is mediated by the EDPs...
September 15, 2016: European Journal of Pain: EJP
Mikhail Romashko, Joseph Schragenheim, Nader G Abraham, John A McClung
Cardiovascular disease remains the leading cause of death worldwide. Among many potential targets for pharmacological intervention, a promising strategy involves epoxyeicosatrienoic acid (EET) and soluble epoxide hydroxylase (sEH) inhibition. sEH is the enzyme that converts EET to its less potent metabolite; therefore, EET is upregulated by its inhibitor. EET has pleotropic effects that collectively reduce inflammation, while increasing vasodilation and insulin sensitivity. Recent reports indicate that EET agonists and sEH inhibitors are capable of not only reversing endothelial dysfunction and hypertension, but also of reversing cardiac remodeling, which is a hallmark of cardiomyopathy and the metabolic syndrome...
September 12, 2016: Trends in Pharmacological Sciences
Vishal R Yadav, Ka L Hong, Darryl C Zeldin, Mohammed A Nayeem
Soluble epoxide hydrolase (sEH) converts epoxyeicosatrienoic acids that are endothelium-derived hyperpolarizing factors into less active dihydroxyeicosatrienoic acids. Previously, we reported a decrease in adenosine A1 receptor (A1AR) protein levels in sEH knockout (sEH(-/-)) and an increase in sEH and A1AR protein levels in A2AAR(-/-) mice. Additionally, KATP channels are involved in adenosine receptor (AR)-dependent vascular relaxation. Thus, we hypothesize that a potential relationship may exist among sEH over-expression, A1AR upregulation, inactivation of KATP channels, and increased in vascular tone...
November 2016: Molecular and Cellular Biochemistry
Mohamed M Katary, Chelsey Pye, Ahmed A Elmarakby
The pro-inflammatory cyclooxygenase (COX)-derived prostaglandins and the anti-inflammatory cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) play an important role in the regulation of renal injury. The current study examined whether COX inhibition augments the reno-protective effects of increased EETs levels via inhibiting EETs degradation by soluble epoxide hydrolase (sEH) in diabetic rats. Streptozotocin (50mg/kg, i.v) was used to induce diabetes in male Sprague Dawley rats. Rats were then divided into 5 groups (n=6-8); control non diabetic, diabetic, diabetic treated with the sEH inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), diabetic treated with the COX inhibitor meloxicam and diabetic treated with meloxicam plus t-AUCB for 2 months...
September 2, 2016: Prostaglandins & Other Lipid Mediators
Ahmad Hanif, Matthew L Edin, Darryl C Zeldin, Christophe Morisseau, Mohammed A Nayeem
Coronary reactive hyperemia (CRH) is a physiological response to ischemic insult that prevents the potential harm associated with an interruption of blood supply. The relationship between the pharmacologic inhibition of soluble epoxide hydrolase (sEH) and CRH response to a brief ischemia is not known. sEH is involved in the main catabolic pathway of epoxyeicosatrienoic acids (EETs), which are converted into dihydroxyeicosatrienoic acids (DHETs). EETs protect against ischemia/reperfusion injury and have numerous beneficial physiological effects...
2016: PloS One
Ah Reum Jo, Jang Hoon Kim, Xi-Tao Yan, Seo Young Yang, Young Ho Kim
Continuous efforts to identify sEH inhibitors using activity-guided fractionation have revealed 12 known compounds, 2-13, from Rheum undulatum. Compounds 2-13 and 1, which was obtained from the in-house library, were tested for inhibitory activity against sEH. Compounds 1-9, 11, and 12 were shown to have inhibitory activity, with IC50 values ranging from 2.5 ± 0.5 to 53.2 ± 4.4 μM. They were subjected to enzyme kinetic studies to explore the binding mode between the ligand and receptor. Based on our results, compounds 1, 2, 5-9, and 11 (mixed type) and compounds 3 and 12 (noncompetitive type) had a preferred allosteric site...
August 23, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
Emilio Márquez-Contreras, Nieves Martell-Carlos, Vincente Gil-Guillén, Mariano De La Figuera-Von Wichmann, Eugenio Sanchez-López, Sara Márquez-Rivero, Ines Gil-Gil, Enrique Hermida-Campa
OBJECTIVE: To assess compliance to treatment with rivaroxaban in patients with non valvular atrial fibrillation. METHODS: Prospective, longitudinal, multicenter study, developed in 160 Spanish primary or specialized care centers. We included 412 patients treated with rivaroxaban, prescribed for stroke prevention. Three visits were conducted: baseline, 6 and 12 months. Compliance was measured by using electronic monitors (MEMS) that use a digital record in the form of a microchip in the lid of the drug container that automatically controls its opening and registers the time and date of the opening...
August 22, 2016: Current Medical Research and Opinion
Martin Kotev, Robert Soliva, Modesto Orozco
After decades of work, the correct determination of the binding mode of a small molecule into a target protein is still a challenging problem, whose difficulty depends on: (i) the sizes of the binding site and the ligand; (ii) the flexibility of both interacting partners, and (iii) the differential solvation of bound and unbound partners. We have evaluated the performance of standard rigid(receptor)/flexible(ligand) docking approaches with respect to last-generation fully flexible docking methods to obtain reasonable poses in a very challenging case: soluble Epoxide Hydrolase (sEH), a flexible protein showing different binding sites...
October 15, 2016: Bioorganic & Medicinal Chemistry
M A Ferreira, L G Bernardo, L S Neves, M R H Campos, J Lamaro-Cardoso, M C P André
The objectives of this study were to characterize Staphylococcus aureus isolated from artisanal and industrialized Minas frescal cheeses, to determine their antimicrobial susceptibility profile as well as the genetic similarity among the isolates. The isolates were also tested for staphylococcal enterotoxin genes and other virulence factors. Fifty-six artisanal raw milk cheeses sold at street fairs and 10 industrialized cheeses commercialized in supermarkets of Goiânia, Goiás, were analyzed. Staphylococcus aureus was confirmed in 19 samples (33...
August 17, 2016: Journal of Dairy Science
M Hamzaoui, C Roche, A Lejeune, V Brunel, V Richard, J Bellien, D Guerrot
OBJECTIVE: Cardiovascular (CV) events are more prevalent in chronic kidney disease (CKD) than in the general population, being the main cause of morbi-mortality. The aim of this project is to study the CV impact of the increase in the bioavailability of epoxyeicosatrienoic acids (EETs) by inhibiting soluble epoxide hydrolase (sEH) in the 5/6 nephrectomy model in 129/Sv mice. DESIGN AND METHOD: 5/6 Nx mice were treated with the sEH inhibitor t-AUCB, a diuretic (amiloride), or placebo for 10 weeks...
September 2016: Journal of Hypertension
Yukinori Terada, Hiroki Toda, Hirokuni Hashikata, Yu Yamamoto, Yasunori Nagai, Naoya Yoshimoto, Masanori Goto, Namiko Nishida, Koichi Iwasaki
<i>Objective</i>:Non-traumatic spinal epidural hematoma(SEH)is relatively rare. We report five cases of SEH, review the relevant literature, and discuss the current treatment strategies for non-traumatic SEH in Japan. <i>Methods</i>:Clinical data of cases with non-traumatic SEH treated at our institute from 2008 to 2015 were retrospectively analyzed. In addition, we identified the relevant literature using the Japan Medical Abstracts Society databases for peer-reviewed articles published from Jan 1, 1995 to Aug 31, 2015...
August 2016: No Shinkei Geka. Neurological Surgery
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