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https://www.readbyqxmd.com/read/29051065/dihydroergotamine-mesylate-loaded-dissolving-microneedle-patch-made-of-polyvinylpyrrolidone-for-management-of-acute-migraine-therapy
#1
Cetin Tas, Jessica C Joyce, Hiep X Nguyen, Padmanabhan Eangoor, Jennifer S Knaack, Ajay K Banga, Mark R Prausnitz
Migraine is a widespread neurological disease with negative effects on quality of life and productivity. Moderate to severe acute migraine attacks can be treated with dihydroergotamine mesylate (DHE), an ergot derivative that is especially effective in non-responders to triptan derivatives. To overcome limitations of current DHE formulations in subcutaneous injection and nasal spray such as pain, adverse side effects and poor bioavailability, a new approach is needed for DHE delivery enabling painless self-administration, quick onset of action, and high bioavailability...
October 16, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29022279/the-role-of-%C3%AE-1-and-%C3%AE-2-adrenoceptor-subtypes-in-the-vasopressor-responses-induced-by-dihydroergotamine-in-ritanserin-pretreated-pithed-rats
#2
Eduardo Rivera-Mancilla, Victor H Avilés-Rosas, Guadalupe Manrique-Maldonado, Alain H Altamirano-Espinoza, Belinda Villanueva-Castillo, Antoinette MaassenVanDenBrink, Carlos M Villalón
BACKGROUND: Dihydroergotamine (DHE) is an acute antimigraine agent that displays affinity for dopamine D2-like receptors, serotonin 5-HT1/2 receptors and α1/α2-adrenoceptors. Since activation of vascular α1/α2-adrenoceptors results in systemic vasopressor responses, the purpose of this study was to investigate the specific role of α1- and α2-adrenoceptors mediating DHE-induced vasopressor responses using several antagonists for these receptors. METHODS: For this purpose, 135 male Wistar rats were pithed and divided into 35 control and 100 pretreated i...
October 11, 2017: Journal of Headache and Pain
https://www.readbyqxmd.com/read/28989026/activation-of-nuclear-%C3%AE-catenin-c-myc-axis-promotes-oxidative-stress-injury-in-streptozotocin-induced-diabetic-cardiomyopathy
#3
Peng Liu, Jianfang Su, Xixi Song, Shixiao Wang
Myocardial oxidative stress injury plays a crucial role in the pathogenesis of diabetic cardiomyopathy (DCM). Wnt/β-catenin signaling has been reported to involve in various heart diseases. However, the underlying mechanism associated with β-catenin in DCM remains elusive. This study intended to explore the effect of β-catenin on oxidative damage of DCM by establishing streptozotocin (STZ)-induced diabetic mouse model and hydrogen peroxide (H2O2)-treated myocardial cell model. Cardiac oxidative stress in DCM was detected by measurements of lipid peroxidation and anti-oxidative enzyme activities as well as DHE staining...
October 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28967922/inhibition-of-usp10-induces-degradation-of-oncogenic-flt3
#4
Ellen L Weisberg, Nathan J Schauer, Jing Yang, Ilaria Lamberto, Laura Doherty, Shruti Bhatt, Atsushi Nonami, Chengcheng Meng, Anthony Letai, Renee Wright, Hong Tiv, Prafulla C Gokhale, Maria Stella Ritorto, Virginia De Cesare, Matthias Trost, Alexandra Christodoulou, Amanda Christie, David M Weinstock, Sophia Adamia, Richard Stone, Dharminder Chauhan, Kenneth C Anderson, Hyuk-Soo Seo, Sirano Dhe-Paganon, Martin Sattler, Nathanael S Gray, James D Griffin, Sara J Buhrlage
Oncogenic forms of the kinase FLT3 are important therapeutic targets in acute myeloid leukemia (AML); however, clinical responses to small-molecule kinase inhibitors are short-lived as a result of the rapid emergence of resistance due to point mutations or compensatory increases in FLT3 expression. We sought to develop a complementary pharmacological approach whereby proteasome-mediated FLT3 degradation could be promoted by inhibitors of the deubiquitinating enzymes (DUBs) responsible for cleaving ubiquitin from FLT3...
October 2, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28961281/chronic-administration-of-mitochondrion-targeted-peptide-ss-31-prevents-atherosclerotic-development-in-apoe-knockout-mice-fed-western-diet
#5
Meng Zhang, Hongting Zhao, Jing Cai, Huihui Li, Qi Wu, Tong Qiao, Kuanyu Li
BACKGROUND: Oxidative stress and inflammatory factors are deeply involved in progression of atherosclerosis. Mitochondrion-targeted peptide SS-31, selectively targeting to mitochondrial inner membrane reacting with cardiolipin, has been reported to inhibit ROS generation and mitigate inflammation. The present study was designed to investigate whether SS-31 could suppress the development of atherosclerosis in vivo. METHODS: Male ApoE-/- mice (8 weeks old) fed with Western diet were treated with normal saline or SS-31 (1 mg/kg/d or 3 mg/kg/d) through subcutaneous injection for 12 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28931831/hyperhomocysteinemia-alters-retinal-endothelial-cells-barrier-function-and-angiogenic-potential-via-activation-of-oxidative-stress
#6
Riyaz Mohamed, Isha Sharma, Ahmed S Ibrahim, Heba Saleh, Nehal M Elsherbiny, Sadanand Fulzele, Khaled Elmasry, Sylvia B Smith, Mohamed Al-Shabrawey, Amany Tawfik
Hyperhomocysteinemia (HHcy) is associated with several human visual disorders, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Breakdown of the blood-retinal barrier (BRB) is linked to vision loss in DR and AMD. Our previous work revealed that HHcy altered BRB in retinal endothelial cells in vivo. Here we hypothesize that homocysteine (Hcy) alters retinal endothelial cell barrier function and angiogenic potential via activation of oxidative stress. Human retinal endothelial cells (HRECs) treated with and without different concentrations of Hcy showed a reduction of tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance and increased angiogenic potential...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28926338/melk-is-not-necessary-for-the-proliferation-of-basal-like-breast-cancer-cells
#7
Hai-Tsang Huang, Hyuk-Soo Seo, Tinghu Zhang, Yubao Wang, Baishan Jiang, Qing Li, Dennis L Buckley, Behnam Nabet, Justin M Roberts, Joshiawa Paulk, Shiva Dastjerdi, Georg E Winter, Hilary McLauchlan, Jennifer Moran, James E Bradner, Michael J Eck, Sirano Dhe-Paganon, Jean J Zhao, Nathanael S Gray
Thorough preclinical target validation is essential for the success of drug discovery efforts. In this study, we combined chemical and genetic perturbants, including the development of a novel selective maternal embryonic leucine zipper kinase (MELK) inhibitor HTH-01-091, CRISPR/Cas9-mediated MELK knockout, a novel chemical-induced protein degradation strategy, RNA interference and CRISPR interference to validate MELK as a therapeutic target in basal-like breast cancers (BBC). In common culture conditions, we found that small molecule inhibition, genetic deletion, or acute depletion of MELK did not significantly affect cellular growth...
September 19, 2017: ELife
https://www.readbyqxmd.com/read/28925291/isolation-of-a-novel-compound-mimo2-from-the-methanolic-extract-of-moringa-oleifera-leaves-protective-effects-against-vanadium-induced-cytotoxity
#8
Olumayowa O Igado, Jan Glaser, Mario Ramos-Tirado, Ezgi Eylül Bankoğlu, Foluso A Atiba, Ulrike Holzgrabe, Helga Stopper, James O Olopade
Moringa oleifera is reported to be a miracle plant, with positive effects on practically every system in the animal body. The methanolic extract of Moringa oleifera leaves was fractionated using liquid-liquid fractionation, column chromatography and preparative high-performance liquid chromatography (HPLC). Bioassay guided fractionation using Ferric Reducing Antioxidant Power (FRAP) was used to determine the fraction with the highest antioxidative power. Chemical structure was elucidated with nuclear magnetic resonance (NMR) spectroscopy...
September 19, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/28921392/resveratrol-attenuates-high-glucose-induced-endothelial-cell-apoptosis-via-mediation-of-store-operated-calcium-entry
#9
Ting Lu, Dayan Zhou, Pan Gao, Liangyi Si, Qiang Xu
The aim of this study was to evaluate the influence of resveratrol on HG-induced calcium entry in islet microvascular (MS-1) endothelial cells. MS-1 cells were pretreated with resveratrol or 2-APB (an inhibitor of store-operated calcium entry) and then incubated with high glucose. Cell viability was determined using the cell counting kit-8 method. Reactive oxygen species, endothelial apoptosis, and NO production were detected by DHE probe, TUNEL detection, and nitrate reductase assay kit. Protein levels of SOCE were detected by western blotting...
September 18, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28891299/spatial-learning-responses-to-lipopolysaccharide-in-adult-and-aged-rats
#10
Barbara J Kupferschmid, Barbara A Therrien
Sickness behaviors, adaptive responses to infections, include lethargy, depression, reduced eating and grooming, and concentration problems resulting from interactions between the immune and neuroendocrine systems. Detecting these responses is especially critical in the elderly, as the infections that cause them can lead to cognitive impairment. While deficits in spatial learning, a hippocampal-dependent form of learning, are part of the sickness response, directional heading errors (DHEs; an indicator of spatial-learning deficits) and their time trajectories need further examination...
January 1, 2017: Biological Research for Nursing
https://www.readbyqxmd.com/read/28880721/role-of-nadph-oxidase-in-radiation-induced-pro-oxidative-and-pro-inflammatory-pathways-in-mouse-brain
#11
Hyung Joon Cho, Won Hee Lee, Olivia Min Ha Hwang, William E Sonntag, Yong Woo Lee
PURPOSE: The present study was designed to investigate our hypothesis that NADPH oxidase plays a role in radiation-induced pro-oxidative and pro-inflammatory environments in brain. MATERIALS AND METHODS: C57BL/6 mice received either fractionated whole brain irradiation or sham-irradiation. The mRNA expression levels of pro-inflammatory mediators, such as TNF-α and MCP-1, were determined by quantitative real-time RT-PCR. The protein expression levels of TNF-α, MCP-1, NOX-2 and Iba1 were detected by immunofluorescence staining...
September 7, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28867950/extracellular-alkaline-lipase-from-a-novel-fungus%C3%A2-curvularia-sp-dhe-5-optimisation-of-physicochemical-parameters-partial-purification-and-characterisation
#12
Dina Helmy El-Ghonemy, Mamdouh S El-Gamal, Amir Elsayed Tantawy, Thanaa Hamed Ali
Thirty isolated fungal strains were screened for lipase production using Phenol Red plates, containing tributyrin as lipidic substrate, and a novel fungus identified genetically as Curvularia sp. DHE 5 was found as the most prominent strain. Various agro-industrial substrates were evaluated as inert supports for lipase production in solid-state fermentation. The highest yield of lipase ((83.4±2.2) U/g on dry mass basis) was reported with wheat bran medium after seven days of fermentation at pH=7.0, temperature of 30 °C, 70% moisture content, inoculum size of 1...
June 2017: Food Technology and Biotechnology
https://www.readbyqxmd.com/read/28830679/angeli-s-salt-a-nitroxyl-anion-donor-reverses-endothelin-1-mediated-vascular-dysfunction-in-murine-aorta
#13
Brandi M Wynne, Hicham Labazi, Zidonia N Carneiro, Rita C Tostes, R Clinton Webb
Nitroglycerin (Gtn) is a treatment for cardiovascular patients due to its vasodilatory actions, but induces tolerance when given chronically. A proposed mechanism is the superoxide (O2(-))-oxidative stress hypothesis, which suggests that Gtn increases O2(-) production. Nitric oxide (NO) exists in three different redox states; the protonated, reduced state, nitroxyl anion (HNO) is an emerging candidate in vascular regulation. HNO is resistant to scavenging and of particular interest in conditions where high levels of reactive oxygen species (ROS) exist...
November 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28761609/evaluation-of-severe-malaria-case-management-in-mazowe-district-zimbabwe-2014
#14
Bargley Makumbe, Cremence Tshuma, Gerald Shambira, More Mungati, Notion Tafara Gombe, Donewell Bangure, Tsitsi Patience Juru, Mufuta Tshimanga
INTRODUCTION: Malaria is a preventable and curable disease. Mazowe district had been experiencing a lower malaria transmission rate in comparison to other districts in the Mashonaland Central province but it experienced a huge outbreak in the 2013-2014 rainy seasons with a case fatality rate (CFR) of 0.21%. This CFR was the highest in the province and it was twice as much as the national CFR (0.12%) for the same period. We evaluated severe malaria case management in Mazowe district to determine if practice is as per standard treatment guidelines...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28733475/gper-modulates-tone-and-coronary-vascular-reactivity-in-male-and-female-rats
#15
Angelina Rafaela Debortoli, Wender do Nascimento Rouver, Nathalie Tristão Banhos Delgado, Vinicius Mengal, Erick Roberto Gonçalves Claudio, Laena Pernomian, Lusiane Maria Bendhack, Margareth Ribeiro Moysés, Roger Lyrio Dos Santos
Compared with age-matched men, premenopausal women are largely protected from coronary artery disease, a difference that is lost after menopause. The effects of oestrogens are mediated by the activation of nuclear receptors (ERα and ERβ) and by the G protein-coupled oestrogen receptor (GPER). This study aims to evaluate the potential role of GPER in coronary circulation in female and male rats. The baseline coronary perfusion pressure (CPP) and the concentration-response curve with a GPER agonist (G-1) were evaluated in isolated hearts before and after the blockade of GPER...
August 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28706450/reactive-oxygen-species-increase-neuronal-excitability-via-activation-of-nonspecific-cation-channel-in-rat-medullary-dorsal-horn-neurons
#16
Hae In Lee, Byung Rim Park, Sang Woo Chun
The caudal subnucleus of the spinal trigeminal nucleus (medullary dorsal horn; MDH) receives direct inputs from small diameter primary afferent fibers that predominantly transmit nociceptive information in the orofacial region. Recent studies indicate that reactive oxygen species (ROS) is involved in persistent pain, primarily through spinal mechanisms. In this study, we aimed to investigate the role of xanthine/xanthine oxidase (X/XO) system, a known generator of superoxide anion (O2(·-)), on membrane excitability in the rat MDH neurons...
July 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28700905/chronic-iron-overload-induces-functional-and-structural-vascular-changes-in-small-resistance-arteries-via-nadph-oxidase-dependent-o2-production
#17
Rogério Faustino Ribeiro Júnior, Vinicius Bermond Marques, Dieli Oliveira Nunes, Ivanita Stefanon, Leonardo Dos Santos
Iron overload leads to excessive free radical formation and induces cardiovascular dysfunction. Thus, our aim was to investigate the structural and endothelial modulation of vascular tone induced by chronic iron overload in mesenteric arteries. Rats were divided into two groups: the control (vehicle) group and the group treated with iron dextran for 28days (100mg/kg, 5days a week). Chronic iron overload altered the following morpho-physiological parameters of third-order mesenteric resistance arteries: decreased lumen and external diameters; increased wall/lumen ratio and wall thickness; decreased distensibility and increased stiffness; and increased pulse wave velocity...
September 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28670490/dehydrocostus-lactone-a-natural-sesquiterpene-lactone-suppresses-the-biological-characteristics-of-glioma-through-inhibition-of-the-nf-%C3%AE%C2%BAb-cox-2-signaling-pathway-by-targeting-ikk%C3%AE
#18
Jinkui Wang, Zhenlong Yu, Chao Wang, Xiangge Tian, Xiaokui Huo, Yan Wang, Chengpeng Sun, Lei Feng, Jing Ma, Baojing Zhang, Qining Yang, Xiaochi Ma, Yinghui Xu
Dehydrocostus lactone (DHE), a natural sesquiterpene lactone, has been used for treatment of various diseases with its anti-inflammatory activity. Recently, it has caused extensive interest in researchers due to it has anti-cancer abilities in some types of carcinomas. However, the anti-cancer effect and mechanism of DHE in glioma remains unclear. The present study conducted to determine the biological effects of DHE on the glioblastoma cells, as well as the mechanisms underlying these effects. After treatment with DHE, the glioblastoma (U118, U251 or U87) cells were significantly inhibited in their viability, proliferation and migration...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28654829/fructose-intake-exacerbates-the-contractile-response-elicited-by-norepinephrine-in-mesenteric-vascular-bed-of-rats-via-increased-endothelial-prostanoids
#19
Glauciene J Sousa, Phablo Wendell C Oliveira, Breno V Nogueira, Antônio F Melo, Thaís de Oliveira Faria, Eduardo Frizera Meira, José G Mill, Nazaré S Bissoli, Marcelo P Baldo
Chronic fructose intake induces major cardiovascular and metabolic disturbances and is associated with the development of hypertension due to changes in vascular function. We hypothesized that high fructose intake for 6 weeks would cause metabolic syndrome and lead to initial vascular dysfunction. Male Wistar rats were assigned to receive fructose (FRU, 10%) or drinking water (CON) for 6 weeks. Systolic blood pressure was evaluated by tail plethysmography. Fasting glucose, insulin and glucose tolerance were measured at the end of the follow-up...
October 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28649860/do-racial-ethnic-disparities-exist-in-recommended-migraine-treatments-in-us-ambulatory-care
#20
Larry Charleston Iv, James Francis Burke
Background Racial disparities in migraine have been reported in the US. Migraine in African Americans (AA) is more frequent, more severe, more likely to become chronic and associated with more depression and lower quality of life compared to non-Hispanic Whites (NHW). It is possible that racial differences in prescribing practices contribute to these differences, but little is known about the quality of migraine prescribing patterns in the US or whether racial differences exist. Objective To determine if racial differences in quality of migraine medical prescription care exist...
January 1, 2017: Cephalalgia: An International Journal of Headache
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