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Pharmacologic study

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https://www.readbyqxmd.com/read/28214329/-p-clphse-2-reduces-hepatotoxicity-induced-by-monosodium-glutamate-by-improving-mitochondrial-function-in-rats
#1
Caroline B Quines, Pietro M Chagas, Diane Hartmann, Nélson R Carvalho, Félix A Soares, Cristina W Nogueira
It is has been demonstrated that mitochondrial dysfunction, oxidative stress and chronic inflammatory process are associated with progress of morbid obesity in human patients. For this reason, the searching for safe and effective antiobesity drugs has been the subject of intense research. In this context, the organic selenium compounds have attracted much attention due to their pharmacological properties, such as antihyperglycemic, antioxidant and anti-inflammatory. The aim of this study was to evaluate the hepatoprotective action of p-chloro-diphenyl diselenide (p-ClPhSe)2 , an organic selenium compound, in a model of obesity induced by monosodium glutamate (MSG) administration in rats...
February 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28214083/the-effect-of-nonpharmacological-training-on-delirium-identification-and-intervention-strategies-of-intensive-care-nurses
#2
Ayşegül Öztürk Birge, Hatice Tel Aydin
OBJECTIVE: This study aims to investigate the effect of nonpharmacological intervention training on delirium recognition and the intervention strategies of intensive care (ICU) nurses. METHOD: This is a quasi-experimental study conducted using a pretest-posttest design. The study sample included a total of 95 patients staying in the medical ICU of a university hospital and 19 nurses working in these units. The data were collected using the Patient and Nurse Introduction, Confusion Assessment Method for the ICU, and Delirium Risk Factors, and Non-pharmacological Interventions in Delirium Prevention Forms...
February 14, 2017: Intensive & Critical Care Nursing: the Official Journal of the British Association of Critical Care Nurses
https://www.readbyqxmd.com/read/28214075/asymmetric-total-synthesis-of-tetrahydroprotoberberine-derivatives-and-evaluation-of-their-binding-affinities-at-dopamine-receptors
#3
David Y W Lee, Jing Liu, Shuzhen Zhang, Peng Huang, Lee-Yuan Liu-Chen
Cocaine addiction remains a serious challenge for clinical and medical research because there is no effective pharmacological treatment. l-THP, a natural product isolated from Corydalis yanhusuo W.T. Wang, is one of the most frequently used traditional herbs to treat drug addiction in China. Our laboratory first reported that its demethylated metabolites l-ICP, l-CD, and l-CP had high affinity at dopamine D1, D2, and D5 receptors. Here we report the chemical synthesis of these metabolites and other derivatives and their binding affinities at dopamine receptors...
January 31, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28213480/a-common-genetic-variant-risk-score-is-associated-with-drug-induced-qt-prolongation-and-torsade-de-pointes-risk-a-pilot-study
#4
David G Strauss, Jose Vicente, Lars Johannesen, Ksenia Blinova, Jay W Mason, Peter Weeke, Elijah R Behr, Dan M Roden, Raymond Woosley, Gulum Kosova, Michael A Rosenberg, Christopher Newton-Cheh
Background -Drug-induced QT interval prolongation, a risk factor for life-threatening ventricular arrhythmias, is a potential side effect of many marketed and withdrawn medications. The contribution of common genetic variants previously associated with baseline QT interval to drug-induced QT prolongation and arrhythmias is not known. Methods -We tested the hypothesis that a weighted combination of common genetic variants contributing to QT interval at baseline, identified through genome-wide association studies, can predict individual response to multiple QT-prolonging drugs...
February 17, 2017: Circulation
https://www.readbyqxmd.com/read/28213467/hypoxia-induces-arginase-ii-expression-and-increases-viable-human-pulmonary-artery-smooth-muscle-cell-numbers-via-ampk%C3%AE-1-signaling
#5
Jianjing Xue, Leif D Nelin, Bernadette Chen
Pulmonary artery smooth muscle cell (PASMC) proliferation is one of the hallmark features of hypoxia-induced pulmonary hypertension. With only supportive treatment options available for this life threatening disease, treating and preventing the proliferation of PASMCs is a viable therapeutic option. A key promoter of hypoxia-induced increases in the number of viable human PASMCs is arginase II, with attenuation of viable cell numbers following pharmacologic inhibition or siRNA knockdown of the enzyme. Additionally, increased levels of arginase have been demonstrated in the pulmonary vasculature of patients with pulmonary hypertension...
February 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28213405/inhibition-of-the-mtor-pathway-in-abdominal-aortic-aneurysm-implication-of-smooth-muscle-cell-contractile-phenotype-inflammation-and-aneurysm-expansion
#6
Guangxin Li, Lingfeng Qin, Lei Wang, Xuan Li, Alexander W Caulk, Jian Zhang, Pei-Yu Chen, Shijie Xin
The development of effective pharmacological treatment of abdominal aortic aneurysm (AAA) potentially offers great benefit to patients with pre-aneurysmal aortic dilation by slowing the expansion of aneurysms and reducing the need for surgery. To date, therapeutic targets for slowing aortic dilation have had low efficacy. Thus, in this study, we aim to elucidate possible mechanisms driving aneurysm progression in order to identify potential targets for pharmacological intervention. We demonstrate that mTOR signaling is over activated in aortic smooth muscle cells (SMCs) which contributes to murine AAA...
February 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28213356/otx2-activity-at-distal-regulatory-elements-shapes-the-chromatin-landscape-of-group-3-medulloblastoma
#7
Gaylor Boulay, Mary E Awad, Nicolo Riggi, Tenley C Archer, Sowmya Iyer, Wannaporn E Boonseng, Nikki E Rossetti, Beverly Naigles, Shruthi Rengarajan, Angela Volorio, James C Kim, Jill P Mesirov, Pablo Tamayo, Scott L Pomeroy, Martin J Aryee, Miguel N Rivera
Medulloblastoma is the most frequent malignant pediatric brain tumor and is divided into at least four subgroups known as WNT, SHH, Group 3, and Group 4. Here, we characterized gene regulation mechanisms in the most aggressive subtype, Group 3 tumors, through genome-wide chromatin and expression profiling. Our results show that most active distal sites in these tumors are occupied by the transcription factor OTX2. Highly active OTX2-bound enhancers are often arranged as clusters of adjacent peaks and are also bound by the transcription factor NEUROD1...
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28213294/a-low-cost-simplified-and-scaleable-pneumotachograph-and-face-mask-for-neonatal-mouse-respiratory-measurements
#8
Jenny J Sun, Roshan Nanu, Russell S Ray
INTRODUCTION: Neonatal respiratory disorders are a leading cause of perinatal mortality due to complications resulting from premature births and prenatal exposure to drugs of abuse, but optimal treatments for these symptoms are still unclear due to a variety of confounds and risk factors. Mouse models present an opportunity to study the underlying mechanisms and efficacy of potential treatments of these conditions with controlled variables. However, measuring respiration in newborn mice is difficult and commercial components are expensive and often require modification, creating a barrier and limiting our understanding of the short and long-term effects of birth complications on respiratory function...
February 14, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28213190/n-acetylcysteine-for-treating-cocaine-addiction-a-systematic-review
#9
REVIEW
Marco Antonio Nocito Echevarria, Tassio Andrade Reis, Giulianno Ruffo Capatti, Victor Siciliano Soares, Dartiu Xavier da Silveira, Thiago Marques Fidalgo
The aim of this paper is to extensively review the current literature available on N-acetylcysteine (NAC) treatment for cocaine dependence (clinical and experimental studies). We screened all articles published before February 2016 reporting on the use of NAC as a pharmacological intervention for cocaine dependence or discussed its potential as a therapeutic approach for cocaine dependence. We described our results qualitatively. 21 studies matched our search criteria: 6 clinical trials and 15 animal studies...
February 11, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28213092/prediction-of-thyroid-c-cell-carcinogenicity-after-chronic-administration-of-glp1-r-agonists-in-rodents
#10
Willem van den Brink, Annette Emerenciana, Francesco Bellanti, Oscar Della Pasqua, Jan Willem van der Laan
Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products...
February 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28213089/monoglyceride-lipase-as-a-drug-target-at-the-crossroads-of-arachidonic-acid-metabolism-and-endocannabinoid-signaling
#11
REVIEW
Gernot F Grabner, Robert Zimmermann, Rudolf Schicho, Ulrike Taschler
Monoglyerides (MGs) are short-lived, intermediary lipids deriving from the degradation of phospho- and neutral lipids, and monoglyceride lipase (MGL), also designated as monoacylglycerol lipase (MAGL), is the major enzyme catalyzing the hydrolysis of MGs into glycerol and fatty acids. This distinct function enables MGL to regulate a number of physiological and pathophysiological processes since both MGs and fatty acids can act as signaling lipids or precursors thereof. The most prominent MG species acting as signaling lipid is 2-arachidonoylglycerol (2-AG) which is the most abundant endogenous agonist of cannabinoid receptors in the body...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28213070/selective-a2a-receptors-blockade-reduces-degeneration-of-substantia-nigra-dopamine-neurons-in-a-rotenone-induced-rat-model-of-parkinson-s-disease-a-histological-study
#12
Ahmed M Fathalla, Amira M Soliman, Ahmed A Moustafa
Parkinson's disease (PD) is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Adenosine is a neuromodulator that inhibit the release of dopamine via a disinhibitory mechanism. In this study, we investigated the neuroprotective effect of 8-cyclopentyl-1,3-dipropylxanthine and ZM241385 (respectively, A1 and A2A receptors antagonists), on nigrostriatal dopamine neurons degradation reduction in a rotenone-induced PD model using histopathological and immunohistochemical methods...
February 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28212943/effects-of-acute-dopaminergic-and-serotonergic-manipulations-in-the-aci-paradigm-depend-on-the-basal-valence-of-cognitive-judgement-bias-in-rats
#13
Joanna Golebiowska, Rafal Rygula
Recent findings have revealed that pharmacological enhancement of dopaminergic (DA) function by the administration of a DA precursor (dihydroxy-L-phenylalanine; L-DOPA), but not the selective serotonin reuptake inhibitor (SSRI) citalopram, increases an optimism bias in humans. To test whether dopamine might play a similar role in non-human animals, in the present study, we evaluated the effects of acute injections of L-DOPA, the D2 receptor antagonist haloperidol, and the SSRI escitalopram on cognitive judgement bias of rats in the ambiguous-cue interpretation (ACI) paradigm...
February 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28212941/injections-of-the-of-the-%C3%AE-1-adrenoceptor-antagonist-prazosin-into-the-median-raphe-nucleus-increase-food-intake-and-fos-expression-in-orexin-neurons-of-free-feeding-rats
#14
Eduardo Simão da Silva, Rafael Appel Flores, Anderson Savaris Ribas, Ana Paula Taschetto, Moacir Serralvo Faria, Leandro Bueno Lima, Martin Metzger, José Donato, Marta Aparecida Paschoalini
Previously, we showed that the blockade of α1-adrenoreceptors in the median raphe nucleus (MnR) increased food intake in free-feeding rats, indicating that adrenergic mechanisms in the MnR participate in the regulation of food intake. However, the impact of such a pharmacological manipulation on other neural circuits related to food intake remains unknown. In the current study, we sought to identify forebrain regions which are responsive to α1-adrenergic receptor blockade and presumably involved in the modulation of the feeding response...
February 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28212889/inhibition-of-proliferation-and-invasion-in-2d-and-3d-models-by-2-methoxyestradiol-in-human-melanoma-cells
#15
R R Massaro, F Faião-Flores, V W Rebecca, S Sandri, D K Alves-Fernandes, P C Pennacchi, K S M Smalley, S S Maria-Engler
Despite the recent advances in the clinical management of melanoma, there remains a need for new pharmacological approaches to treat this cancer. 2-methoxyestradiol (2ME) is a metabolite of estrogen that has shown anti-tumor effects in many cancer types. In this study we show that 2ME treatment leads to growth inhibition in melanoma cells, an effect associated with entry into senescence, decreased pRb and CyclinB1 expression, increased p21/Cip1 expression and G2/M cell cycle arrest. 2ME treatment also inhibits melanoma cell growth in colony formation assays, including cell lines with acquired resistance to BRAF and BRAF+MEK inhibitors...
February 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28212842/pathophysiological-consequences-of-receptor-mistraffic-tales-from-the-platelet-p2y12-receptor
#16
Margaret R Cunningham, Riyaad Aungraheeta, Stuart J Mundell
Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function...
February 14, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28212826/pharmacological-postconditioning-with-sevoflurane-activates-pi3k-akt-signaling-and-attenuates-cardiopulmonary-bypass-induced-lung-injury-in-dog
#17
Yu Zhang, Dongdong Li, Junli Luo, Song Chen, Xuejiao Dou, Ming Han, Hong Zhang
AIMS: Sevoflurane, a widely used inhaled anesthetic, showed valid protective effect against ischemia reperfusion injury in lung, however, the underlying molecular mechanisms has yet to be explained. MATERIALS AND METHODS: Dogs were divided into four groups: control group, cardiopulmonary bypass (CPB) group, sevoflurane postconditioning group and wortmannin group. Arterial blood was obtained from each group to test the respiratory index and oxygenation index and pulmonary tissues were sampled for apoptotic TUNEL stain...
February 14, 2017: Life Sciences
https://www.readbyqxmd.com/read/28212580/network-pharmacology-based-and-clinically-relevant-prediction-of-the-active-ingredients-and-potential-targets-of-chinese-herbs-in-metastatic-breast-cancer-patients
#18
Yu Mao, Jian Hao, Zi-Qi Jin, Yang-Yang Niu, Xue Yang, Dan Liu, Rui Cao, Xiong-Zhi Wu
Chinese Herbal Medicine (CHM) plays a significant role in breast cancer treatment. We conduct the study to ascertain the relative molecular targets of effective Chinese herbs in treating stage IV breast cancer.Survival benefit of CHM was verified by Kaplan-Meier method and Cox regression analysis. A bivariate correlation analysis was used to find and establish the effect of herbs in complex CHM formulas. A network pharmacological approach was adopted to explore the potential mechanisms of CHM.Patients in the CHM group had a median survival time of 55 months, which was longer than the 23 months of patients in the non-CHM group...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212543/metabotropic-glutamate-receptors-as-a-new-therapeutic-target-for-malignant-gliomas
#19
REVIEW
Mery Stefani Leivas Pereira, Fábio Klamt, Chairini Cássia Thomé, Paulo Valdeci Worm, Diogo Losch de Oliveira
Metabotropic glutamate receptors (mGluR) are predominantly involved in maintenance of cellular homeostasis of central nervous system. However, evidences have suggested other roles of mGluR in human tumors. Aberrant mGluR signaling has been shown to participate in transformation and maintenance of various cancer types, including malignant brain tumors. This review intends to summarize recent findings regarding the involvement of mGluR-mediated intracellular signaling pathways in progression, aggressiveness, and recurrence of malignant gliomas, mainly glioblastomas (GBM), highlighting the potential therapeutic applications of mGluR ligands...
February 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212459/structural-studies-of-nicotinoids-cotinine-vs-nicotine
#20
Iciar Uriarte, Cristóbal Pérez, Elena Caballero-Mancebo, Francisco J Basterretxea, Alberto Lesarri, José A Fernández, Emilio J Cocinero
Nicotinoids are agonists of the acetylcholine receptor (nAChR) and play important biochemical and pharmacological roles. Here we report on the structural and conformational landscape of cotinine, and compare its molecular properties with the nicotine prototype, from which it only differs in the addition of a carbonyl group. The investigation of cotinine included a theoretical survey of the effects of rotamerization of the pyridine moiety, the puckering of the pyrrolidinone ring and the internal rotation of the methyl group...
February 17, 2017: Chemistry: a European Journal
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