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https://www.readbyqxmd.com/read/28646742/image-analysis-for-tsh-mrna-in-situ-hybridization-in-pituitary-glands-from-rats-with-thyroid-follicular-cell-hypertrophy-after-treatment-with-three-different-test-compounds
#1
Juergen Funk, Martin Ebeling, Thomas Singer, Christian Landes
The goal of this in situ hybridization and image analysis technique is to study the effects of new pharmacological/chemical entities on the thyroid and pituitary gland in rats, reveal the pathogenesis of thyroid follicular cell hypertrophy and to retrospectively exclude the risk of thyroid tumor development in humans. In the present study, we describe the increase of thyroid-stimulating hormone- (TSH-) beta subunit mRNA in the pars distalis of the pituitary gland and the quantitative measurement of TSH mRNA positive cells from rats of three 4-week toxicity studies treated with three different test compounds inducing thyroid follicular cell and hepatocellular hypertrophy in rats...
June 11, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28646732/effects-of-stimulants-and-atomoxetine-on-emotional-lability-in-adults-a-systematic-review-and-meta-analysis
#2
T R Moukhtarian, R E Cooper, E Vassos, P Moran, P Asherson
BACKGROUND: Emotional lability (EL) is an associated feature of attention-deficit/hyperactivity disorder (ADHD) in adults, contributing to functional impairment. Yet the effect of pharmacological treatments for ADHD on EL symptoms is unknown. We conducted a systematic review and meta-analysis to examine the effects of stimulants and atomoxetine on symptoms of EL and compare these with the effects on core ADHD symptoms. METHODS: A systematic search was conducted on the databases Embase, PsychInfo, and Ovid Medline(®) and the clinicaltrials...
May 25, 2017: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28646714/synthetic-cathinones-and-stereochemistry-s-enantiomer-of-mephedrone-reduces-anxiety-and-depressant-like-effects-in-cocaine-or-mdpv-abstinent-rats
#3
Helene L Philogene-Khalid, Callum Hicks, Allen B Reitz, Lee-Yuan Liu-Chen, Scott M Rawls
BACKGROUND AND PURPOSE: The neuropharmacological profile of the synthetic cathinone mephedrone (MEPH) is influenced by stereochemistry. Both MEPH enantiomers are monoamine transporter substrates, but R-MEPH is primarily responsible for rewarding effects of MEPH as it produces greater locomotor activation and intracranial self-stimulation than S-MEPH. S-MEPH is a 50-fold more potent 5-HT releaser than R-MEPH and does not place preference in rats. MEPH is also structurally similar to the cathinone derivative bupropion, an antidepressant and smoking cessation medication, suggesting MEPH has therapeutic and addictive properties...
June 13, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28646531/morin-a-novel-lxr%C3%AE-%C3%AE-dual-antagonist-has-potent-therapeutic-efficacy-for-nonalcoholic-fatty-liver-diseases
#4
Ming Gu, Yu Zhang, Chuhe Liu, Dongshan Wang, Li Feng, Shengjie Fan, Baican Yang, Qingchun Tong, Guang Ji, Cheng Huang
BACKGROUND AND PURPOSE: Morin is a natural occurring flavonoid in many dietary plants and has a wide range of beneficial effects on metabolism; however, the mechanism underlying its action remains elusive. EXPERIMENTAL APPROACH: Reporter assay and the Time-Resolved Fluorescence Resonance Energy Transfer assay were used to identify morin as a dual antagonist of LXRα and LXRβ. High fat-diet mixed with morin (100 mg/100 g diet) was administrated to high-fat diet-induced obese or LXRβ(-/-) mice combining with Western blot and RT-PCR analysis to evaluate the pharmacological effect and mechanism of morin treatment...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28646467/symptom-management-challenges-in-heart-failure-pharmacotherapy-considerations
#5
REVIEW
Diana Stewart, Mary Lynn McPherson
Heart failure is a chronic, progressive illness that is increasing in prevalence in the USA. Patients with advanced heart failure experience a high symptom burden that is comparable to patients with advanced cancer. Palliative care, however, is underutilized in patients with heart failure, and symptoms may go untreated as the disease progresses. A combination of pharmacologic and non-pharmacologic interventions should be used to address symptoms and maintain quality of life. While there have been significant advances in evidence-based heart failure treatments in recent years, selection of appropriate palliative medications as symptoms progress is challenging due to limited clinical studies in this patient population...
June 24, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/28646427/tanshinone-iia-attenuates-atherosclerosis-in-apolipoprotein-e-knockout-mice-infected-with-porphyromonas-gingivalis
#6
Yan Xuan, Yue Gao, Hao Huang, Xiaoxuan Wang, Yu Cai, Qing Xian Luan
Tanshinone IIA (TSA), a pharmacologically active component isolated from Danshen, may prevent cardiovascular diseases due to its anti-inflammatory, anti-oxidative, and anti-adipogenic effects. Porphyromonas gingivalis, a major periodontal pathogen, may contribute to the progression of atherosclerosis. Here, we studied the effects of TSA on atherosclerosis in ApoE(-/-) mice with P. gingivalis infection. Eight-week-old ApoE(-/-) mice were randomized to (a) phosphate-buffered saline (PBS), (b) P. gingivalis, and (c) P...
June 23, 2017: Inflammation
https://www.readbyqxmd.com/read/28646394/the-antihypertensive-efficacy-of-the-triple-fixed-combination-of-perindopril-indapamide-and-amlodipine-the-results-of-the-petra-study
#7
György Ábrahám, Csaba András Dézsi
INTRODUCTION: The etiology of essential hypertension is multifactorial. Therefore, treatment with combinations of antihypertensive agents acting on multiple targets is necessary for successful therapy in the majority of patients. According to the experience and clinical data accumulated so far, combination therapy with three agents from different pharmacological classes is required in approx. 30% of patients in order to achieve long-term blood pressure control. The primary objective of the PETRA study was to evaluate the efficacy of blood pressure (BP) control with once daily administration of the different dosage strengths of the once-daily, triple fixed combination of perindopril, indapamide, and amlodipine...
June 23, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28646348/tau-induced-ca-2-calmodulin-dependent-protein-kinase-iv-activation-aggravates-nuclear-tau-hyperphosphorylation
#8
Yu-Ping Wei, Jin-Wang Ye, Xiong Wang, Li-Ping Zhu, Qing-Hua Hu, Qun Wang, Dan Ke, Qing Tian, Jian-Zhi Wang
Hyperphosphorylated tau is the major protein component of neurofibrillary tangles in the brains of patients with Alzheimer's disease (AD). However, the mechanism underlying tau hyperphosphorylation is not fully understood. Here, we demonstrated that exogenously expressed wild-type human tau40 was detectable in the phosphorylated form at multiple AD-associated sites in cytoplasmic and nuclear fractions from HEK293 cells. Among these sites, tau phosphorylated at Thr205 and Ser214 was almost exclusively found in the nuclear fraction at the conditions used in the present study...
June 23, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28646272/rhesus-cochlear-and-vestibular-functions-are-preserved-after-inner-ear-injection-of-saline-volume-sufficient-for-gene-therapy-delivery
#9
Chenkai Dai, Mohamed Lehar, Daniel Q Sun, Lani Swarthout Rvt, John P Carey, Tim MacLachlan, Doug Brough, Hinrich Staecker, Alexandra M Della Santina, Timothy E Hullar, Charles C Della Santina
Sensorineural losses of hearing and vestibular sensation due to hair cell dysfunction are among the most common disabilities. Recent preclinical research demonstrates that treatment of the inner ear with a variety of compounds, including gene therapy agents, may elicit regeneration and/or repair of hair cells in animals exposed to ototoxic medications or other insults to the inner ear. Delivery of gene therapy may also offer a means for treatment of hereditary hearing loss. However, injection of a fluid volume sufficient to deliver an adequate dose of a pharmacologic agent could, in theory, cause inner ear trauma that compromises functional outcome...
June 23, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28646078/stereospecific-metabolism-of-r-and-s-warfarin-by-human-hepatic-cytosolic-reductases
#10
Dustyn A Barnette, Bryce Johnson, Dakota L Pouncey, Robert Nshimiyimana, Linda Desrochers, Thomas E Goodwin, Grover Paul Miller
Coumadin (rac-warfarin) is the most commonly used anticoagulant in the world, yet its clinical use is often challenging due to a narrow therapeutic range and inter-individual variations in response. A critical contributor to the uncertainty is variability in warfarin metabolism, which includes mostly oxidative but also reductive pathways. Reduction of each warfarin enantiomer yields two warfarin alcohol isomers, and the corresponding four alcohols retain varying levels of anticoagulant activity. Studies on the kinetics of warfarin reduction have often lacked resolution of parent drug enantiomers and suffered from co-elution of pairs of alcohol metabolites; thus, those studies fail to establish the importance of individual, stereospecific reductive pathways...
June 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28646031/metabolism-and-acetylation-contribute-to-leucine-mediated-inhibition-of-cardiac-glucose-uptake
#11
Edith Renguet, Audrey Ginion, Roselle Gélinas, Laurent Bultot, Julien Auquier, Isabelle Robillard Frayne, Caroline Daneault, Jean-Louis Vanoverschelde, Christine Des Rosiers, Louis Hue, Sandrine Horman, Christophe Beauloye, Luc Bertrand
High plasma leucine levels strongly correlate with type 2 diabetes. Studies of muscle cells suggest that leucine alters the insulin response for glucose transport by activating an insulin-negative feedback loop driven by the mammalian target of rapamycin/p70 ribosomal S6 kinase (mTOR/p70S6K) pathway. Here, we examined the molecular mechanism involved in leucine's action on cardiac glucose uptake. Leucine was indeed able to curb glucose uptake after insulin stimulation in both cultured cardiomyocytes and perfused hearts...
June 23, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28645995/mepolizumab-for-the-treatment-of-severe-eosinophilic-asthma
#12
REVIEW
Mara N Poulakos, Shawna M Cargill, Melissa F Waineo, Allen L Wolford
PURPOSE: Published data on the pharmacology, pharmacokinetics and pharmacodynamics, and clinical efficacy and safety of the interleukin-5 antagonist mepolizumab are reviewed. SUMMARY: Asthma of the eosinophilic phenotype is characterized by persistent eosinophilic airway inflammation promoted primarily by T-helper type 2 cytokines, the key regulator of eosinophils. Patients with severe eosinophilic asthma are burdened by the need to administer high doses of corticosteroids to help manage their symptoms...
July 1, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28645967/the-bipolar-illness-onset-study-research-protocol-for-the-bio-cohort-study
#13
Lars Vedel Kessing, Klaus Munkholm, Maria Faurholt-Jepsen, Kamilla Woznica Miskowiak, Lars Bo Nielsen, Ruth Frikke-Schmidt, Claus Ekstrøm, Ole Winther, Bente Klarlund Pedersen, Henrik Enghusen Poulsen, Roger S McIntyre, Flavio Kapczinski, Wagner F Gattaz, Jakob Bardram, Mads Frost, Oscar Mayora, Gitte Moos Knudsen, Mary Phillips, Maj Vinberg
INTRODUCTION: Bipolar disorder is an often disabling mental illness with a lifetime prevalence of 1%-2%, a high risk of recurrence of manic and depressive episodes, a lifelong elevated risk of suicide and a substantial heritability. The course of illness is frequently characterised by progressive shortening of interepisode intervals with each recurrence and increasing cognitive dysfunction in a subset of individuals with this condition. Clinically, diagnostic boundaries between bipolar disorder and other psychiatric disorders such as unipolar depression are unclear although pharmacological and psychological treatment strategies differ substantially...
June 23, 2017: BMJ Open
https://www.readbyqxmd.com/read/28645655/5-lipoxygenase-in-monocytes-emerges-as-a-therapeutic-target-for-intimal-hyperplasia-in-a-murine-wire-injured-femoral-artery
#14
Seung Eun Baek, Min A Jang, Seung Jin Lee, So Youn Park, Sun Sik Bae, Chi Dae Kim
Given the importance of leukotrienes in vascular inflammation induced by local tissue injury, this study investigated the role for 5-lipoxygenase (5-LO) in monocytes in the development of intimal hyperplasia. As a mechanistic study, the importance of monocyte 5-LO in monocyte-macrophage differentiation with subsequent infiltration in neointima was evaluated. In a mouse model of wire-injured femoral artery, intimal hyperplasia started as early as 2 wks after injury, and luminal area and blood flow were reduced due to increased neointima formation...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28645644/-antiplatelet-agents-and-transfusion
#15
P Gaussem, A-C Martin, T Belleville-Rolland, D Helley, C Bachelot-Loza, A Godier
Antiplatelet agents are at risk for bleeding complications, the management of which differs depending on the clinical situation and on the antiplatelet agent itself. Neutralization of antiplatelets is sometimes necessary, most often leading to platelet transfusion, although the benefit of this strategy is poorly documented. In addition, if platelet transfusion corrects the platelet inhibition induced by aspirin and probably by clopidogrel and prasugrel, it does not neutralize ticagrelor, as a consequence of its pharmacological properties...
June 20, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/28645622/in-vivo-effects-of-knocking-down-metabotropic-glutamate-receptor-5-in-the-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis
#16
Tiziana Bonifacino, Luca Cattaneo, Elena Gallia, Aldamaria Puliti, Marcello Melone, Francesca Provenzano, Simone Bossi, Ilaria Musante, Cesare Usai, Fiorenzo Conti, Giambattista Bonanno, Marco Milanese
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder due to loss of upper and lower motor neurons (MNs). The mechanisms of neuronal death are largely unknown, thus prejudicing the successful pharmacological treatment. One major cause for MN degeneration in ALS is represented by glutamate(Glu)-mediated excitotoxicity. We have previously reported that activation of Group I metabotropic Glu receptors (mGluR1 and mGluR5) at glutamatergic spinal cord nerve terminals produces abnormal Glu release in the widely studied SOD1(G93A) mouse model of ALS...
June 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28645296/myd88-dependent-pro-interleukin-1%C3%AE-induction-in-dendritic-cells-exposed-to-food-grade-synthetic-amorphous-silica
#17
Hans Christian Winkler, Julian Kornprobst, Peter Wick, Lea Maria von Moos, Ioannis Trantakis, Elisabeth Maria Schraner, Barbara Bathke, Hubertus Hochrein, Mark Suter, Hanspeter Naegeli
BACKGROUND: Dendritic cells (DCs) are specialized first-line sensors of foreign materials invading the organism. These sentinel cells rely on pattern recognition receptors such as Nod-like or Toll-like receptors (TLRs) to launch immune reactions against pathogens, but also to mediate tolerance to self-antigens and, in the intestinal milieu, to nutrients and commensals. Since inappropriate DC activation contributes to inflammatory diseases and immunopathologies, a key question in the evaluation of orally ingested nanomaterials is whether their contact with DCs in the intestinal mucosa disrupts this delicate homeostatic balance between pathogen defense and tolerance...
June 23, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28645211/akr1c3-mediated-adipose-androgen-generation-drives-lipotoxicity-in-women-with-polycystic-ovary-syndrome
#18
Michael W O'Reilly, Punith Kempegowda, Mark Walsh, Angela E Taylor, Konstantinos N Manolopoulos, J William Allwood, Robert K Semple, Daniel Hebenstreit, Warwick B Dunn, Jeremy W Tomlinson, Wiebke Arlt
Context: Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder, occurring in up to 10% of women of reproductive age. PCOS is associated with insulin resistance and cardiovascular risk. Androgen excess is a defining feature of PCOS and has been suggested as causally associated with insulin resistance; however, mechanistic evidence linking both is lacking. We hypothesized that adipose tissue is an important site linking androgen activation and metabolic dysfunction in PCOS...
June 22, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28645025/decreased-functional-connectivity-and-disrupted-neural-network-in-the-prefrontal-cortex-of-affective-disorders-a-resting-state-fnirs-study
#19
Huilin Zhu, Jie Xu, Jiangxue Li, Hongjun Peng, Tingting Cai, Xinge Li, Shijing Wu, Wei Cao, Sailing He
BACKGROUND: Affective disorders (AD) have been conceptualized as neural network-level diseases. In this study, we utilized functional near infrared spectroscopy (fNIRS) to investigate the spontaneous hemodynamic activities in the prefrontal cortex (PFC) of the AD patients with or without medications. METHODS: 42 optical channels were applied to cover the superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG), which constitute one of the most important affective networks of the brain...
June 17, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28644981/chemical-profiling-and-antioxidant-evaluation-of-yangxinshi-tablet-by-hplc-esi-q-tof-ms-ms-combined-with-dpph-assay
#20
Junfeng Zhu, Xiaojiao Yi, Jinghui Zhang, Shuqing Chen, Yongjiang Wu
Yangxinshi Tablet (YXST) is a Chinese patent medicine commonly used to treat cardiovascular diseases. However, its detailed chemical basis and mechanisms of action have not been clarified. In this study, high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-Q-TOF-MS) was applied for comprehensive analysis of the chemical constituents in YXST. A total of 127 compounds, including 19 phenolic acids, 12 alkaloids, 51 flavanoids, 32 triterpenoids, 2 lignans, 2 phenylethanoid glycosides, 2 anthraquinones, 1 coumarin, and 6 other compounds, were identified or tentatively deduced by comparing their retention times and MS spectra with those of authentic standards or literature data...
June 15, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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