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Clinical and Experimental Pharmacology & Physiology

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https://www.readbyqxmd.com/read/29786873/in-vivo-profiling-of-four-centrally-administered-opioids-for-antinociception-constipation-and-respiratory-depression-between-colony-differences-in-sprague-dawley-rats
#1
A Kuo, M T Smith
Outbred rodent stocks including Sprague Dawley rats, are known for their genetic diversity and so they are often used to develop animal models of human disease. Although between-colony differences in pharmaco-behavioural studies have been published previously, a direct head-to-head comparison study, whereby all research was performed in the same laboratory by the same experimenter utilising the supraspinal route of drug administration in the same strain of rat, is lacking. Herein, we report our head-to-head comparison study, involving assessment of antinociception, constipation and respiratory depression evoked by single bolus intracerebroventricular (ICV) doses of morphine, buprenorphine, DPDPE and U69,593 using male Sprague Dawley rats sourced from a different breeding colony (BC2) from that (BC1) used by us previously...
May 22, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29781531/down-regulation-of-kif2a-inhibits-gastric-cancer-cell-invasion-via-suppressing-mt1-mmp
#2
Peng Zhao, Fei Lan, Hui Zhang, Guangwei Zeng, Dong Liu
Gastric cancer accounts for a sizeable proportion of global cancer mortality with high morbidity and poor prognosis. Kinesin superfamily proteins (KIFs) are microtubule-dependent motor proteins that function as oncogenes in cancer cells, it has been discovered in recent years. Kinesin family member 2a (KIF2A), a member of KIFs, has received attention for its role in carcinogenesis and its prognostic value in several human cancers such as breast cancer, colorectal cancer, and squamous cell carcinoma. However, the role of KIF2A in human gastric cancer remains unknown...
May 21, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29781520/associations-of-candidate-gene-polymorphisms-with-poor-responsiveness-to-aspirin-a-meta-analysis
#3
Juesheng Yang, Xianglai Chen, Jianliang Zhou, Shan Hu, Yanhua Tang
Recently, the roles of gene polymorphisms in poor responsiveness to aspirin were extensively investigated, with conflicting results. Therefore, we performed this meta-analysis to better assess the relationship between candidate genetic variants and poor responsiveness to aspirin. Eligible articles were searched in PubMed, Medline, Embase and CNKI. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to detect possible associations of gene polymorphisms with poor responsiveness to aspirin. Among 53 eligible articles, a total of 22 candidate gene polymorphisms were analyzed...
May 21, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29781509/comparative-analgesic-efficacy-of-pregabalin-administered-according-to-either-a-prevention-protocol-or-an-intervention-protocol-in-rats-with-cisplatin-induced-peripheral-neuropathy
#4
F Y Han, A Kuo, J R Nicholson, L Corradinni, M T Smith
Chemotherapy-induced peripheral neuropathy (CIPN) is a type of peripheral neuropathic pain that may be dose-limiting in patients administered potentially curative cancer chemotherapy dosing regimens. In cancer survivors, persistent CIPN adversely affects patient quality of life and so adjuvant drugs (anticonvulsants e.g. pregabalin or antidepressants e.g. amitriptyline) are recommended for the relief of CIPN. However, most studies in rodent models of CIPN involve administration of single bolus doses of adjuvant drugs to assess pain-relieving efficacy...
May 21, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29779214/cyanidin-3-glucoside-inhibits-inflammatory-activities-in-human-fibroblast-like-synoviocytes-and-in-mice-with-collagen-induced-arthritis
#5
Yan Sun, Lingling Li
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint tissue inflammation. Cyanidin-3-glucoside (C3G) is a major component in the flavonoid family and has shown anti-inflammatory, anti-oxidant and anti-tumor activity. In this study, we investigated the effects of C3G on lipopolysaccharides (LPS)-induced inflammation on human rheumatoid fibroblast-like synoviocytes (FLS) and on collagen-induced arthritis (CIA) mice model. We treated FLS with C3G followed by LPS induction, the expressions of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and IL-6 and the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway were analyzed...
May 19, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29772060/nucleocytoplasmic-shuttling-the-ins-and-outs-of-quantitative-imaging
#6
Chris Molenaar, Kate L Weeks
Nucleocytoplasmic protein shuttling is integral to the transmission of signals between the nucleus and the cytoplasm. The nuclear/cytoplasmic distribution of proteins of interest can be determined via fluorescence microscopy, following labelling of the target protein with fluorophore-conjugated antibodies (immunofluorescence) or by tagging the target protein with an autofluorescent protein, such as green fluorescent protein (GFP). The latter enables live cell imaging, a powerful approach that precludes many of the artefacts associated with indirect immunofluorescence in fixed cells...
May 17, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29770478/the-endocannabinoid-alcohol-crosstalk-recent-advances-on-a-bi-faceted-target
#7
REVIEW
Gianluca Lavanco, Valentina Castelli, Anna Brancato, Giuseppe Tringali, Fulvio Plescia, Carla Cannizzaro
Increasing evidence focuses on the endocannabinoid system as a relevant player in the induction of aberrant synaptic plasticity and related addictive phenotype following chronic excessive alcohol drinking. Besides, the endocannabinoid system is implicated in the pathogenesis of alcoholic liver disease. Interestingly, whereas the involvement of CB1 cannabinoid receptors in alcohol rewarding properties is established, the central and peripheral action of CB2 cannabinoid signalling is still to be elucidated. This review aims at giving the input to deepen knowledge on the role of the endocannabinoid system, highlighting the advancing evidence that suggests that CB1 and CB2 receptors may play opposite roles in the regulation of both the reinforcing properties of alcohol in the brain and the mechanisms responsible for cell injury and inflammation in the hepatic tissue...
May 16, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29770473/icotinib-enhances-lung-cancer-cell-radiosensitivity-in-vitro-and-in-vivo-by-inhibiting-mapk-erk-and-akt-activation
#8
Yonghong Fu, Sen Zhang, Dongjie Wang, Jing Wang
Icotinib hydrochloride is a small epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that was developed by Chinese scientists. While clinical trials have revealed its efficacy in the treatment of lung cancer, very little is known about its role in enhancing radiosensitivity. In this study, we investigated the effectiveness of Icotinib in enhancing lung cancer cell radiosensitivity and have detailed its underlying molecular mechanism. The lung cancer cell line H1650 was pretreated with or without Icotinib for 24 hours before radiation, and clonogenic survival assay was performed...
May 16, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29767416/utility-of-electrical-velocimetry-based-noninvasive-stroke-volume-variation-in-predicting-fluid-responsiveness-under-different-ventilation-modes-in-anaesthetized-dogs
#9
Kazumasu Sasaki, Tatsushi Mutoh, Shuzo Yamamoto, Yasuyuki Taki, Ryuta Kawashima
We evaluated the utility of noninvasive stroke volume variation (SVV) as a functional haemodynamic predictor for fluid responsiveness under different ventilation modes [assist control (A/C), synchronized intermittent mandatory ventilation (SIMV), and continuous positive airway pressure (CPAP)] in 45 anaesthetized dogs, using an electrical velocimetry device. Receiver operating curve analysis confirmed the best predictive value during SVVA /C (12.5% of cut-off value; 75% sensitivity and 86% specificity) followed by SVVSIMV (13...
May 16, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29757463/depression-related-behavioural-and-neuroendocrine-changes-in-the-spontaneously-diabetic-torii-sdt-fatty-rat-an-animal-model-of-type-2-diabetes-mellitus
#10
Katsuya Sakimura, Tatsuya Maekawa, Kazuo Sasagawa, Yukihito Ishii, Shin-Ichi Kume, Takeshi Ohta
Depression is one of the most common psychiatric diseases and is commonly comorbid with type 1 or 2 diabetes mellitus (DM). However, the pathophysiology underlying the depressive state in DM remains poorly understood. Animal models are useful tools to investigate the association between depression and DM. In the present study we investigated whether the Spontaneously Diabetic Torii (SDT) fatty rat, a novel animal model of type 2 DM, shows depression-related features. We assessed depression-like behaviour, hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, and neurotransmitter levels in the brain...
May 14, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29751366/synthesis-characterization-and-electrochemistry-studies-of-iron-iii-complex-with-curcumin-ligand
#11
Gülüzar Özbolat, Arash Alizadeh Yegani, Abdullah Tuli
Iron overload is a serious clinical condition for humans and is a key target in drug development. The aim of this study was to investigate the coordination of iron(III) ions with curcumin ligand that may be used in the treatment of iron overload. Iron(III) complex of curcumin was synthesized and structurally characterized in its solid and solution state by FT-IR, UV-Vis, elemental analysis, and magnetic susceptibility. Electrochemical behavior of the ligand and the complexes were examined using cyclic voltammetry...
May 11, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29751356/exploring-novel-pharmacotherapeutic-applications-and-repurposing-potential-of-sodium-glucose-cotransporter-2-sglt2-inhibitors
#12
REVIEW
Tushar Madaan, Ibraheem Husain, Mohamad Akhtar, Abul Kalam Najmi
Sodium glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of anti-hyperglycemic drugs with a distinctive mechanism of action focusing on renal absorption ofglucose. Apart from its anti-hyperglycemic effects, a multitude of research studies on this classhave revealed that these drugs have far more versatile and comprehensive pharmacologicaleffects than previously believed. Approximately 30% of FDA approved drugs are repurposedand used for indications other than those they were initially intended for...
May 11, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29733120/thymoquinone-protects-rat-liver-after-partial-hepatectomy-under-ischemia-reperfusion-through-oxidative-stress-and-endoplasmic-reticulum-stress-prevention
#13
Ahlem Bouhlel, Mohamed Bejaoui, Ismail Ben Mosbah, Najet Hadj Abdallah, Catherine Ribault, Roselyne Viel, Hassen Hentati, Anne Corlu, Hassen Ben Abdennebi
Ischemia reperfusion (I/R) is associated with liver injury and impaired regeneration during partial hepatectomy (PH). The aim of this study was to investigate the effect of thymoquinone (TQ), the active compound of essential oil obtained from Nigella sativa seeds, on rat liver after PH. Male Wistar rats were equally divided into four groups (n=6) receiving an oral administration of either vehicle solution (Sham and PH groups) or TQ at 30 mg/kg (TQ and TQ+PH groups) for ten consecutive days. Then, rats underwent PH (70%) with 60 min of ischemia followed by 24h of reperfusion (PH and TQ+PH groups)...
May 7, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29733109/synthesis-characterization-molecular-modeling-and-biological-evaluation-of-thieno-pyrimidinone-methanesulphonamide-thio-derivatives-as-non-steroidal-anti-inflammatory-agents
#14
Adriana Carol Eleonora Graziano, Giovanna Pannuzzo, Ettore Salemi, Andrea Santagati, Rosanna Avola, Emanuele Longo, Venera Cardile
The present study reports the synthesis, molecular docking and biological evaluation of eight (5-8 and 5a-8a) newly synthesized thieno-pyrimidinone methanesulphonamide thio-derivatives. The synthetic route used to prepare the new isomers thioaryl and thio-cycloesyl derivatives of the heterocyclic system 6-phenylthieno[3,2]pyrimidinone was economically and environmentally very advantageous and characterized by the simplicity of procedure, reduction of isolation steps, purification phases, time, costs, and waste production...
May 7, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29702725/effects-of-the-kv7-voltage-activated-potassium-channel-inhibitor-linopirdine-in-rat-models-of-hemorrhagic-shock
#15
Sean P Nassoiy, Favin S Babu, Heather M LaPorte, Kenneth L Byron, Matthias Majetschak
Recently, we demonstrated that Kv7 voltage-activated potassium channel inhibitors reduce fluid resuscitation requirements in short-term rat models of hemorrhagic shock. The aim of the present study was to further delineate the therapeutic potential and side effect profile of the Kv7 channel blocker linopirdine in various rat models of severe hemorrhagic shock over clinically relevant time periods. Intravenous administration of linopirdine, either before (1 or 3 mg/kg) or after (3 mg/kg) a 40% blood volume hemorrhage, did not affect blood pressure and survival in lethal hemorrhage models without fluid resuscitation...
April 27, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29701913/the-influence-of-abcb1-and-p2y12-genetic-variants-on-clinical-outcomes-in-chinese-intracranial-artery-stenosis-patients
#16
Xingang Li, Liqun Jiang, Shusen Sun, Wei Li, Xiaoqing Li, Zhongrong Miao, Zhigang Zhao, Ning Ma
For intracranial artery stenosis patients, high inter-individual variability in response to antiplatelet drug therapy results in recurrent ischemic events. We aimed to evaluate the association of drug-related genetic polymorphisms with adverse clinical outcomes. We consecutively enrolled 157 patients receiving dual-antiplatelet therapy (aspirin plus clopidogrel), and adverse clinical events occurred in 10 patients during the one year follow-up. The P2Y12 polymorphisms (rs9859538 and rs10935842) were associated with increased likelihood of relapse events (OR=2...
April 27, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29701904/trpv4-activates-cytosolic-phospholipase-a-2-via-ca-2-dependent-pkc-erk1-2-signaling-in-controlling-hypertensive-contraction
#17
Hongjuan Li, Hao Kan, Xiaodong Zhang, Zhenyu Yang, Jian Jin, Peng Zhang, Xin Ma
Activation of TRPV4 (transient receptor potential vanilloid 4) has been reported to result in endothelium-dependent contraction in the aortae of hypertensive mice. This contraction involved increased cPLA2 (cytosolic phospholipase A2 ) activity. The mechanism by which TRPV4 regulates cPLA2 activity to induce contraction in hypertension, however, is unknown. Through measurements of arterial tension and protein level, we showed that high salt diet induced hypertension increases activity of PKC (protein kinase C) and ERK1/2 (extracellular signal-regulated kinase 1/2)...
April 27, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29701902/low-doses-of-paclitaxel-repress-breast-cancer-invasion-through-dj-1-klf17-signaling-pathway
#18
Ismail Ahmed Ismail, Gamal H El-Sokkary, Saber H Saber
Paclitaxel (taxol) is an important agent against many tumors, including breast cancer. Ample data documents that paclitaxel inhibits breast cancer metastasis while others prove that paclitaxel enhances breast cancer metastasis. The mechanisms by which paclitaxel exerts its action are not well established. This study focused on the effect of paclitaxel, particularly the low doses on breast cancer metastasis and the mechanisms that regulate it. Current results show that, paclitaxel exerts significant cytotoxicity even at low doses in both MCF-7 and MDA-MB-231 cells...
April 27, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29699000/spermidine-prevents-high-glucose-induced-senescence-in-ht-22-cells-by-upregulation-of-cb1-receptor
#19
Wei-Wen Zhu, Fan Xiao, Yi-Yun Tang, Wei Zou, Xiang Li, Ping Zhang, Ai-Ping Wang, Xiao-Qing Tang
Hyperglycemia-induced neurotoxicity involves in the pathogenesis of diabetic encephalopathy and neuronal senescence is one of the worst effects of hyperglycemic neurotoxicity. Cannabinoid receptor type 1 (CB1) has neuroprotective function in a series of neuropathy. Spermidine (Spd) has anti-aging function in many tissues. However, the role of Spd in hyperglycemia-induced neuronal senescence remains unexplored. Therefore, we used high glucose (HG)-treated HT-22 cell as vitro model to investigate whether Spd protects neurons against hyperglycemia-induced senescence and the mediatory role of CB1 receptor...
April 26, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29697857/the-protective-effects-of-melatonin-and-glucagon-like-peptide-1-receptor-agonist-liraglutide-on-gastric-ischemia-reperfusion-injury-in-high-fat-sucrose-fed-rats
#20
Hanan A Mubarak, Manal M Mahmoud, Heba S Shoukry, Dina H Merzeban, Safinaz S Sayed, Laila A Rashed
Ischemia-reperfusion (I-R) injury is a serious pathology that is often encountered with thrombotic events, during surgery when blood vessels are cross-clamped, and in organs for transplantation. Increased oxidative stress is the main pathology in I-R injury, as assessed in studies on the heart, kidney, and brain with little data available on gastric I-R (GI-R). Liraglutide is a GLP-1receptor agonist that has insulinotropic and weight reducing actions, and melatonin that has much studied as a chronotropic hormone; have also studied as being antioxidative stress agents...
April 26, 2018: Clinical and Experimental Pharmacology & Physiology
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