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Verapamil

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https://www.readbyqxmd.com/read/28342290/verapamil-treatment-induces-cytoprotective-autophagy-by-modulating-cellular-metabolism
#1
Elzbieta Kania, Beata Pajak, Jim O'Prey, Pablo Sierra Gonzalez, Anna Litwiniuk, Kaja Urbańska, Kevin M Ryan, Arkadiusz Orzechowski
Verapamil, an L-type calcium channel blocker, has been used successfully to treat cardiovascular diseases. Interestingly, we have recently shown that treatment of cancer cells with Verapamil causes an effect on autophagy. As autophagy is known to modulate chemotherapy responses, this prompted us to explore the impact of Verapamil on autophagy and cell viability in greater detail. We report here that Verapamil causes an induction of autophagic flux in a number or tumor cells and immortalized normal cells. Moreover, we found that inhibition of autophagy in COLO 205 cells, via treatment with the chloroquine or by CRISPR/Cas9-mediated disruption of the autophagy genes Atg7 and Atg5, causes an upregulation of apoptotic markers in response to Verapamil...
March 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28329903/-headache-treatment
#2
Hans Christoph Diener, Dagny Holle-Lee, Steffen Nägel, Charly Gaul
A precondition for the successful treatment of headaches is the correct headache diagnosis. Triptans are effective for attack treatment of migraine and cluster headache. However, there are not effective for the treatment of tension-type headache. For the prevention of frequent episodic migraine betablockers, flunarizine, topiramate and amitriptyline are recommended. For the prevention of chronic migraine evidence is only available for onabotulinumtoxinA and topiramate. For prophylactic treatment of tension-type headaches tricyclic antidepressants are used...
March 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28321045/characterization-of-human-ips-cell-derived-cardiomyocyte-sheets-as-a-model-to-detect-drug-induced-conduction-disturbance
#3
Hiroko Izumi-Nakaseko, Yuji Nakamura, Takeshi Wada, Kentaro Ando, Yasunari Kanda, Yuko Sekino, Atsushi Sugiyama
In order to characterize human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) sheets as a model for detecting drug-induced conduction disturbance, we examined their electrophysiological and electropharmacological properties by using the multi-electrode array system with a programmed electrical stimulation protocol. At pre-drug control, the conduction speed, effective refractory period and field potential duration were 0.14 ± 0.01 m/sec, 453 ± 10 msec and 361 ± 9 msec, respectively at a cycle length of 1,000 msec (n = 18)...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28315791/neurotoxic-effects-molecular-responses-and-oxidative-stress-biomarkers-in-nile-tilapia-oreochromis-niloticus-linnaeus-1758-exposed-to-verapamil
#4
Malachy N O Ajima, Pramod K Pandey, Kundan Kumar, Nalini Poojary
Pharmaceutical drugs and their metabolites are detected in aquatic ecosystems and have been reported to cause ecotoxicological consequences to resident aquatic organisms The study investigated the effects of acute and long-term exposure to verapamil on activities of acetylcholinesterase and antioxidant enzymes as well as mRNA expression of stress-related genes in brain and muscle tissues of Nile tilapia, Oreochromis niloticus. The 96h LC50 of verapamil to O. niloticus was 2.29mgL(-1). Exposure to sub-lethal concentrations of verapamil (0...
March 16, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28314475/pharmacokinetic-based-study-on-lagged-stimulation-of-curcumae-longae-rhizoma-piper-nigrum-couplet-in-their-main-active-components-metabolism-using-uplc-ms-ms
#5
Zhao Chen, Dongmei Sun, Xiaoli Bi, Xiaohui Zeng, Wenhui Luo, Dake Cai, Qiaohuang Zeng, Aili Xu
BACKGROUND: Curcumae Longae Rhizoma is one of the commonly used traditional Chinese medicines, which has multiple biological activities such as relieving stagnation and stasis, pain alleviation, curing amenorrhea and wounds. However, its main active component-curcumin has poor absorption and very fast metabolism in body. To solve this problem, Piper nigrum was introduced for its ability to strengthen bioavailability of other compounds. PURPOSE: In most cases of TCM couplets, all ingredients were prepared and taken simultaneously, which in our opinion did not take full advantage of their interactions...
April 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28301155/exploration-of-2-pyridin-4-ylmethyl-amino-nicotinamide-derivatives-as-potent-reversal-agents-against-p-glycoprotein-mediated-multidrug-resistance
#6
Qianqian Qiu, Wei Shi, Zheng Li, Bo Zhang, Miaobo Pan, Jian Cui, Yuxuan Dai, Wenlong Huang, Hai Qian
Overexpression of the ATP-binding cassette (ABC) transport proteins, like ABCB1, commonly referred to as P-glycoprotein (P-gp), initiates active efflux of a broad spectrum of unrelated chemotherapeutic drugs in structure and function, leading to chemotherapy failure. A series of 2-((pyridin-4-ylmethyl)amino)nicotinamide derivatives as potent reversal agents against P-glycoprotein-mediated multidrug resistance (MDR) were designed and synthesized. The majority of target compounds displayed great reversal potency, especially 9n...
March 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28301084/the-effect-of-verapamil-a-p-glycoprotein-inhibitor-on-the-pharmacokinetics-of-peficitinib-an-orally-administered-once-daily-jak-inhibitor
#7
Tong Zhu, Corrie Howieson, Tomasz Wojtkowski, Jay P Garg, David Han, Ogert Fisniku, James Keirns
Peficitinib is an orally administered, once-daily Janus kinase inhibitor currently in development for the treatment of rheumatoid arthritis. It has been shown to be a P-glycoprotein (P-gp) substrate in vitro. The effects of verapamil, an inhibitor of the efflux pump P-gp, on the pharmacokinetic profile of peficitinib were assessed in this open-label, single-center, single-sequence, crossover drug-interaction study. Twenty-four healthy volunteers received a single 150-mg dose of peficitinib on days 1 and 12 of a 14-day treatment period and received verapamil 80 mg 3 times daily on days 5-14...
March 16, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28299835/multiple-atp-binding-cassette-transporters-are-involved-in-insecticide-resistance-in-the-small-brown-planthopper-laodelphax-striatellus
#8
H Sun, J Pu, F Chen, J Wang, Z Han
ATP-binding cassette (ABC) transporters are membrane-bound proteins involved in the movement of various substrates, including drugs and insecticides, across the lipid membrane. Demonstration of the role of human ABC transporters in multidrug resistance has led to speculation that they might be an important mechanism controlling the fate of insecticides in insects. However, the role of ABC transporters in insects remains largely unknown. The small brown planthopper, Laodelphax striatellus Fallén, has developed resistance to most of the insecticides used for its control...
March 16, 2017: Insect Molecular Biology
https://www.readbyqxmd.com/read/28296590/transport-of-a-novel-angiotensin-i-converting-enzyme-inhibitory-peptide-ala-his-leu-leu-across-human-intestinal-epithelial-caco-2-cells
#9
Ying Li, Jiangtao Zhao, Xiaoli Liu, Xiudong Xia, Ying Wang, Jianzhong Zhou
The transport behavior and absorption mechanism of Ala-His-Leu-Leu (AHLL) intestinal absorption in Caco-2 cell monolayers were clarified systemically. The safe absorptive concentration of AHLL was 200 μg/mL, which was determined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. The permeation of AHLL was concentration dependent in a bidirectional transfer and reached a plateau at 90 min. The efflux ratio was above 0.5, suggesting that AHLL was absorbed by both active transport and passive diffusion...
March 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28294237/surface-assisted-laser-desorption-ionization-time-of-flight-mass-spectrometry-of-small-drug-molecules-and-high-molecular-weight-synthetic-biological-polymers-using-electrospun-composite-nanofibers
#10
Juan Bian, Susan V Olesik
Polyacrylonitrile/Nafion®/carbon nanotube (PAN/Nafion®/CNT) composite nanofibers were prepared using electrospinning. These electrospun nanofibers were studied as possible substrates for surface-assisted laser desorption/ionization (SALDI) and matrix-enhanced surface-assisted laser desorption/ionization time-of-flight mass spectrometry (ME-SALDI/TOF-MS) for the first time in this paper. Electrospinning provides this novel substrate with a uniform morphology and a narrow size distribution, where CNTs were evenly and firmly immobilized on polymeric nanofibers...
March 15, 2017: Analyst
https://www.readbyqxmd.com/read/28292752/fascicular-ventricular-tachycardia-originating-from-papillary-muscles-purkinje-network-involvement-in-the-reentrant-circuit
#11
Yuki Komatsu, Akihiko Nogami, Kenji Kurosaki, Itsuro Morishima, Keita Masuda, Tomoya Ozawa, Takashi Kaneshiro, Yuichi Hanaki, Yasutoshi Shinoda, Ahmed Karim Talib, Shinya Kowase, Yukio Sekiguchi, Kazutaka Aonuma
BACKGROUND: Verapamil-sensitive fascicular ventricular tachycardia (FVT) has been demonstrated to be a reentrant mechanism using the Purkinje network as a part of its reentrant circuit. Although the papillary muscles (PMs) are implicated in arrhythmogenic structure, reentrant FVT originating from the PMs has not been well defined. METHODS AND RESULTS: We studied 13 patients in whom FVT was successfully eliminated by ablation at the posterior PMs (n=8; PPM-FVT) and anterior PMs (n=5; APM-FVT)...
March 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28290801/-comparison-of-verapamil-and-amlodipine-for-treatment-of-chronic-heart-failure-with-preserved-left-ventricular-ejection-fraction-in-patients-with-hypertensive-disease
#12
S G Kanorskii, A F Sereda
OBJECTIVE: to compare efficacy of verapamil and amlodipine in treatment of chronic heart failure (CHF) with preserved left ventricular (LV) ejection fraction (EF) in patients with hypertensive disease (HD). MATERIAL AND METHODS: Patients with stage III HD, class II-III CHF, and LVEF more or equal 50% (n=167, age 48-70 years) underwent complex examination before and after 12 months of treatment with perindopril combined either with verapamil SR (n=85) or amlodipine (n=82)...
December 2016: Kardiologiia
https://www.readbyqxmd.com/read/28283574/effect-of-detergent-micelle-environment-on-p-glycoprotein-abcb1-ligand-interactions
#13
Suneet Shukla, Biebele Abel, Eduardo E Chufan, Suresh V Ambudkar
P-glycoprotein (P-gp) is a multidrug transporter that utilizes energy from ATP hydrolysis to efflux a variety of structurally dissimilar hydrophobic and amphipathic compounds including anticancer drugs from cells. Several structural studies on purified P-gp have been reported and there is very limited and in some cases conflicting information available on ligand interactions with isolated transporter in a dodecyl maltoside detergent environment. In this report, we compare the biochemical properties of human and mouse P-gp in native membranes, detergent micelles, and after reconstitution in artificial membranes...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28283479/pkc-dependent-regulation-of-kv7-5-channels-by-the-bronchoconstrictor-histamine-in-human-airway-smooth-muscle-cells
#14
Jennifer M Haick, Lioubov I Brueggemann, Leanne L Cribbs, Mitchell F Denning, Jeffrey Schwartz, Kenneth L Byron
Kv7 potassium channels have recently been found to be expressed and functionally important for relaxation of airway smooth muscle. Previous research suggests that native Kv7 currents are inhibited following treatment of freshly isolated airway smooth muscle cells with bronchoconstrictor agonists, and in intact airways inhibition of Kv7 channels is sufficient to induce bronchiolar constriction. However, the mechanism by which Kv7 currents are inhibited by bronchoconstrictor agonists has yet to be elucidated...
March 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28277420/regional-to-the-rescue-axillary-brachial-plexus-nerve-block-facilitates-removal-of-entrapped-transradial-catheter-placed-for-cardiac-catheterization
#15
Brian M Fitzgerald, Lee A Babbel, Ferdinand K Bacomo, Sandeep T Dhanjal
OBJECTIVE: Our objective was to describe the first reported use of an axillary brachial plexus block to treat the entrapment of a transradial artery catheter due to vasospasm. CASE REPORT: A 42-year-old man undergoing transradial arterial cardiac catheterization suffered arterial vasospasm causing the catheter to become entrapped and refractory to conservative (warm compresses) and standard pharmacologic interventions (intracatheter verapamil, intravenous infusions of nitroglycerin and nicardipine, and subcutaneous lidocaine and topical nitroglycerin)...
March 8, 2017: Regional Anesthesia and Pain Medicine
https://www.readbyqxmd.com/read/28274876/hypotonic-stress-promotes-atp-release-reactive-oxygen-species-production-and-cell-proliferation-via-trpv4-activation-in-rheumatoid-arthritis-rat-synovial-fibroblasts
#16
Fen Hu, Zhenhai Hui, Wei Wei, Jianyu Yang, Ziyuan Chen, Bu Guo, Fulin Xing, Xinzheng Zhang, Leiting Pan, Jingjun Xu
Rheumatoid arthritis (RA) is a chronic and systemic autoimmune-disease with complex and unclear etiology. Hypotonicity of synovial fluid is a typical characteristic of RA, which may play pivotal roles in RA pathogenesis. In this work, we studied the responses of RA synovial fibroblasts to hypotonic stress in vitro and further explored the underlying mechanisms. Data showed that hyposmotic solutions significantly triggered increases in cytosolic calcium concentration ([Ca(2+)]c) of synoviocytes. Subsequently, it caused rapid release of ATP, as well as remarkable production of intracellular reactive oxygen species (ROS)...
April 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28272881/role-of-aromatic-and-negatively-charged-residues-of-drrb-in-multi-substrate-specificity-conferred-by-the-drrab-system-of-streptomyces-peucetius
#17
Kenneth Brown, Wen Li, Parjit Kaur
Resistance to the anticancer antibiotics, doxorubicin and daunorubicin, in the producer organism Streptomyces peucetius is conferred by an ABC transporter made of two proteins DrrA and DrrB, which together form a dedicated exporter for these two antibiotics. Surprisingly, however, the DrrAB system exhibits broad substrate specificity overlapping with well-studied multidrug resistance transporters, including P-glycoprotein. Therefore it provides an excellent model to study molecular basis of multi-specificity in a prototype efflux system with the potential to unravel the origin and evolution of multidrug resistance...
March 8, 2017: Biochemistry
https://www.readbyqxmd.com/read/28270141/pharmacological-basis-for-the-medicinal-use-of-polyherbal-formulation-and-its-ingredients-in-cardiovascular-disorders-using-rodents
#18
Abdul Malik, Malik Hassan Mehmood, Hajra Channa, Muhammad Shoaib Akhtar, Anwarul-Hassan Gilani
BACKGROUND: A compound herbal formulation (POL4) has been used in the indigenous system of medicine to treat cardiometabolic disorders like diabetes and associated hypertension. POL4 and most of its constituents have not been studied widely for its therapeutic use in hypertension. This study is aimed to determine the efficacy and possible insight into mechanism(s) for the medicinal use of POL4 and its ingredients in hypertension. METHODS: The aqueous methanolic extracts of POL4 (POL4...
March 7, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28245963/characterization-of-microminipigs-as-an-in%C3%A2-vivo-experimental-model-for-cardiac-safety-pharmacology
#19
Suchitra Matsukura, Yuji Nakamura, Xin Cao, Takeshi Wada, Hiroko Izumi-Nakaseko, Kentaro Ando, Hiroshi Yamazaki, Atsushi Sugiyama
We pharmacologically characterized microminipigs as an in vivo experimental model by assessing cardiovascular effects of pilsicainide, verapamil and E-4031, which can preferentially inhibit cardiac Na(+), Ca(2+) and K(+) channels, respectively. Intravenous infusion of 1 mg/kg of pilsicainide (n = 4), 0.1 mg/kg of verapamil (n = 4) and 0.01 followed by 0.1 mg/kg of E-4031 (n = 5) over 10 min decreased the heart rate, mean blood pressure and ventricular contractility. Moreover, pilsicainide prolonged the PR interval, QRS width and QTc; verapamil prolonged the PR interval, but shortened the QRS width and QTc; and E-4031 prolonged the QTc, whereas no substantial change was detected in the PR interval or QRS width...
February 11, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28223391/evaluation-of-para-aminosalicylic-acid-pas-as-a-substrate-of-multiple-solute-carrier-slc-uptake-transporters-and-possible-drug-interactions-with-nsaids-in-vitro
#20
Md Masud Parvez, Ho Jung Shin, Jin Ah Jung, Jae-Gook Shin
para-Aminosalicylic acid (PAS) is a second-line anti-tuberculosis drug used to treat multidrug-resistant and extensively drug-resistant tuberculosis for more than 60 years. Renal secretion and glomerular filtration are the major pathways for elimination of PAS. We comprehensively studied PAS transport by using cell lines that overexpressed various transporters, and found that PAS acts as a novel substrate of organic anionic polypeptide (OATP1B1), organic cationic transporters (OCT1 and OCT2), and organic anion transporters (OAT1 and OAT3) but not a substrate of any ATP-binding cassette (ABC) transporters...
February 21, 2017: Antimicrobial Agents and Chemotherapy
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