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https://www.readbyqxmd.com/read/29785630/calcium-channels-rho-kinase-protein-kinase-c-and-phospholipase-c-pathways-mediate-mercury-chloride-induced-myometrial-contractions-in-rats
#1
Swati Koli, Atul Prakash, Soumen Choudhury, Rajesh Mandil, Satish K Garg
Adverse effects of mercury on female reproduction are reported; however, its effect on myogenic activity of uterus and mechanism thereof is obscure. Present study was undertaken to unravel the mechanistic pathways of mercuric chloride (HgCl2 )-induced myometrial contraction in rats. Isometric tension in myometrial strips of rats following in vitro exposure to HgCl2 was recorded using data acquisition system-based physiograph. HgCl2 produced concentration-dependent (10 nM-100 μM) uterotonic effect which was significantly (p < 0...
May 21, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29781736/comparison-of-real-world-effectiveness-between-valsartan-and-non-ras-inhibitor-monotherapy-on-the-incidence-of-new-diabetes-in-chinese-hypertensive-patients-an-electronic-health-recording-system-based-study
#2
Tian Shen, Jiwei Wang, Yingjun Yu, Jinming Yu
This study aimed to compare the real-world effectiveness of valsartan and non renin-angiotensin system (non-RAS) agent monotherapy on the incidence of new on-set diabetes (NOD) in Chinese hypertensive patients. It was based on an electronic Health Recording System database from Minhang District of Shanghai. Hypertensive patients aged ≥18 years continuously taking either valsartan or non-RAS agent monotherapy for >12 months were included. Hazard ratios (HR) of NOD events were estimated using propensity score matching method and multivariate regression...
May 21, 2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29777040/obe022-an-oral-and-selective-prostaglandin-f2%C3%AE-receptor-antagonist-as-an-effective-and-safe-modality-for-the-treatment-of-preterm-labor
#3
Oliver Pohl, Andre Chollet, Sung Hye Kim, Lucia Riaposova, Francois Spezia, Frederic Gervais, Philippe Guillaume, Philippe Lluel, Murielle Meen, Frederique Lemaux, Vasso Terzidou, Phillip R Bennett, Jean-Pierre Gotteland
Preterm birth is the major challenge in obstetrics affecting ~10% of pregnancies. Pan-prostaglandin synthesis inhibitors (NSAID) prevent preterm labor and prolong pregnancy but raise concerns about fetal renal and cardiovascular safety. We conducted preclinical studies examining the tocolytic effect and fetal safety of the oral prodrug candidate OBE022 and its parent OBE002, both potent and highly selective antagonist of the contractile PGF2α prostaglandin receptor (FP). Efficacy of OBE022 and OBE002, alone and in combination with other tocolytics, was assessed in human tissues and pregnant animal models for inhibition of uterine contraction and delay of parturition...
May 18, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29767558/molecular-basis-of-the-counteraction-by-calcium-channel-blockers-of-cyclosporine-nephrotoxicity
#4
Safaa Hicham Hammoud, Sahar Alkhansa, Neamah Mahjoub, Amal Galal Omar, Mahmoud M El-Mas, Assaad A Eid
Nephrotoxicity is a serious side effect for the immunosuppressant drug cyclosporine (CSA). In this study, we tested the hypothesis that administration of calcium channel blockers such as verapamil or nifedipine ameliorate renal CSA-induced renal dysfunction. Furthermore, our study investigates the roles of inflammatory, oxidative, and fibrotic pathways in CSA-induced renal dysfunction. Six groups of male rats (n=6/group) were used and received one of the following treatments for 7 consecutive days: vehicle (cremophor EL, i...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29756401/alpha-1-adrenergic-stimulation-selectively-enhances-endothelium-mediated-vasodilation-in-rat-cremaster-arteries
#5
Ramesh C Mishra, Mohammad M Rahman, Michael J Davis, Heike Wulff, Michael A Hill, Andrew P Braun
We have systematically investigated how vascular smooth muscle α1 -adrenoceptor activation impacts endothelium-mediated vasodilation in isolated, myogenically active, rat cremaster muscle 1A arteries. Cannulated cremaster arteries were pressurized intraluminally to 70 mmHg to induce myogenic tone, and exposed to vasoactive agents via bath superfusion at 34°C. Smooth muscle membrane potential was measured via sharp microelectrode recordings in pressurized, myogenic arteries. The α1 -adrenergic agonist phenylephrine (25-100 nmol/L) produced further constriction of myogenic arteries, but did not alter the vasorelaxant responses to acetylcholine (0...
May 2018: Physiological Reports
https://www.readbyqxmd.com/read/29748133/retinoic-acid-inhibits-neuronal-voltage-gated-calcium-channels
#6
Eric de Hoog, Mark K Lukewich, Gaynor E Spencer
Retinoic acid is the active metabolite of vitamin A and regulates several important cellular processes by activating retinoic acid receptors (RAR) and retinoid X receptors (RXR). These receptors generally act as transcription factors, though non-genomic actions of both retinoic acid and the receptors have also been reported. One such nongenomic effect includes the modulation of Ca2+ levels during homeostatic synaptic plasticity in the hippocampus. Retinoic acid can thus affect Ca2+ signaling and can potentially control both synaptic plasticity and neuronal firing...
February 13, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29740911/the-sphingosine-analog-fingolimod-fty720-enhances-tone-and-contractility-of-rat-gastric-fundus-smooth-muscle
#7
M Kraft, U K Zettl, T Noack, R Patejdl
BACKGROUND: Sphingosine and its metabolite sphingosine phosphate (S1P) regulate a multitude of biological functions, including the contractile state of smooth. Gastrointestinal side effects have been reported in patients treated with FTY720, a sphingosine analog that is approved for the treatment of multiple sclerosis. The aim of this study was to characterize the effects of FTY720 on rat gastric fundus smooth muscle under basal conditions and during activation induced by high-K+ solution...
May 8, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29740519/repurposing-drugs-to-fast-track-therapeutic-agents-for-the-treatment-of-cryptococcosis
#8
Megan Truong, Leigh G Monahan, Dee A Carter, Ian G Charles
Many infectious diseases disproportionately affect people in the developing world. Cryptococcal meningitis is one of the most common mycoses in HIV-AIDS patients, with the highest burden of disease in sub-Saharan Africa. Current best treatment regimens still result in unacceptably high mortality rates, and more effective antifungal agents are needed urgently. Drug development is hampered by the difficulty of developing effective antifungal agents that are not also toxic to human cells, and by a reluctance among pharmaceutical companies to invest in drugs that cannot guarantee a high financial return...
2018: PeerJ
https://www.readbyqxmd.com/read/29738666/co-stabilization-of-amorphous-pharmaceuticals-the-case-of-nifedipine-and-nimodipine
#9
Justyna Knapik-Kowalczuk, Wenkang Tu, Krzysztof Chmiel, Marzena Rams-Baron, Marian Paluch
Currently, a research hotspot in amorphous active pharmaceutical ingredients (APIs) is to understand the key factors that dominate the recrystallization and to develop effective methods for stabilizing the amorphous forms. Consequently, we investigated the influence of the global molecular mobility and structural properties on the crystallization tendency of three 1, 4-dihydropyridine derivatives (nifedipine, nisoldipine and nimodipine) in their supercooled states using differential scanning calorimeter (DSC) and broadband dielectric spectroscopy (BDS) techniques...
May 8, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29730174/a-systematic-review-of-the-aetiology-and-management-of-post-cholecystectomy-syndrome
#10
REVIEW
Jennifer Isherwood, Kathryn Oakland, Achal Khanna
BACKGROUND: 10% of patients who undergo a cholecystectomy go on to develop post-cholecystectomy syndrome (PCS). The majority of these patients may suffer from extra-biliary or unrelated organic disorders that may have been present before cholecystectomy. The numerous aetiological causes of PCS result in a wide spectrum of management options, each with varying success in abating symptoms. This systematic review aims to provide a summary of the causative aetiologies of post cholecystectomy syndrome, their incidences and efficacy of available management options...
May 2, 2018: Surgeon: Journal of the Royal Colleges of Surgeons of Edinburgh and Ireland
https://www.readbyqxmd.com/read/29718449/cross-site-reliability-of-human-induced-pluripotent-stem-cell-derived-cardiomyocyte-based-safety-assays-using-microelectrode-arrays-results-from-a-blinded-cipa-pilot-study
#11
Daniel Millard, Qianyu Dang, Hong Shi, Xiaou Zhang, Chris Strock, Udo Kraushaar, Haoyu Zeng, Paul Levesque, Hua-Rong Lu, Jean-Michel Guillon, Joseph C Wu, Yingxin Li, Greg Luerman, Blake Anson, Liang Guo, Mike Clements, Yama A Abassi, James Ross, Jennifer Pierson, Gary Gintant
Recent in vitro cardiac safety studies demonstrate the ability of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to detect electrophysiologic effects of drugs. However, variability contributed by unique approaches, procedures, cell lines and reagents across laboratories makes comparisons of results difficult, leading to uncertainty about the role of hiPSC-CMs in defining proarrhythmic risk in drug discovery and regulatory submissions. A blinded pilot study was conducted to evaluate the electrophysiologic effects of eight well-characterized drugs on four cardiomyocyte lines using a standardized protocol across three microelectrode array (MEA) platforms (18 individual studies)...
April 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29715711/effects-of-fengliao-changweikang-in-diarrhea-predominant-irritable-bowel-syndrome-rats-and-its-mechanism-involving-colonic-motility
#12
Mengdi Jia, Xiaofang Lu, Luqing Zhao, Zhengfang Wang, Shengsheng Zhang
Background/Aims: This study was designed to investigate the effect of Fengliao-Changweikang (FLCWK) in diarrhea-predominant irritable bowel syndrome (IBS-D) rats and explore its underlying mechanisms. Methods: IBS-D model rats were induced by neonatal maternal separation (NMS) combined with restraint stress (RS). In in vivo experiments, the model rats were randomly divided into 5 groups: NMS + RS, FLCWK (low dose, middle dose, and high dose), and pinaverium bromide...
April 30, 2018: Journal of Neurogastroenterology and Motility
https://www.readbyqxmd.com/read/29709270/selectivity-of-ca-2-channel-blockers-for-dilator-actions-on-the-isolated-lower-esophageal-sphincter-and-aorta-from-rats
#13
Akira Takahara, Shuhei Nozaki, Akane Ishiguro, Kaori Okamura, Xin Cao, Megumi Aimoto, Yoshinobu Nagasawa
We compared dilator actions of representative four Ca2+ channel blockers on the isolated lower esophagus sphincter (LES) and thoracic aorta from rats. Verapamil, diltiazem, nifedipine and cilnidipine suppressed KCl-induced contractions of LES and thoracic aorta in a concentration-dependent manner. The order of selectivity for LES, which was calculated as ratio of IC50 value for thoracic aorta divided by that for LES, was diltiazem > verapamil > nifedipine > cilnidipine. These results suggest that diltiazem more preferentially dilates the LES whereas cilnidipine is expected to have lower potential risk of gastroesophageal dysfunction during the antihypertensive therapy...
April 19, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29694371/voltage-dependent-inward-currents-in-smooth-muscle-cells-of-skeletal-muscle-arterioles
#14
Alexandra V Ulyanova, Roman E Shirokov
Voltage-dependent inward currents responsible for the depolarizing phase of action potentials were characterized in smooth muscle cells of 4th order arterioles in mouse skeletal muscle. Currents through L-type Ca2+ channels were expected to be dominant; however, action potentials were not eliminated in nominally Ca2+-free bathing solution or by addition of L-type Ca2+ channel blocker nifedipine (10 μM). Instead, Na+ channel blocker tetrodotoxin (TTX, 1 μM) reduced the maximal velocity of the upstroke at low, but not at normal (2 mM), Ca2+ in the bath...
2018: PloS One
https://www.readbyqxmd.com/read/29687449/influence-of-3-calcium-channel-blockers-on-gingival-overgrowth-in-a-population-of-severe-refractory-hypertensive-patients
#15
F Vidal, R C de Souza, D C Ferreira, R G Fischer, L S Gonçalves
OBJECTIVE: The aim of the current study was to assess the association between 3 different calcium channel blockers (CCBs) (nifedipine, amlodipine and felodipine) and gingival overgrowth in patients with a diagnosis of severe refractory hypertension. METHODS: One hundred and sixty-two patients with severe refractory hypertension, taking CCBs, were selected. Gingival overgrowth was graded and periodontal measurements were recorded (probing pocket depth, clinical attachment level, plaque index and bleeding on probing)...
April 23, 2018: Journal of Periodontal Research
https://www.readbyqxmd.com/read/29684406/conservation-of-cardiac-l-type-ca-2-channels-and-their-regulation-in-drosophila-a-novel-genetically-pliable-channelopathic-model
#16
Worawan B Limpitikul, Meera C Viswanathan, Brian O'Rourke, David T Yue, Anthony Cammarato
Dysregulation of L-type Ca2+ channels (LTCCs) underlies numerous cardiac pathologies. Understanding their modulation with high fidelity relies on investigating LTCCs in their native environment with intact interacting proteins. Such studies benefit from genetic manipulation of endogenous channels in cardiomyocytes, which often proves cumbersome in mammalian models. Drosophila melanogaster, however, offers a potentially efficient alternative as it possesses a relatively simple heart, is genetically pliable, and expresses well-conserved genes...
April 20, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29674046/development-of-a-chromatographic-method-with-multi-criteria-decision-making-design-for-simultaneous-determination-of-nifedipine-and-atenolol-in-content-uniformity-testing
#17
Sameh Ahmed, Abdulmalik Alqurshi, Abdel-Maaboud Ismail Mohamed
A new robust and reliable high-performance liquid chromatography (HPLC) method with multi-criteria decision making (MCDM) approach was developed to allow simultaneous quantification of atenolol (ATN) and nifedipine (NFD) in content uniformity testing. Felodipine (FLD) was used as an internal standard (I.S.) in this study. A novel marriage between a new interactive response optimizer and a HPLC method was suggested for multiple response optimizations of target responses. An interactive response optimizer was used as a decision and prediction tool for the optimal settings of target responses, according to specified criteria, based on Derringer's desirability...
July 1, 2018: Talanta
https://www.readbyqxmd.com/read/29665423/evaluation-of-four-calcium-channel-blockers-as-fluconazole-resistance-inhibitors-in-candida-glabrata
#18
Lina M Alnajjar, Nailya R Bulatova, Rula M Darwish
OBJECTIVES: In this study we aimed to evaluate the ability of four calcium channel blockers, verapamil, diltiazem, nicardipine and nifedipine to enhance sensitivity of Candida glabrata strains to fluconazole. METHODS: The synergistic antifungal effect was examined by checkerboard method; fractional inhibitory concentration index (FIC) was determined. Time-kill curve method was used for the most promising combination to further evaluate the synergetic effects. RESULTS: nicardipine showed additive effect with fluconazole against fluconazole-resistant and fluconazole-susceptible-dose-dependent strains (DSY565 and CBS138) known to express efflux pumps but not against fluconazole-sensitive strains...
April 14, 2018: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29663150/preparation-of-a-novel-lipid-core-micelle-using-a-low-energy-emulsification-method
#19
Hans F Fritz, Andrea C Ortiz, Sitaram P Velaga, Javier O Morales
High-energy methods for the manufacturing of nanomedicines are widely used; however, interest in low-energy methods is increasing due to their simplicity, better control over the process, and energy-saving characteristics during upscaling. Here, we developed a novel lipid-core micelle (LCM) as a nanocarrier to encapsulate a poorly water-soluble drug, nifedipine (NFD), by hot-melt emulsification, a low-energy method. LCMs are self-assembling colloidal particles composed of a hydrophobic core and a hydrophilic shell...
April 16, 2018: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29656005/the-uricosuric-effects-of-dihydropyridine-calcium-channel-blockers-in-vivo-using-urate-under-excretion-animal-models
#20
Takayuki Hori, Motoshi Ouchi, Naoyuki Otani, Masakatsu Nohara, Asuka Morita, Yusuke Otsuka, Promsuk Jutabha, Ikuko Shibasaki, Yasushi Matsushita, Tomoe Fujita, Hirotsugu Fukuda, Naohiko Anzai
The purpose of this study was to create novel urate under-excretion animal models using pyrazinamide and to evaluate whether dihydropyridine calcium channel blockers (CCBs) have uricosuric effects in vivo. Adult male ICR mice were treated with pyrazinamide, vehicle (dimethyl sulfoxide: DMSO), or tap water. Thirty minutes later, pyrazinamide-treated mice were given benzbromarone, losartan, nilvadipine, nitrendipine, nifedipine or azelnidipine. Six hours after the second administration, urine (by urinary bladder puncture) and plasma were collected to measure uric acid and creatinine levels, and fractional excretion of uric acid (FEUA) and creatinine clearance (Ccr) were calculated and evaluated...
March 8, 2018: Journal of Pharmacological Sciences
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