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https://www.readbyqxmd.com/read/28629211/effect-of-methoxsalen-on-ca%C3%A2-%C3%A2-%C2%BA-homeostasis-and-viability-in-human-osteosarcoma-cells
#1
Yi-Chau Lu, Chiang-Ting Chou, Wei-Zhe Liang, Chun-Chi Kuo, Shu-Shong Hsu, Jue-Long Wang, Chung-Ren Jan
Methoxsalen is a natural compound found in many seed plants. The effect of methoxsalen on Ca²⁺- related physiology in human osteosarcoma is unclear. This study investigated the effect of methoxsalen on cytosolic free Ca²⁺ concentrations ([Ca²⁺]i) in MG63 human osteosarcoma cells. Methoxsalen induced [Ca²⁺]i rises concentration-dependently. Methoxsalen-induced Ca²⁺ entry was confirmed by Mn²⁺-induced quench of fura-2 fluorescence. This Ca²⁺ entry was suppressed by nifedipine, econazole, and SKF96365...
June 30, 2017: Chinese Journal of Physiology
https://www.readbyqxmd.com/read/28611390/protective-and-therapeutic-effect-of-felodipine-against-bleomycin-induced-pulmonary-fibrosis-in-mice
#2
Ken-Ichiro Tanaka, Tomomi Niino, Tomoaki Ishihara, Ayaka Takafuji, Takahiro Takayama, Yuki Kanda, Toshifumi Sugizaki, Fumiya Tamura, Shota Kurotsu, Masahiro Kawahara, Tohru Mizushima
Idiopathic pulmonary fibrosis (IPF) involves alveolar epithelial injury and abnormal collagen production caused by activated fibroblasts; transforming growth factor (TGF)-β1 is implicated in this activation. In this study, we screened for chemicals capable of inhibiting TGF-β1-induced collagen production in cultured fibroblasts from medicines already in clinical use. We selected felodipine based on its extent of collagen production inhibition, clinical safety profile, and other pharmacological activity. Felodipine is a dihydropyridine Ca(2+) channel blocker that has been used clinically to treat patients with high blood pressure...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611128/decreased-kcne2-expression-participates-in-the-development-of-cardiac-hypertrophy-by-regulation-of-calcineurin-nfat-nuclear-factor-of-activated-t-cells-and-mitogen-activated-protein-kinase-pathways
#3
Wenjuan Liu, Jianxin Deng, Wenwen Ding, Gang Wang, Yuanyuan Shen, Junmeng Zheng, Xiaoming Zhang, Yizhi Luo, Chifei Lv, Yonghui Wang, Liqing Chen, Dewen Yan, Ryan L Boudreau, Long-Sheng Song, Jie Liu
BACKGROUND: KCNE2 is a promiscuous auxiliary subunit of voltage-gated cation channels. A recent work demonstrated that KCNE2 regulates L-type Ca(2+) channels. Given the important roles of altered Ca(2+) signaling in structural and functional remodeling in diseased hearts, this study investigated whether KCNE2 participates in the development of pathological hypertrophy. METHODS AND RESULTS: We found that cardiac KCNE2 expression was significantly decreased in phenylephrine-induced cardiomyocyte hypertrophy in neonatal rat ventricular myocytes and in transverse aortic constriction-induced cardiac hypertrophy in mice, as well as in dilated cardiomyopathy in human...
June 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28600547/modeling-congenital-hyperinsulinism-with-abcc8-deficient-human-embryonic-stem-cells-generated-by-crispr-cas9
#4
Dongsheng Guo, Haikun Liu, Aynisahan Ruzi, Ge Gao, Abbas Nasir, Yanli Liu, Fan Yang, Feima Wu, Guosheng Xu, Yin-Xiong Li
Congenital hyperinsulinism (CHI) is a rare genetic disorder characterized by excess insulin secretion, which results in hypoglycemia. Mutation of sulfonylurea receptor 1 (SUR1), encoded by the ABCC8 gene, is the main cause of CHI. Here, we captured the phenotype of excess insulin secretion through pancreatic differentiation of ABCC8-deficient stem cells generated by the CRISPR/Cas9 system. ABCC8-deficient insulin-producing cells secreted higher insulin than their wild-type counterparts, and the excess insulin secretion was rescued by nifedipine, octreotide and nicorandil...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28598453/effectiveness-of-0-2-glyceryl-trinitrate-and-0-5-nifedipine-in-the-treatment-of-chronic-anal-fissure
#5
S K Shrestha, P B Thapa, D K Maharjan, T Y Tamang
INTRODUCTION: Anal fissure is an ischemic ulcer caused by combination of spasm of internal anal sphincter and poor blood supply to the posterior midline of anal canal. This study aimed to assess the efficacy of Glyceryl Trinitrate and Nifedipine in the treatment of chronic anal fissure. METHODS: Ninety patients with symptomatic anal fissure in Kathmandu Medical College Teaching Hospital are allocated for study in two groups of 45 each from March 2013 to April 2014...
January 2017: JNMA; Journal of the Nepal Medical Association
https://www.readbyqxmd.com/read/28590211/a-systematic-review-of-the-effectiveness-of-palliative-interventions-to-treat-rectal-tenesmus-in-cancer
#6
Áine Ní Laoire, Lucy Fettes, Fliss Em Murtagh
BACKGROUND: Rectal tenesmus is a distressing symptom in patients with advanced cancer and challenging to treat. There is lack of consensus on the appropriate management of tenesmus in this patient population. AIM: To identify and examine the effectiveness of interventions to palliate rectal tenesmus caused by advanced cancer when surgery, radiotherapy or chemotherapy are no longer treatment options. DESIGN: A systematic review of the literature following standard systematic review methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance...
March 1, 2017: Palliative Medicine
https://www.readbyqxmd.com/read/28588206/in-situ-freeze-drying-forming-amorphous-solids-directly-within-capsules-an-investigation-of-dissolution-enhancement-for-a-poorly-soluble-drug
#7
Abdulmalik Alqurshi, K L Andrew Chan, Paul G Royall
Conversion into the amorphous form enhances the dissolution of poorly soluble drugs, however the barrier to market for medicines containing an amorphous drug is poor stability. The aim was to produce the amorphous form of a drug within a capsule, without thermal or mechanical stress during manufacture. To facilitate this aim, the mechanism for drug-polymer interaction was explored. Nifedipine and polyvinylpyrrolidone were dissolved in tert-butanol at different drug/polymer ratios. These solutions were dispensed into gelatin capsules and freeze-dried...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28587834/spasmogenic-effects-of-the-proteasome-inhibitor-carfilzomib-on-coronary-resistance-vascular-tone-and-reactivity
#8
Carol Chen-Scarabelli, Giovanni Corsetti, Evasio Pasini, Francesco S Dioguardi, Gagan Sahni, Jagat Narula, Mara Gavazzoni, Hemang Patel, Louis Saravolatz, Richard Knight, Riccardo Raddino, Tiziano M Scarabelli
BACKGROUND: Carfilzomib (CFZ) is a new proteasome inhibitor used for the treatment of multiple myeloma. Besides heart failure, angina and myocardial ischemia occurred following administration of CFZ, which is not contraindicated in patients with recent myocardial infarction/unstable angina excluded from the safety trials. AIM OF STUDY: To test the effects of CFZ (10(-9) to 10(-7)mol/L) on vascular tone and reactivity in the isolated rabbit heart and aorta. METHODS AND RESULTS: CFZ administered by bolus injection to the isolated heart increased coronary perfusion pressure (CPP) at all tested concentrations and mildly raised left ventricular pressure and heart rate, only at the highest concentration...
May 23, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28580512/comparative-effect-of-calcium-channel-blockers-on-glomerular-function-in-hypertensive-patients-with-diabetes-mellitus
#9
Yayoi Nishida, Yasuo Takahashi, Kotoe Tezuka, Satoshi Takeuchi, Tomohiro Nakayama, Satoshi Asai
BACKGROUND: We conducted a retrospective cohort study to evaluate and compare the longitudinal effect of monotherapy with L-, L/T-, L/N-, and L/N/T-type calcium channel blockers (CCBs) on estimated glomerular filtration rate (eGFR), and to investigate the association of treatment duration with eGFR in diabetic patients with hypertension. METHODS: Using a clinical database, we identified new users of five CCBs, i.e. amlodipine (L-type, n = 693), nifedipine (L-type, n = 189), azelnidipine (L/T-type, n = 91), benidipine (L/N/T-type, n = 183), and cilnidipine (L/N-type, n = 61)...
June 3, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28579067/the-beneficial-effect-of-fesoterodine-a-competitive-muscarinic-receptor-antagonist-on-erectile-dysfunction-in-streptozotocin-induced-diabetic-rats
#10
Didem Yilmaz-Oral, Nur Bayatli, Serap Gur
OBJECTIVE: To investigate the possible role of fesoterodine (a competitive muscarinic receptor antagonist) on erectile dysfunction (ED) in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: A total of 16 adult male Sprague-Dawley rats were equally divided into control and diabetic group. Diabetes was induced by a single intravenous injection of streptozotocin (25-35mg/kg). In vivo erectile responses were evaluated by the stimulation of cavernosal nerves and repeated after intracavernosal injection of fesoterodine (1µM) in rats...
June 1, 2017: Urology
https://www.readbyqxmd.com/read/28568606/coupling-of-excitation-to-ca-2-release-is-modulated-by-dysferlin
#11
Valeriy Lukyanenko, Joaquin M Muriel, Robert J Bloch
Dysferlin concentrates in the transverse tubules of skeletal muscle and stabilizes Ca(2+) transients when muscle fibres are subjected to osmotic shock injury (OSI). We show here that voltage-induced Ca(2+) transients elicited in dysferlin-null A/J myofibers are smaller than control A/WySnJ fibres. Regional expression of Venus-dysferlin chimeras in A/J fibres restores the full amplitude of the Ca(2+) transients and protects against OSI. We also show that drugs that target ryanodine receptors (RyR1: dantrolene, tetracaine, S107) and L-type Ca(2+) channels (LTCC: nifedipine, verapamil, diltiazem) prevent the decrease in Ca(2+) transients in A/J fibres following OSI...
June 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28562313/friedreich-s-ataxia-induced-pluripotent-stem-cell-derived-cardiomyocytes-display-electrophysiological-abnormalities-and-calcium-handling-deficiency
#12
Duncan E Crombie, Claire L Curl, Antonia Ja Raaijmakers, Priyadharshini Sivakumaran, Tejal Kulkarni, Raymond Cb Wong, Itsunari Minami, Marguerite V Evans-Galea, Shiang Y Lim, Lea Delbridge, Louise A Corben, Mirella Dottori, Norio Nakatsuji, Ian A Trounce, Alex W Hewitt, Martin B Delatycki, Martin F Pera, Alice Pébay
We sought to identify the impacts of Friedreich's ataxia (FRDA) on cardiomyocytes. FRDA is an autosomal recessive degenerative condition with neuronal and non-neuronal manifestations, the latter including progressive cardiomyopathy of the left ventricle, the leading cause of death in FRDA. Little is known about the cellular pathogenesis of FRDA in cardiomyocytes. Induced pluripotent stem cells (iPSCs) were derived from three FRDA individuals with characterized GAA repeats. The cells were differentiated into cardiomyocytes to assess phenotypes...
May 30, 2017: Aging
https://www.readbyqxmd.com/read/28558250/direct-nmr-monitoring-of-phase-separation-behavior-of-highly-supersaturated-nifedipine-solution-stabilized-with-hypromellose-derivatives
#13
Keisuke Ueda, Kenjirou Higashi, Kunikazu Moribe
We investigated the phase separation behavior and maintenance mechanism of the supersaturated state of poorly water-soluble nifedipine (NIF) in hypromellose (HPMC) derivative solutions. Highly supersaturated NIF formed NIF-rich nanodroplets through phase separation from aqueous solution containing HPMC derivative. Dissolvable NIF concentration in the bulk water phase was limited by the phase separation of NIF from the aqueous solution. HPMC derivatives stabilized the NIF-rich nanodroplets and maintained the NIF supersaturation with phase-separated NIF for several hours...
June 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28554131/protective-role-of-the-novel-hybrid-3-5-dipalmitoyl-nifedipine-in-a-cardiomyoblast-culture-subjected-to-simulated-ischemia-reperfusion
#14
Eduarda Santa-Helena, Stefanie Teixeira, Micheli Rosa de Castro, Diego da Costa Cabrera, Caroline Da Ros Montes D'Oca, Marcelo G Montes D'Oca, Ana Paula S Votto, Luiz Eduardo Maia Nery, Carla Amorim Neves Gonçalves
This work investigated the acute effects of the calcium channel blocker nifedipine and its new fatty hybrid derived from palmitic acid, 3,5-dipalmitoyl-nifedipine, compared to endocannabinoid anandamide during the process of inducing ischemia and reperfusion in cardiomyoblast H9c2 heart cells. The cardiomyoblasts were treated in 24 or 96-well plates (according to the test being performed) and maintaining the treatment until the end of hypoxia induction. The molecules were tested at concentrations of 10 and 100μM, cells were treated 24h after assembling the experimental plates and immediately before the I/R...
May 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28554023/uptake-biotransformation-and-elimination-of-selected-pharmaceuticals-in-a-freshwater-invertebrate-measured-using-liquid-chromatography-tandem-mass-spectrometry
#15
Thomas H Miller, Nicolas R Bury, Stewart F Owen, Leon P Barron
Methods were developed to assess uptake and elimination kinetics in Gammarus pulex of nine pharmaceuticals (sulfamethazine, carbamazepine, diazepam, temazepam, trimethoprim, warfarin, metoprolol, nifedipine and propranolol) using targeted LC-MS/MS to determine bioconcentration factors (BCFs) using a 96 h toxicokinetic exposure and depuration period. The derived BCFs for these pharmaceuticals did not trigger any regulatory thresholds and ranged from 0 to 73 L kg(-1) (sulfamethazine showed no bioconcentration)...
May 13, 2017: Chemosphere
https://www.readbyqxmd.com/read/28551705/nerve-induced-responses-of-mouse-vaginal-smooth-muscle
#16
Dirk F van Helden, Ayumi Kamiya, Sam Kelsey, Derek R Laver, Phillip Jobling, Retsu Mitsui, Hikaru Hashitani
Neural and agonist-induced contractions of proximal (i.e. upper half adjacent to the cervix) and distal mouse vaginal smooth muscle strips were investigated. We hypothesised that nerve-mediated vaginal contractions arise through activity of cholinergic nerves. Nerve activation by bursts of electrical field stimulation (EFS) caused a primary transient contraction often accompanied by a secondary transient contraction, both larger in proximal than distal tissues (i.e. primary: 7-fold larger; secondary: 3-fold larger)...
May 27, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28538203/uhplc-ms-ms-method-with-sample-dilution-to-test-therapeutic-adherence-through-quantification-of-ten-antihypertensive-drugs-in-urine-samples
#17
Amedeo De Nicolò, Valeria Avataneo, Franco Rabbia, Mauro Sciandra, Francesco Tosello, Jessica Cusato, Elisa Perlo, Paolo Mulatero, Franco Veglio, Giovanni Di Perri, Antonio D'Avolio
Nowadays, hypertension represents an important health problem, particularly in developed countries. In some cases the standard therapeutic approaches are not able to reestablish the normal blood pressure values: this condition is called "resistant hypertension". However, a fraction of cases of resistant hypertension are actually due to poor adherence to the prescribed therapy. Therapeutic Drug Monitoring could represent a direct and useful tool to correctly identify non-compliant patients. Nevertheless, high throughput methods for the simultaneous monitoring of a wide panel of drugs in the same analysis are lacking and, furthermore, there is not a generally acknowledged "standard" matrix for this test (plasma or urine)...
May 13, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28531362/a-trial-of-oral-nifedipine-and-oral-labetalol-in-preeclampsia-hypertensive-emergency-treatment
#18
Jorge Duro-Gómez, Ana B Rodríguez-Marín, Mercedes Giménez de Azcárete, Lourdes Duro-Gómez, Claudio Hernández-Angeles, José E Arjona-Berral, Camil Castelo-Branco
This observational retrospective cohort study was conducted to compare oral nifedipine and labetalol for emergency treatment of hypertension in preeclamptic patients. Time (minutes) and necessary doses were outlined to achieve blood pressure lower than 150/95 mmHg. In 14 patients with preeclampsia, 55 hypertensive emergencies were identified (BP >150/95). Of these emergencies, 43 were treated with oral nifedipine 10 mg (10 patients) and 12 with oral labetalol 100 mg (4 patients). To achieve a target blood pressure under 150/95, these doses were repeated as necessary every 20 min, up to a maximum of 4 doses...
May 20, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28526517/regulation-of-rhoa-rock-and-sustained-arterial-contraction-by-low-cytosolic-ca-2-levels-during-prolonged-depolarization-of-arterial-smooth-muscle
#19
Cristina Porras-González, Antonio Ordóñez, Antonio Castellano, Juan Ureña
The role of L-type Ca(2+) channels (LTCCs) and RhoA/Rho kinase (ROCK) on depolarization-induced sustained arterial contraction lasting several minutes is already known. However, in vivo, vascular smooth muscle cells can be depolarized for longer periods, inducing substantial inactivation of LTCCs and markedly reducing Ca(2+) influx into the myocytes. We have examined, in femoral arterial rings, the role of LTCCs and RhoA/ROCK during long-lasting depolarization. Our results reveal a new vasoreactive response after 20-30min of depolarization in 2...
May 16, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28524699/comparison-of-ambulatory-blood-pressure-lowering-effects-of-higher-doses-of-different-calcium-antagonists-in-uncontrolled-hypertension-the-calcium-antagonist-controlled-release-high-dose-therapy-in-uncontrolled-refractory-hypertensive-patients-carillon-study
#20
Hiroyuki Mizuno, Satoshi Hoshide, Naoko Tomitani, Kazuomi Kario
BACKGROUND: Data are sparse regarding ambulatory blood pressure (BP) reduction of up-titration from a standard dose to a high dose in both nifedipine controlled-release (CR) and amlodipine. This was a prospective, randomized, multicenter, open-label trial. PATIENTS AND METHODS: Fifty-one uncontrolled hypertensives medicated by two or more antihypertensive drugs including a renin-angiotensin system inhibitor and a calcium antagonist were randomly assigned to either the nifedipine CR (80 mg)/candesartan (8 mg) group or the amlodipine (10 mg)/candesartan (8 mg) group...
May 19, 2017: Blood Pressure
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