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https://www.readbyqxmd.com/read/28924743/a-physiologically-based-pharmacokinetic-model-for-pregnant-women-to-predict-the-pharmacokinetics-of-drugs-metabolized-via-several-enzymatic-pathways
#1
André Dallmann, Ibrahim Ince, Katrin Coboeken, Thomas Eissing, Georg Hempel
BACKGROUND: Physiologically based pharmacokinetic modeling is considered a valuable tool for predicting pharmacokinetic changes in pregnancy to subsequently guide in-vivo pharmacokinetic trials in pregnant women. The objective of this study was to extend and verify a previously developed physiologically based pharmacokinetic model for pregnant women for the prediction of pharmacokinetics of drugs metabolized via several cytochrome P450 enzymes. METHODS: Quantitative information on gestation-specific changes in enzyme activity available in the literature was incorporated in a pregnancy physiologically based pharmacokinetic model and the pharmacokinetics of eight drugs metabolized via one or multiple cytochrome P450 enzymes was predicted...
September 18, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28922987/admissions-for-hypoglycaemia-after-35%C3%A2-weeks-of-gestation-perinatal-predictors-of-cost-of-stay
#2
Theodore Dassios, Anne Greenough, Stamatina Leontiadi, Ann Hickey, Nick Kametas
BACKGROUND: Hypoglycaemia accounts for approximately one tenth of term admissions to neonatal units, can cause long-term neurodevelopmental impairment and is associated with significant burden to the affected infants, families and the health system. OBJECTIVE: To define the prevalence, length and cost of admissions for hypoglycaemia in infants born at greater than 35 weeks gestation and to identify antenatal and perinatal predictors of those outcomes. MATERIAL AND METHODS: This was a retrospective audit of infants admitted for hypoglycaemia between 1/1/2012 and 31/12/2015, in a level three neonatal intensive care unit at King's College Hospital NHS Foundation Trust, London...
September 18, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28916261/differential-involvement-of-l-and-t-type-ca-2-channels-store-operated-calcium-channel-trpc-and-rho-kinase-signaling-pathway-s-in-pgf2%C3%AE-induced-contractions-in-myometrium-of-non-pregnant-and-pregnant-buffaloes-bubalus-bubalis
#3
Abhishek Sharma, Udayraj P Nakade, Pooja Jaitley, Vipin Sharma, Soumen Choudhury, Satish Kumar Garg
This study unravels the differential involvement of calcium signaling pathway(s) in PGF2α-induced contractions in myometrium of non-pregnant and pregnant buffaloes. Compared to the myometrium of pregnant animals, myometrium of non-pregnant buffaloes was more sensitive to PGF2α-induced contractile effect as manifested by the changes in mean integral tension (MIT) and tonicity. However, phasic contraction was significantly more in myometrium of pregnant animals. The uterotonic effect of PGF2α was dependent on extracellular Ca(2+) and its influx through nifedipine-sensitive L-type Ca(2+) channels both in non-pregnant and pregnant animals, but T-type Ca(2+) channels play an additional role during pregnancy...
September 12, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28904098/characterization-of-ion-channels-and-o2-sensitivity-in-gill-neuroepithelial-cells-of-the-anoxia-tolerant-goldfish-carassius-auratus
#4
Peter C Zachar, Wen Pan, Michael G Jonz
The neuroepithelial cell (NEC) of the fish gill is an important model for O2 sensing in vertebrates; however, a complete picture of the chemosensory mechanisms in NECs is lacking, and O2 chemoreception in vertebrates that are tolerant to anoxia has yet not been explored. Using whole-cell patch-clamp recording, we characterized four types of ion channels in NECs isolated from the anoxia-tolerant goldfish. A Ca(2+)-dependent K(+) current (IKCa) peaked at ~20 mV, was potentiated by increased intracellular Ca(2+), and was reduced by 100 μM Cd(2+) A voltage-dependent inward current in Ba(2+) solution, with peak at 0 mV, confirmed the presence of Ca(2+) channels...
September 13, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28899749/cyp4a-cyp2c-modulation-of-the-interaction-of-calcium-channel-blockers-with-cyclosporine-on-edhf-mediated-renal-vasodilations-in-rats
#5
Safaa H Hammoud, Amal G Omar, Assaad A Eid, Mahmoud M El-Mas
The endothelium-derived hyperpolarizing factor (EDHF) serves as a back-up mechanism that compensates for reduced nitric oxide (NO)/prostanoids bioavailability. Here we investigated whether (i) under conditions of vascular endothelium dysfunction, the immunosuppressant drug cyclosporine (CSA) upregulates EDHF-dependent renal vasodilations through altering CYP4A/CYP2C signaling, and (ii) calcium channel blockers modulate the CSA/EDHF/CYP interaction. Rats were treated with CSA, verapamil, nifedipine, or their combinations for 7days...
September 9, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28893900/labetalol-versus-nifedipine-as-antihypertensive-treatment-for-chronic-hypertension-in-pregnancy-a-randomized-controlled-trial
#6
Louise M Webster, Jenny E Myers, Catherine Nelson-Piercy, Kate Harding, J Kennedy Cruickshank, Ingrid Watt-Coote, Asma Khalil, Cornelia Wiesender, Paul T Seed, Lucy C Chappell
Data from randomized controlled trials to guide antihypertensive agent choice for chronic hypertension in pregnancy are limited; this study aimed to compare labetalol and nifedipine, additionally assessing the impact of ethnicity on treatment efficacy. Pregnant women with chronic hypertension (12(+0)-27(+6) weeks' gestation) were enrolled at 4 UK centers (August 2014 to October 2015). Open-label first-line antihypertensive treatment was randomly assigned: labetalol- (200-1800 mg/d) or nifedipine-modified release (20-80 mg/d)...
September 11, 2017: Hypertension
https://www.readbyqxmd.com/read/28877214/direct-versus-indirect-actions-of-ghrelin-on-hypothalamic-npy-neurons
#7
Hiroshi Hashiguchi, Zhenyu Sheng, Vanessa Routh, Volodymyr Gerzanich, J Marc Simard, Joseph Bryan
OBJECTIVES: Assess direct versus indirect action(s) of ghrelin on hypothalamic NPY neurons. MATERIALS AND METHODS: Electrophysiology was used to measure ion channel activity in NPY-GFP neurons in slice preparations. Ca2+ imaging was used to monitor ghrelin activation of isolated NPY GFP-labeled neurons. Immunohistochemistry was used to localize Trpm4, SUR1 and Kir6.2 in the hypothalamus. RESULTS: Acylated ghrelin depolarized the membrane potential (MP) of NPY-GFP neurons in brain slices...
2017: PloS One
https://www.readbyqxmd.com/read/28867601/hydralazine-vs-nifedipine-for-acute-hypertensive-emergency-in-pregnancy-a-randomized-controlled-trial
#8
Chanderdeep Sharma, Anjali Soni, Amit Gupta, Ashok Verma, Suresh Verma
OBJECTIVE: We sought to compare the efficacy of intravenously administered hydralazine and oral nifedipine for acute blood pressure control in acute hypertensive emergency of pregnancy. STUDY DESIGN: In this double-blind, randomized, controlled trial, pregnant women (≥24 weeks POG) with sustained increase in systolic blood pressure of ≥160 mm Hg or diastolic blood pressure of ≥110 mm Hg were randomized to receive intravenous hydralazine injection in doses of 5, 10, 10, and 10 mg and a placebo tablet or oral nifedipine (10 mg tablet up to 4 doses) and intravenous saline injection every 20 minutes until the target blood pressure of 150 mm Hg systolic and ≤100 mm Hg diastolic was achieved...
September 1, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28858832/synthesis-and-photodegradation-studies-of-analogues-of-muscle-relaxant-1-4-dihydropyridine-compounds
#9
Miyase Gözde Gündüz, Gaetano Ragno, Rahime Şimşek, Michele De Luca, Cihat Şafak, Fedora Grande, Ahmed El-Khouly, Fatma İşli, Şeniz Yildirim, Gökçe Sevim Öztürk Fincan, Giuseppina Ioele
This paper describes the synthesis of 1,4-dihydropyridine compounds (DHPs) endowed with good muscle relaxant activity and stability to light. Six new condensed DHPs were synthesized by the microwave irradiation method. A long-chain ester moiety [2-(methacryloyloxy)ethyl] and various substituents on the phenyl ring were demonstrated to affect the muscle relaxant activity occurring in isolated rabbit gastric fundus smooth muscle strips. Forced photodegradation conditions were applied to the molecules according to the ICH rules...
September 1, 2017: Acta Pharmaceutica
https://www.readbyqxmd.com/read/28858300/development-of-a-high-throughput-fluorescence-polarization-assay-for-the-discovery-of-ezh2-eed-interaction-inhibitors
#10
Mao-Rong Zhu, Dao-Hai Du, Jun-Chi Hu, Lian-Chun Li, Jing-Qiu Liu, Hong Ding, Xiang-Qian Kong, Hua-Liang Jiang, Kai-Xian Chen, Cheng Luo
Aberrant activity of enhancer of zeste homolog 2 (EZH2) is associated with a wide range of human cancers. The interaction of EZH2 with embryonic ectoderm development (EED) is required for EZH2's catalytic activity. Inhibition of the EZH2-EED complex thus represents a novel strategy for interfering with the oncogenic potentials of EZH2 by targeting both its catalytic and non-catalytic functions. To date, there have been no reported high-throughput screening (HTS) assays for inhibitors acting at the EZH2-EED interface...
August 31, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28855109/the-vasorelaxant-effect-of-mitiglinide-via-activation-of-voltage-dependent-k-channels-and-serca-pump-in-aortic-smooth-muscle
#11
Hongliang Li, Hye Won Kim, Sung Eun Shin, Mi Seon Seo, Jin Ryeol An, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Amy L Firth, Il-Whan Choi, Il Yong Han, Dae-Sung Lee, Mi-Jin Yim, Won Sun Park
AIMS: The vasorelaxant effects of the anti-diabetic drug, mitiglinide in phenylephrine (Phe)-pre-contracted aortic rings were examined. MATERIALS AND METHODS: Arterial tone measurement was performed in aortic smooth muscle cells. KEY FINDINGS: Mitiglinide dose-dependently induced vasorelaxation. Application of the large-conductance Ca(2+)-activated K(+) (BKCa) channel blocker paxilline, inwardly rectifying K(+) (Kir) channel blocker Ba(2+), and ATP-sensitive K(+) (KATP) channel blocker glibenclamide did not affect the vasorelaxant effect of mitiglinide...
August 27, 2017: Life Sciences
https://www.readbyqxmd.com/read/28851254/quantitative-prediction-of-the-extent-of-drug-drug-interaction-using-a-physiologically-based-pharmacokinetic-model-that-includes-inhibition-of-drug-metabolism-determined-in-cryopreserved-hepatocytes
#12
Shinji Iwasaki, Hideki Hirabayashi, Nobuyuki Amano
1. A physiologically based pharmacokinetic (PBPK) model that includes inhibition constant evaluated in cryopreserved hepatocytes was used to predict drug-drug interactions (DDIs) between orally administered nifedipine, a CYP substrate, and fluconazole or ketoconazole, CYP inhibitors, in rats. 2. The Kp,uu, ratio of unbound inhibitor concentration in liver ([I]liver,u) to that in plasma ([I]sys,u), of fluconazole and ketoconazole was 1.0 and 13.0, indicating that ketoconazole accumulates in liver. The ratios of inhibition constants in rat liver microsomes (Ki,mic,u) to that in rat cryopreserved hepatocytes (Ki,hep,u) for fluconazole and ketoconazole were 1...
September 4, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28844005/synaptic-potentiation-mediated-by-l-type-voltage-dependent-calcium-channels-mediates-the-antidepressive-effects-of-lateral-habenula-stimulation
#13
Qinji Zhou, Jianyang Dong, Ting Xu, Xiang Cai
Although deep-brain stimulation (DBS) of the lateral habenula (LHb) has been successfully applied to treatment-resistant depression for years, the mechanism is still unclear. Previous researches have demonstrated that LHb-DBS elevates brain monoamine neurotransmitters. However, these changes do not account for the treatment efficacy on treatment-resistant depression, or the rapid behavioral effects in rats; the evidence suggests that altered synaptic potentiation may contribute to the treatment effects. We applied LHb-DBS in a rat model of learned helplessness (LH) and analyzed mammalian target of rapamycin (mTOR) phosphorylation...
August 24, 2017: Neuroscience
https://www.readbyqxmd.com/read/28836972/access-to-medicines-and-diagnostic-tests-integral-in-the-management-of-diabetes-mellitus-and-cardiovascular-diseases-in-uganda-insights-from-the-accodad-study
#14
Davis Kibirige, David Atuhe, Leaticia Kampiire, Daniel Ssekikubo Kiggundu, Pamela Donggo, Juliet Nabbaale, Raymond Mbayo Mwebaze, Robert Kalyesubula, William Lumu
BACKGROUND: Despite the burgeoning burden of diabetes mellitus (DM) and cardiovascular diseases (CVD) in low and middle income countries (LMIC), access to affordable essential medicines and diagnostic tests for DM and CVD still remain a challenge in clinical practice. The Access to Cardiovascular diseases, Chronic Obstructive pulmonary disease, Diabetes mellitus and Asthma Drugs and diagnostics (ACCODAD) study aimed at providing contemporary information about the availability, cost and affordability of medicines and diagnostic tests integral in the management of DM and CVD in Uganda...
August 24, 2017: International Journal for Equity in Health
https://www.readbyqxmd.com/read/28834298/the-vasorelaxant-effect-of-anti-diabetic-drug-nateglinide-via-activation-of-voltage-dependent-k-channels-in-aortic-smooth-muscle
#15
Hongliang Li, Hye Won Kim, Sung Eun Shin, Mi Seon Seo, Jin Ryeol An, Won-Kyo Jung, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Hyoweon Bang, Il-Whan Choi, Sung Hun Na, Won Sun Park
AIMS: We investigated the vasorelaxant effect of nateglinide and its related mechanisms using phenylephrine (Phe)-induced pre-contracted aortic rings. METHODS: Arterial tone measurement was performed in aortic smooth muscle. RESULTS: The application of nateglinide induced vasorelaxation in a concentration-dependent manner. Pretreatment with the large conductance Ca(2+) -activated K(+) (BKCa ) channel inhibitor paxilline, the inwardly rectifying K(+) (Kir) channel inhibitor Ba(2+) , and ATP-sensitive K(+) (KATP ) channel inhibitor glibenclamide, did not affect the vasorelaxant effect of nateglinide...
August 20, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28832423/clarithromycin-nifedipine-induced-acute-kidney-injury
#16
Samarth P Shah, Timothy H Self, Robert W Bradsher, Ryan E Owens
No abstract text is available yet for this article.
September 21, 2017: Nurse Practitioner
https://www.readbyqxmd.com/read/28801600/cav1-3-l-type-ca-2-channel-contributes-to-the-heartbeat-by-generating-a-dihydropyridine-sensitive-persistent-na-current
#17
Futoshi Toyoda, Pietro Mesirca, Stefan Dubel, Wei-Guang Ding, Joerg Striessnig, Matteo E Mangoni, Hiroshi Matsuura
The spontaneous activity of sinoatrial node (SAN) pacemaker cells is generated by a functional interplay between the activity of ionic currents of the plasma membrane and intracellular Ca(2+) dynamics. The molecular correlate of a dihydropyridine (DHP)-sensitive sustained inward Na(+) current (I st), a key player in SAN automaticity, is still unknown. Here we show that I st and the L-type Ca(2+) current (I Ca,L) share CaV1.3 as a common molecular determinant. Patch-clamp recordings of mouse SAN cells showed that I st is activated in the diastolic depolarization range, and displays Na(+) permeability and minimal inactivation and sensitivity to I Ca,L activators and blockers...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28774813/virtual-bioequivalence-for-achlorhydric-subjects-the-use-of-pbpk-modelling-to-assess-the-formulation-dependent-effect-of-achlorhydria
#18
Kosuke Doki, Adam S Darwich, Nikunjkumar Patel, Amin Rostami-Hodjegan
Majority of bioequivalence studies are conducted in healthy volunteers. It has been argued that bioequivalence may not necessarily hold true in relevant patient populations due to a variety of reasons which affect one formulation more than the other for instance in achlorhydric patients where elevated gastric pH may lead to differential effects on formulations which are pH-sensitive with respect to release or dissolution. We therefore examined achlorhydria-related disparity in bioequivalence of levothyroxine and nifedipine formulations using virtual bioequivalence within a physiologically-based pharmacokinetic (PBPK) modelling framework...
August 1, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28757749/successful-treatment-of-a-newborn-with-congenital-hyperinsulinism-having-a-novel-heterozygous-mutation-in-the-abcc8-gene-using-subtotal-pancreatectomy
#19
Chi-Feng Yen, Chi-Yu Huang, Chon-In Chan, Chiung-Hsing Hsu, Nien-Lu Wang, Tao-Yeuan Wang, Chiung-Ling Lin, Wei-Hsin Ting
Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in newborns and infants. CHI is characterized by unregulated secretion of insulin from pancreatic β: cells. Here, we reported the case of a large-for-gestational-age, full-term newborn that suffered from CHI and developed severe and persistent hypoglycemia at an early stage of life. The infant was nearly unresponsive to medical treatment, which included continuous intravenous glucagon infusion, oral diazoxide, and nifedipine...
October 2016: Ci Ji Yi Xue za Zhi, Tzu-chi Medical Journal
https://www.readbyqxmd.com/read/28757108/celastrol-synergizes-with-oral-nifedipine-to-attenuate-hypertension-in-preeclampsia-a-randomized-placebo-controlled-and-double-blinded-trial
#20
Sha Xiao, Ming Zhang, Yuan Liang, Deling Wang
Preeclampsia, a disease mainly manifesting as serious hypertension during pregnancy, affects expectant mothers around the globe. Celastrol, a naturally existing triterpenoid, is known to exhibit beneficial effects attenuating cardiovascular symptoms including hypertension. We here assessed the treatment outcome against preeclampsia with a combined use of celastrol and nifedipine. A total of 626 patients with preeclampsia were enrolled, screened, and assigned by random to groups receiving either nifedipine + placebo or nifedipine + celastrol orally...
July 20, 2017: Journal of the American Society of Hypertension: JASH
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