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https://www.readbyqxmd.com/read/28431965/origin-of-nanodroplet-formation-upon-dissolution-of-an-amorphous-solid-dispersion-a-mechanistic-isotope-scrambling-study
#1
Anura S Indulkar, Jan E Waters, Huaping Mo, Yi Gao, Shweta A Raina, Geoff G Z Zhang, Lynne S Taylor
It has been observed that certain amorphous solid dispersions (ASDs), upon dissolution, generate drug-rich amorphous nanodroplets. These nanodroplets, present as a dispersed phase, can potentially enhance oral bioavailability of poorly soluble drugs by serving as a drug reservoir that efficiently feeds the continuous aqueous solution phase following absorption of drug. The purpose of this study was to probe the formation mechanism of the nanodroplets. The model system studied was nifedipine (NFD) formulated as an ASD with hydroxypropyl methylcellulose E5 Premium LV (HPMC-E5) or polyvinylpyrrolidone/vinyl acetate (PVPVA)...
April 18, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28429868/clarification-of-serotonin-induced-effects-in-peripheral-artery-disease-observed-through-the-femoral-artery-response-in-models-of-diabetes-and-vascular-occlusion-the-role-of-calcium-ions
#2
Marko Stojanović, Milica Prostran, Radmila Janković, Miroslav Radenković
Recent findings have demonstrated that serotonin is an important participant in the development and progression of peripheral artery diseases. Taking this into consideration, the goals of this study were to investigate the effects of serotonin on isolated Wistar rat femoral arteries in both healthy and diabetic animals, with and without artery occlusion, with a particular focus on determining the role of calcium in this process. Contraction experiments with serotonin on intact and denuded femoral artery rings, in the presence or absence of nifedipine and ouabain (both separately, or in combination), as well as Ca(2+) -free Krebs-Ringer bicarbonate solution were performed...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28429696/polymorphic-ventricular-tachycardia-due-to-variant-angina-diagnosed-on-holter-monitoring-and-confirmed-with-cold-pressor-test
#3
Semi Öztürk, Tuğba Aktemur, Muhsin Kalyoncuoğlu, Gündüz Durmuş, Mehmet Can
A 52-year-old man complaining of persistent recurring chest pain at night underwent coronary angiogram at another institution. Normal coronaries were observed and he was discharged with muscle spasmolytic prescription. Since symptoms had continued, 24-hour Holter monitoring was ordered at our facility and results revealed huge ST elevation and polymorphic ventricular tachycardia. Cold pressor test performed in catheterization laboratory also resulted in ventricular tachycardia. Nifedipine was prescribed and follow-up Holter monitoring revealed no further vasospastic episodes...
April 2017: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
https://www.readbyqxmd.com/read/28429070/properties-of-synchronous-spontaneous-ca-2-transients-in-the-mural-cells-of-rat-rectal-arterioles
#4
Retsu Mitsui, Hikaru Hashitani
Synchrony of spontaneous Ca(2+) transients among venular mural cells (smooth muscle cells and pericytes) in visceral organs relies on the intercellular spread of L-type voltage-dependent Ca(2+) channel (LVDCC)-dependent depolarisations. However, the mechanisms underlying the synchrony of spontaneous Ca(2+) transients between arteriolar mural cells are less understood. The spontaneous intracellular Ca(2+) dynamics of arteriolar mural cells in the rat rectal submucosa were visualised by Cal-520 Ca(2+) imaging to analyse their synchrony...
April 21, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28426127/postpartum-hypertension-etiology-diagnosis-and-management
#5
Kathryn J Sharma, Sarah J Kilpatrick
Importance: Postpartum hypertension complicates approximately 2% of pregnancies and, similar to antepartum severe hypertension, can have devastating consequences including maternal death. Objective: This review aims to increase the knowledge and skills of women's health care providers in understanding, diagnosing, and managing hypertension in the postpartum period. Results: Hypertension complicating pregnancy, including postpartum, is defined as systolic blood pressure 140 mm Hg or greater and/or diastolic blood pressure 90 mm Hg or greater on 2 or more occasions at least 4 hours apart...
April 2017: Obstetrical & Gynecological Survey
https://www.readbyqxmd.com/read/28425104/inactivation-kinetics-and-residual-activity-of-cyp3a4-after-treatment-with-erythromycin
#6
Yuko Ishikawa, Takeshi Akiyoshi, Ayuko Imaoka, Hisakazu Ohtani
This study aimed to characterize the inactivation kinetics of cytochrome P450 3A4 (CYP3A4) by erythromycin, which involves mechanism-based inhibition (MBI), in detail. In addition to an MBI assay based on the conventional method in which erythromycin and recombinant CYP3A4 were pre-incubated for 15 min, we also evaluated the long-term MBI kinetics of this reaction by pre-incubating for 120 min. MBI profiles were obtained using three typical substrates, testosterone, midazolam, and nifedipine. In the long-term assay, erythromycin evoked a time-dependent biphasic reduction in enzyme activity, but some residual activity (α) was detected in the terminal phase...
April 20, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28421606/role-of-mucosa-in-generating-spontaneous-activity-in-the-guinea-pig-seminal-vesicle
#7
Mitsue Takeya, Hikaru Hashitani, Tokumasa Hayashi, Ryuhei Higashi, Kei-Ichiro Nakamura, Makoto Takano
The role of the mucosa in generating the spontaneous activity of guinea-pig seminal vesicle (SV) was explored. Changes in contractility, membrane potential and intracellular Ca(2+) dynamics of SV smooth muscle cells (SMCs) were recorded using isometric tension recording, intracellular microelectrode recording and epi-fluorescence Ca(2+) imaging, respectively. Mucosa-intact but not mucosa-denuded SV preparations generated TTX (1 μm)-resistant spontaneous phasic contractions that were abolished by nifedipine (3 μm)...
April 19, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28413728/mechanism-of-endothelial-nitric-oxide-synthase-phosphorylation-and-activation-by-tentacle-extract-from-the-jellyfish-cyanea-capillata
#8
Beilei Wang, Dan Liu, Chao Wang, Qianqian Wang, Hui Zhang, Guoyan Liu, Xia Tao, Liming Zhang
Our previous study demonstrated that tentacle extract (TE) from the jellyfish Cyanea capillata (C. capillata) could cause a weak relaxation response mediated by nitric oxide (NO) using isolated aorta rings. However, the intracellular mechanisms of TE-induced vasodilation remain unclear. Thus, this study was conducted to examine the role of TE on Akt/eNOS/NO and Ca(2+) signaling pathways in human umbilical vein endothelial cells (HUVECs). Our results showed that TE induced dose- and time-dependent increases of eNOS activity and NO production...
2017: PeerJ
https://www.readbyqxmd.com/read/28405241/design-and-synthesis-of-a-new-steroid-macrocyclic-derivative-with-biological-activity
#9
Maria López-Ramos, Lauro Figueroa-Valverde, Socorro Herrera-Meza, Marcela Rosas-Nexticapa, Francisco Díaz-Cedillo, Elodia García-Cervera, Eduardo Pool-Gómez, Regina Cahuich-Carrillo
The aims of this study were to evaluate the positive inotropic effect of a new macrocyclic derivative (compound 11) and characterize the molecular mechanism involved in its biological activity. The first step was achieved by synthesis of a macrocyclic derivative involving a series of reactions for the preparation of several steroid derivatives such as (a) steroid-pyrimidinone (3 and 4), (b) steroid-amino (5), (c) steroid-imino (6), (d) ester-steroid (7 and 8), and (e) amido-steroid (9 and 10). Finally, 11 was prepared by removing the tert-butyldimethylsilane fragment of 10...
April 2017: Journal of Chemical Biology
https://www.readbyqxmd.com/read/28384516/effects-of-puerarin-on-intracellular-ca-2-and-cell-viability-of-mdck-renal-tubular-cells
#10
He-Hsiung Cheng, Chiang-Ting Chou, Wei-Zhe Liang, Chun-Chi Kuo, Pochuan Shieh, Jue-Long Wang, Chung-Ren Jan
Puerarin is a natural compound and has been used as herb medication in a number of countries, especially in Asia. The effect of puerarin on Ca(2+) signaling is unknown in renal cells. This study examined whether puerarin affected Ca(2+) physiology in MDCK renal tubular cells. Cytosolic free Ca(2+) levels ([Ca(2+)]i) were measured using the fluorescent dye fura-2. Cell viability was examined by using WST-1 assay. Puerarin induced [Ca(2+)]i rises and the response was reduced by removing extracellular Ca(2+). Puerarin-induced Ca(2+) entry was not altered by protein kinase C (PKC) activity, but was inhibited by nifedipine...
March 24, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28358601/pharmacogenetics-in-the-treatment-of-pre-eclampsia-current-findings-challenges-and-perspectives
#11
Marcelo R Luizon, Ana Ct Palei, Ricardo C Cavalli, Valeria C Sandrim
Pre-eclampsia (PE) is defined as pregnancy-induced hypertension and proteinuria, and is a major cause of maternal and perinatal morbidity and mortality. A large subgroup of pregnant women with PE is nonresponsive to antihypertensive drugs, including methyldopa, nifedipine and hydralazine. Pharmacogenomics may help to guide the individualized therapy for this nonresponsive subgroup. However, just a few pharmacogenetic studies examined the effects of genetic polymorphisms on response to antihypertensive drugs in PE, and the criteria of responsiveness used to define responsive or nonresponsive subgroups to antihypertensive therapy should be replicated by others...
March 30, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28355887/micro-to-nanoneedles-a-trend-of-modernized-transepidermal-drug-delivery-system
#12
Pravin Shende, Mrunmayi Sardesai, R S Gaud
The transdermal route of drug delivery is convenient, pain-free and follows controlled rate release pattern. However, many therapeutically active drugs cannot cross the stratum corneum effectively. Lipophilic drugs like nifedipine cross the outer skin barrier easily and polar drugs, such as epinephrine are ineffective in showing the same effect. Due to these reasons, advancements in drug delivery have taken place to deliver a wide range of drugs, especially macromolecules through the transdermal route and directly into systemic circulation bypassing hepatic metabolism and GIT degradation...
March 30, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28348009/polymerization-incompetent-uromodulin-in-the-pregnant-stroke-prone-spontaneously-hypertensive-rat
#13
Sheon Mary, Heather Yvonne Small, Justyna Siwy, William Mullen, Ashok Giri, Christian Delles
The kidney is centrally involved in blood pressure regulation and undergoes extensive changes during pregnancy. Hypertension during pregnancy may result in an altered urinary peptidome that could be used to indicate new targets of therapeutic or diagnostic interest. The stroke-prone spontaneously hypertensive rat (SHRSP) is a model of maternal chronic hypertension. Capillary electrophoresis-mass spectrometry was conducted to interrogate the urinary peptidome in SHRSP and the control Wistar-Kyoto strain at three time points: prepregnancy and gestational days 12 and 18...
March 27, 2017: Hypertension
https://www.readbyqxmd.com/read/28344498/investigation-of-the-in-vitro-performance-difference-of-drug-soluplus%C3%A2-and-drug-peg-6000-dispersions-when-prepared-using-spray-drying-or-lyophilization
#14
Mohammad A Altamimi, Steven H Neau
PURPOSE: To evaluate the physicochemical and in vitro characteristics of solid dispersions using BCS II model drugs with Soluplus® and one of its component homopolymers, PEG 6000. METHODS: Nifedipine (NIF) and sulfamethoxazole (SMX) of 99.3% and 99.5% purity, respectively, were selected as BCS II model drugs, such that an improved dissolution rate and concentration in the gastrointestinal tract should increase oral bioavailability. Soluplus® is an amorphous, tri-block, graft co-polymer with polyvinyl caprolactam, polyvinyl acetate, and polyethylene glycol (PCL:PVAc:PEG6000) in the ratio 57:30:13...
March 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28344076/inhibition-of-human-cyp3a4-and-cyp3a5-enzymes-by-gomisin-c-and-gomisin-g-two-lignan-analogs-derived-from-schisandra-chinensis
#15
Jin Zhao, Tao Sun, Jing-Jing Wu, Yun-Feng Cao, Zhong-Ze Fang, Hong-Zhi Sun, Zhi-Tu Zhu, Kun Yang, Yong-Zhe Liu, Frank J Gonzalez, Jun Yin
Gomisin C (GC) and gomisin G (GG) are two lignan analogs isolated from the Traditional Chinese Medicine Schisandra chinensis which possesses multiple pharmacological activities. However, the potential herb-drug interactions (HDI) between these lignans and other drugs through inhibiting human cytochrome P450 3A4 (CYP3A4) and CYP3A5 remains unclear. In the present study, the inhibitory action of GC and GG on CYP3A4 and CYP3A5 were investigated. The results demonstrated that both GC and GG strongly inhibited CYP3A-mediated midazolam 1'-hydroxylation, nifedipine oxidation and testosterone 6β-hydroxylation...
March 24, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28337264/ip3r-and-ryr-calcium-channels-are-involved-in-neonatal-rat-cardiac-myocyte-hypertrophy-induced-by-tumor-necrosis-factor-%C3%AE
#16
Gui-Jun Wang, Lian-Yi Guo, Hong-Xin Wang, Yu-Sheng Yao
To investigate which calcium channels are involved in cardiac myocyte hypertrophy induced by TNF-α, cultured cardiomyocytes were treated with 100 μg/L TNF-α. In addition, three different calcium channel blockers (2-APB, ryanodine and nifedipine) were used, and the effects of each calcium channel blocker on cardiac hypertrophy induced by TNF-α were carefully observed. Measurements included cytosolic calcium transients ([Ca(2+)]i), the level of intracellular calcium in individual cells, cell protein content, cell protein synthesis and cell volume...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28333939/maintenance-nifedipine-therapy-for-preterm-symptomatic-placenta-previa-a-randomized-multicenter-double-blind-placebo-controlled-trial
#17
Eric Verspyck, Claire de Vienne, Charles Muszynski, Michael Bubenheim, Isabella Chanavaz-Lacheray, Michel Dreyfus, Philippe Deruelle, Jacques Benichou
OBJECTIVE: To assess the impact of maintenance nifedipine therapy on pregnancy duration in women with preterm placenta previa bleeding. METHODS: PPADAL was a randomized, double-blind, placebo-controlled trial conducted between 05/2008 and 05/2012 in five French hospitals. The trial included 109 women, aged ≥ 18 years, with at least one episode of placenta previa bleeding, intact membranes and no other pregnancy complication, at gestational age 24 to 34 weeks and after 48 hours of complete acute tocolysis...
2017: PloS One
https://www.readbyqxmd.com/read/28333820/committee-opinion-no-692-emergent-therapy-for-acute-onset-severe-hypertension-during-pregnancy-and-the-postpartum-period
#18
(no author information available yet)
Acute-onset, severe systolic hypertension; severe diastolic hypertension; or both can occur during the prenatal, intrapartum, or postpartum periods. Pregnant women or women in the postpartum period with acute-onset, severe systolic hypertension; severe diastolic hypertension; or both require urgent antihypertensive therapy. Introducing standardized, evidence-based clinical guidelines for the management of patients with preeclampsia and eclampsia has been demonstrated to reduce the incidence of adverse maternal outcomes...
April 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28333812/committee-opinion-no-692-summary-emergent-therapy-for-acute-onset-severe-hypertension-during-pregnancy-and-the-postpartum-period
#19
(no author information available yet)
Acute-onset, severe systolic hypertension; severe diastolic hypertension; or both can occur during the prenatal, intrapartum, or postpartum periods. Pregnant women or women in the postpartum period with acute-onset, severe systolic hypertension; severe diastolic hypertension; or both require urgent antihypertensive therapy. Introducing standardized, evidence-based clinical guidelines for the management of patients with preeclampsia and eclampsia has been demonstrated to reduce the incidence of adverse maternal outcomes...
April 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28333087/magnetically-bioprinted-human-myometrial-3d-cell-rings-as-a-model-for-uterine-contractility
#20
Glauco R Souza, Hubert Tseng, Jacob A Gage, Arunmani Mani, Pujan Desai, Fransisca Leonard, Angela Liao, Monica Longo, Jerrie S Refuerzo, Biana Godin
Deregulation in uterine contractility can cause common pathological disorders of the female reproductive system, including preterm labor, infertility, inappropriate implantation, and irregular menstrual cycle. A better understanding of human myometrium contractility is essential to designing and testing interventions for these important clinical problems. Robust studies on the physiology of human uterine contractions require in vitro models, utilizing a human source. Importantly, uterine contractility is a three-dimensionally (3D)-coordinated phenomenon and should be studied in a 3D environment...
March 23, 2017: International Journal of Molecular Sciences
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