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https://www.readbyqxmd.com/read/27934636/impact-of-probe-substrate-selection-on-cytochrome-p450-reaction-phenotyping-using-relative-activity-factor
#1
Yin Fai Amy Siu, Weidong George Lai
Accurately assessing the contribution of cytochrome P450 (CYP) isoforms to overall metabolic clearance is important for prediction of clinical drug-drug interaction (DDI). The relative activity factor (RAF) approach in CYP reaction phenotyping assumes that the interaction between CYP selective probes and testing systems is the same as to drug candidate with those systems. To test this assumption, Intersystem Clearance Ratio (ICR) was created to evaluate the difference in values between RAF-scaled intrinsic clearance (CLint) and measured CLint in human liver microsomes (HLM)...
December 1, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27930653/characterisation-of-development-and-electrophysiological-mechanisms-underlying-rhythmicity-of-the-avian-lymph-heart
#2
Sajjida Jaffer, Petr Valasek, Graham Luke, Munirah Batarfi, Benjamin Jason Whalley, Ketan Patel
Despite significant advances in tissue engineering such as the use of scaffolds, bioreactors and pluripotent stem cells, effective cardiac tissue engineering for therapeutic purposes has remained a largely intractable challenge. For this area to capitalise on such advances, a novel approach may be to unravel the physiological mechanisms underlying the development of tissues that exhibit rhythmic contraction yet do not originate from the cardiac lineage. Considerable attention has been focused on the physiology of the avian lymph heart, a discrete organ with skeletal muscle origins yet which displays pacemaker properties normally only found in the heart...
2016: PloS One
https://www.readbyqxmd.com/read/27918914/transformation-of-jaw-muscle-satellite-cells-to-cardiomyocytes
#3
Randall S Daughters, Susan A Keirstead, Jonathan M W Slack
In the embryo a population of progenitor cells known as the second heart field forms not just parts of the heart but also the jaw muscles of the head. Here we show that it is possible to take skeletal muscle satellite cells from jaw muscles of the adult mouse and to direct their differentiation to become heart muscle cells (cardiomyocytes). This is done by exposing the cells to extracellular factors similar to those which heart progenitors would experience during normal embryonic development. By contrast, cardiac differentiation does not occur at all from satellite cells isolated from trunk and limb muscles, which originate from the somites of the embryo...
December 2, 2016: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/27906598/managing-high-altitude-pulmonary-edema-with-oxygen-alone-results-of-a-randomized-controlled-trial
#4
Uday Yanamandra, Velu Nair, Surinderpal Singh, Amul Gupta, Deepak Mulajkar, Sushma Yanamandra, Konchok Norgais, Ruchira Mukherjee, Vikrant Singh, Srinivasa A Bhattachar, Sagarika Patyal, Rajan Grewal, Bhushan Chopra
Yanamandra, Uday, Velu Nair, Surinderpal Singh, Amul Gupta, Deepak Mulajkar, Sushma Yanamandra, Konchok Norgais, Ruchira Mukherjee, Vikrant Singh, Srinivasa A. Bhattachar, Sagarika Patyal, and Rajan Grewal. High-altitude pulmonary edema management: Is anything other than oxygen required? Results of a randomized controlled trial. High Alt Med Biol. 00:000-000, 2016.-Treatment strategies for management of high-altitude pulmonary edema (HAPE) are mainly based on the observational studies with only two randomized controlled trials, thus the practice is very heterogeneous and individualized as per the choice of treating physician...
December 1, 2016: High Altitude Medicine & Biology
https://www.readbyqxmd.com/read/27904663/t-type-calcium-channel-blocker-attenuates-unilateral-ureteral-obstruction-induced-renal-interstitial-fibrosis-by-activating-the-nrf2-antioxidant-pathway
#5
Sungjin Chung, Soojeong Kim, Minyoung Kim, Eun Sil Koh, Hye Eun Yoon, Ho-Shik Kim, Cheol Whee Park, Yoon Sik Chang, Seok Joon Shin
Besides its effect on high blood pressure, T-type calcium channel blocker is renoprotective in experimental models of renal fibrosis. However, the exact mechanism of T-type calcium channel blocker on tubulointerstitial fibrosis is unclear. We investigated whether the renoprotective effect of T-type calcium channel blocker is associated with modulation of the signaling of oxidative stress-induced renal fibrosis. Treatment with a non-hypotensive dose of efonidipine, a T-type calcium channel blocker, or nifedipine, an L-type channel blocker, was initiated one day before unilateral ureteral obstruction (UUO) in C57BL6/J mice, and was continued until 3 and 7 days after UUO...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27898257/assessment-of-nifedipine-therapy-in-hyperinsulinemic-hypoglycemia-due-to-mutations-in-the-abcc8-gene
#6
M Güemes, P Shah, S Silvera, K Morgan, C Gilbert, L Hinchey, K Hussain
CONTEXT: Previous case reports have documented the effectiveness of L-type calcium channel blockers (such as Nifedipine and Verapamil) for treating different forms of hyperinsulinemic hypoglycemia (HH). OBJECTIVE: To systematically assess the glycemic response to Nifedipine therapy in 11 patients with HH due to mutations in the ABCC8 gene. DESIGN: Dose escalation of Nifedipine therapy Setting: Inpatients at a tertiary hospital Patients or Other Participants: 11 children with diazoxide unresponsive HH due to mutations in the ABCC8 gene...
November 29, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27895534/an-automated-perifusion-system-for-modifying-cell-culture-conditions-over-time
#7
Nicholas B Whitticar, Elisha W Strahler, Parthiban Rajan, Savas Kaya, Craig S Nunemaker
BACKGROUND: Cells are continuously exposed to changes in their environment. Endocrine systems, in particular, communicate by rhythms and feedback loops. In this study, we developed an automated system to produce such conditions for cultured cells in a precisely timed manner. We utilized a programmable pair of syringe pumps for inflow and a peristaltic pump for outflow to create rhythmic pulses at 5-min intervals in solutions that mimic the endogenous patterns of insulin produced by pancreatic islets as a test case...
2016: Biological Procedures Online
https://www.readbyqxmd.com/read/27877916/study-of-local-intracellular-signals-regulating-axonal-morphogenesis-using-a-microfluidic-device
#8
Daiki Uryu, Tomohiro Tamaru, Azusa Suzuki, Rie Sakai, Yoshiyuki Konishi
The establishment and maintenance of axonal patterning is crucial for neuronal function. To identify the molecular systems that operate locally to control axonal structure, it is important to manipulate molecular functions in restricted subcellular areas for a long period of time. Microfluidic devices can be powerful tools for such purposes. In this study, we demonstrate the application of a microfluidic device to clarify the function of local Ca(2+) signals in axons. Membrane depolarization significantly induced axonal branch-extension in cultured cerebellar granule neurons (CGNs)...
2016: Science and Technology of Advanced Materials
https://www.readbyqxmd.com/read/27867361/calcium-sensing-receptor-regulates-cytosolic-ca-2-and-plays-a-major-role-in-the-development-of-pulmonary-hypertension
#9
REVIEW
Kimberly A Smith, Ramon J Ayon, Haiyang Tang, Ayako Makino, Jason X-J Yuan
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary vascular resistance (PVR) leading to right heart failure and premature death. The increased PVR results in part from pulmonary vascular remodeling and sustained pulmonary vasoconstriction. Excessive pulmonary vascular remodeling stems from increased pulmonary arterial smooth muscle cell (PASMC) proliferation and decreased PASMC apoptosis. A rise in cytosolic free Ca(2+) concentration ([Ca(2+)]cyt) in PASMC is a major trigger for pulmonary vasoconstriction and a key stimulus for PASMC proliferation and migration, both contributing to the development of pulmonary vascular remodeling...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27866274/ryanodine-receptor-type-3-does-not-contribute-to-contractions-in-the-mouse-myometrium-regardless-of-pregnancy
#10
Katsuhito Matsuki, Masashi Takemoto, Yoshiaki Suzuki, Hisao Yamamura, Susumu Ohya, Hiroshi Takeshima, Yuji Imaizumi
Ryanodine receptor type 3 (RyR3) is expressed in myometrial smooth muscle cells (MSMCs). The short isoform of RyR3 is a dominant negative variant (DN-RyR3) and negatively regulates the functions of RyR2 and full-length (FL)-RyR3. DN-RyR3 has been suggested to function as a major RyR3 isoform in non-pregnant (NP) mouse MSMCs, and FL-RyR3 may also be upregulated during pregnancy (P). This increase in the FL-RyR3/DN-RyR3 ratio may contribute to the strong contractions by MSMCs for parturition. In the present study, spontaneous contractions by the myometrium in NP and P mice were highly susceptible to nifedipine but were not affected by ryanodine...
November 20, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27863686/formulation-design-space-for-stable-ph-sensitive-crystalline-nifedipine-nanoparticles
#11
Rajan Jog, Kenechi Unachukwu, Diane J Burgess
Enteric coated formulations protect drugs from degrading in the harsh environment of the stomach (acidic pH and enzymes), and promotes drug delivery to and absorption into the duodenum and/or later parts of the intestine. Four DoE models were applied to optimize formulation parameters for the preparation of pH sensitive nifedipine nanoparticles. Stability studies were performed on the optimized formulations to monitor any possible variation in particle size distribution, homogeneity index, surface charge and drug release (pH 1...
November 30, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27858253/microemulsion-transdermal-formulation-for-simultaneous-delivery-of-valsartan-and-nifedipine-formulation-by-design
#12
Jatin Sood, Bharti Sapra, Ashok K Tiwary
The objective of the study was to optimize the proportion of different components for formulating oil in water microemulsion formulation meant for simultaneous transdermal delivery of two poorly soluble antihypertensive drugs. Surface response methodology of Box-Behnken design was utilized to evaluate the effect of two oils (Captex 500 - x1 and Capmul MCM - x2) and surfactant (Acrysol EL135 - x3) on response y1 (particle size), y2 (solubility of valsartan), and y3 (solubility of nifedipine). The important factors which significantly affected the responses were identified and validated using ANOVA...
November 17, 2016: AAPS PharmSciTech
https://www.readbyqxmd.com/read/27856310/l-type-calcium-channel-antagonism-translation-from-in-vitro-to-in-vivo
#13
Bernard Fermini, David S Ramirez, Sunny Sun, Asser Bassyouni, Michelle Hemkens, Todd Wisialowski, Stephen Jenkinson
INTRODUCTION: Although therapeutically beneficial in the treatment of certain diseases, L-type calcium channel antagonism can result in unwanted off-target pharmacology leading to adverse drug reactions and to the termination of the development of otherwise promising compounds. In the present study three marketed calcium channel inhibitors, nifedipine, verapamil and diltiazem were profiled in a series of in vitro and ex-vivo assays in an effort to determine the ability of these assays to discriminate, between dihydropyridine versus non-dihydropyridine-like compounds, and how well they can predict the cardiovascular effects observed in a conscious telemetered rat model...
November 15, 2016: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/27836377/-prevention-of-spontaneous-preterm-birth-excluding-preterm-premature-rupture-of-membranes-guidelines-for-clinical-practice%C3%A2-%C3%A2-text-of-the-guidelines-short-text
#14
L Sentilhes, M-V Sénat, P-Y Ancel, E Azria, G Benoist, J Blanc, G Brabant, F Bretelle, S Brun, M Doret, C Ducroux-Schouwey, A Evrard, G Kayem, E Maisonneuve, L Marcellin, S Marret, N Mottet, S Paysant, D Riethmuller, P Rozenberg, T Schmitz, H Torchin, B Langer
OBJECTIVES: To determine the measures to prevent spontaneous preterm birth (excluding preterm premature rupture of membranes)and its consequences. MATERIALS AND METHODS: The PubMed database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. RESULTS: In France, premature birth concerns 60,000 neonates every year (7.4 %), half of them are delivered after spontaneous onset of labor...
December 2016: Journal de Gynécologie, Obstétrique et Biologie de la Reproduction
https://www.readbyqxmd.com/read/27835048/furosemide-in-postpartum-management-of-severe-preeclampsia-a-randomized-controlled-trial
#15
P Veena, Lakshmideepthi Perivela, S Soundara Raghavan
BACKGROUND: Hypertension in the postpartum period is a common phenomenon and is often a cause for concern. Following delivery, fluid that has been sequestered in the extravascular space is mobilized, producing a large auto-infusion of fluid from the extravascular to the intravascular compartment. As a result of this fluid mobilization process, there is an increase in central venous pressure and pulmonary capillary wedge pressure, which might favor the development of pulmonary edema. Thus, diuretics logically might be a better choice as antihypertensive medication in such a scenario...
November 11, 2016: Hypertension in Pregnancy
https://www.readbyqxmd.com/read/27830272/role-of-nifedipine-and-hydrochlorothiazide-in-mapk-activation-and-vascular-smooth-muscle-cell-proliferation-and-apoptosis
#16
J Wang, K Liu, H Wang, Z Li, Y Li, S Ping, A S A Bardeesi, Y Guo, Y Zhou, T Pei, L Deng, P Sheng, S Liu, C Li
BACKGROUND: Once hypertension is established, increased mechanical stretch stress becomes a leading cause of vascular remodeling. Clinical antihypertension guidelines demonstrate that antihypertension drugs prevent vascular remodeling in hypertensive patients mainly by lowering blood pressure, suggesting an indirect way of reducing the effects of stretch stress (hypertension). Whether these drugs can directly block the effects of the stretch stress on vascular remodeling has not been reported to date...
November 9, 2016: Herz
https://www.readbyqxmd.com/read/27805790/interplay-among-distinct-ca-2-conductances-drives-ca-2-sparks-stocs-in-rat-cerebral-arteries
#17
Ahmed M Hashad, Neil Mazumdar, Monica Romero, Anders Nygren, Kamran Bigdely-Shamloo, Osama F Harraz, Jose L Puglisi, Edward J Vigmond, Sean M Wilson, Donald G Welsh
Ca(2+) sparks are generated in a voltage dependent manner to initiate spontaneous transient outward currents (STOC), events that moderate arterial constriction. In this study, we defined the mechanisms by which membrane depolarization increases Ca(2+) sparks and subsequent STOC production. Using perforated patch clamp electrophysiology and rat cerebral arterial myocytes, we monitored STOC in the presence and absence of agents that modulate Ca(2+) entry. Beginning with CaV 3.2 inhibition, Ni(2+) was shown to decrease STOC frequency in cells held at hyperpolarized (-40 mV) but not depolarized (-20 mV) voltages...
November 2, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27799740/early-intervention-of-long-acting-nifedipine-gits-reduces-brachial-ankle-pulse-wave-velocity-and-improves-arterial-stiffness-in-chinese-patients-with-mild-hypertension-a-24-week-single-arm-open-label-prospective-study
#18
Jidong Zhang, Yan Wang, Haijuan Hu, Xiaohong Yang, Zejun Tian, Demin Liu, Guoqiang Gu, Hongmei Zheng, Ruiqin Xie, Wei Cui
BACKGROUND: Nifedipine gastrointestinal therapeutic system (GITS) is used to treat angina and hypertension. The authors aimed to study the early intervention impact on arterial stiffness and pulse wave velocity (PWV) independent of its blood-pressure-(BP) lowering effect in mild hypertensive patients. METHODS: This single-center, single-arm, open-label, prospective, Phase IV study recruited patients with mild hypertension and increased PWV from December 2013 to December 2014 (N=138; age, 18-75 years; systolic blood pressure, 140-160 mmHg; diastolic BP, 90-100 mmHg; increased brachial-ankle pulse wave velocity [baPWV, ≥12 m/s])...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27790936/effect-of-protriptyline-on-ca-2-i-and-viability-in-mg63-human-osteosarcoma-cells
#19
Ching-Kai Su, Chiang-Ting Chou, Ko-Long Lin, Wei-Zhe Liang, Jin-Shiung Cheng, Hong-Tai Chang, I-Shu Chen, Ti Lu, Chun-Chi Kuo, Chia-Cheng Yu, Pochuen Shieh, Daih-Huang Kuo, Fu-An Chen, Chung-Ren Jan
Tricyclic antidepressants (TCA) have been clinically prescribed in the auxiliary treatment of cancer patients. Although protriptyline, a type of TCA, was used primarily in the clinical treatment of mood disorders in cancer patients, the effect of protriptyline on physiology in human osteosarcoma is unknown. This study examined the effect of protriptyline on cytosolic free Ca(2+ )concentrations ([Ca(2+)]i) and viability in MG63 human osteosarcoma cells. Protriptyline between 50 and 250 μM evoked [Ca(2+)]i rises concentration-dependently...
October 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27786578/oral-labetalol-compared-to-oral-nifedipine-for-postpartum-hypertension-a-randomized-controlled-trial
#20
Kathryn J Sharma, Naomi Greene, Sarah J Kilpatrick
OBJECTIVE: To determine whether oral labetalol is associated with a shorter time to blood pressure control compared to oral extended release nifedipine for management of persistent postpartum hypertension. STUDY DESIGN: This randomized controlled trial conducted between June 2014 and June 2015 included women who delivered at ≥32 weeks' gestation with persistent postpartum hypertension (sustained blood pressure ≥150/100 mmHg) requiring an oral antihypertensive agent...
October 27, 2016: Hypertension in Pregnancy
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