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https://www.readbyqxmd.com/read/29385292/advanced-continuous-flow-platform-for-on-demand-pharmaceutical-manufacturing
#1
Ping Zhang, Nopphon Weeranoppanant, Dale A Thomas, Kohei Tahara, Torsten Stelzer, Mary Grace Russell, Marcus O'Mahony, Allan S Myerson, Hongkun Lin, Liam P Kelly, Klavs F Jensen, Timothy F Jamison, Chunhui Dai, Yuqing Cui, Naomi Briggs, Rachel L Beingessner, Andrea Adamo
As a demonstration of an alternative to the challenges faced with batch pharmaceutical manufacturing including the large production footprint and lengthy time-scale, we previously reported a refrigerator-sized continuous flow system for the on-demand production of essential medicines. Building on this technology, herein we report a second-generation, reconfigurable and 25 % smaller (by volume) continuous flow pharmaceutical manufacturing platform featuring advances in reaction and purification equipment. Consisting of two compact [0...
January 31, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29383731/ca2-signalling-in-mouse-urethral-smooth-muscle-in-situ-role-of-ca2-stores-and-ca2-influx-mechanisms
#2
Bernard T Drumm, Benjamin E Rembetski, Caroline A Cobine, Salah A Baker, Gerard P Sergeant, Mark A Hollywood, Keith D Thornbury, Kenton M Sanders
Urethral smooth muscle cells (USMC) generate myogenic tone and contribute to urinary continence. Currently, little is known about Ca2+ signalling in USMC in situ, and therefore little is known about the source(s) of Ca2+ required for excitation-contraction coupling. We characterized Ca2+ signalling in USMC within intact urethral muscles using a genetically encoded Ca2+ sensor, GCaMP3, expressed selectively in USMC. USMC fired spontaneous intracellular Ca2+ waves that did not propagate cell-to-cell across muscle bundles...
January 31, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29290374/physical-compatibility-of-meropenem-and-vaborbactam-with-select-intravenous-drugs-during-simulated-y-site-administration
#3
James M Kidd, Lindsay M Avery, Tomefa E Asempa, David P Nicolau, Joseph L Kuti
PURPOSE: Meropenem/vaborbactam is a novel intravenous antibiotic combining the carbapenem, meropenem, with a novel β-lactamase inhibitor, vaborbactam. Meropenem/vaborbactam is administered as a 3-hour infusion given every 8 hours, thereby potentially restricting an intravenous line for 9 h/d. Intravenous medications may be given concurrently via Y-site when compatibility data are available. Herein, physical compatibility was determined for the identification which medications can be coadministered with meropenem/vaborbactam via Y-site...
December 28, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/29250113/encapsulation-of-nicardipine-hydrochloride-and-release-from-biodegradable-poly-d-l-lactic-co-glycolic-acid-microparticles-by-double-emulsion-process-effect-of-emulsion-stability-and-different-parameters-on-drug-entrapment
#4
Nopparuj Soomherun, Narumol Kreua-Ongarjnukool, Sorayouth Chumnanvej, Saowapa Thumsing
Poly(D,L-lactic-co-glycolic acid) (PLGA) is an important material used in drug delivery when controlled release is required. The purpose of this research is to design and characterize PLGA microparticles (PLGA MPs) implants for the controlled release of nicardipine hydrochloride (NCH) in vitro. This study used the water-in-oil-in-water (w1/o/w2) double emulsion and solvent diffusion/evaporation approach to prepare PLGA MPs. Optimal processing conditions were found, such as polymer content, surfactant type, stabilizer concentration, inner and outer aqueous phase volumes, and stirring speed...
2017: International Journal of Biomaterials
https://www.readbyqxmd.com/read/29198152/development-of-sustained-release-gastro-retentive-tablet-formulation-of-nicardipine-hydrochloride-using-quality-by-design-qbd-approach
#5
Vijay S Chudiwal, Sadhana Shahi, Swapnil Chudiwal
The objective of the present study was to develop sustained release gastro-retentive (SRGR) tablet formulation of Nicardipine Hydrochloride for once-a-day dosing using quality by design (QbD) approach. Quality target product profile (QTPP) of Nicardipine HCl SRGR tablet formulation was defined and critical quality attributes (CQAs) were identified. Potential risk factors were identified using a fish bone diagram and failure mode effect analysis (FMEA) tool and screened by Plackett-Burman design and finally Nicardipine HCl SRGR tablet formulation was optimized using Box-Behnken design...
December 2, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29192124/drugs-and-scaffold-that-inhibit-cytochrome-p450-27a1-cyp27a1-in-vitro-and-in-vivo
#6
Morrie Lam, Natalia Mast, Irina Pikuleva
Cytochrome P450 27A1 (CYP27A1) is a ubiquitous enzyme that hydroxylates cholesterol and other sterols. Complete CYP27A1 deficiency due to genetic mutations is detrimental to human health, whereas 50% of activity retention is not and does not affect the whole body cholesterol levels. CYP27A1 is considered as a potential therapeutic target in breast cancer and age-related neurodegenerative diseases; however CYP27A1 inhibition should be 50%. Herein, 131 pharmaceuticals were tested for their effect on CYP27A1-mediated cholesterol 27-hydroxylation by in vitro enzyme assay...
November 30, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29159314/vasoconstriction-triggered-by-hydrogen-sulfide-evidence-for-na-k-2cl-cotransport-and-l-type-ca-2-channel-mediated-pathway
#7
Sergei N Orlov, Svetlana V Gusakova, Liudmila V Smaglii, Svetlana V Koltsova, Svetalana V Sidorenko
Objectives: This study examined the dose-dependent actions of hydrogen sulfide donor sodium hydrosulphide (NaHS) on isometric contractions and ion transport in rat aorta smooth muscle cells (SMC). Methods: Isometric contraction was measured in ring aortas segments from male Wistar rats. Activity of Na(+)/K(+)-pump and Na(+),K(+),2Cl(-)cotransport was measured in cultured endothelial and smooth muscle cells from the rat aorta as ouabain-sensitive and ouabain-resistant, bumetanide-sensitive components of the (86)Rb influx, respectively...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29159148/endovascular-treatment-of-symptomatic-vasospasm-after-aneurysmal-subarachnoid-hemorrhage-a-three-year-experience
#8
Eun-Sung Park, Dae-Won Kim, Sung-Don Kang
Objective: The cause of severe clinical vasospasm after aneurysmal subarachnoid hemorrhage remains unknown, despite extensive research over the past 30 years. However, the intra-arterial administration of vasodilating agents and balloon angioplasty have been successfully used in severe refractory cerebral vasospasm. Materials and Methods: We retrospectively analyzed the data of 233 patients admitted to our institute with aneurysmal subarachnoid hemorrhage (SAH) over the past 3 years...
September 2017: Journal of Cerebrovascular and Endovascular Neurosurgery
https://www.readbyqxmd.com/read/29129208/augmented-gene-expression-triggered-by-na-k-atpase-inhibition-role-of-ca-2-i-mediated-and-independent-excitation-transcription-coupling
#9
Larisa V Smolyaninova, Svetlana V Koltsova, Svetlana V Sidorenko, Sergei N Orlov
In rat vascular smooth muscle cells (RVSMC), 3-h Na(+),K(+)-ATPase inhibition by ouabain or in K(+)-free medium resulted in the inversion of the [Na(+)]i/[K(+)]i ratio and elevation up to 7-fold the content of Egr1, Atf3, Nr4a1 and Ptgs2 mRNAs. Ouabain increased the rate of 45Ca(2+) influx by 2-fold that was abolished by L-type voltage-gated Ca(2+) channel blocker nicardipine, but it was resistant to Na(+)/Ca(2+) exchanger inhibitor KB-R7943. To study the role of Ca(2+)-mediated signaling in the expression of Na(+)i/K(+)i-sensitive genes we used intracellular Ca(2+) chelator BAPTA and incubated RVSMC in Ca(2+)-free medium...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29092768/continuous-infusion-labetalol-vs-nicardipine-for-hypertension-management-in-stroke-patients
#10
Jason P Hecht, Patrick G Richards
BACKGROUND: Labetalol and nicardipine are antihypertensives commonly used in the management of elevated blood pressure (BP) following an acute stroke, but there is limited evidence to suggest which agent as a continuous infusion should be used preferentially in this setting. OBJECTIVE: This study aimed to compare the safety, efficacy, and ease of administration of continuous-infusion labetalol with continuous-infusion nicardipine following an acute stroke. METHODS: This retrospective cohort study of patients with acute ischemic stroke or intracerebral hemorrhage included patients if they received either study agent within 24 hours of admission...
October 30, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29067537/posterior-reversible-encephalopathy-syndrome-pres-induced-by-pazopanib-a-multi-targeting-tyrosine-kinase-inhibitor-in-a-patient-with-soft-tissue-sarcoma-case-report-and-review-of-the-literature
#11
Shoichi Deguchi, Koichi Mitsuya, Yoko Nakasu, Nakamasa Hayashi, Hirohisa Katagiri, Hideki Murata, Junji Wasa, Mitsuru Takahashi, Masahiro Endo
Posterior reversible encephalopathy syndrome (PRES) is a clinical entity characterized by acute neurological symptoms such as severe headache, seizures, and visual disturbance, and by typical reversible lesion on brain magnetic resonance (MR) images. Since PRES is thought to be caused by vascular endothelial injury due to cytotoxic agents or acute systemic hypertension, the number of reports on PRES associated with angiogenesis inhibitors has been increasing. Although five cases that developed PRES due to pazopanib for renal cell carcinoma have already been reported, none of PRES due to pazopanib for soft-tissue sarcoma has been reported thus far...
October 25, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29058775/comparative-molecular-dynamics-simulation-of-aggregating-and-non-aggregating-inhibitor-solutions-understanding-the-molecular-basis-of-promiscuity
#12
Mohammad A Ghattas, Richard A Bryce, Sara Al Rawashdah, Noor Atatreh, Waleed A Zalloum
Obtaining false positives in enzyme inhibition assays is a common problem in early drug discovery, especially those compounds which form colloid aggregates in solution. The molecular basis of these aggregates could not be thoroughly explored because of their transient stability. Here, we conduct comparative MD simulations of miconazole, a strong aggregator, and fluconazole, a known non-aggregator. Interestingly, miconazole displays full aggregation within only 50 ns, whilst fluconazole shows no aggregation over the 500 ns simulation...
October 23, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29046519/the-effects-of-anti-hypertensive-drugs-and-the-mechanism-of-hypertension-in-vascular-smooth-muscle-cell-specific-atp2b1-knockout-mice
#13
Yuki Okuyama, Nobuhito Hirawa, Megumi Fujita, Akira Fujiwara, Yosuke Ehara, Keisuke Yatsu, Koichiro Sumida, Minako Kagimoto, Mari Katsumata, Yusuke Kobayashi, Sanae Saka, Satoshi Umemura, Kouichi Tamura
ATP2B1 is a gene associated with hypertension. We reported previously that mice lacking ATP2B1 in vascular smooth muscle cells (VSMC ATP2B1 KO mice) exhibited high blood pressure and increased intracellular calcium concentration. The present study was designed to investigate whether lack of the ATP2B1 gene causes a higher response to calcium channel blockers (CCBs) than to other types of anti-hypertensive drugs. Both VSMC ATP2B1 KO and control mice were administered anti-hypertensive drugs while monitoring blood pressure shifts...
October 19, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/29037200/spontaneous-isolated-dissection-of-the-superior-mesenteric-artery-and-aneurysm-formation-resulting-from-segmental-arterial-mediolysis-a-case-report
#14
Nobuhiro Akuzawa, Makoto Kurabayashi, Tsukasa Suzuki, Daisuke Yoshinari, Mitsunobu Kobayashi, Yoshifumi Tanahashi, Fujio Makita, Ryusei Saito
BACKGROUND: Spontaneous isolated dissection of the superior mesenteric artery (SMA) can lead to bowel ischemia, aneurysm rupture, or even death. Studies have suggested that mechanical or hemodynamic stress on the vascular wall of the SMA may be a contributor, but its pathogenesis is unclear. CASE PRESENTATION: A 57-year-old Japanese man with a history of untreated hypertension and hyperuricemia was admitted to our hospital with the sudden onset of severe epigastric pain...
October 16, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28992471/parkia-speciosa-empty-pod-prevents-hypertension-and-cardiac-damage-in-rats-given-n-g-nitro-l-arginine-methyl-ester
#15
Yusof Kamisah, Japar Sidik Fadhlullah Zuhair, Abdul Hamid Juliana, Kamsiah Jaarin
Parkia speciosa Hassk is a plant found abundantly in Southeast Asia region. Its seeds with or without pods and roots have been used in traditional medicine in this region to treat hypertension. Therefore, we aimed to investigate the potential effect of the plant empty pod extract on hypertension development and changes in heart induced by N(G)-nitro-l-arginine methyl ester (l-NAME) administration in rats. Twenty-four male Sprague Dawley rats were divided into four groups. Groups 1 to 3 were given l-NAME (25mg/kg, intraperitoneally) for 8 weeks...
October 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28987396/use-of-nicardipine-after-cardiac-operations-is-safe-in-children-regardless-of-age
#16
Matthew L Stone, John Kelly, Maanasi Mistry, Marcia Buck, James Gangemi, Jeffrey Vergales
BACKGROUND: Control of postoperative hypertension is central to the care of infants and children after cardiac operations. Continuous pharmacologic delivery affords the advantage of rapid onset and ease of titration. Although well established in older children and adults, calcium channel blockers are routinely avoided in children aged younger than 1 year secondary to concerns of safety and efficacy in the setting of sarcoplasmic reticulum development. Thus, the purpose of this study was to review a single-institution experience with nicardipine, a selective calcium channel blocker, in pediatric patients after cardiac operations...
October 4, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28904237/labetalol-use-is-associated-with-increased-in-hospital-infection-compared-with-nicardipine-use-in-intracerebral-hemorrhage
#17
COMPARATIVE STUDY
Jordan B Starr, David L Tirschwell, Kyra J Becker
BACKGROUND AND PURPOSE: Increased sympathetic tone causes hypertension after intracerebral hemorrhage, and blood pressure reduction has been studied as a way to decrease hemorrhage growth and improve outcomes. It is unknown if the antihypertensive used to achieve blood pressure goals influences either. Because sympatholytic drugs reduce death and infection in animal models, we hypothesized that labetalol would improve outcomes compared with nicardipine. METHODS: Prospective data from a single center were retrospectively reviewed...
October 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28895453/extracranial-internal-carotid-artery-vasospasm-during-thrombectomy
#18
Isamu Miura, Akitsugu Kawashima, Masataka Hayashi, Akane Tanda, Tomomi Ishikawa, Takakazu Kawamata
The use of a stent retriever increases the risk of intracranial vasospasm. Here, we report the case of a man who developed severe vasospasm in a long segment of the extracranial internal carotid artery after mechanical irritation by a stent retriever inserted for the treatment of acute cerebral ischemia. A 47-year-old right-handed man presented with sudden-onset right-sided weakness and difficulty speaking. The patient's National Institutes of Health Stroke Scale score was 6 and he had an Alberta Stroke Program Early Computed Tomography Score of 9...
January 1, 2017: Neuroradiology Journal
https://www.readbyqxmd.com/read/28845316/acute-heart-failure-exacerbation-with-cardiogenic-shock-and-elevated-systemic-vascular-resistance-treated-with-a-combination-of-nicardipine-and-dobutamine-therapy
#19
Lydia E Issac, Setri Fugar, Naser Yamani, Burhan Mohamedali
Acute heart failure is a common reason for hospital admission and is usually caused by decreased cardiac output either as a result of an intrinsic cardiac issue or as a result of severe hypertension with elevated afterload. We present a patient with a history of HFrEF who presented with acute heart failure, found to have hypotension requiring Dobutamine support and an elevated systemic vascular resistance requiring Nicardipine drip, with subsequent recovery of cardiac function.
2017: Case Reports in Cardiology
https://www.readbyqxmd.com/read/28843762/preventing-cerebral-vasospasm-after-aneurysmal-subarachnoid-hemorrhage-with-aggressive-cisternal-clot-removal-and-nicardipine
#20
Nakao Ota, Hidetoshi Matsukawa, Hiroyasu Kamiyama, Toshiyuki Tsuboi, Kosumo Noda, Atsumu Hashimoto, Takanori Miyazaki, Yu Kinoshita, Norihiro Saito, Sadahisa Tokuda, Kyousuke Kamada, Rokuya Tanikawa
BACKGROUND: A subarachnoid clot is the strongest predictor of cerebral vasospasm. Our purpose was to analyze the relationship between the number of postoperative cisternal clots and cerebral vasospasm and to assess the efficacy of surgical clot removal. METHODS: The subjects were 158 patients with aneurysmal subarachnoid hemorrhage. All patients underwent clipping with cisternal clot removal. The preoperative and postoperative number of clots was analyzed semiquantitatively using computed tomography, and cerebral vasospasm and its severity were analyzed using magnetic resonance angiography in a blind fashion...
November 2017: World Neurosurgery
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