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https://www.readbyqxmd.com/read/29342085/development-of-a-region-specific-physiologically-based-pharmacokinetic-brain-model-to-assess-hippocampus-and-frontal-cortex-pharmacokinetics
#1
Zaril Zakaria, Raj Badhan
Central nervous system drug discovery and development is hindered by the impermeable nature of the blood-brain barrier. Pharmacokinetic modeling can provide a novel approach to estimate CNS drug exposure; however, existing models do not predict temporal drug concentrations in distinct brain regions. A rat CNS physiologically based pharmacokinetic (PBPK) model was developed, incorporating brain compartments for the frontal cortex (FC), hippocampus (HC), "rest-of-brain" (ROB), and cerebrospinal fluid (CSF). Model predictions of FC and HC Cmax, tmax and AUC were within 2-fold of that reported for carbamazepine and phenytoin...
January 17, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/29341370/real-world-clinical-outcomes-and-predictors-of-glycaemic-and-weight-response-to-exenatide-once-weekly-in-patients-with-type-2-diabetes-the-cibeles-project
#2
Juan José Gorgojo-Martínez, Manuel Angel Gargallo-Fernández, Miguel Brito-Sanfiel, Arturo Lisbona-Catalán
AIMS: To evaluate in a real-world setting the effectiveness of exenatide once-weekly (ExQW) in patients with T2D and to determine predictors of glycaemic and weight response to this drug at 6 months. METHODS: Observational, retrospective, multicenter study in adult patients with T2D and BMI ≥30 kg/m2 from 4 tertiary Spanish hospitals who started ExQW therapy at least 6 months before the inclusion and had not achieved adequate glycaemic control on oral therapies or other GLP-1 receptor agonists...
January 17, 2018: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/29340825/laparoscopic-surgery-in-colon-cancer-patients-treated-with-chronic-anti-thrombotic-therapy
#3
Hiroaki Nozawa, Takahide Shinagawa, Kazushige Kawai, Keisuke Hata, Toshiaki Tanaka, Takeshi Nishikawa, Kensuke Otani, Kazuhito Sasaki, Manabu Kaneko, Shigenobu Emoto, Koji Murono
BACKGROUND: Anti-thrombotic medications are commonly used for the treatment and prevention of cardiovascular diseases. Laparoscopic resection of colon cancer has generally been accepted with favorable outcomes being reported in randomized control trials. However, the safety and efficacy of laparoscopic surgery for colon cancer patients receiving chronic anti-thrombotic therapy (AT) remain unclear. METHODS: We identified 951 patients who underwent elective resection for colon cancer between 2009 and 2016 from our database...
January 16, 2018: Surgical Endoscopy
https://www.readbyqxmd.com/read/29340545/effects-of-cold-ischemia-time-on-hepatic-allograft-function
#4
Alexandre Coutinho Teixeira de Freitas, Desirée de Marillac Nascimento de Matos, Jorge Amilton Tosato Milsted, Julio Cezar Uili Coelho
BACKGROUND: Cold ischemia time is related to success of liver transplantation. AIM: To compare the impact of cold ischemia time on allografts locally collected to those collected distantly. METHODS: Were evaluated 83 transplantations. The patients were divided in two groups: those who received liver grafts collected from cities out of Curitiba (n=42) and locally (n=41). From the donors were compared: cause of death, days at ICU, cardiac arrest, vasoactive drugs, lab exams, gender, age, and BMI...
October 2017: Arquivos Brasileiros de Cirurgia Digestiva: ABCD, Brazilian Archives of Digestive Surgery
https://www.readbyqxmd.com/read/29339391/intrapulmonary-pharmacokinetics-of-lascufloxacin-in-healthy-adult-volunteers
#5
Hidetoshi Furuie, Sayoko Tanioka, Keiko Shimizu, Shigeru Manita, Masaharu Nishimura, Hisao Yoshida
This study was performed to investigate the intrapulmonary penetration of lascufloxacin in humans. Thirty healthy adult male Japanese subjects, allocated into five groups, received lascufloxacin in single oral dose of 75 mg. Bronchoalveolar lavage and blood sampling were performed simultaneously in each subject at 1, 2, 4, 6, or 24 hours after administration, and lascufloxacin concentrations in plasma, epithelial lining fluid, and alveolar macrophages were determined. Lascufloxacin was rapidly distributed to the epithelial lining fluid with Tmax of 1 hour, which was identical to that in plasma...
January 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29338544/a-direct-comparison-between-norepinephrine-and-phenylephrine-for-augmenting-spinal-cord-perfusion-in-a-porcine-model-of-spinal-cord-injury
#6
Femke Streijger, Kitty So, Neda Manouchehri, Ana Gheorghe, Elena B Okon, Ryan M Chan, Benjamin Ng, Katelyn Shortt, Mypinder Singh Sekhon, Donald E Griesdale, Brian K Kwon
Current clinical guidelines recommend elevating the mean arterial blood pressure (MAP) to increase spinal cord perfusion in patients with acute spinal cord injury (SCI). This is typically achieved with vasopressors such as norepinephrine (NE) and phenylephrine (PE). These drugs differ in their pharmacologic properties and potentially have different effects on spinal cord blood flow (SCBF), oxygenation (PO2), and downstream metabolism after injury. Using a porcine model of thoracic SCI, we evaluated how these vasopressors influenced intraparenchymal SCBF, PaPO2, hydrostatic pressure, and metabolism within the spinal cord adjacent to the injury site...
January 16, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29338184/design-of-ph-sensitive-nanovesicles-via-cholesterol-analogue-incorporation-for-improving-in-vivo-delivery-of-chemotherapeutics
#7
Lina Liang, Jun Fu, Liyan Qiu
pH-responsive polymersomes have emerged as promising nanocarriers for antitumor drugs to realize their fast release and action in weak acidic microenvironment of tumor cells. Herein, however, we designed a remarkably pH-responsive polymersome self-assembled from amphiphilic benzimidazole-based polyphosphazenes via the incorporation of cholesteryl hemisuccinate (CholHS), a type of cholesteric molecule, into the polymersome bilayers to inhibit the drug release during blood circulation. Actually, unwanted premature drug leakage before arriving at acidic tumor site has become a serious problem for polymersomes encapsulating water-soluble drugs, especially when the drug-loading is at a high level, thus limiting the therapeutic efficacy...
January 17, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29337597/hydroxyurea-for-lifelong-transfusion-dependent-%C3%AE-thalassemia-a-meta-analysis
#8
Ali H Algiraigri, Nicola A M Wright, Elizabeth Oddone Paolucci, Aliya Kassam
OBJECTIVE: Chronic blood transfusion remains the most feasible therapeutic option for lifelong transfusion-dependent β-thalassemia (lifelong TDβT). However, it is associated with serious risks and complications. Hydroxyurea (HU), an oral chemotherapeutic drug, is expected to increase hemoglobin levels, thereby minimizing the burden of blood transfusion and its complications. Growing literature over the last twenty years suggests promising results of the use HU in lifelong TDβT; however, its role and safety remain unanswered questions...
January 16, 2018: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29337301/hepatic-gi-signaling-regulates-whole-body-glucose-homeostasis
#9
Mario Rossi, Lu Zhu, Sara M McMillin, Sai Prasad Pydi, Shanu Jain, Lei Wang, Yinghong Cui, Regina J Lee, Amanda H Cohen, Hideaki Kaneto, Morris J Birnbaum, Yanling Ma, Yaron Rotman, Jie Liu, Travis J Cyphert, Toren Finkel, Owen P McGuinness, Jürgen Wess
An increase in hepatic glucose production (HGP) is a key feature of type 2 diabetes. Excessive signaling through hepatic Gs-linked glucagon receptors critically contributes to pathologically elevated HGP. Here, we tested the hypothesis that this metabolic impairment can be counteracted by enhancing hepatic Gi signaling. Specifically, we used a chemogenetic approach to selectively activate Gi-type G proteins in mouse hepatocytes in vivo. Unexpectedly, activation of hepatic Gi signaling triggered a pronounced increase in HGP and severely impaired glucose homeostasis...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29336990/failure-of-intracardiac-pacing-after-fatal-propafenone-overdose-a-case-report
#10
Ivan Zeljković, Nikola Bulj, Matea Kolačević, Vedran Čabrilo, Diana Delić Brkljačić, Šime Manola
BACKGROUND: Propafenone is a sodium-channel blocker, class IC antiarrhythmic drug, frequently used to manage supraventricular dysrhythmias, especially atrial fibrillation. We report a self mono-intoxication with propafenone. CASE REPORT: A 68-year-old woman presented with a decreased level of consciousness, hypotension, and electrocardiogram showing QRS widening with atrial asystole and extreme bradycardia < 20 beats/min. After initial stabilization with transcutaneous pacing, laboratory findings detected normal electrolyte ranges and metabolic acidosis, and her medical history revealed availability of propafenone due to paroxysmal atrial fibrillation and depressive syndrome, which led to the suspicion of intoxication...
January 11, 2018: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29336875/systems-pharmacology-dissection-of-the-anti-stroke-mechanism-for-the-chinese-traditional-medicine-xing-nao-jing
#11
Yuhua Chen, Yue Sun, Wende Li, Hong Wei, Tianlin Long, Hua Li, Quanhua Xu, Wei Liu
Xing-Nao-Jing (XNJ) is a well-known injection that has been extensively applied in clinical treatment of stroke in China. However, the underlying mechanism of clinical administration of XNJ in stroke remains unclear. In this study, a systems pharmacology strategy based on pharmacokinetic and pharmacodynamics data was applied to analyze the pharmacological effect of XNJ on stroke. Sixteen active compounds were filtered from XNJ through Drug-likeness (DL) and Brain-blood-barrier (BBB) evaluations. Ninety-four potential targets of these active components were identified by SysDT and SEA...
December 20, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29335619/cytokine-mif-enhances-blood-brain-barrier-permeability-impact-for-therapy-in-ischemic-stroke
#12
Yu-Chuan Liu, Yung-Hsu Tsai, Sung-Chun Tang, Houng-Chi Liou, Kai-Hsiang Kang, Horng-Huei Liou, Jiann-Shing Jeng, Wen-Mei Fu
Ischemic stroke is a devastating disease with limited therapeutic options. It is very urgent to find a new target for drug development. Here we found that the blood level of MIF in ischemic stroke patients is upregulated. To figure out the pathological role of MIF in ischemic stroke, both in vitro and in vivo studies were conducted. For in vitro studies, primary cortical neuron cultures and adult rat brain endothelial cells (ARBECs) were subjected to oxygen-glucose deprivation (OGD)/reoxygenation. Middle cerebral artery occlusion (MCAo) rodent models were used for in vivo studies...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29334707/-comparing-the-immunogenicity-and-safety-of-sequential-inoculation-of-sipv-followed-by-bopv-%C3%A2-%C3%A2-in-different-dosage-forms
#13
H Ye, T Huang, Z F Ying, G L Li, Y C Che, Z M Zhao, J F Wang, X L Yang, L Shi, R J Jiang, X C Liu, Z J Mo, C G Li, J S Yang
Objective: To compare the safety and immunogenicity of two different sequential schedules of inactivated poliomyelitis vaccine made from Sabin strain (sIPV) followed by typeⅠ+Ⅲ bivalent oral poliovirus vaccine (bOPV) in Drug Candy (DC) form or liquid dosage form). Methods: This randomized, blinded, single center, parallel-group controlled trial was done from September 2015 to June 2016 in Liuzhou, Guangxi province. Healthy infants aged ≥2 months were eligible for enrollment and divided into 1sIPV+2bOPV or 2sIPV+1bOPV sequential schedules...
January 6, 2018: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/29333875/ultrafast-determination-of-vitamin-e-using-lc-esi-ms-ms-for-preclinical-development-of-new-nutraceutical-formulations
#14
Noemi Villaseca-González, Virginia Rodríguez Robledo, Lucía Castro-Vázquez, María Victoria Lozano, Manuel J Santander-Ortega, Joaquín González-Fuentes, Pilar Marcos, María Del Mar Arroyo-Jiménez
AIM: We proposed a rapid and high quality method to determine α-tocopherol (α-T) in different biopharmaceutical samples using liquid chromatography-diode array detector on-line ESI-MS/MS. MATERIALS & METHODS: A working standard solution of α-T and internal standard, phenyl-5,7-dimethyl-d6-α-tocopherol, were used for optimization and validation of the method. Levels of α-T in nanoemulsions, serum and plasma samples were evaluated. RESULTS & CONCLUSION: Precision (1% for retention time, 5% for peak area and 3% for relative peak area), linearity range (among 0...
January 15, 2018: Bioanalysis
https://www.readbyqxmd.com/read/29333379/broccoli-brassica-oleracea-reduces-oxidative-damage-to-pancreatic-tissue-and-combats-hyperglycaemia-in-diabetic-rats
#15
Sithara Suresh, Mostafa Ibrahim Waly, Mohammad Shafiur Rahman, Nejib Guizani, Mohamed Abdullah Badar Al-Kindi, Halima Khalfan Ahmed Al-Issaei, Sultan Nasser Mohd Al-Maskari, Bader Rashid Said Al-Ruqaishi, Ahmed Al-Salami
Oxidative stress plays a pivotal role in the development of diabetes and hyperglycaemia. The protective effects of natural extracts against diabetes are mainly dependent on their antioxidant and hypoglycaemic properties. Broccoli (Brassica oleracea) exerts beneficial health effects in several diseases including diabetes; however, the mechanism has not been elucidated yet. The present study was carried out to evaluate the potential hypoglycaemic and antioxidant properties of aqueous broccoli extracts (BEs) in diabetic rats...
December 2017: Preventive Nutrition and Food Science
https://www.readbyqxmd.com/read/29333044/antiplasmodial-activity-of-isolated-polyphenols-from-alectryon-serratus-leaves-against-3d7-plasmodium-falciparum
#16
Uswatun Khasanah, Aty WidyaWaruyanti, Achmad Fuad Hafid, Mulyadi Tanjung
Background: Alectryon serratus was selected from a screening program devoted to search naturally occurring antimalarial compound from plants in Alas Purwo National Park, Banyuwangi, East Java, Indonesia. The previous studies showed that ethanol extract of A. serratus leaves contains some polyphenol compounds. Objective: This study was designed to isolate and investigate antiplasmodial activity of polyphenol compounds. Material and Methods: The ethanol extract of A...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29333041/pharmacological-evaluation-of-hepatoprotective-activity-of-ahpl-aytab-0613-tablet-in-carbon-tetrachloride-ethanol-and-paracetamol-induced-hepatotoxicity-models-in-wistar-albino-rats
#17
Sanjay U Nipanikar, Sohan S Chitlange, Dheeraj Nagore
Background: Hepatotoxicity ultimately leads to liver failure. Conventional treatment options for hepatotoxicity are limited and not safe. Objective: Formulation AHPL/AYTAB/0613 is developed to provide safer and effective hepatoprotective drug of natural origin. A study was conducted to evaluate hepatoprotective activity of AHPL/AYTAB/0613 (three dosages) in comparison with marketed formulations in carbon tetrachloride (CCl4), ethanol, and paracetamol-induced hepatotoxicity in Wistar albino rats...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29333040/pharmacological-screening-of-trachyspermum-ammi-for-antihyperlipidemic-activity-in-triton-x-100-induced-hyperlipidemia-rat-model
#18
Uzma Saleem, Saba Riaz, Bashir Ahmad, Mohammad Saleem
Background: Mortality rate is increasing due to cardiovascular problems throughout the world. These cardiac problems are directly associated with dyslipidemia. Aim: The aim of this study was to evaluate the antihyperlipidemic effect of aqueous extract and methanol extract of Trachyspermum ammi at 1 g/kg, 3 g/kg, and 5 g/kg dose levels in rats. Materials and Methods: For this purpose, 45 male albino rats were used and randomly divided into nine equal groups (n = 5)...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29333038/antihyperglycemic-potential-of-saponin-enriched-fraction-from-pithecellobium-dulce-benth-seed-extract
#19
Mahesh Kumar, Jeyabalan Govindrajan, Narendra Kumar Nyola
Background: Indian traditional system of medicine uses Pithecellobium dulce for the treatment of diabetes mellitus. Objectives: This study aims to develop an extract rich in saponins derived from seeds of the plant and to evaluate its antihyperglycemic potential in vitro and in vivo. Materials and Methods: Defatted seeds were extracted with methanol and processed to afford saponin-enriched fraction (Pithecellobium dulce saponin-enriched fraction [PDSEF])...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29332567/nociceptin-orphanin-fq-peptide-nop-receptor-modulators-an-update-in-structure-activity-relationships
#20
Carlo Mustazza, Stefano Pieretti, Francesca Marzoli
Nociceptin /Orphanin FQ Peptide" receptor (NOPr) is a G-protein-coupled receptor with the nociceptin/orphanin FQ peptide (N/OFQ) as endogenous agonist. It is expressed in the nervous system as well as in some non-neural tissues. Its activation has pronociceptive effect at the supraspinal level, whereas at the spinal level it produces nociceptive effects at low doses and antinociceptive effects at higher doses. NOPr is also involved in mood and blood pressure regulation, immunoregulation, airway constriction, feeding, urination, bowel motility, learning and memory...
January 10, 2018: Current Medicinal Chemistry
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