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https://www.readbyqxmd.com/read/28927064/bortezomib-carfilzomib-and-ixazomib-do-not-mediate-relevant-transporter-based-drug-drug-interactions
#1
Jannick Clemens, Lukas Welti, Julia Schäfer, Anja Seckinger, Jürgen Burhenne, Dirk Theile, Johanna Weiss
In order to optimize the clinical application of an increasing number of proteasome inhibitors, investigations into the differences between their respective pharmacodynamic and pharmacokinetic profiles, including their ability to act as a perpetrator in drug-drug interactions, are warranted. Therefore, in the present in vitro study, it was investigated whether bortezomib, carfilzomib and ixazomib are able to alter the expression, and/or the activity, of specific drug transporters generally relevant for pharmacokinetic drug-drug interactions...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926976/chemical-composition-antibacterial-activity-and-synergistic-effects-with-conventional-antibiotics-and-nitric-oxide-production-inhibitory-activity-of-essential-oil-from-geophila-repens-l-i-m-johnst
#2
Huijuanzi Rao, Pengxiang Lai, Yang Gao
Geophila repens (L.) I.M. Johnst, a perennial herb, belongs to the Rubiaceae family. In this study, we identified the chemical composition of the Geophila repens essential oil (GR-EO) for the first time. Totally, seventy-seven compounds were identified according to GC and GC-MS, which represent 98.0% of the oil. And the major components of GR-EO were β-caryophyllene (23.3%), β-elemene (8.0%), farnesyl butanoate (7.4%), myrcene (3.5%), and trans-nerolidol (3.3%). Then we evaluated the antibacterial activities of GR-EO and the synergistic effects of GR-EO in combination with commercial antibiotics using the microdilution and Checkerboard method...
September 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28926955/identification-of-novel-bisbenzimidazole-derivatives-as-anticancer-vacuolar-h%C3%A2-%C2%BA-atpase-inhibitors
#3
Renukadevi Patil, Arpita Kulshrestha, Anjali Tikoo, Sara Fleetwood, Gajendra Katara, Bala Kolli, William Seibel, Alice Gilman-Sachs, Shivaputra A Patil, Kenneth D Beaman
The vacuolar (H⁺)-ATPases (V-ATPases) are a family of ATP-driven proton pumps and they have been associated with cancer invasion, metastasis, and drug resistance. Despite the clear involvement of V-ATPases in cancer, the therapeutic use of V-ATPase-targeting small molecules has not reached human clinical trials to date. Thus, V-ATPases are emerging as important targets for the identification of potential novel therapeutic agents. We identified a bisbenzimidazole derivative (V) as an initial hit from a similarity search using four known V-ATPase inhibitors (I-IV)...
September 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28926883/-etiological-analysis-and-in-vitro-drug-sensitivity-of-bacterial-keratitis-in-northern-china-in-the-period-of-2006-2015
#4
Y Zhang, Z Q Wang, X G Sun
Objective: To analyze the etiology and drug sensitivity of bacterial keratitis and their changes, and to provide evidence for treatment and drug selection of bacterial keratitis. Methods: Retrospective case series study. From January 2006 to December 2015, corneal specimens suspected of bacterial infection were collected and cultured in Beijing Tongren Eye Center. General information of patients, etiological results and drug sensitivity test results were summarized and analyzed. The Chi-square test and Spearman correlation analysis were performed using SPSS 20...
September 11, 2017: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
https://www.readbyqxmd.com/read/28926841/beneficial-combination-of-lacosamide-with-retigabine-in-experimental-animals-an-isobolographic-analysis
#5
Jarogniew J Luszczki, Mirosław Zagaja, Barbara Miziak, Maria W Kondrat-Wrobel, Katarzyna Zaluska, Paula Wroblewska-Luczka, Piotr Adamczuk, Stanislaw J Czuczwar, Magdalena Florek-Luszczki
BACKGROUND/AIM: To isobolographically determine the types of interactions that occur between retigabine and lacosamide (LCM; two third-generation antiepileptic drugs) with respect to their anticonvulsant activity and acute adverse effects (sedation) in the maximal electroshock-induced seizures (MES) and chimney test (motor performance) in adult male Swiss mice. METHODS: Type I isobolographic analysis for nonparallel dose-response effects for the combination of retigabine with LCM (at the fixed-ratio of 1:1) in both the MES and chimney test in mice was performed...
September 20, 2017: Pharmacology
https://www.readbyqxmd.com/read/28926784/synthesis-of-thiobarbituric-acid-derivatives-in-vitro-%C3%AE-glucosidase-inhibition-and-molecular-docking-studies
#6
Assem Barakat, M Ali, Abdullah Mohammed Al-Majid, Sammer Yousuf, M Iqbal Choudhary, Ruqaiya Khalil, Zaheer Ul-Haq
Synthesis, structure, and evaluation of in vitro α-glucosidase enzyme inhibition of a new class of diethylammonium salts of aryl substituted thiobarbituric acid is described. This protocol is straight, environmentally benign and efficient, involving Aldol-Michael addition reaction in one pot fashion. The 3D chemical structures of the synthesized compounds were assigned based on spectroscopic methods and X-ray single crystal diffraction analyses. All synthesized compounds 3a-3n were evaluated for their in vitro α-glucosidase enzyme inhibitory activity, whereas acarbose was used as the standard drug (IC50=840±1...
September 12, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28926763/synthesis-and-2d-qsar-studies-of-neolignan-based-diaryl-tetrahydrofuran-and-furan-analogues-with-remarkable-activity-against-trypanosoma-cruzi-and-assessment-of-the-trypanothione-reductase-activity
#7
Ana Paula Hartmann, Marcelo Rodrigues de Carvalho, Lilian Sibelle Campos Bernardes, Milena Hoehr de Moraes, Eduardo Borges de Melo, Carla Duque Lopes, Mario Steindel, João Santana da Silva, Ivone Carvalho
Two series of diaryl-tetrahydrofuran and -furan were synthesised and screened for anti-trypanosomal activity against trypomastigote and amastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. Based on evidence that modification of a natural product may result in a more effective drug than the natural product itself, and using known neolignan inhibitors veraguensin 1 and grandisin 2 as templates to synthesise simpler analogues, remarkable anti-trypanosomal activity and selectivity were found for 3,5-dimethoxylated diaryl-furan 5c and 2,4-dimethoxylated diaryl-tetrahydrofuran 4e analogues with EC50 0...
September 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28926560/hiv-and-hcv-in-u-s-prisons-and-jails-the-correctional-facility-as-a-bellwether-over-time-for-the-community-s-infections
#8
Anne C Spaulding, Emeli J Anderson, Mohammed A Khan, Cesar A Taborda-Vidarte, Jennifer A Phillips
Screening and treating correctional populations for HIV and HCV infections is essential to successfully addressing both epidemics in the USA. The prevalence of HIV and HCV infection is high in prisons and jails due to increased rates of incarceration among disproportionately affected groups such as injection drug users. Through a search of the published and grey literature and surveying persons overseeing health programs in prisons, we collected data on efforts to determine prevalence first for HIV and then for HCV...
September 19, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28926524/prognostic-significance-of-tnfr-associated-factor-1-and-2-traf1-and-traf2-in-glioblastoma
#9
Wenqing Zhang, Ying Sun, Lei Liu, Zongpeng Li
BACKGROUND TNFR-associated factor 1 (TRAF1) and TRAF2 have been demonstrated to inhibit apoptosis and promote cell survival in glioblastoma (GBM) cells with experiments in vitro. However, their clinical and prognostic significance have not been elucidated. MATERIAL AND METHODS In our study, we for the first time investigated the expression of TRAF1 and TRAF2 in 105 GBM tissues. Furthermore, we evaluated their clinical significance, including their association with clinicopathologic factors and prognostic value...
September 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28926192/testing-of-a-bioactive-moldable-bone-graft-substitute-in-an-infected-critically-sized-segmental-defect-model
#10
Matt E Brown, Yuan Zou, Rebecca Peyyala, Sarandeep S Huja, Larry L Cunningham, Todd A Milbrandt, Thomas D Dziubla, David A Puleo
Large infected bone defects, often resulting from high energy traumas, are difficult to treat due to their variability in complexity and location. Standard treatment for infected bone defects begins with a protocol that includes a series of debridements in conjunction with an extended course of systemic antibiotics. Only after the infection has been eliminated will repair of the defect commence, typically with implantation of autologous bone. To address some of the shortcomings of the standard treatment methods, such as serial procedures, limited grafting material, and the need for a second surgical site for autologous bone, a sequential, dual drug-releasing, moldable, calcium sulfate-based bone graft substitute was developed previously...
September 19, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28926095/model-based-assessment-using-conventional-bioequivalence-limits-to-ensure-safety-and-efficacy-of-rivaroxaban-in-patients-undergoing-hip-or-knee-replacement
#11
Mario González-Sales, Lanyan Fang, Myong-Jin Kim, Liang Zhao
We evaluated whether the current bioequivalence limit is adequate to ensure safety and efficacy of rivaroxaban in patients under total hip arthroplasty and total knee arthroplasty based on its model informed benefit/risk profile. Clinical data from a total of 7145 patients from 3 phase 2 and 4 phase 3 clinical trials were included in the current model-based exposure-response analysis. The relationships between rivaroxaban exposure measurements (ie, minimum or trough, maximum, average concentration, and area under the concentration-time curve [AUC] at steady state) and clinical outcomes (ie, the probabilities of major bleeding [MB] and venous thromboembolism [VTE]) were modeled using NONMEM 7...
September 19, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28925989/development-of-a-symptom-focused-patient-reported-outcome-measure-for-functional-dyspepsia-the-functional-dyspepsia-symptom-diary-fdsd
#12
Fiona Taylor, Sophie Higgins, Robyn T Carson, Sonya Eremenco, Catherine Foley, Brian E Lacy, Henry P Parkman, David S Reasner, Alan L Shields, Jan Tack, Nicholas J Talley
OBJECTIVES: The Functional Dyspepsia Symptom Diary (FDSD) was developed to address the lack of symptom-focused, patient-reported outcome (PRO) measures designed for use in functional dyspepsia (FD) patients and meeting Food and Drug Administration recommendations for PRO instrument development. METHODS: Concept elicitation interviews were conducted with FD participants to identify symptoms important and relevant to FD patients. A preliminary version of the FDSD was constructed, then completed by FD participants on an electronic device in cognitive interviews to evaluate the readability, comprehensibility, relevance, and comprehensiveness of the FDSD, and to preliminarily evaluate its measurement properties...
September 19, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28925968/recent-progress-in-the-development-of-diagnostic-tests-for-malaria
#13
REVIEW
Francis D Krampa, Yaw Aniweh, Gordon A Awandare, Prosper Kanyong
The impact of malaria on global health has continually prompted the need to develop effective diagnostic strategies. In malaria endemic regions, routine diagnosis is hampered by technical and infrastructural challenges to laboratories. These laboratories lack standard facilities, expertise or diagnostic supplies; thus, therapy is administered based on clinical or self-diagnosis. There is the need for accurate diagnosis of malaria due to the continuous increase in the cost of medication, and the emergence and spread of drug resistant strains...
September 19, 2017: Diagnostics
https://www.readbyqxmd.com/read/28925959/preventing-surgical-site-infections-using-a-natural-biodegradable-antibacterial-coating-on-surgical-sutures
#14
Jochen Reinbold, Ann-Kristin Uhde, Ingrid Müller, Tobias Weindl, Jürgen Geis-Gerstorfer, Christian Schlensak, Hans-Peter Wendel, Stefanie Krajewski
Surgical site infections (SSIs) are one of the most common nosocomial infections, which can result in serious complications after surgical interventions. Foreign materials such as implants or surgical sutures are optimal surfaces for the adherence of bacteria and subsequent colonization and biofilm formation. Due to a significant increase in antibiotic-resistant bacterial strains, naturally occurring agents exhibiting antibacterial properties have great potential in prophylactic therapies. The aim of this study was to develop a coating for surgical sutures consisting of the antibacterial substance totarol, a naturally occurring diterpenoid isolated from Podocarpustotara in combination with poly(lactide-co-glycolide acid) (PLGA) as a biodegradable drug delivery system...
September 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28925874/preclinical-assessment-of-steroidal-nanostructured-lipid-carriers-based-gels-for-atopic-dermatitis-optimization-and-product-development
#15
Upendra Nagaich, Neha Gulati
BACKGROUND: Betamethasone Valerate (BV) is potent topical corticosteroid. Preparation of nanostructured lipid carreirs (NLC) involves process parameters optimization and formulations were developed. It is available in several conventional formulations like creams and ointments which have well-known problems of frequent dosing and consequently additional side effects. The aim is to ascertain the probability of NLC as an exclusive carrier for betamethasone valerate topical application with regard to release modulation and improved therapeutic effect...
September 18, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/28925755/toward-smart-design-of-retinal-drug-carriers-a-novel-bovine-retinal-explant-model-to-study-the-barrier-role-of-the-vitreoretinal-interface
#16
Karen Peynshaert, Joke Devoldere, Valérie Forster, Serge Picaud, Christian Vanhove, Stefaan C De Smedt, Katrien Remaut
Retinal gene delivery via intravitreal injection is hampered by various physiological barriers present in the eye of which the vitreoretinal (VR) interface represents the most serious hurdle. In this study, we present a retinal explant model especially designed to study the role of this interface as a barrier for the penetration of vectors into the retina. In contrast to all existing explant models, the developed model is bovine-derived and more importantly, keeps the vitreous attached to the retina at all times to guarantee an intact VR interface...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28925725/light-sensitive-drugs-in-topical-formulations-stability-indicating-methods-and-photostabilization-strategies
#17
Giuseppina Ioele, Lorena Tavano, Michele De Luca, Rita Muzzalupo, Annalisa Mancuso, Gaetano Ragno
Photostability tests applied on commercial specialties for topical use have demonstrated a greater vulnerability of several drugs, due to greater exposure to light than other pharmaceutical forms. Photodegradation of a drug can considerably modify its pharmacokinetic behavior by varying the therapeutic index. The evaluation of the degradation profile of a drug, according to the ICH rules, is of primary importance in developing an appropriate topical formulation. Advanced strategies have been proposed to increase the protection from the light of the photolabile drugs...
September 19, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28925655/pleuritic-chest-pain-sorting-through-the-differential-diagnosis
#18
Brian V Reamy, Pamela M Williams, Michael Ryan Odom
Pleuritic chest pain is characterized by sudden and intense sharp, stabbing, or burning pain in the chest when inhaling and exhaling. Pulmonary embolism is the most common serious cause, found in 5% to 21% of patients who present to an emergency department with pleuritic chest pain. A validated clinical decision rule for pulmonary embolism should be employed to guide the use of additional tests such as d-dimer assays, ventilation-perfusion scans, or computed tomography angiography. Myocardial infarction, pericarditis, aortic dissection, pneumonia, and pneumothorax are other serious causes that should be ruled out using history and physical examination, electrocardiography, troponin assays, and chest radiography before another diagnosis is made...
September 1, 2017: American Family Physician
https://www.readbyqxmd.com/read/28925167/-analysis-on-intestinal-absorption-of-paeoniflorin-lipid-liquid-crystalline-nanoparticles-via-everted-intestinal-sacs
#19
Shuang Teng, Ling Qiu, Hong-Ge Chen, Bao-de Shen, Cheng-Ying Shen, Ping-Hua Xu, Jin Han, Hai-Long Yuan
To study the absorption kinetics of paeoniflorin lipid liquid crystalline nanoparticles (Pae-LLCN) in different intestinal segments of rats and compare them with paeoniflorin(Pae) solution. Rat everted gut sac models were adopted for intestinal absorption test, and Pae content was determined by HPLC method to study the absorption characteristics of Pae-LLCN in rat duodenum, jejunum, ileum and colon, and investigate the effects of different drug concentrations on intestinal absorption. Results showed that Pae-LLCN and Pae were well absorbed at different intestine segments and different concentrations...
October 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28925162/-effect-of-corydalis-rhizoma-and-l-tetrahydropalmatine-on-dopamine-system-of-hippocampus-and-striatum-in-morphine-induced-conditioned-place-preference-rats
#20
Shou-Yang Yu, Wei-Feng Bai, Ping Tu, Cheng-Kai Qiu, Pei-Run Yang, Su-Yuan Luo
To investigate the effects of Corydalis Rhizoma and L-tetrahydropalma-tine (L-THP) on the levels of dopamine neurotransmitter (DA), dopamine transporter (DAT) and the second dopamine receptor (D2R) in learning and memory-related brain areas, hippocampus and striatum, the DA, DAT and D2R were detected in conditioned place preference (CPP) rats suffered from morphine. And comparation the degree of similarity and consistency of the pharmacological effects was also studied. The rats were trained in black compartments and white ones (drug-paired compartment) with the increasing doses of morphine for 10 days (hypodermically injected from 10 mg•kg⁻¹ to 100 mg•kg⁻¹)...
October 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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