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https://www.readbyqxmd.com/read/28092865/investigations-on-the-immunosuppressive-activity-of-derivatives-of-mycophenolic-acid-in-immature-dendritic-cells
#1
Dorota Iwaszkiewicz-Grzes, Grzegorz Cholewinski, Agata Kot-Wasik, Piotr Trzonkowski, Krystyna Dzierzbicka
The main activity of mycophenolic acid 1 (MPA) and its analogs is the inhibition of proliferation of T cells. Here, we hypothesized that MPA and its conjugates inhibits also the activity of antigen-presenting cells (APC) including dendritic cells (DCs). We tested the effect of novel amino acid derivatives of MPA and conjugates of MPA with acridines/acridones on DCs by flow cytometry, ELISA and MLR assay. Both acridines/acridone derivatives could inhibit the maturation of DC, as shown by the decreased expression of B7 family receptors...
January 13, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28092854/biopharmaceutical-characterization-of-praziquantel-cocrystals-and-cyclodextrin-complexes-prepared-by-grinding
#2
Martina Cugovčan, Jasna Jablan, Jasmina Lovrić, Dominik Cinčić, Nives Galić, Mario Jug
Mechanochemical activation using several different co-grinding additives was applied as a green chemistry approach to improve physiochemical and biopharmaceutical properties of praziquantel (PZQ). Liquid assisted grinding with an equimolar amount of citric acid (CA), malic acid (MA), salicylic acid (SA) and tartaric acid (TA) gained in cocrystal formation, which all showed pH-dependent solubility and dissolution rate. However, the most soluble cocrystal of PZQ with MA was chemically unstable, as seen during the stability testing...
January 10, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28092844/enhanced-effect-in-combination-of-curcumin-and-ketoconazole-loaded-methoxy-poly-ethylene-glycol-poly-%C3%AE%C2%B5-caprolactone-micelles
#3
Fangfang Teng, Peizong Deng, Zhimei Song, Feilong Zhou, Runliang Feng
In order to enhance water-solubility and realize controlled release while keeping synergistic effects of ketoconazole and curcumin, drug-loaded methoxy poly (ethylene glycol)-b-poly (ε-caprolactone) micelles were prepared through thin membrane hydration method. Transmission electric microscopy and dynamitic light scattering characterization revealed the formation of ketoconazole- and curcumin-loaded micelles with an average size of 44.70nm and 39.56nm, respectively. The drug-loaded micelles endowed the two drugs' slow controlled release with water-solubility enhanced to 85 and 82000 folds higher than the corresponding raw drugs, respectively...
January 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28092838/development-and-validation-of-the-stigma-scale-for-epilepsy-in-turkey
#4
Sevim Baybaş, Zerrin Yıldırım, Harika Ertem Özhan, Ayten Dirican, Ahmet Dirican
OBJECTIVE: Epilepsy is a chronic disease with an increased risk of stigma. The aim of this study was to investigate the efficacy of a scale developed by the authors to determine the level of stigma in Turkish patients with epilepsy and their relatives. METHODS: In this pilot study, two scales were developed, one consisting of 32 questions for the patients and one of 20 questions for the patients' relatives. Initially, a total of 30 patients with epilepsy and 30 relatives of the patients were included...
January 13, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28092483/photodynamic-inactivation-of-cariogenic-pathogens-using-curcumin-as-photosensitizer
#5
Natália Costa Araújo, Rebeca Ferraz de Menezes, Vanda Sanderana Macêdo Carneiro, Alexandrino Pereira Dos Santos-Neto, Carla Raquel Fontana, Vanderlei Salvador Bagnato, Catherine Malinda Harvey, Marleny Elizabeth Martinez Gerbi
OBJECTIVE: This investigation assessed the susceptibility of Streptococcus mutans and Lactobacillus acidophilus to Photodynamic Therapy (PDT) when grown simultaneously in dentine carious lesions. BACKGROUND DATA: PDT is a technique that utilizes light to activate photosensitizers in the presence of oxygen to produce reactive radicals. MATERIALS AND METHODS: A culture medium of 1% glucose, 2% sucrose, 1% young primary culture of L. acidophilus 10(8) CFU/mL, and S...
January 12, 2017: Photomedicine and Laser Surgery
https://www.readbyqxmd.com/read/28092409/quantification-of-brown-and-white-adipose-tissue-based-on-gaussian-mixture-model-using-water-fat-and-t2-mri-in-adolescents
#6
Steve C N Hui, Jacky K L Ko, Teng Zhang, Lin Shi, David K W Yeung, Defeng Wang, Queenie Chan, Winnie C W Chu
PURPOSE: To develop a technique for the separation and quantification of brown adipose tissue (BAT) and white adipose tissue (WAT) using fat fraction and T2* intensity based on the Gaussian mixture model (GMM). MATERIALS AND METHODS: Chemical-shift water-fat and T2* images were acquired at the neck, supraclavicular, interscapular, and paravertebral regions in 24 volunteers (Obese: n = 12, female/male = 6/6, body mass index [BMI] = 31.3 ± 2.3 kg/m(2) , age = 16...
January 16, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28092392/the-in-silico-identification-of-human-bile-salt-export-pump-abcb11-inhibitors-associated-with-cholestatic-drug-induced-liver-injury
#7
Lili Xi, Jia Yao, Yuhui Wei, Xin'an Wu, Xiaojun Yao, Huanxiang Liu, Shuyan Li
Drug-induced liver injury (DILI) is one of the major causes of drug attrition and failure. Currently, there is increasing evidence that direct inhibition of the human bile salt export pump (BSEP/ABCB11) by drugs and/or metabolites is one of the most important mechanisms of cholestatic DILI. In the present study, we employ two in silico methods, random forest (RF) and the pharmacophore method, to recognize potential BSEP inhibitors that could cause cholestatic DILI, with the aim of mitigating the risk of cholestatic DILI to some extent...
January 16, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28092388/exploration-and-analysis-of-drug-modes-of-action-through-feature-integration
#8
Mingyuan Xin, Jun Fan, Mingyao Liu, Zhenran Jiang
Identifying drug modes of action (MoA) is of paramount importance for having a good grasp of drug indications in clinical tests. Anticipating MoA can help to discover new uses for approved drugs. Here we first used a drug-set enrichment analysis method to discover significant biological activities in every mode of action category. Then, we proposed a new computational model, a probability ensemble approach based on Bayesian network theory, which integrated chemical, therapeutic, genomic and phenotypic properties of over a thousand of FDA approved drugs to assist with the prediction of MoA...
January 16, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28092219/the-21st-century-cures-act-pharmacoeconomic-boon-or-bane
#9
Roger Lee Mendoza
Barriers to entry in healthcare markets constitute one of the overriding concerns of health economists. The recent enactment of the 21st Century Cures Act in the United States is one landmark legislation that reduces statutory entry barriers to the discovery, development, testing and licensing of drugs and medical devices. However, it brings with it many critical challenges concerning the safety, efficacy and value of drugs and devices, along with novel opportunities for medical innovation and faster treatment of diseases...
January 16, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28092111/design-and-synthesis-of-5-substituted-benzo-d-1-3-dioxole-derivatives-as-potent-anticonvulsant-agents
#10
Shiyang Dong, Tiantian Wang, Chundi Hu, Xiaodong Chen, Yi Jin, Zengtao Wang
A series of 5-substituted benzo[d][1,3]dioxole derivatives was designed, synthesized, and tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens. Neurotoxicity was determined by rotarod test. In the preliminary screening, six compounds, 3a, 3c, 3d, and 4d-f, showed promising anticonvulsant activities in the MES model, and compounds 4c and 4d exhibited full protection against seizures at doses of 300 mg/kg in the scPTZ model. Among the synthesized compounds, 3c as the most active compound showed high protection against the MES-induced seizures with an ED50 value of 9...
January 16, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28092108/pharmacokinetics-and-pharmacodynamics-of-the-injectable-formulation-of-methadone-hydrochloride-and-methadone-in-lipid-nanocarriers-administered-orally-to-horses
#11
N Crosignani, S P Luna, T Dalla Costa, E L Pimenta, C B Detoni, S S Guterres, J N Puoli Filho, J C Pantoja, M C Pigatto
We investigated the thermal, electrical and mechanical antinociceptive and physiological effects (heart rate, respiratory rate, arterial blood pressure, head height and abdominal auscultation score), and pharmacokinetics, of 0.5 mg/kg of the injectable formulation (ORAL) or nanoparticulated methadone (NANO) given orally, in six adult mares, using a crossover, blind and prospective design. Repeated-measure models were used to compare parametric data between and within treatments, followed by Tukey's test. Nonparametric data were analysed with Wilcoxon signed-rank, adjusted by Bonferroni tests...
January 16, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28092103/species-differences-in-hepatic-biotransformation-of-the-anthelmintic-drug-flubendazole
#12
M L Maté, T Geary, C Mackenzie, C Lanusse, G Virkel
Flubendazole (FLBZ) is a broad-spectrum benzimidazole anthelmintic used in pigs, poultry, and humans. It has been proposed as a candidate for development for use in elimination programmes for lymphatic filariasis and onchocerciasis in humans. Moreover, FLBZ has shown promise in cancer chemotherapy, particularly for neuroblastoma. This work investigated the hepatic carbonyl-reducing pathway of FLBZ in different species, including humans. Microsomal and cytosolic fractions were obtained from sheep, cattle, pig, hen, rat, and human liver...
January 16, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28091953/fullerene-c60-penetration-into-leukemic-cells-and-its-photoinduced-cytotoxic-effects
#13
D Franskevych, K Palyvoda, D Petukhov, S Prylutska, I Grynyuk, C Schuetze, L Drobot, O Matyshevska, U Ritter
Fullerene C60 as a representative of carbon nanocompounds is suggested to be promising agent for application in photodynamic therapy due to its unique physicochemical properties. The goal of this study was to estimate the accumulation of fullerene C60 in leukemic cells and to investigate its phototoxic effect on parental and resistant to cisplatin leukemic cells. Stable homogeneous water colloid solution of pristine C60 with average 50-nm diameter of nanoparticles was used in experiments. Fluorescent labeled C60 was synthesized by covalent conjugation of C60 with rhodamine B isothiocyanate...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28091881/identifying-metabolites-of-meclonazepam-by-high-resolution-mass-spectrometry-using-human-liver-microsomes-hepatocytes-a-mouse-model-and-authentic-urine-samples
#14
Svante Vikingsson, Ariane Wohlfarth, Mikael Andersson, Henrik Gréen, Markus Roman, Martin Josefsson, Fredrik C Kugelberg, Robert Kronstrand
Meclonazepam is a benzodiazepine patented in 1977 to treat parasitic worms, which recently appeared as a designer benzodiazepine and drug of abuse. The aim of this study was to identify metabolites suitable as biomarkers of drug intake in urine using high-resolution mass spectrometry, authentic urine samples, and different model systems including human liver microsomes, cryopreserved hepatocytes, and a mice model. The main metabolites of meclonazepam found in human urine were amino-meclonazepam and acetamido-meclonazepam; also, minor peaks for meclonazepam were observed in three of four urine samples...
January 13, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28091857/lack-of-heart-rate-variability-during-sleep-related-apnea-in-patients-with-temporal-lobe-epilepsy-tle-an-indirect-marker-of-sudep
#15
C S Nayak, S Sinha, M Nagappa, K Thennarasu, A B Taly
PURPOSE: Apneas occurring during sleep may precipitate autonomic instability in epilepsy patients making them susceptible to sudden death (SUDEP). Literature on heart rate variability (HRV) during apnea among patients with temporal lobe epilepsy (TLE) is sparse. The aim of this study was to characterize the HRV during the peri-apneic period in patients with TLE and compare with HRV of matched healthy individuals during the overnight polysomnographic (PSG) recording. Further, the role of carbamazepine (CBZ) in modulating peri-apneic HRV in the above cohort was also assessed...
January 14, 2017: Sleep & Breathing, Schlaf & Atmung
https://www.readbyqxmd.com/read/28091786/a-new-look-at-the-drug-resistance-investigation-of-uropathogenic-e-coli-strains
#16
Wioletta Adamus-Białek, Łukasz Lechowicz, Anna B Kubiak-Szeligowska, Monika Wawszczak, Ewelina Kamińska, Magdalena Chrapek
Bacterial drug resistance and uropathogenic tract infections are among the most important issues of current medicine. Uropathogenic Escherichia coli strains are the primary factor of this issue. This article is the continuation of the previous study, where we used Kohonen relations to predict the direction of drug resistance. The characterized collection of uropathogenic E. coli strains was used for microbiological (the disc diffusion method for antimicrobial susceptibility testing), chemical (ATR/FT-IR) and mathematical (artificial neural networks, Ward's hierarchical clustering method, the analysis of distributions of inhibition zone diameters for antibiotics, Cohen's kappa measure of agreement) analysis...
January 13, 2017: Molecular Biology Reports
https://www.readbyqxmd.com/read/28091572/a-computational-psychiatry-approach-identifies-how-alpha-2a-noradrenergic-agonist-guanfacine-affects-feature-based-reinforcement-learning-in-the-macaque
#17
S A Hassani, M Oemisch, M Balcarras, S Westendorff, S Ardid, M A van der Meer, P Tiesinga, T Womelsdorf
Noradrenaline is believed to support cognitive flexibility through the alpha 2A noradrenergic receptor (a2A-NAR) acting in prefrontal cortex. Enhanced flexibility has been inferred from improved working memory with the a2A-NA agonist Guanfacine. But it has been unclear whether Guanfacine improves specific attention and learning mechanisms beyond working memory, and whether the drug effects can be formalized computationally to allow single subject predictions. We tested and confirmed these suggestions in a case study with a healthy nonhuman primate performing a feature-based reversal learning task evaluating performance using Bayesian and Reinforcement learning models...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28090798/switching-from-branded-to-generic-glatiramer-acetate-15-month-gate-trial-extension-results
#18
Krzysztof Selmaj, Frederik Barkhof, Anna N Belova, Christian Wolf, Evelyn Rw van den Tweel, Janine Jl Oberyé, Roel Mulder, David F Egging, Norbert P Koper, Jeffrey A Cohen
BACKGROUND: Open-label 15-month follow-up of the double-blind, placebo-controlled Glatiramer Acetate clinical Trial to assess Equivalence with Copaxone(®) (GATE) trial. OBJECTIVE: To evaluate efficacy, safety, and tolerability of prolonged generic glatiramer acetate (GTR) treatment and to evaluate efficacy, safety, and tolerability of switching from brand glatiramer acetate (GA) to GTR treatment. METHODS: A total of 729 patients received GTR 20 mg/mL daily...
January 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28090779/preparation-and-in-vitro-in-vivo-evaluation-of-metformin-hydrochloride-rectal-dosage-forms-for-treatment-of-patients-with-type-ii-diabetes
#19
Abdel-Azim Zaghloul, Ahmad Lila, Fathy Abd-Allah, Aly Nada
BACKGROUND: Metformin hydrochloride (MtHCL) is an oral antidiabetic drug and has many other therapeutic benefits. It has poor bioavailability, narrow absorption window and extensive liver metabolism. Moreover, children and elders face difficulty to swallow the commercial oral tablets. OBJECTIVES: Preparation, in vitro/in vivo evaluation of MtHCL suppositories for rectal administration to solve some of these problems. METHODS: Suppository fatty bases (Witepsol®, Suppocire® and Massa®; different grades) and PEG bases 1000, 4000 and 6000 (different ratios), were used to prepare rectal suppository formulations each containing 500 mg drug...
January 16, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28090742/a-novel-scale-linking-potency-and-dosage-to-estimate-anticholinergic-exposure-in-older-adults-the-muscarinic-acetylcholinergic-receptor-antagonist-exposure-scale
#20
Therese T Klamer, Maarten Wauters, Majda Azermai, Carlos Durán, Thierry Christiaens, Monique Elseviers, Robert Vander Stichele
Quantification of the anticholinergic exposure insufficiently or imprecisely incorporates dosage information, leading to inaccurate estimations. The aim was to construct a novel scale, including potency and dosage for the quantification of the anticholinergic exposure in older adults. Potency information was retrieved from a previous systematic review. The dosage range for each drug was delineated in minimal, maintenance and maximal dosage for adults and older adults. Dosage information was collected from authoritative sources and reviewed in an expert panel...
November 7, 2016: Basic & Clinical Pharmacology & Toxicology
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