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https://www.readbyqxmd.com/read/28651217/modeling-in-sewer-transformations-at-catchment-scale-implications-on-drug-consumption-estimates-in-wastewater-based-epidemiology
#1
Ann-Kathrin McCall, Rocco Palmitessa, Frank Blumensaat, Eberhard Morgenroth, Christoph Ort
To which extent illicit drugs are transformed during in-sewer transport, depends on a number of factors: i) substance-specific transformation rates, ii) environmental conditions, iii) point of discharge (location of drug user) and iv) sewer network properties, primarily hydraulic residence time (HRT) and the ratio of biofilm contact area to wastewater volume (A/Veq). Assessing associated uncertainties typically requires numerous simulations. Therefore, we propose a new two-step modeling framework: 1) Quantify hydrodynamic conditions...
May 20, 2017: Water Research
https://www.readbyqxmd.com/read/28651173/development-validation-and-clinical-application-of-a-method-for-the-simultaneous-quantification-of-lamivudine-emtricitabine-and-tenofovir-in-dried-blood-and-dried-breast-milk-spots-using-lc-ms-ms
#2
Catriona Waitt, Sujan Diliiy Penchala, Adeniyi Olagunju, Alieu Amara, Laura Else, Mohammed Lamorde, Saye Khoo
OBJECTIVES: To present the validation and clinical application of a LC-MS/MS method for the quantification of lamivudine (3TC), emtricitabine (FTC) and tenofovir (TFV) in dried blood spots (DBS) and dried breast milk spots (DBMS). METHODS: DBS and DBMS were prepared from 50 and 30μL of drug-spiked whole blood and human breast milk, respectively. Following extraction with acetonitrile and water, chromatographic separation utilised a Synergi polar column with a gradient mobile phase program consisting of 0...
June 17, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28651154/new-comprehensive-studies-of-a-gold-iii-dithiocarbamate-complex-with-proven-anticancer-properties-aqueous-dissolution-with-cyclodextrins-pharmacokinetics-and-upstream-inhibition-of-the-ubiquitin-proteasome-pathway
#3
Marianna F Tomasello, Chiara Nardon, Valeria Lanza, Giuseppe Di Natale, Nicolò Pettenuzzo, Stefano Salmaso, Danilo Milardi, Paolo Caliceti, Giuseppe Pappalardo, Dolores Fregona
The gold(III)-dithiocarbamate complex AuL12 (dibromo [ethyl-N-(dithiocarboxy-kS,kS')-N-methylglycinate] gold(III)), is endowed with promising in vitro/in vivo antitumor activity and toxicological profile. Here, we report our recent strategies to improve its water solubility and stability under physiological conditions along with our efforts for unravelling its tangled mechanism of action. We used three types of α-cyclodextrins (CDs), namely β-CD, Me-β-CD and HP-β-CD to prepare aqueous solutions of AuL12...
June 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28651144/improved-anticancer-effects-of-albumin-bound-paclitaxel-nanoparticle-via-augmentation-of-epr-effect-and-albumin-protein-interactions-using-s-nitrosated-human-serum-albumin-dimer
#4
Ryo Kinoshita, Yu Ishima, Victor T G Chuang, Hideaki Nakamura, Jun Fang, Hiroshi Watanabe, Taro Shimizu, Keiichiro Okuhira, Tatsuhiro Ishida, Hiroshi Maeda, Masaki Otagiri, Toru Maruyama
In the latest trend of anticancer chemotherapy research, there were many macromolecular anticancer drugs developed based on enhanced permeability and retention (EPR) effect, such as albumin bound paclitaxel nanoparticle (nab- PTX, also called Abraxane(®)). However, cancers with low vascular permeability posed a challenge for these EPR based therapeutic systems. Augmenting the intrinsic EPR effect with an intrinsic vascular modulator such as nitric oxide (NO) could be a promising strategy. S-nitrosated human serum albumin dimer (SNO-HSA Dimer) shown promising activity previously was evaluated for the synergistic effect when used as a pretreatment agent in nab-PTX therapy against various tumor models...
June 22, 2017: Biomaterials
https://www.readbyqxmd.com/read/28651105/heterogeneous-epigenetic-regulation-of-hace1-in-burkitt-lymphoma-derived-cells
#5
Abdelilah Bouzelfen, Hafid Kora, Marion Alcantara, Philippe Bertrand, Jean-Baptiste Latouche, Fabrice Jardin
We examined the consequences of 3-deazaneplanocin A (DZNep) on HACE1 expression in human Burkitt- Lymphoma-derived cells to investigate fundamental molecular mechanisms that control its expression. We treated the human Burkitt- Lymphoma-derived cells lines Ramos and Raji with DZNep and examined HACE1 mRNA expression by RT-PCR. We also studied the effect of DZNep on the methylation of lysine 9 and 27 of histone 3 (H3K27me3 and H3K9me2) associated with the CpG88 and CpG177 islands of the HACE1 promoters by chromatin immunoprecipitation and quantitative PCR...
June 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28651041/interaction-of-vivo-acac-2-with-human-serum-transferrin-and-albumin
#6
João Costa Pessoa, Isabel Correia, Ielyzaveta Chorna, Isabel Cavaco, Somnath Roy, Maxim L Kuznetsov, Nádia Ribeiro, Gonçalo Justino, Fernanda Marques, Teresa Santos Silva, Marino Santos, Hugo M Santos, José L Capelo, James Doutch
[VO(acac)2] is a remarkable vanadium compound and has potential as a therapeutic drug. It is important to clarify how it is transported in blood, but the reports addressing its binding to serum proteins have been contradictory. We use several spectroscopic and mass spectrometric techniques (ESI and MALDI-TOF), small-angle X-ray scattering and size exclusion chromatography (SEC) to characterize solutions containing [VO(acac)2] and either human serum apotransferrin (apoHTF) or albumin (HSA). DFT and modeling protein calculations are carried out to disclose the type of binding to apoHTF...
June 26, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28650901/application-of-quality-by-design-approach-to-bioanalysis-development-of-a-method-for-elvitegravir-quantification-in-human-plasma
#7
Sara Baldelli, Giorgio Marrubini, Dario Cattaneo, Emilio Clementi, Matteo Cerea
BACKGROUND: The application of Quality by Design (QbD) principles in clinical laboratories can help to develop an analytical method through a systematic approach, providing a significant advance over the traditional heuristic and empirical methodology. In the present work, we applied for the first time the QbD concept in the development of a method for drug quantification in human plasma using elvitegravir as the test molecule. METHODS: The goal of the study was to develop a fast and inexpensive quantification method, with precision and accuracy as requested by the EMA guidelines on bioanalytical method validation...
June 22, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28650900/a-high-throughput-hplc-ms-ms-assay-for-the-detection-quantification-and-simultaneous-structural-confirmation-of-136-drugs-and-metabolites-in-human-urine
#8
Jacek Klepacki, Baharak Davari, Marion Boulet, Ryan Lizarraga, Uwe Christians
BACKGROUND: Due to its superior sensitivity and specificity, multi-analyte high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) has become the gold standard in clinical toxicology. Although several qualitative and quantitative LC-MS/MS assays on various mass spectrometry platforms have been described in the literature, the majority of these methods either analyze only a limited number of compounds, and/or require tedious and time-consuming sample preparation...
June 22, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28650823/bi-level-and-bi-objective-p-median-type-problems-for-integrative-clustering-application-to-analysis-of-cancer-gene-expression-and-drug-response-data
#9
Anton V Ushakov, Xenia Klimentova, Igor Vasilyev
Recent advances in high-throughput technologies have given rise to collecting large amounts of multidimensional heterogeneous data that provide diverse information on the same biological samples. Integrative analysis of such multisource datasets may reveal new biological insights into complex biological mechanisms and therefore remains an important research field in systems biology. Most of the modern integrative clustering approaches rely on independent analysis of each dataset and consensus clustering, probabilistic or statistical modeling, while flexible distance-based integrative clustering techniques are sparsely covered...
October 27, 2016: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28650820/terahertz-channel-model-and-link-budget-analysis-for-intrabody-nanoscale-communication
#10
Hadeel Elayan, Raed M Shubair, Josep M Jornet, Pedram Johari
Nanosized devices operating inside the human body open up new prospects in the healthcare domain. In vivo wireless nanosensor networks (iWNSNs) will result in a plethora of applications ranging from intrabody health-monitoring to drug- delivery systems. With the development of miniature plasmonic signal sources, antennas and detectors, wireless communications among intrabody nanodevices will expectedly be enabled at both the Terahertz Band (0.1-10 THz) as well as optical frequencies (400-750 THz). This result motivates the analysis of the phenomena affecting the propagation of electromagnetic signals inside the human body...
June 22, 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28650707/a-review-of-radiation-countermeasures-focusing-on-injury-specific-medicinals-and-regulatory-approval-status-part-i-radiation-sub-syndromes-animal-models-and-fda-approved-countermeasures
#11
Vijay K Singh, Thomas M Seed
PURPOSE: The increasing global risk of nuclear and radiological accidents or attacks has driven renewed research interest in developing medical countermeasures to potentially injurious exposures to acute irradiation. Clinical symptoms and signs of a developing acute radiation injury, i.e. the acute radiation syndrome, are grouped into three sub-syndromes named after the dominant organ system affected, namely the hematopoietic, gastrointestinal, and neurovascular systems. The availability of safe and effective countermeasures against the above threats currently represents a significant unmet medical need...
June 26, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28650650/prodrugs-of-pyrazolo-3-4-d-pyrimidines-from-library-synthesis-to-evaluation-as-potential-anticancer-agents-in-an-orthotopic-glioblastoma-model
#12
Giulia Vignaroli, Giulia Iovenitti, Claudio Zamperini, Federica Coniglio, Pierpaolo Calandro, Alessio Molinari, Anna Lucia Fallacara, Andrea Sartucci, Alessia Calgani, David Colecchia, Andrea Mancini, Claudio Festuccia, Elena Dreassi, Massimo Valoti, Francesca Musumeci, Mario Chiariello, Adriano Angelucci, Maurizio Botta, Silvia Schenone
Pyrazolo[3,4-d]pyrimidines are potent protein kinase inhibitors with promising antitumor activity but suboptimal aqueous solubility, consequently worth to be further optimized. Herein, we present the one-pot two-step procedure for the synthesis of a set of pyrazolo[3,4-d]pyrimidine prodrugs (1a-9a,e) with higher aqueous solubility and enhanced pharmacokinetic and therapeutic properties. ADME studies demonstrated for the most promising prodrugs a better aqueous solubility, a favorable hydrolysis in human and murine serum and an increased ability to cross cell membranes with respect to the parental drugs, explaining their better 24h in vitro cytotoxicity against human glioblastoma U87 cell line...
June 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28650560/uncovering-the-role-of-brain-derived-neurotrophic-factor-bdnf-trkb-signaling-in-head-and-neck-malignancies
#13
REVIEW
Juliana Kern de Moraes, Vivian Petersen Wagner, Felipe Paiva Fonseca, Pablo Agustin Vargas, Caroline Brunetto de Farias, Rafael Roesler, Manoela Domingues Martins
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that was first known as responsible for sustain the growth, function and plasticity of neural cells. BDNF exerts its effects by binding to the tyrosine kinase receptor B (TrkB). The BDNF/TrkB axis has been reported to be overexpressed in several neurogenic and non-neurogenic tumors. Its higher expression was associated with a poor prognosis to patients affected by different human malignancies, tumor growth, invasion and metastasis; epithelial-mesenchymal transition (EMT) and resistance to chemotherapy...
June 26, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28650333/simultaneous-determination-of-ace-inhibitors-and-dexibuprofen-in-active-pharmaceutical-ingredient-formulations-and-human-serum-by-rp-hplc
#14
Aisha Sana, Safila Naveed, Fatima Qamar, Sadia Shakeel
The contemporary work describes a rapid and cost effective reversed phase High Performance Liquid Chromatography (RP-HPLC) method for the quantification of Captopril, Lisinopril and Dexibuprofen (DXP) simultaneously in dosage formulations, active pharmaceutical ingredients and human serum. The chromatographic system included LC-20A pump, Sil-20A auto sampler and SPD-20A UV/visible detector. The estimation was carried out by using a C18 (5μm, 250 ×4.6 mm) column with mobile phase methanol: water (80:20 v/v, pH 3...
March 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28650325/evaluation-of-three-plant-extracts-against-biofilm-formation-and-expression-of-quorum-sensing-regulated-virulence-factors-in-pseudomonas-aeruginosa
#15
Vajihe Karbasizade, Parichehr Dehghan, Maryam Mohammadi Sichani, Kahin Shahanipoor, Reyhaneh Jafari, Rozita Yousefian
Following the increasing antibiotic resistance of pathogenic bacteria, the use of medicinal herbs as antibacterial agents has attracted growing attention. Pseudomonas aeruginosa is a human opportunistic pathogen that uses quorum sensing for regulating virulence gene expression (pyocyanin, protease, and elastase production and biofilm formation). This study examined the anti-quorum sensing activity of Quercus infectoria, Zataria multiflora and Trachyspermum copticum extracts on standard P. aeruginosa strain...
March 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28650313/molecular-mechanisms-and-epidemiology-of-resistance-in-streptococcus-pneumoniae-in-the-middle-east-region
#16
Grace El Moujaber, Marwan Osman, Rayane Rafei, Fouad Dabboussi, Monzer Hamze
PURPOSE: Streptococcus pneumoniae is a commensal bacterium that normally colonizes the human nasopharyngeal cavity. Once disseminated, it can cause several diseases, ranging from non-invasive infections such as acute otitis media and sinusitis through to invasive infections with higher mortality, including meningitis and septicaemia. Since the identification of the first S. pneumoniae strain with decreased susceptibility to penicillin in the 1960s, antibiotic resistance among S. pneumoniae has increased disturbingly and the mechanisms of resistance have begun to unfold...
June 26, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28650029/nanoparticle-encapsulated-baicalein-markedly-modulates-pro-inflammatory-response-in-gingival-epithelial-cells
#17
Xuan Li, Wei Luo, Tsz Wing Ng, Ping Chung Leung, Chengfei Zhang, Ken Cham-Fai Leung, Lijian Jin
Severe gum disease (periodontitis), which is one of the major global oral diseases, results from microbe-host dysbiosis and dysregulated immuno-inflammatory responses. It seriously affects oral health and general wellbeing with significant socio-economic implications. It has been well documented that natural flavonoids such as baicalin (BA) and baicalein (BE) possess potent anti-inflammatory effects. However, their intrinsic poor solubility and low bioavailability severely limit their biomedical applications...
June 26, 2017: Nanoscale
https://www.readbyqxmd.com/read/28650001/brodalumab-the-first-anti-il-17-receptor-agent-for-psoriasis
#18
L Puig
Psoriasis is a chronic immune-mediated inflammatory skin disease in which the alteration of the interleukin-23 (IL-23)/IL-17 cytokine axis appears to be crucial from a pathogenetic perspective. This has been confirmed by the efficacy of monoclonal antibodies blocking IL-17A, such as secukinumab and ixekizumab. Brodalumab is a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody that inhibits the biological activity of IL-17A, IL-17F and other IL-17 isoforms, and has been approved (210 mg s.c. at weeks 0, 1, 2 and every 2 weeks thereafter) for the treatment of psoriasis vulgaris, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma in Japan (Lumicef)...
May 2017: Drugs of Today
https://www.readbyqxmd.com/read/28650000/andexanet-alfa-a-recombinant-mimetic-of-human-factor-xa-for-the-reversal-of-anticoagulant-therapies
#19
G Escolar, M Diaz-Ricart, E Arellano-Rodrigo
Activated coagulation factor X (FXa) is a common target for classic and newer anticoagulants. Parenteral anticoagulants with an indirect inhibitory action on FXa (low-molecular-weight heparins) have a well-established clinical efficacy in the prophylaxis and therapy of thromboembolic conditions. More recently developed direct oral anticoagulants (DOACs) have emerged as a new class of antithrombotic drugs. Rivaroxaban, apixaban and edoxaban are direct inhibitors of FXa approved for the management of venous thromboembolism and stroke prevention in atrial fibrillation...
May 2017: Drugs of Today
https://www.readbyqxmd.com/read/28649895/the-safety-and-efficacy-of-palbociclib-in-the-treatment-of-metastatic-breast-cancer
#20
Johannes Ettl, Nadia Harbeck
Palbociclib (Ibrance(®)) is the first-in-class CDK4/6 inhibitor which has been introduced into clinical practice for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). It is an orally administered drug, which acts by selectively inhibiting cyclin-dependant kinases CDK4 and CDK6. Given together with anti-estrogens like letrozole and fulvestrant it enhances the antiproliferative effect of these drugs without compromising the favorable toxicity profile of endocrine therapy...
June 26, 2017: Expert Review of Anticancer Therapy
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