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https://www.readbyqxmd.com/read/27922183/the-significance-of-sampling-time-in-therapeutic-drug-monitoring-of-clozapine
#1
M I Jakobsen, J R Larsen, C K Svensson, S S Johansen, K Linnet, J Nielsen, A Fink-Jensen
OBJECTIVE: Therapeutic drug monitoring (TDM) of clozapine is standardized to 12-h postdose samplings. In clinical settings, sampling time often deviates from this time point, although the importance of the deviation is unknown. To this end, serum concentrations (s-) of clozapine and its metabolite N-desmethyl-clozapine (norclozapine) were measured at 12 ± 1 and 2 h postdose. METHOD: Forty-six patients with a diagnosis of schizophrenia, and on stable clozapine treatment, were enrolled for hourly, venous blood sampling at 10-14 h postdose...
December 6, 2016: Acta Psychiatrica Scandinavica
https://www.readbyqxmd.com/read/27922065/detc-based-bacterial-cellulose-bio-curatives-for-topical-treatment-of-cutaneous-leishmaniasis
#2
Fabiana S Celes, Eliane Trovatti, Ricardo Khouri, Johan Van Weyenbergh, Sidney J L Ribeiro, Valeria M Borges, Hernane S Barud, Camila I de Oliveira
The treatment of leishmaniasis still relies on drugs with potentially serious adverse effects. Herein, we tested a topical formulation of bacterial cellulose (BC) membranes containing Diethyldithiocarbamate (DETC), a superoxide dismutase 1 inhibitor. Leishmania-infected macrophages exposed to BC-DETC resulted in parasite killing, without pronounced toxic effects to host cells. This outcome was associated with lower SOD1 activity and higher production of superoxide and cytokine mediators. Topical application of BC-DETC significantly decreased lesion size, parasite load and the inflammatory response at the infection site, as well as the production of both IFN-γ and TNF...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922010/mek-inhibitors-block-growth-of-lung-tumours-with-mutations-in-ataxia-telangiectasia-mutated
#3
Michal Smida, Ferran Fece de la Cruz, Claudia Kerzendorfer, Iris Z Uras, Barbara Mair, Abdelghani Mazouzi, Tereza Suchankova, Tomasz Konopka, Amanda M Katz, Keren Paz, Katalin Nagy-Bojarszky, Markus K Muellner, Zsuzsanna Bago-Horvath, Eric B Haura, Joanna I Loizou, Sebastian M B Nijman
Lung cancer is the leading cause of cancer deaths, and effective treatments are urgently needed. Loss-of-function mutations in the DNA damage response kinase ATM are common in lung adenocarcinoma but directly targeting these with drugs remains challenging. Here we report that ATM loss-of-function is synthetic lethal with drugs inhibiting the central growth factor kinases MEK1/2, including the FDA-approved drug trametinib. Lung cancer cells resistant to MEK inhibition become highly sensitive upon loss of ATM both in vitro and in vivo...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27922003/blood-flow-controls-bone-vascular-function-and-osteogenesis
#4
Saravana K Ramasamy, Anjali P Kusumbe, Maria Schiller, Dagmar Zeuschner, M Gabriele Bixel, Carlo Milia, Jaba Gamrekelashvili, Anne Limbourg, Alexander Medvinsky, Massimo M Santoro, Florian P Limbourg, Ralf H Adams
While blood vessels play important roles in bone homeostasis and repair, fundamental aspects of vascular function in the skeletal system remain poorly understood. Here we show that the long bone vasculature generates a peculiar flow pattern, which is important for proper angiogenesis. Intravital imaging reveals that vessel growth in murine long bone involves the extension and anastomotic fusion of endothelial buds. Impaired blood flow leads to defective angiogenesis and osteogenesis, and downregulation of Notch signalling in endothelial cells...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27922002/targeting-the-notch-regulated-non-coding-rna-tug1-for-glioma-treatment
#5
Keisuke Katsushima, Atsushi Natsume, Fumiharu Ohka, Keiko Shinjo, Akira Hatanaka, Norihisa Ichimura, Shinya Sato, Satoru Takahashi, Hiroshi Kimura, Yasushi Totoki, Tatsuhiro Shibata, Mitsuru Naito, Hyun Jin Kim, Kanjiro Miyata, Kazunori Kataoka, Yutaka Kondo
Targeting self-renewal is an important goal in cancer therapy and recent studies have focused on Notch signalling in the maintenance of stemness of glioma stem cells (GSCs). Understanding cancer-specific Notch regulation would improve specificity of targeting this pathway. In this study, we find that Notch1 activation in GSCs specifically induces expression of the lncRNA, TUG1. TUG1 coordinately promotes self-renewal by sponging miR-145 in the cytoplasm and recruiting polycomb to repress differentiation genes by locus-specific methylation of histone H3K27 via YY1-binding activity in the nucleus...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27921633/healthcare-resources-are-inadequate-to-address-the-burden-of-illness-among-hiv-infected-male-prisoners-in-malaysia
#6
Joseph Bick, Gabriel Culbert, Haider A Al-Darraji, Clayton Koh, Veena Pillai, Adeeba Kamarulzaman, Frederick Altice
Purpose Criminalization of drug use in Malaysia has concentrated people who inject drugs (PWID) and people living with HIV into prisons where health services are minimal and HIV-related mortality is high. Few studies have comprehensively assessed the complex health needs of this population. The paper aims to discuss these issues. Design/methodology/approach From October 2012 through March 2013, 221 sequentially selected HIV-infected male prisoners underwent a comprehensive health assessment that included a structured history, physical examination, and clinically indicated diagnostic studies...
December 19, 2016: International Journal of Prisoner Health
https://www.readbyqxmd.com/read/27921442/nebulized-antibiotics-in-mechanically-ventilated-patients-roadmap-and-challenges
#7
G Poulakou, G Siakallis, S Tsiodras, A Arfaras Melainis, G Dimopoulos
Nebulized antibiotics use has become common practice in the therapeutics of pneumonia in cystic fibrosis patients. There is an increasing interest in their use for respiratory infections in mechanically ventilated (MV) patients in order to a) overcome pharmacokinetic issues in the lung compartment with traditional systemic antibiotic use and b) prevent the emergence of multi-drug-resistant (MDR) pathogens. Areas covered: The beneficial effects of antibiotic nebulization in MV patients e.g. increasing efficacy, reduced toxicity and prevention of resistance are described...
December 6, 2016: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/27921436/-diabetes-mellitus-in-older-adults-from-the-point-of-view-of-the-clinical-diabetologist
#8
Alena Šmahelová
Disorders of glucose homeostasis affect quite a large part of the older population and their incidence including manifest diabetes is growing. Diabetes in older adults is associated with an increased risk of geriatric syndrome expressed in various ways (decrease in muscle size, functional disability, frailty) and early mortality. Diabetes care for the elderly requires, also in view of heterogeneity of diabetes itself, an individual specific approach. This involves not only diagnostics and a clinical picture, but also the treatment goals and the therapy of diabetes and complications in itself...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27921432/-composition-of-macronutrients-in-the-diabetic-diet
#9
Zdeněk Rušavý, Michal Žourek
The diabetic diet is one of the pillars of diabetes treatment. The rapid development of knowledge relating to the treatment of diabetes also includes diet. The paper focuses on the importance of a diet in the treatment of type 2 diabetes and prevention of atherosclerosis. Its main goal is to assess the impact of a composition of macronutrients on individuals with type 2 diabetes. The paper is divided into several parts, each of which ends with a conclusion. The first part examines weight reduction. The diet aimed at a weight loss is effective, it can effectively prevent diabetes, it leads to improvements in glucose control and reduction of the risk factors for atherosclerosis, however it will not impact on cardiovascular morbidity and mortality until after more than 20 years...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27921428/-promising-molecules-for-treatment-of-hyperglycemia-in-patients-with-type-2-diabetes
#10
Milan Kvapil
New antidiabetic drugs are being developed today that expand the range of pharmacological intervention, in particular for patients with type 2 diabetes (imeglimin, semaglutide, dulaglutide, FGF 21 analogue). At the same time innovations take place that "better" the well-proven molecules, they offer new application forms we have no experience of diabetology (osmotic pump for exenatide, faster acting insulin aspart). New properties are brought by just the change of concentration (insulin glargine in a concentration of 300 U/ml), unexpected positive results are also brought by new fixed-ratio combinations of antidiabetics (fixed-ratio combination of insulin degludec and liraglutide, fixed-ratio combination of insulin glargine and lixisenatide)...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27921426/-gestational-diabetes-mellitus
#11
Hana Krejčí
The present generation of women of childbearing age more frequently suffer from overweight, obesity, initial as well as fully established metabolic syndrome, which together with postponing motherhood until the third decade in life plays an important role in the increasing incidence of gestational diabetes (GDM) that currently affects about 1/5 of pregnant women. However the causal link between diabetes during pregnancy and metabolic diseases in the whole population is mutual. By way of epigenetic changes, maternal diabetes unfavourably programmes metabolism of the offspring, who tend to transfer the disorder to the next generations...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27921393/the-role-of-the-microvascular-network-structure-on-diffusion-and-consumption-of-anti-cancer-drugs
#12
P Mascheroni, R Penta
We investigate the impact of microvascular geometry on the transport of drugs in solid tumors, focusing on the diffusion and consumption phenomena. We embrace recent advances in the asymptotic homogenization literature starting from a double Darcy, double advection-diffusion-reaction system of partial differential equations that is obtained exploiting the sharp length separation between the intercapillary distance and the average tumor size. The geometric information on the microvascular network is encoded into effective hydraulic conductivities and diffusivities, which are numerically computed by solving periodic cell problems on appropriate microscale representative cells...
December 6, 2016: International Journal for Numerical Methods in Biomedical Engineering
https://www.readbyqxmd.com/read/27921382/core-shell-silk-hydrogels-with-spatially-tuned-conformations-as-drug-delivery-system
#13
Le-Ping Yan, Joaquim M Oliveira, Ana L Oliveira, Rui L Reis
Hydrogels of spatially controlled physicochemical properties are appealing platforms for tissue engineering and drug delivery. In this study, core-shell silk fibroin (SF) hydrogels of spatially controlled conformation were developed. The core-shell structure in the hydrogels was formed by means of soaking the preformed (enzymatically crosslinked) random coil SF hydrogels in methanol. When increasing the methanol treatment time from 1 to 10 min, the thickness of the shell layer can be tuned from about 200 to about 850 μm as measured in wet status...
December 5, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27921344/uhplc-ms-based-hdac-assay-applied-to-bio-guided-microfractionation-of-fungal-extracts
#14
Vincent Zwick, Pierre-Marie Allard, Lucie Ory, Claudia A Simões-Pires, Laurence Marcourt, Katia Gindro, Jean-Luc Wolfender, Muriel Cuendet
INTRODUCTION: Histone deacetylases (HDAC) are considered as promising targets for cancer treatment. Today, four HDAC inhibitors, vorinostat, romidepsin, belinostat, and panobinostat, have been approved by the Food and Drug Administration (FDA) for cancer treatment, while others are in clinical trials. Among them, several are naturally occurring fungal metabolites. OBJECTIVE: To develop and optimise an enzyme assay for bio-guided identification of HDAC inhibitors in fungal strains...
December 5, 2016: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/27921324/statins-and-mortality-the-untold-story
#15
Michael S Kostapanos, Moses S Elisaf
Statins are first-line evidence-based drugs for the management of dyslipidaemias and to reduce the risk of cardiovascular events. However, statin clinical trials have shown marginally significant benefits on mortality, especially in the primary prevention setting. A major limitation of those trials is their relatively short follow-up. A reduced number of fatal events within a 5-year follow-up make mortality benefits unlikely to arise. This is particularly relevant for the primary prevention trials, whereby the risk of cardiovascular death is low...
December 6, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27921196/danshen-injection-as-adjuvant-treatment-for-unstable-angina-pectoris-a-systematic-review-and-meta-analysis
#16
Jia-Rui Wu, Shi Liu, Xiao-Meng Zhang, Bing Zhang
OBJECTIVE: To systematically evaluate the clinical effectiveness and safety of Danshen Injection (, DS) as one adjuvant treatment for conventional therapy with Western medicine (WM) for unstable angina pectoris (UAP). METHODS: Using literature databases, a thorough and systematic retrieval of randomized controlled trials (RCTs) comparing DS plus WM with WM was conducted from inception to April 2015. The extracted data from included studies was analyzed by Review Manager 5...
December 5, 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/27921039/clinical-manifestation-and-management-of-adpkd-in-western-countries
#17
REVIEW
Claudia Sommerer, Martin Zeier
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease in Western countries. The prevalence is between 2.4/10,000 and 3.9/10,000. ADPKD represents a systemic disease resulting in deterioration in renal function. Until now, mutations in two genes (PKD1 and PKD2) have been identified. Recently, the European Medicines Agency (EMA) approved the use of the vasopressin V2 receptor antagonist tolvaptan to slow the progression of cyst development and renal insufficiency connected with ADPKD in adult patients with chronic kidney disease stages 1-3 at initiation of treatment with evidence of rapidly progressing disease...
October 2016: Kidney Diseases
https://www.readbyqxmd.com/read/27921038/the-clinical-manifestation-and-management-of-autosomal-dominant-polycystic-kidney-disease-in-china
#18
REVIEW
Cheng Xue, Chen-Chen Zhou, Ming Wu, Chang-Lin Mei
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic hereditary kidney disease characterized by progressive enlargement of renal cysts. The incidence is 1-2‰ worldwide. Mutations in two genes (PKD1 and PKD2) cause ADPKD. Currently, there is no pharmaceutical treatment available for ADPKD patients in China. Summary: This review focused on advances in clinical manifestation, gene diagnosis, risk factors, and management of ADPKD in China. There is an age-dependent increase in total kidney volume (TKV) and decrease in renal function in Chinese ADPKD patients...
October 2016: Kidney Diseases
https://www.readbyqxmd.com/read/27921022/the-protective-effect-of-hydro-alcoholic-extract-of-mangrove-avicennia-marina-l-leaves-on-kidney-injury-induced-by-carbon-tetrachloride-in-male-rats
#19
Naser Mirazi, Seyedeh-Nahid Movassagh, Mahmoud Rafieian-Kopaei
BACKGROUND: Materials can cause liver and kidney damage which carbon tetrachloride is one of these substances. Medicinal plants and their essential oils and extracts have been used to a large extent as drugs to better control and management of kidney diseases. OBJECTIVES: The aim of this study was to investigate the effect of hydro-alcoholic extract of Avicennia marina leaves in the treatment of renal toxicity induced by carbon tetrachloride. METHODS: Forty-two male rats were randomly divided into 6 groups (n = 7): control (taking normal saline, 0...
October 2016: Journal of Nephropathology
https://www.readbyqxmd.com/read/27921007/long-term-response-to-nivolumab-and-acute-renal-failure-in-a-patient-with-metastatic-papillary-renal-cell-carcinoma-and-a-pd-l1-tumor-expression-increased-with-sunitinib-therapy-a-case-report
#20
Juan Ruiz-Bañobre, Urbano Anido, Ihab Abdulkader, José Antúnez-López, Rafael López-López, Jorge García-González
INTRODUCTION: Papillary renal cell carcinoma (PRCC), which represents around 20% of renal cell carcinomas, is a heterogeneous disease that includes different tumor types with several clinical and molecular phenotypes. Nivolumab, a fully human IgG4 programed cell death protein 1 immune checkpoint inhibitor antibody, has shown not only an overall survival advantage when compared to everolimus but also a relatively good side-effect profile among patients with previously treated advanced or metastatic renal cell carcinoma...
2016: Frontiers in Oncology
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