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https://www.readbyqxmd.com/read/29458233/pharmacokinetic-modelling-to-predict-fviii-c-response-to-desmopressin-and-its-reproducibility-in-nonsevere-haemophilia-a-patients
#1
L M Schütte, R M van Hest, S C M Stoof, F W G Leebeek, M H Cnossen, M J H A Kruip, R A A Mathôt
BACKGROUND: Nonsevere haemophilia A (HA) patients can be treated with desmopressin. Response of factor VIII activity (FVIII:C) differs between patients and is difficult to predict. OBJECTIVES: Our aims were to describe FVIII:C response after desmopressin and its reproducibility by population pharmacokinetic (PK) modelling. PATIENTS AND METHODS: Retrospective data of 128 nonsevere HA patients (age 7-75 years) receiving an intravenous or intranasal dose of desmopressin were used...
February 19, 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29458210/preparation-of-a-solid-self-microemulsifying-drug-delivery-system-by-hot-melt-extrusion
#2
Luis Antonio D Silva, Susana L Almeida, Ellen C P Alonso, Priscila B R Rocha, Felipe T Martins, Luís A P Freitas, Stephania F Taveira, Marcilio S S Cunha-Filho, Ricardo N Marreto
Hot-melt extrusion (HME) has gained increasing attention in the pharmaceutical industry; however, its potential in the preparation of solid self-emulsifying drug delivery systems (S-SMEDDS) is still unexplored. This study sought to prepare enteric S-SMEDDS by HME and evaluate the effects of the process and formulation variables on S-SMEDDS properties via Box-Behnken design. Liquid SMEDDS were developed, and carvedilol was used as a class II model drug. Mean size, polydispersity index (PdI) and zeta potential of the resulting microemulsions were determined...
February 16, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29458207/co-spray-drying-of-hygroscopic-kanamycin-with-the-hydrophobic-drug-rifampicin-to-improve-the-aerosolization-of-kanamycin-powder-for-treating-respiratory-infections
#3
Mohammad A M Momin, Ian G Tucker, Colin S Doyle, John A Denman, Shubhra Sinha, Shyamal C Das
High dose delivery of drugs to the lung using a dry powder inhaler (DPI) is an emerging approach to combat drug-resistant local infections. To achieve this, highly aerosolizable powders are required. We hypothesized that co-spray-drying kanamycin, a hydrophilic hygroscopic antibiotic, with rifampicin, a hydrophobic antibiotic, would produce inhalable particles with surfaces enriched in rifampicin. Such particles would have higher aerosolization than kanamycin alone, and minimise the mass of powder for inhalation avoiding use of non-active excipients...
February 16, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29458166/statistical-approach-for-selection-of-biologically-informative-genes
#4
Samarendra Das, Anil Rai, D C Mishra, S N Rai
Selection of informative genes from high dimensional gene expression data has emerged as an important research area in genomics. Many gene selection techniques have been proposed so far are either based on relevancy or redundancy measure. Further, the performance of these techniques has been adjudged through post selection classification accuracy computed through a classifier using the selected genes. This performance metric may be statistically sound but may not be biologically relevant. A statistical approach, i...
February 16, 2018: Gene
https://www.readbyqxmd.com/read/29458161/multiple-mycotoxin-analysis-in-nut-products-occurrence-and-risk-characterization
#5
Sara C Cunha, S Sá, José O Fernandes
Nuts consumption plays an important role in Mediterranean diet, being a good source of proteins, vitamins, minerals and unsaturated fatty acids. However, nuts can be also a source of harmful mycotoxins with negative impact on human health. In this work, the occurrence of 16 mycotoxins belonging to different chemical classes, was assessed in several nut products. The analytical method used was based on modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) procedure followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis...
February 16, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29458127/calmodulin-induced-conformational-control-and-allostery-underlying-neuronal-nitric-oxide-synthase-activation
#6
Quinlin M Hanson, Jeffrey R Carley, Tyler J Gilbreath, Brian C Smith, Eric S Underbakke
Nitric oxide synthase (NOS) is the primary generator of nitric oxide signals controlling diverse physiological processes such as neurotransmission and vasodilation. NOS activation is contingent on Ca2+ /calmodulin binding at a linker between its oxygenase and reductase domains to induce large conformational changes that orchestrate inter-domain electron transfer. However, the structural dynamics underlying activation of full-length NOS remain ambiguous. Employing hydrogen-deuterium exchange mass spectrometry, we reveal mechanisms underlying neuronal NOS (nNOS) activation by calmodulin and regulation by phosphorylation...
February 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29458126/structural-and-mechanistic-analysis-of-the-choline-sulfatase-from-sinorhizobium-melliloti-a-class-i-sulfatase-specific-for-an-alkyl-sulfate-ester
#7
Bert van Loo, Markus Schober, Eugene Valkov, Magdalena Heberlein, Erich Bornberg-Bauer, Kurt Faber, Marko Hyvönen, Florian Hollfelder
Hydrolysis of organic sulfate esters proceeds by two distinct mechanisms, water attacking at either sulfur (S-O bond cleavage) or carbon (C-O bond cleavage). In primary and secondary alkyl sulfates attack at carbon is favored, whereas in aromatic sulfates and sulfated sugars attack at sulfur is preferred. This mechanistic distinction is mirrored in the classification of enzymes that catalyze sulfate ester hydrolysis: arylsulfatases catalyze S-O cleavage in sulfate sugars and arylsulfates and alkyl sulfatases break the C-O bond of alkyl sulfates...
February 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29458118/neuroprotective-effect-of-melatonin-against-lipopolysaccharide-induced-depressive-like-behavior-in-mice
#8
E H Taniguti, Y S Ferreira, I J V Stupp, E B Fraga-Junior, C B Mendonça, F L Rossi, H N Ynoue, D L Doneda, L Lopes, E Lima, Z S Buss, S Vandresen-Filho
Accumulating evidence indicates an interaction between inflammation and depression since increased levels of pro-inflammatory cytokines are associated with depression-related symptoms. Melatonin is a hormone synthesized and secreted by the pineal gland with antioxidant, anti-inflammatory and antidepressant-like effects. In this way, it would be interesting to evaluate the putative antidepressant-like effect of melatonin treatment in an acute inflammation mice model of depression. The present study aimed to investigate the effect of melatonin treatment on lipopolysaccharide (LPS) induced depressive-like behavior, neuroinflammation, oxidative stress and alteration on brain-derived neurotrophic fator (BDNF) levels...
February 16, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29458106/combi-metal-organic-framework-combi-mof-of-%C3%AE-amylase-and-glucoamylase-for-one-pot-starch-hydrolysis
#9
Manish Salgaonkar, Shamraja S Nadar, Virendra K Rathod
The multi-enzyme biocatalyst allows to run in vitro multi-step cascade reactions in a single pot. An efficient combi-metal organic frameworks (combi-MOF) of α-amylase and glucoamylase for one pot starch hydrolysis was constructed by mixing zinc acetate and 2‑methylimmidazole with enzyme mixture in one pot under biocompatible conditions. The prepared combi-MOF was characterized and analyzed by powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM)...
February 16, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29458104/a-new-l-glutaminase-from-streptomyces-pratensis-nrc-10-gene-identification-enzyme-purification-and-characterization
#10
Sanaa E Tork, Magda M Aly, Omar Elsemin
In the current study, the purified l-glutaminase from Streptomyces pratensis NRC10 (GenBank number KC857622) was characterized. Its molecular weight was estimated to be 46 kDa and isoelectric point 7.4. Its Vmax was calculated to be 2.19 U/mg/min, while Km was 0.175 mM. The optimum pH and temperature were 9 and 45 °C, respectively. It was thermostable at 45 °C but thermally inactivated at 60 °C after 50 min. Moreover, its enzymatic activity was enhanced by K+ ions and inhibited by Mg2+ , Cu2+ , Ag+ , Hg2+ , Ni2+ , Fe2+ , Cr2 , Na+ , Ca2+ , and EDTA...
February 16, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29458072/influence-of-xenorhabdus-gamma-proteobacteria-enterobacteriaceae-symbionts-on-gonad-postembryonic-development-in-steinernema-nematoda-steinernematidae-nematodes
#11
Alexandra C Roder, S Patricia Stock
Steinernema nematodes and their Xenorhabdus partners form an obligate mutualistic association. This partnership is insecticidal to a wide range of insects. Steinernema rely on their Xenorhabdus partner to produce toxins inside the insect cadaver to liberate nutrients from the insect, as well as antimicrobials to sterilize the cadaver, thus creating a suitable environment for reproduction. In return, Steinernema vector their Xenorhabdus between insect hosts. Disruption of this partnership may affect the success of both partners...
February 16, 2018: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/29458066/volitional-voiding-of-the-bladder-following-spinal-cord-injury-validation-of-bilateral-lower-extremity-motor-function-as-a-key-predictor
#12
Christopher S Elliott, Kai B Dallas, Dimitar Zlatev, Craig V Comiter, James Crew, Kazuko Shem
INTRODUCTION: For many with spinal cord injury (SCI), a return of volitional bladder voiding is considered more important than regaining motor function. Recently a predictive model using only composite bilateral lower extremity motor (LEM) scores for levels L2-S1 (range 0-50) was put forth by the European Multicenter Spinal Cord Injury (EMSCI) study group that showed exceptional predictive power with an area under the curve (AUC) of 0.912. We sought to further validate the EMSCI model using a national SCI cohort...
February 16, 2018: Journal of Urology
https://www.readbyqxmd.com/read/29458038/diagnosing-distensible-venous-malformations-of-the-orbit-with-diffusion-weighted-magnetic-resonance-imaging
#13
Evan Kalin-Hajdu, John B Colby, Oluwatobi Idowu, F Lawson Grumbine, Jessica M Kang, Kristin S Hirabayashi, Christine M Glastonbury, M Reza Vagefi, Robert C Kersten
PURPOSE: To compare the diffusion-weighted imaging characteristics of non-thrombosed distensible venous malformations of the orbit with that of other histologically-proven orbital tumors. DESIGN: Retrospective case-control study. METHODS: Patients with non-thrombosed distensible venous malformations of the orbit and patients with other histologically-proven orbital tumors were selected for chart review. The main outcome measure was the apparent diffusion coefficient of these lesions...
February 16, 2018: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/29458023/structural-characterization-of-the-hcov-229e-fusion-core
#14
Wei Zhang, Qianqian Zheng, Mengrong Yan, Xiaobo Chen, Haitao Yang, Weihong Zhou, Zihe Rao
HCoV-229E spike (S) protein mediates virion attachment to cells and subsequent fusion of the viral and cellular membranes. This protein is composed of an N-terminal receptor-binding domain (S1) and a C-terminal trans-membrane fusion domain (S2). S2 contains a highly conserved heptad repeat 1 and 2 (HR1 and HR2). In this study, the HRs sequences were designed and connected with a flexible linker. The recombinant fusion core protein was crystallized and its structure was solved at a resolution of 2.45 Å. Then we characterized the binding of HR1s and HR2s via both sequence alignment and structural analysis...
February 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29457996/the-tyg-index-cutoff-point-and-its-association-with-body-adiposity-and-lifestyle-in-children
#15
Sarah A Vieira Ribeiro, Poliana C A Fonseca, Cristiana S Andreoli, Andréia Q Ribeiro, Helen H M Hermsdorff, Patrícia F Pereira, Silvia E Priore, Sylvia C C Franceschini
OBJECTIVE: To investigate the factors associated with insulin resistance in children aged 4-7 years, and to identify the cutoff point of the triglyceride-glucose index for the prediction of IR in this population. METHODS: A cross-sectional study was conducted with 403 children from a retrospective cohort. Insulin resistance was also evaluated in a sub-sample using the HOMA index. Four indicators of body adiposity were assessed: body mass index, waist-to-height ratio, and the percentages of total and central body fat...
February 16, 2018: Jornal de Pediatria
https://www.readbyqxmd.com/read/29457995/validation-of-a-brazilian-portuguese-version-of-the-transition-readiness-assessment-questionnaire-traq-in-a-population-of-transitional-youth-with-chronic-rheumatologic-disorders
#16
Catherine G Anelli, Claudio A Len, Maria T Terreri, Gleice C S Russo, Andreas O Reiff
OBJECTIVE: To translate and validate the Brazilian Portuguese version of the Transition Readiness Assessment Questionnaire in a population of adolescents and young adults with chronic rheumatologic disorders. This questionnaire evaluates the patient's readiness for making the transition from the pediatric health service to adult care. METHODS: The four-phase methodology for the translation and validation of generic questionnaires was followed, including translation, back-translation, pilot testing and clinical validation of the final tool...
February 16, 2018: Jornal de Pediatria
https://www.readbyqxmd.com/read/29457991/protection-of-sheep-by-vaccination-against-experimental-challenge-with-leptospira-borgpetersenii-serovar-hardjo-and-l-interrogans-serovar-pomona
#17
W J Clough, P R Little, A Hodge, V C Chapman, D K Holz
AIMS: To evaluate a multivalent leptospiral and clostridial vaccine for prevention of renal colonisation and urinary shedding in sheep, following experimental challenge with New Zealand strains of Leptospira borgpetersenii serovar Hardjo type Hardjobovis and Leptospira interrogans serovar Pomona. METHODS: Two separate but similarly designed studies were conducted. In both studies, Romney cross lambs, aged 9-11 weeks, were randomly allocated to a vaccinated group and a control group...
February 19, 2018: New Zealand Veterinary Journal
https://www.readbyqxmd.com/read/29457892/boronic-acid-catalyzed-regio-and-1-2-cis-stereoselective-glycosylation-of-unprotected-sugar-acceptors-via-s-n-i-type-mechanism
#18
Masamichi Tanaka, Akira Nakagawa, Nobuya Nishi, Kiyoko Iijima, Ryuichi Sawa, Daisuke Takahashi, Kazunobu Toshima
Regio- and 1,2-cis-stereoselective chemical glycosylation of unprotected glycosyl acceptors has been in great demand for the efficient synthesis of natural glycosides. However, simultaneously regulating these selectivities has been a long-standing problem in synthetic organic chemistry. In nature, glycosyl transferases catalyze regioselective 1,2-cis-glycosylations via the SN i mechanism, yet no useful chemical glycosylations based on this mechanism have been developed. In this paper, we report a highly regio- and 1,2-cis-stereoselective SN i-type glycosylation of 1,2-anhydro donors and unprotected sugar acceptors using p-nitrophenylboronic acid (10e) as a catalyst in the presence of water under mild conditions...
February 19, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29457866/epigenetic-effects-of-metformin-from-molecular-mechanisms-to-clinical-implications
#19
REVIEW
S C Bridgeman, G C Ellison, P E Melton, P Newsholme, Cds Mamotte
There is a growing body of evidence that links epigenetic modifications to type 2 diabetes. Researchers have more recently investigated effects of commonly used medications, including those prescribed for diabetes, on epigenetic processes. This work reviews the influence of the widely used antidiabetic drug metformin on epigenomics, microRNA levels and subsequent gene expression and potential clinical implications. Metformin may influence the activity of numerous epigenetic modifying enzymes, mostly via modulating the activation of AMP-activated protein kinase (AMPK)...
February 19, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29457841/erectile-dysfunction-they-don-t-talk-we-don-t-ask
#20
A Rakovac Tisdall, T F J King, W A W Mahmood, C S Keat, R Ali, R Abdin, C M Koo, M Alali, S Sreenan, J H McDermott
Erectile dysfunction is an under-reported complication of diabetes mellitus affecting over half of male patients [1]. Although many men with diabetes consider that erectile dysfunction has a negative influence on their quality of life, they are reluctant to report it; and while most would like treatment, they prefer physicians to start the conversation [2-4]. Erectile dysfunction predicts future cardiovascular disease, and screening for erectile dysfunction is advocated in several cardiovascular risk assessment algorithms [5]...
February 19, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
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