bluuebunny/crossref_metadata_2025_split huggingface dataset:
HTLV‐1 positive and negative T cells cloned from infected individuals display telomerase and telomere genes deregulation that predominate in activated but untransformed CD4+ T cells
Authors: Zane Linda , Sibon David , Capraro Valérie , Galia Perrine , Karam Maroun , Delfau‐Larue Marie‐Hélène , Gilson Eric , Gessain Antoine , Gout Olivier , Hermine Olivier , Mortreux Franck , Wattel Eric 
Published: June 2011

AbstractUntransformed HTLV‐1 positive CD4+ cells from infected individuals are selected for expressing tax and displaying morphological features consistent with telomere dysfunctions. We show that in resting HTLV‐1 positive CD4+ cells cloned from patients, hTERT expression parallels tax expression and cell cycling. Upon activation, these cells dramatically augment tax expression, whereas their increase in telomerase activity is about 20 times lower than that of their uninfected counterpart. Activated HTLV‐1 positive CD4+ but not uninfected CD4+ or CD8+ clones also repress the transcription of TRF1, TPP1, TANK1, POT1, DNA‐PKc and Ku80. Both infected and uninfected lymphocytes from infected individuals shared common telomere gene deregulations toward a pattern consistent with premature senescence. ATLL cells displayed the highest telomerase activity (TA) whereas recovered a telomere gene transcriptome close to that of normal CD4+ cells. In conclusion HTLV‐1‐dependent telomere modulations seem involved in clonal expansion, immunosuppression, tumor initiation and progression.
Loss of p16 expression is associated with the stem cell characteristics of surface markers and therapeutic resistance in estrogen receptor‐negative breast cancer
Authors: Arima Yoshimi , Hayashi Naoki , Hayashi Hidemi , Sasaki Mikako , Kai Kazuharu , Sugihara Eiji , Abe Eriko , Yoshida Atsushi , Mikami Shuji , Nakamura Seigo , Saya Hideyuki 
Published: June 2011

AbstractTriple‐negative breast cancer [TNBC, which is negative for the estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2] is a high‐risk form of the disease without a specific therapy. DNA microarray and immunohistochemical analyses have shown that most TNBCs fall within the basal‐like histological subset of breast cancers, which frequently exhibit inactivation of the retinoblastoma tumor suppressor (Rb) and upregulation of the cyclin‐dependent kinase inhibitor p16INK4a (p16). However, downregulation of p16 expression has been observed in some basal‐like breast cancer cell lines, suggesting that such cells can be divided into two groups according to Rb and p16 status. We now show that cells that are CD44+ and CD24−, a phenotype associated with stem‐like breast cancer cells, are more abundant in ER−/p16− breast cancer cell lines than in ER−/p16+ lines. It was also found that p16 expression was downregulated in mammospheres from an ER‐negative breast cancer cell line. Depletion of p16 by RNA interference in ER‐negative breast cancer cells increased the percentage of CD44+/CD24− cells and increased the expression of mRNA of the ES‐like genes Nanog, Oct4, and Sox2 through an Rb‐independent pathway. Furthermore, such depletion of p16 reduced chemosensitivity. The loss of p16 expression may thus reduce the response of ER‐negative breast cancer cells to chemotherapy by conferring cancer stem cell‐like properties. Consistent with this conclusion, immunohistochemical analysis of the clinical samples suggests that low p16 expression in TNBC is associated with resistance to preoperative chemotherapy.
DIAGNOSTIC ANALYSIS AND FINE TUNING OF SKIMMING WELL DESIGN AND OPERATIONAL STRATEGIES FOR SUSTAINABLE GROUNDWATER MANAGEMENT ‐ INDUS BASIN OF PAKISTAN
Authors: Ashraf M. , Zeeshan A. Bhatti , Zakaullah  
Published: June 2011

ABSTRACTA survey was conducted in the Chaj Doab (the area between the rivers Chenab and Jhelum) to characterize the skimming wells used to extract freshwater layer. The survey revealed a drastic increase in the number of skimming wells installed during the drought period from 2000 to 2002. About 36% of skimming wells were found to pump water of EC greater than 2.0 dS/m. The number of strainers varied from 2 to 20 and the size varied from 5 to15 cm. The prevailing depth to the water table in the area ranged from 2 to 10 m, whereas the strainers of the wells were usually at 18 m depth.The spatial and temporal variability of groundwater quality was very high. Based on pumping test results and analysis, it is suggested that skimming wells of about 28 lps discharge should not be installed within a radius of 350 m. Six strainers of 7.5 cm diameter are recommended for installation within a depth of 20 m to pump about 28 lps of water. The skimming wells may be operated continuously for 4 to 12 hours/day, depending on the source of recharge, without having adverse effect on groundwater and pumped water quality. Copyright © 2011 John Wiley & Sons, Ltd.
BAFFLE MODULES: IMPROVED DESIGN BASED ON THE VARIABLE HYDRAULIC SENSITIVITY CONCEPT
Authors: Bijankhan Mohammad , Kouchakzadeh Salah 
Published: June 2011

ABSTRACTA baffle sluice module minimizes water delivery deviation for relatively large upstream flow depth variations; further studies are required to establish sound design criteria. A constant relative hydraulic sensitivity was assumed for the structure when previous design methods were developed. This paper highlights the invalidity of the assumption, and based on a variable equivalent sensitivity index, two design schemes for three‐ and two‐baffle modules were proposed. In the first scheme, the criteria of previous design methods were adopted but variable relative hydraulic sensitivity is applied. The results indicated that such a scheme would facilitate the structure design procedure; however, it does not resolve the theoretical drawback of other design methods, which deliver a smaller amount of water than the design discharge. Consequently, the second design scheme was proposed to overcome the problem. Comparing the results of the best available design method with that of the proposed second scheme indicated a significant improvement in the performance of the three‐baffle module, i.e. it decreased the discharge deviation range and theoretically provided both negative and positive deviations in the discharge delivery. Copyright © 2011 John Wiley & Sons, Ltd.
Targeted therapeutics and nanodevices for vascular drug delivery: Quo vadis?
Authors: Muzykantov Vladimir R. 
Published: June 2011

AbstractThis issue of the journal is dedicated to targeted delivery of therapeutics in the vasculature, an approach that holds promise to optimize treatment of diverse pathological conditions ranging from ischemia and tumor growth to metabolic and genetic diseases. From the standpoint of drug delivery, circulation system represents the natural route to the targets, whereas its components (blood and vascular cells) represent targets, carriers or barriers for drug delivery. Diverse nanodevices and targeted therapeutic agents that are designed and tested in animal and early clinical studies to achieve optimal and precise spatiotemporal control of the pharmacokinetics, destination, metabolism and effect of pharmacological agents will be discussed in this introductory essay and subsequent critical reviews in this series. © 2011 IUBMB IUBMB Life, 2011
Lung vascular targeting through inhalation delivery: Insight from filamentous viruses and other shapes
Authors: Mahmud Abdullah , Discher Dennis E. 
Published: June 2011

AbstractSystemic delivery of therapeutic agents via inhalation of particulates remains an attractive, noninvasive means of administration due to the possibilities of high bioavailability and high patient compliance. Optimization of particle shapes and particle properties for deep lung deposition after inhalation continues to be one of the key challenges. Here, we review several aspects of nanoparticle design for deep lung deposition as well as the nature and extent of translocation through the air–blood barrier for local or systemic vascular targeting. We describe filamentous influenza virus in comparison to worm‐like “filomicelle” polymers as one example of a nature inspired design. © 2011 IUBMB IUBMB Life, 2011
Novel platforms for vascular carriers with controlled geometry
Authors: Pillai Jonathan D. , Dunn Stuart S. , Napier Mary E. , DeSimone Joseph M. 
Published: June 2011

AbstractThe first‐generation platforms for vascular drug delivery adopted spherical morphologies. These carriers relied primarily on the size dependence of the enhanced permeability and retention effect to passively target vasculature, resulting in inefficient delivery due to significant variation in endothelial permeability. Enhanced delivery typically requires active targeting via receptor‐mediated endocytosis by surface conjugation of targeting ligands. However, vascular carriers (VCs) still face numerous challenges en route to reaching their targets before delivery. The control of carrier shape offers opportunities to overcome in vivo barriers and enhance vascular drug delivery. Geometric features influence the ability of carrier particles to navigate physiological flow patterns, evade biological clearance mechanisms, sustain circulation, adhere to the vascular surface, and finally transport across or internalize into the endothelium. Although previous formulation strategies limited the fabrication of nonspherical carriers, numerous recent advances in both top‐down and bottom‐up fabrication techniques have enabled shape modulation as a key design element. As part of a series on vascular drug delivery, this review focuses on recent developments in novel vascular platforms with controlled geometry that enhance or modulate delivery functions. Starting with an overview of controlled geometry platforms, we review their shape‐dependent functional characteristics for each stage of their vascular journey in vivo. We sequentially explore carrier geometries that evade reticuloendothelial system uptake, display enhanced circulation persistence and margination dynamics in flow, encourage adhesion to the vascular surface or extravasation through endothelium, and impact extravascular transport and cell internalization. The eventual biodistribution of VCs results from the culmination of their successive navigation of all these barriers and is profoundly influenced by their morphology. To enhance delivery efficacy, carrier designs synergistically combining controlled geometry with standard drug delivery strategies such as targeting moieties, surface decorations, and bulk material properties are discussed. Finally, we speculate on possibilities for innovation, harnessing shape as a design parameter for the next generation of vascular drug delivery platforms. © 2011 IUBMB IUBMB Life, 2011
Pharmacokinetic study of two acetylcholinesterase reactivators, trimedoxime and newly synthesized oxime K027, in rat plasma
Authors: Karasova Jana Zdarova , Chladek Jaroslav , Hroch Milos , Josef Fusek , Hnidkova Daniela , Kuca Kamil 
Published: June 2011

ABSTRACTK027 [1‐(4‐hydroxyiminomethylpyridinium)‐3‐(4‐carbamoylpyridinium)–propane dibromide] is a promising new reactivator of organophosphate‐ or organophosphonate‐inhibited acetylcholinesterase (AChE) with low acute toxicity and broad spectrum efficacy. The aim of the present study was to compare the pharmacokinetics of both compounds. Male Wistar rats (body weight = 320 ± 10 g) were administered a single intramuscular dose of K027 (22.07 mg kg−1) and an equimolar dose of trimedoxime. Blood was collected at various time intervals until 180 min. Plasma samples were analyzed by reversed‐phase HPLC with ultraviolet (UV) detection. The recovery of both oximes from the plasma was approximately 90% and a linear relationship (R2 > 0.998) was observed between the peak areas and concentrations of calibrated standards in the range 1–100 µg ml−1. Near‐identical plasma profiles were obtained for both compounds. No differences were found in the mean ± SD values of Cmax (18.6 ± 2.5 vs 20.0 ± 6.3 µg ml−1, P = 0.72) and AUC0–180min (2290 ± 304 vs 2269 ± 197 min µg ml−1, P = 0.84). However, the percentage coefficient of variation of the first‐order rate constant of absorption (ka) was 3‐fold higher (P < 0.01) providing evidence for more erratic absorption of intramuscular trimedoxime as compared with K027. In conclusion, oxime K027 might have superior pK properties that may be translated in its faster absorption and subsequent tissue distribution. Copyright © 2011 John Wiley & Sons, Ltd.
Nandrolone androgenic hormone presents genotoxic effects in different cells of mice
Authors: do Carmo Carolina Almeida , Gonçalves Álvaro Luiz Martini , Salvadori Daisy Maria Fávero , Maistro Edson Luis 
Published: June 2011

ABSTRACTNandrolone is an androgenic–anabolic steroid (AAS) with diverse medical applications but taken indiscriminately by some to rapidly increase muscle mass. The aim of this study was to evaluate the genotoxic and clastogenic potential of nandrolone (deca‐durabolin®) in vivo in different cells of mice, using the comet assay and micronucleus test, respectively. The animals received subcutaneous injection of the three doses of the steroid (1.0, 2.5 and 5.0 mg kg−1 body weight). Cytotoxicity was assessed by scoring 200 consecutive total polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE–NCE ratio). The results showed a significant dose‐related increase in the frequency of DNA damage in leukocytes, liver, bone marrow, brain and testicle cells at the three tested doses and a significant increase of the micronucleated polychromatic erythrocytes at all tested doses. Under our experimental conditions, the nandrolone steroid hormone showed genotoxic and clastogenic effects when administered subcutaneously to mice. Copyright © 2011 John Wiley & Sons, Ltd.
In vivo characterization of tumor and tumor vascular network using multi‐modal imaging approach
Authors: Kalchenko Vyacheslav , Madar‐Balakirski Noa , Meglinski Igor , Harmelin Alon 
Published: June 2011

AbstractWe present a multi‐modal optical diagnostic approach utilizing a combined use of Fluorescence Intravital Microscopy (FIM), Dynamic Light Scattering (DLS) and Spectrally Enhanced Microscopy (SEM) modalities for in vivo imaging of tumor vascular network and blood microcirculation. FIM is used for imaging of tumor surroundings and microenvironment, SEM provides information regarding blood vessels topography, whereas DLS is applied for functional imaging of vascular network and blood microcirculation. This complementary combination of the imaging approaches is extremely useful for functional in vivo imaging of blood vasculature and tumor microenvironment. The technique has also a great potential in vascular biology and can significantly expand the capabilities of tumor angiogenesis studies and notably contribute to the development of cancer treatment. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Thermoresponsive poly(N‐isopropylacrylamide)‐g‐methylcellulose hydrogel as a three‐dimensional extracellular matrix for cartilage‐engineered applications
Authors: Sá‐Lima Helena , Tuzlakoglu Kadriye , Mano João F. , Reis Rui L. 
Published: June 2011

AbstractRecent advances in tissue engineering and regenerative medicine fields can offer alternative solutions to the existing techniques for cartilage repair. In this context, a variety of materials has been proposed, and the injectable hydrogels are among the most promising alternatives. The aim of this work is to explore the ability of poly(N‐isopropylacrylamide)‐g‐methylcellulose (PNIPAAm‐g‐MC) thermoreversible hydrogel as a three‐dimensional support for cell encapsulation toward the regeneration of articular cartilage through a tissue engineering approach. The PNIPAAm‐g‐MC copolymer was effectively obtained using ammonium‐persulfate and N,N,N′,N′‐tetramethylethylenediamine as initiator as confirmed by Fourier transform infrared spectroscopy and 1H NMR results. The copolymer showed to be temperature responsive, becoming a gel at temperatures above its lower critical solution temperature (∼ 32°C) while turning into a liquid below it. Results obtained from the MTS test showed that extracts of the hydrogel were clearly noncytotoxic to L929 fibroblast cells. ATDC5 cells, a murine chondrogenic cell line, were used as the in vitro model for this study; they were encapsulated at high cell density within the hydrogel and cultured for up to 28 days. PNIPAAm‐g‐MC did not affect the cell viability and proliferation, as indicated by both MTS and DNA assays. The results also revealed an increase in synthesis of glycosoaminoglycans within culture time measured by the dimethylmethylene blue quantification assay. These results suggest the viability of using PNIPAAm‐g‐MC thermoresponsive hydrogel as a three‐dimensional scaffold for cartilage tissue engineering using minimal‐invasive strategies. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Influence of processing parameters on pore structure of 3D porous chitosan–alginate polyelectrolyte complex scaffolds
Authors: Florczyk Stephen J. , Kim Dae‐Joon , Wood David L. , Zhang Miqin 
Published: June 2011

AbstractFabrication of porous polymeric scaffolds with controlled structure can be challenging. In this study, we investigated the influence of key experimental parameters on the structures and mechanical properties of resultant porous chitosan–alginate (CA) polyelectrolyte complex (PEC) scaffolds, and on proliferation of MG‐63 osteoblast‐like cells, targeted at bone tissue engineering. We demonstrated that the porous structure is largely affected by the solution viscosity, which can be regulated by the acetic acid and alginate concentrations. We found that the CA PEC solutions with viscosity below 300 Pa.s yielded scaffolds of uniform pore structure and that more neutral pH promoted more complete complexation of chitosan and alginate, yielding stiffer scaffolds. CA PEC scaffolds produced from solutions with viscosities below 300 Pa.s also showed enhanced cell proliferation compared with other samples. By controlling the key experimental parameters identified in this study, CA PEC scaffolds of different structures can be made to suit various tissue engineering applications. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
A new approach in self‐etching adhesive formulations: Replacing HEMA for surfactant dimethacrylate monomers
Authors: Zanchi Cesar Henrique , Münchow Eliseu Aldrighi , Ogliari Fabricio Aulo , de Carvalho Rodrigo Varella , Chersoni Stefano , Prati Carlo , Demarco Flávio Fernando , Piva Evandro 
Published: June 2011

AbstractThis study evaluated the influence of surfactant dimethacrylates (SD) on the resin‐to‐dentin microtensile bond strength (μTBS) and characterized the interfacial micromorphology of the hybrid layer of the experimental HEMA‐free self‐etching systems. Five experimental HEMA‐free two‐step self‐etching systems containing different SD (Bis‐EMA 10, Bis‐EMA 30, PEG 400, PEG 1000, and PEG 400 UDMA) and a HEMA‐containing system (control) were compared. Each experimental adhesive system was applied and resin composite restorations were incrementally built up in bovine incisors. After 24 h, restored teeth were sectioned to obtain 24 sticks per group. Thereafter, the specimens were subjected to the μTBS test. Data (MPa) were analyzed by One‐way ANOVA and Tukey's test. Adhesive‐dentin interfaces were analyzed through Scanning Electron Microscopy (SEM). The adhesive system formulated with PEG 400 UDMA produced μTBS similar to the HEMA‐containing group and statistically higher than the HEMA‐free groups. Similar failure percentages were observed in the PEG 400 UDMA and the control group. In the SEM analysis, all the adhesive systems presented similar partially demineralized hybrid layer (1.5–3.0 μm thickness) with well‐formed resin tags. All SD presented reasonable initial μTBS, with the PEG 400 UDMA being a promising monomer to be considered as a HEMA substitute in adhesive systems compositions. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
Mechanical stability of two‐step chemically deposited hydroxyapatite coating on Ti substrate: Effects of various surface pretreatments
Authors: Zavgorodniy Alexander V. , Borrero‐López Oscar , Hoffman Mark , LeGeros Racquel Z. , Rohanizadeh Ramin 
Published: June 2011

AbstractThe success of implants in orthopaedic and dental load‐bearing applications crucially depends on the initial biological fixation of implants in surrounding bone tissues. Using hydroxyapatite (HA) coating on Ti implant as carrier for bone morphogenetic proteins (BMPs) may promote the osteointegration of implants; therefore, reduce the risk of implant failure. The goal of this study was to develop an HA coating method in conditions allowing the incorporation of protein‐based drugs into the coating materials, while achieving a mechanical stable coating on Ti implant. HA coatings were deposited on six different groups of Ti surfaces: control (no pretreatment), pretreated with alkali, acid, heat at 800°C, grit blasted with Al2O3, and grit blasted followed by heat treatment. HA coating was prepared using a two‐step procedure. First step was the chemical deposition of a monetite coating on Ti substrate in acidic condition at 75°C and the second step was the hydrolysis of the monetite coating to HA. Coatings were characterized by scanning electron microscope (SEM), energy‐dispersive X‐ray spectroscopy (EDS), and X‐ray diffraction (XRD). The roughness of substrates and coatings was measured using profilometry technique. The mechanical stability of the coatings deposited on the pretreated substrates was assessed using scratch test. The coatings deposited on the grit‐blasted Ti surface demonstrated superior adhesive properties with critical shearing stress 131.6 ± 0.2 MPa. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
Biocompatibility of magnesium particles evaluated by in vitro cytotoxicity and genotoxicity assays
Authors: Di Virgilio Ana L. , Reigosa Miguel , de Mele Monica Fernández Lorenzo 
Published: June 2011

AbstractMg is a biodegradable biomaterial which may release particles (MP) to the environment. The possible cyto‐ and genotoxic effects of MP derived from magnesium powder (mesh 325) were analyzed on rat osteosarcoma UMR106 cells in order simulate the effect of Mg debris. Neutral red (NR) incorporation and acridine orange/ethidium bromide (AO/EB) staining techniques were used as endpoints to analyze the cytotoxic effects at 25–1000 μg/mL concentration range. Genotoxicity was estimated according to micronucleus (MN) formation and the Comet assay (CA). Results showed that MP size changes with time due to corrosion. Changes in lysosomal activity were observed after 24 h only at 1000 μg/mL. Accordingly, AO/EB staining showed a significant decrease in the number of living cells at 500 μg/mL. Transmission electronic microscopy showed MP internalization (60 and 200 nm diameter) in cells after 2‐h treatment, whereas no MP was detected after 24 h. A significant dose‐dependent increase in MN frequencies was observed at 25–100 μg/mL range (nontoxic range). DNA damage induction was assessed by CA only at 500 μg/mL. Results showed dose‐dependent cytotoxic and genotoxic effects of MP on UMR106 cells with different threshold values of MP concentration. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.