INVESTIGATON OF BRAF MUTATION ANALYSIS WITH DIFFERENT TECHNICAL PLATFORMS IN METASTATİC MELANOMA

Publication date: Available online 21 January 2017
Source:Pathology - Research and Practice
Author(s): Ebru Sener, Pinar Yildirim, Ayca Tan, Ozay Gokoz, Gaye Guler Tezel
In metastatic melanoma, the detection of somatic mutations in the BRAF gene is crucial regarding patient selection for targeted therapy. Several screening methodsve been developed to identify BRAF gene mutations. In this study, our objective was to evaluate the detection of the BRAF V600 mutations using two molecular methods, real-time polymerase chain (real-time PCR) assay and pyrosequencing, and immunohistochemistry (IHC), and to compare the results of these different technical platforms.This study included 98 patients diagnosed with metastatic melanoma at the Hacettepe University, Department of Pathology between 2002 and 2014. BRAF mutation analysis was tested with real-time PCR, pyrosequencing and IHC methods. The results of all three tests were compared with are reference test, and the sensitivity, specificity rates and kappa coefficient values were analysed for each test.We successfully analysed BRAF mutations using all three methods in 92 patients. According to our findings, the pyrosequencing method had the highest kappa value regarding the determination of BRAF V600 mutations. The kappa values were at almost perfect agreement levels in pyrosequencing and real-time PCR assay (kappa coefficient for pyrosequencing=0.895 (95% CI: 0.795–0.995); kappa coefficient for real-time PCR=0.871 (95% CI: 0.761–0.981). The kappa value was at a substantial agreement level in the IHC analysis (kappa coefficient=0.776 (95% CI: 0.629–0.923).According to our results, we found that real-time PCR and pyrosequencing methods were equally excellent in determination of BRAF V600 mutations. The IHC method, which is commonly used in routine pathology practice, can also be safely used as a screening test for determination of BRAF V600 mutations.



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Chicoric acid suppresses BAFF expression in B lymphocytes by inhibiting NF-κB activity

Publication date: March 2017
Source:International Immunopharmacology, Volume 44
Author(s): Lingxi Chen, Gang Huang, Min Gao, Xiaodong Shen, Wei Gong, Zhizhen Xu, Yijun Zeng, Fengtian He
B cell activating factor belonging to the TNF family (BAFF) plays a critical role in the pathogenesis of autoimmune diseases. The inhibition of BAFF expression is an emerging therapeutic approach for these disorders. Chicoric acid (CA), a bioactive phytochemical found in several widely used traditional medicinal plants, has significant anti-inflammatory activity and anti-arthritic effects. However, the role of CA in modulation of BAFF expression remains unknown. In this study, we demonstrated that CA reduced BAFF expression in human B lymphocyte cell lines and decreased the DNA-binding activity of nuclear factor-κB (NF-κB) in the BAFF promoter region. Furthermore, CA inhibited both the nuclear translocation of p65 (the subunit of NF-κB) and the phosphorylation of IκBα (inhibitor of NF-κB). These results suggest that CA suppresses BAFF expression by inhibiting NF-κB activity, and CA may serve as a novel therapeutic agent to down-regulate excessive BAFF expression in autoimmune diseases.



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Effect of bone morphogenetic protein on Zn-HAp and Zn-HAp/collagen composite: A systematic in vivo study

Publication date: December 2017
Source:Research in Veterinary Science, Volume 115
Author(s): Howa Begam, Samit Kumar Nandi, Abhijit Chanda, Biswanath Kundu
Due to good biocompatibility and osteoconductivity, hydroxyapatite (HAp) and its composite with different polymers have been widely investigated for the application in the field of bone tissue engineering. The present study reports the, in vivo performance of zinc doped HAp and HAp/collagen composite (HAC) using bone morphogenetic protein-2. It was done for a span of two months on New Zealand rabbit model. After two months postoperatively, there was no marked inflammatory reaction in experimental groups and control groups. The histological images showed well-formed bony matrix with well differentiated haversian system. From the fluorochrome labeling study, it was observed that higher amount of new bone formed in case of bone morphogenetic protein-2 (BMP-2) loaded Zn-HAp (50%) and HAC (27%) specimens than control. The percentage of new bone formation was significantly higher in case of BMP loaded Zn-HAp group than BMP loaded HAC group. From the SEM images similar trend was observed. As the HAC specimen consists of amorphous phase, it had a negative impact on new bone formation.

Graphical abstract

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Chemical degradation of selected Zn-based corrosion products induced by C60 cluster, Ar cluster and Ar+ ion sputtering in the focus of X-ray photoelectron spectroscopy (XPS)

Publication date: 1 May 2017
Source:Applied Surface Science, Volume 403
Author(s): R. Steinberger, J. Sicking, J. Weise, J. Duchoslav, T. Greunz, D.C. Meyer, D. Stifter
Monoatomic ion sputtering is a common concept for surface sensitive analysis methods to clean surfaces prior investigation or to obtain information from deeper regions. However, severe damage of the materials – linked to preferential sputtering, ion implantation, atomic mixing and in worst case chemical degradation – can affect the validity of the analysis. Hence, the impact of C60 cluster etching, furthermore, of Ar⁺ ion bombardment with and without azimuthal sample rotation and also the application of heavy projectiles (Xe⁺ ions) was investigated to find a concept, which is less destructive or with less critical influence on the chemical nature of the investigated materials. In this work the focus is set on hydrozincite and zinc oxide, two common corrosion products of Zn-based coatings. As a main point, all the obtained results from (i) Ar⁺ ion, (ii) Ar cluster, and (iii) C60 cluster etching on the degradation kinetics of hydrozincite were compared with respect to the reached sputter depth. In addition, the sputter rate of all three methods was experimentally determined for ZnO. In total, fully non-destructive conditions could not be found, but valuable knowledge on the type and rate of degradation, which is essential to choose the most suited sputter concept.

Graphical abstract

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Measurement uncertainty from physical sample preparation of moss samples: Estimation of mechanical cleaning vs. rinsing

Publication date: May 2017
Source:Ecological Indicators, Volume 76
Author(s): Sabina Dołęgowska
Next to sampling, the physical sample preparation step is a second large source of uncertainty. To assess the level of uncertainty from sampling, sample preparation and analysis of moss material, 27 combined and duplicate samples of moss species Pleurozium schreberi (Brid.) Mitt were collected and prepared for analysis using two different treatment methods After sampling had been done, samples were dried at an ambient temperature and then each primary and duplicate sample was divided into two sub-samples for preparation. The first sub-sample was manually cleaned whereas the second one was triple rinsed with deionized water and left to dry. Subsequently, the samples were milled and digested in a close microwave system with 8mL of HNO3 (1:1) and 1mL of 30% H2O2. In all samples Cu, Fe and Zn were determined using GFAAS and FAAS techniques. Each sample was analyzed twice. Sampling, sample preparation and analytical uncertainty were calculated using ANOVA, RANOVA, modified RANOVA and range statistics methods. Sampling and sample preparation uncertainty varied from 3.8 to 19.8% and from 3.6 to 11.2%, respectively. For all the elements examined analytical uncertainty was below 1.1%. The comparison of element concentrations in manually cleaned and rinsed samples showed that rinsed samples were enriched in Cu and Zn, as opposed to manually cleaned that in turn displayed raised levels of Fe. However, except for Zn, these differences were not statistically significant.



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A novel π–conjugated Zn⟵S→Zn unit interface in the ZnS/Zn(S)2L inorganic/orgainc hybrids for significant photoelectric response

Publication date: 30 April 2017
Source:Applied Surface Science, Volume 402
Author(s): Yuanhao Gao, Xiaofei Zhang, Peipei Wang, Yan Lei, Xiaognag Yang, Wenjun Fa, Helin Niu, Zhi Zheng
By using a novel Zn(S)2L complex (L=N–hexyl–3–{2–(4–(2,2′:6′,2′′–terpyridin–4′–yl)phenyl)ethenyl}carbazole) as a surface stabilizing agent, the self–assembled microspheres of Zn(S)2L–capped ZnS nanocrystals are obtained in a simple ethanol solvothermal process. Because of the strong π character of the two terminal sulfur atoms (S^1– valence state) in the Zn(S)2L complex, the Zn(S)2L complex could incorporate ZnS nanocrystals together by a homologous Zn⟵S→Zn unit interface. In the work, the homologous Zn⟵S→Zn unit interface is proposed to function as a π–conjugated bridge for effective electron–transfer transition from Zn(S)2L moiety to ZnS nanocrystal to significantly improve the photoelectric response performance, such as the long lifetime of photogenerated charge carriers from 8×10⁻⁸s to 4×10⁻⁵s and the high recombination luminescence quantum efficiency (QE) up to 69%, which are confirmed by the systematically investigation with Raman spectra, XPS spectra, Uv–vis absorption spectra, photoluminescence (PL) spectra and transient photovoltage (TPV) technique. The ZnS/Zn(S)2L used as extra electron donor in organic/inorganic hybrid solar cell device could increase performance up to about 30%.

Graphical abstract

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The mobile monitoring of black carbon and its association with roadside data in the Chinese megacity of Shanghai

Abstract

High-level black carbon (BC) pollution is associated with traffic emissions in metropolitan areas with high vehicle density. Mobile monitoring was conducted to assess the in-vehicle BC exposure on three backbone ring roads (inner, middle, and outer ring roads) on October 14 and October 18, 2015 in Shanghai. Ambient BC monitoring was also simultaneously conducted in three fixed roadside stations from October 14 to October 20, 2015. Results of the mobile monitoring showed median BC personal exposure concentrations ranging from 5.0 μg m⁻³ on the inner ring road to 13.5 μg m⁻³ on the outer ring road. The ambient BC concentrations during the entire observation period showed an arithmetic mean and a standard deviation of 3.5 ± 2.9 μg m⁻³. The correlation analysis of urban roadside monitoring (Caoxi Road and South Zhongshan Road) and personal data showed a high and significant correlation. The results of this study highlight the critical level of BC pollution in Shanghai and facilitate the development of evidence-based public health interventions and control strategies to prevent the adverse health effects of BC pollution.

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Removal of elevated level of chromium in groundwater by the fabricated PANI/Fe 3 O 4 nanocomposites

Abstract

In this work, we report the reduction of chromium concentration in the polluted groundwater samples from Madurai Kamaraj University area, India, where the dissolved salts in groundwater are reported as serious health hazards for its inhabitants. The water samples have intolerable amounts of total dissolved solids (TDS) and chromium is a prominent pollutant among them. Chromium reduction was achieved by treating the polluted groundwater with PANI/Fe₃O₄ nanocomposites synthesized by in situ polymerization method. Further experimentation showed that the nanocomposites exhibit better chromium removal characteristics upon increasing the aniline concentration during the synthesis. We were able to reduce chromium concentration in the samples from 0.295 mg L⁻¹ to a tolerable amount of 0.144 mg L⁻¹. This work is expected to open doors for chromium-free groundwater in various regions of India, when improved to an industrial scale.

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1-Ethyl-3-methylimidazolium tetrafluoroborate-doped high ionic conductivity gel electrolytes with reduced anodic reaction potentials for electrochromic devices

Publication date: 15 March 2017
Source:Materials & Design, Volume 118
Author(s): Quanfeng Tang, Haizeng Li, Yanfang Yue, Qinghong Zhang, Hongzhi Wang, Yaogang Li, Pei Chen
The electrolyte plays an important role in an electrochromic device (ECD), and an ideal electrolyte can greatly improve the electrochromic performance of the device. Here, we report the preparation of a 1-Ethyl-3-methylimidazolium tetrafluoroborate ([Emim]BF4)-doped Poly(methyl methacrylate) (PMMA)-based gel electrolyte for electrochromic applications. By the doping of the [Emim]BF4, the ionic conductivity of the gel electrolyte is improved (2.9×10⁻³S/cm at room temperature and 10⁻²S/cm at 40°C). Most importantly, the addition of the [Emim]BF4 could reduce the anodic reaction potentials in an ECD, which could enable ECD bleaching at smaller applied voltages and avoid the degradation of optical modulation induced by ion-trapping in tungsten oxide (WO3) films. This novel electrolyte provides a promising platform for low anodic reaction potential electrochromic devices.

Graphical abstract

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Repair of arc welded DH36 joint by underwater friction stitch welding

Publication date: 15 March 2017
Source:Materials & Design, Volume 118
Author(s): Jinhu Teng, Dongpo Wang, Zhijiang Wang, Xunda Zhang, Yuhao Li, Jun Cao, Wei Xu, Fan Yang
Repair of arc welded DH36 joint by friction stitch welding was investigated in underwater condition to identify the influence of axial force and heat treatment on the defects, microstructure characteristics and mechanical properties of the repaired joint. The bonding quality of the subsequent overlapped friction taper plug weld (FTPW) and the overlapping FTPW were not as well as that of the previous overlapped FTPW. The conduct of the overlapping friction taper plug welding would induce cracking at the rounded transient of the overlapped FTPWs. High quality friction stitch welds could be obtained under the axial force of 35kN with the result that tensile strength was more than 500MPa. Microstructure of overlapping FTPW was mainly composed of lath bainite with maximum hardness up to 380HV10. Heat treatment, soaking at 550°C, 600°C and 650°C for an hour before and after the overlapping FTPW, could significantly decrease the hardness of friction stitch weld and improve the drilling process of the overlapping FTPWs and could improve the impact toughness of friction stitch weld, but it did little contributions to defects elimination and tensile strength of the friction stitch weld.

Graphical abstract

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Residual stress evaluation at the micro- and nano-scale: Recent advancements of measurement techniques, validation through modelling, and future challenges

Publication date: 15 March 2017
Source:Materials & Design, Volume 118
Author(s): Marco Sebastiani, Tan Sui, Alexander M. Korsunsky




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A bridge role of Tb3+ in broadband excited Sr3Y(PO4)3:Ce3+, Tb3+, Sm3+ phosphors with superior thermal stability

Publication date: 15 March 2017
Source:Materials & Design, Volume 118
Author(s): Zhihua Leng, Liping Li, Xiangli Che, Guangshe Li
In this work, we report on a comprehensive study about the bridge role of Tb³⁺ in broadband excited Sr3Y(PO4)3:Ce³⁺, Tb³⁺, Sm³⁺ phosphors. With Tb³⁺ acting as an energy transfer bridge, Ce³⁺→(Tb³⁺)n→Sm³⁺ energy transfer process was utilized to circumvent Ce³⁺-Sm³⁺ metal-metal charge transfer (MMCT) quenching in Sr3Y(PO4)3 host. Sm³⁺ was efficiently sensitized by the broad absorption band (4f¹→5d¹ transition) of Ce³⁺ in near-ultraviolet spectral region. The color tones of Sr3Y(PO4)3:Ce³⁺, yTb³⁺, zSm³⁺ phosphors were tuned from blue through green and finally to orange with increasing Tb³⁺/Sm³⁺ doping concentration. Furthermore, energy transfer mechanisms from Ce³⁺ to Tb³⁺ (dipole-dipole mechanism) and Tb³⁺ to Sm³⁺ (exchange interaction) as well as the corresponding energy transfer efficiencies (higher than 90%) are systematically investigated. Sr3Y(PO4)3:0.02Ce³⁺, 0.90Tb³⁺, 0.02Sm³⁺ phosphor shows a thermal stability up to 493K, superior to that in analogous reports. The quantum efficiency of Sr3Y(PO4)3:0.02Ce³⁺, 0.90Tb³⁺, 0.02Sm³⁺ phosphor with 315nm excitation was calculated to be 60%.

Graphical abstract

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Mechanical characterization of 3D printed polymers for fiber reinforced polymers processing

Publication date: 15 March 2017
Source:Materials & Design, Volume 118
Author(s): Daniel-Alexander Türk, Franco Brenni, Markus Zogg, Mirko Meboldt
This paper presents an investigation in the thermo-mechanical creep properties of additive manufactured (AM) polymeric materials for the processing of AM parts with fiber reinforced polymers (FRP). Commercially available Acrylonitrile Butadiene Styrene ABSplus-P430 (ABS) for applications in Fused Deposition Modeling (FDM), Polyamide 12 (PA12) and DuraForm HST Composite (HST) made by Selective Laser Sintering (SLS) are investigated for in- and out-of-plane building orientations. The materials were subjected to tensile and three-point bending creep tests to assess tensile Young's modulus, tensile yield strength, and flexural creep modulus at a creep time of 180min and temperatures ranging from to 110°C. The material properties were then used in the identification of the optimal processing pressure and temperature for the autoclave curing of an AM honeycomb. The results indicated that the mechanical properties decreased as the temperature increased. Building orientations significantly impact the mechanical properties for ABS and HST. Processing recommendations of the AM honeycomb reflect the variation of the mechanical properties over temperature: the pressure decreases as the temperature increases. Numerical results correlate well with experiments conducted for an AM honeycomb made with HST and processed in an autoclave at 100°C and pressures of 2.26 and 4bar.

Graphical abstract

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Meetings

Publication date: 1 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 97, Issue 3





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Issue Highlights

Publication date: 1 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 97, Issue 3





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Local Treatment of the Primary Tumor in Patients Presenting With Stage IV Breast Cancer: A First, and What's Up Ahead

Publication date: 1 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 97, Issue 3
Author(s): Pauline T. Truong




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Smart Radiation Therapy Biomaterials

Publication date: 1 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 97, Issue 3
Author(s): Wilfred Ngwa, Francis Boateng, Rajiv Kumar, Darrell J. Irvine, Silvia Formenti, Twalib Ngoma, Carsten Herskind, Marlon R. Veldwijk, Georg Lars Hildenbrand, Michael Hausmann, Frederik Wenz, Juergen Hesser
Radiation therapy (RT) is a crucial component of cancer care, used in the treatment of over 50% of cancer patients. Patients undergoing image guided RT or brachytherapy routinely have inert RT biomaterials implanted into their tumors. The single function of these RT biomaterials is to ensure geometric accuracy during treatment. Recent studies have proposed that the inert biomaterials could be upgraded to "smart" RT biomaterials, designed to do more than 1 function. Such smart biomaterials include next-generation fiducial markers, brachytherapy spacers, and balloon applicators, designed to respond to stimuli and perform additional desirable functions like controlled delivery of therapy-enhancing payloads directly into the tumor subvolume while minimizing normal tissue toxicities. More broadly, smart RT biomaterials may include functionalized nanoparticles that can be activated to boost RT efficacy. This work reviews the rationale for smart RT biomaterials, the state of the art in this emerging cross-disciplinary research area, challenges and opportunities for further research and development, and a purview of potential clinical applications. Applications covered include using smart RT biomaterials for boosting cancer therapy with minimal side effects, combining RT with immunotherapy or chemotherapy, reducing treatment time or health care costs, and other incipient applications.



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Internal Mammary Misfortune

Publication date: 1 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 97, Issue 3
Author(s): Penny Fang




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Oligometastasis-Directed Ablative Therapy: A Clinical Trial Question

Publication date: 1 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 97, Issue 3
Author(s): James M. Melotek, Steven J. Chmura




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Ablative Therapy: A Reasonable Approach

Publication date: 1 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 97, Issue 3
Author(s): Asal Rahimi, Robert Timmerman




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2017 Red Journal Conflict of Interest/Photographs

Publication date: 1 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 97, Issue 3





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Chemotherapy First, Then Select for Local Therapy

Publication date: 1 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 97, Issue 3
Author(s): Benjamin D. Smith




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In Reply to Mazeron et al

Publication date: 1 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 97, Issue 3
Author(s): Cameron W. Swanick, Patricia J. Eifel, Ann H. Klopp




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Subgroup Analysis According to Human Papillomavirus Status and Tumor Site of a Randomized Phase II Trial Comparing Cetuximab and Cisplatin Combined With Radiation Therapy for Locally Advanced Head and Neck Cancer

Publication date: 1 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 97, Issue 3
Author(s): Michela Buglione, Marta Maddalo, Renzo Corvò, Luigi Pirtoli, Fabiola Paiar, Luciana Lastrucci, Marco Stefanacci, Liliana Belgioia, Monica Crociani, Stefania Vecchio, Pierluigi Bonomo, Silvia Bertocci, Paolo Borghetti, Nadia Pasinetti, Luca Triggiani, Loredana Costa, Sandro Tonoli, Salvatore Grisanti, Stefano Maria Magrini
PurposeWe report a subgroup analysis primarily focused on human papillomavirus (HPV)-related oropharyngeal cancer (OPC) from the Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer (CTXMAB+RT; ClinicalTrials.gov identifier NCT01216020) trial comparing radiation therapy with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced head and neck cancer.Methods and MaterialsThe data from all the patients in the CTXMAB+RT trial were reviewed and separately analyzed in 3 groups: p16-positive OPC, p16-negative OPC, and all other cancer sites. The endpoints of interest were locoregional control (LC), metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS). Severe and fatal infectious complications were also reanalyzed to more thoroughly investigate the association between CTX treatment and potentially life-threatening reactions.ResultsA total of 33 patients had OPC. The HPV status was available for 30 of the 33 patients. Thus, 3 patients treated with CDDP but with unknown HPV status were excluded from the survival analysis. The small number of patients in each group did not allow for significance to be reached for any of the outcomes analyzed. A trend favored the CDDP arm in the p16-positive group for the 2-year LC and OS/CSS rates (100% vs 72.9% and 100% vs 77.8% for CDDP vs CTX). In this group of patients, the hazard ratio for the treatment arm (CTX vs CDDP) was 4.7 (95% confidence interval [CI] 0.5-40.3) for LC, 3.4 (95% CI 0.4-30.5) for OS, and 2.4 for CSS (95% CI 0.2-23.2). A survival benefit favoring the CDDP arm was not evident in the p16-negative OPC group or for patients with cancer located in other sites. Serious or fatal infectious complications occurred only in the CTX arm.ConclusionsIn patients with p16-positive OPC in the CTXMAB+RT trial, CTX had lower efficacy than CDDP, with possible implications for treatment selection in this clinical setting.



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In Regard to Swanick et al

Publication date: 1 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 97, Issue 3
Author(s): Renaud Mazeron, Eleonor Rivin del Campo, Christine Haie-Meder, Cyrus Chargari




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In Regard to Pan et al and Falit et al

Publication date: 1 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 97, Issue 3
Author(s): John Leung




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Molecular Contrast-Enhanced Ultrasound Imaging of Radiation-Induced P-Selectin Expression in Healthy Mice Colon

Publication date: 1 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 97, Issue 3
Author(s): Ahmed El Kaffas, Kevin Smith, Pooja Pradhan, Steven Machtaler, Huaijun Wang, Rie von Eyben, Jürgen K. Willmann, Dimitre Hristov
PurposeTo evaluate the feasibility of using molecular contrast-enhanced ultrasound (mCEUS) to image radiation (XRT)-induced expression of cell adhesion molecules that mediate inflammatory response to XRT in healthy mouse colon tissue.Methods and MaterialsThe colons of male BALB/c mice (aged 6-8 weeks, n=9) were irradiated with 14 Gy using a Kimtron IC-225 x-ray irradiator operating at 225 kV/13.0 mA at a dose rate of 0.985 Gy/min. The head and thorax regions were shielded during irradiation. A second control cohort of mice was left untreated (n=6). Molecular CEUS was carried out before and 24 hours after irradiation using a VEVO2100 system and MS250 21-MHz center frequency transducer. Each imaging session comprised mCEUS imaging with P-selectin targeted microbubbles and control microbubbles targeted with an isotype control IgG. Quantification of mCEUS was carried out by measuring the differential targeted enhancement (dTE) parameter. The perfusion parameters peak enhancement and area under the curve were also extracted from the initial injection bolus. Animals were sacrificed at 24 hours and the colon was resected for immunohistochemistry analysis (P-selectin/CD31-stained vessel).ResultsFor P-selectin targeted microbubble, a significant increase (40 a.u.; P=.013) in dTE (P-dTE) was observed in irradiated mice over 24 hours. In contrast, a nonsignificant change in P-selectin dTE was observed in control mice. For control microbubbles, no significant difference in the IgG dTE parameter was noted in treated and control animals over 24 hours. A nonsignificant increase in the peak enhancement and area under the curve perfusion parameters associated with blood volume was noted in animals treated with radiation. Quantitative histology indicated significantly elevated P-selectin expression per blood vessel (36% in treated; 14% in control).ConclusionOur results confirm the feasibility of using mCEUS for imaging of XRT-induced expression of P-selectin as a potential approach to monitoring healthy tissue inflammatory damage during radiation therapy.



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Colorectal carcinoma: Ex vivo evaluation using 3-T high-spatial-resolution quantitative T2 mapping and its correlation with histopathologic findings

Publication date: May 2017
Source:Magnetic Resonance Imaging, Volume 38
Author(s): Ichiro Yamada, Norio Yoshino, Keigo Hikishima, Naoyuki Miyasaka, Shinichi Yamauchi, Hiroyuki Uetake, Masamichi Yasuno, Yukihisa Saida, Ukihide Tateishi, Daisuke Kobayashi, Yoshinobu Eishi
PurposeIn this study, we aimed to evaluate the feasibility of determining the mural invasion depths of colorectal carcinomas using high-spatial-resolution (HSR) quantitative T2 mapping on a 3-T magnetic resonance (MR) scanner.Materials and methodsTwenty colorectal specimens containing adenocarcinomas were imaged on a 3-T MR system equipped with a 4-channel phased-array surface coil. HSR quantitative T2 maps were acquired using a spin-echo sequence with a repetition time/echo time of 7650/22.6–361.6ms (16 echoes), 87×43.5-mm field of view, 2-mm section thickness, 448×224 matrix, and average of 1. HSR fast-spin-echo T2-weighted images were also acquired. Differences between the T2 values (ms) of the tumor tissue, colorectal wall layers, and fibrosis were measured, and the MR images and histopathologic findings were compared.ResultsIn all specimens (20/20, 100%), the HSR quantitative T2 maps clearly depicted an 8-layer normal colorectal wall in which the T2 values of each layer differed from those of the adjacent layer(s) (P<0.001). Using this technique, fibrosis (73.6±9.4ms) and tumor tissue (104.2±6.4ms) could also be clearly differentiated (P<0.001). In 19 samples (95%), the HSR quantitative T2 maps and histopathologic data yielded the same findings regarding the tumor invasion depth.ConclusionsOur results indicate that 3-T HSR quantitative T2 mapping is useful for distinguishing colorectal wall layers and differentiating tumor and fibrotic tissues. Accordingly, this technique could be used to determine mural invasion by colorectal carcinomas with a high level of accuracy.



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Safety of externally stimulated intracranial electrodes during functional MRI at 1.5T

Publication date: May 2017
Source:Magnetic Resonance Imaging, Volume 38
Author(s): Pallab K. Bhattacharyya, Jeffery Mullin, Bryan S. Lee, Jorge A. Gonzalez-Martinez, Stephen E. Jones
Surgical resection of the epileptogenic zone (EZ) is a potential cure for medically refractory focal epilepsy. Proper identification of the EZ is essential for such resection. Synergistic application of functional magnetic resonance imaging (fMRI) simultaneously with stimulation of a single externalized intracranial stereotactic EEG (SEEG) electrode has the potential to improve identification of the EZ. While most EEG-fMRI studies use the electrodes passively to record electrical activity, it is possible to stimulate the brain using the electrodes by connecting them with conducting cables to the stimulation hardware. In this study, we investigated the effect of MRI-induced heating on a single SEEG electrode and its sensitivity to geometry, configuration, and associated connections required for the stimulation. The temperature increase of a single electrode embedded within a gel phantom and connected to an external stimulation system was measured during 1.5T MRI scans using adjacent fluoroptic temperature sensors. A receive-only split-array head coil and a transmit-receive head coil were used for testing. Sequences included a standard localizer, T1-weighted axial fast low-angle shot (FLASH), gradient echo-planar imaging (GE-EPI) axial fMRI, and a high specific absorption rate T2-weighted turbo spin-echo (TSE) axial scan. Variations of the electrode location and connecting cable configuration were tested. No unacceptable heating was observed with the standard sequences used for evaluation of the EZ. Considerable heating (up to 14°C) was observed with the TSE sequence, which is not used clinically. The temperature increase was insignificant (<0.05°C) for electrode contacts closest to the isocenter and connecting cables lying along the isocenter, and varied with configurations of the connecting cable assembly. Simultaneous intracranial electrode stimulation during fMRI using an externalized stimulation system may be safe with strict adherence to settings tested prior to the fMRI. Localizer, FLASH, and GE-EPI fMRI may be safely performed in patients with a single SEEG electrode following the configurations tested in this study, but high SAR TSE scans should not be performed in these patients.



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Two-component regulatory system ActS/ActR is required for Sinorhizobium meliloti adaptation to oxidative stress

Publication date: Available online 21 January 2017
Source:Microbiological Research
Author(s): Guirong Tang, Sunjun Wang, Dawei Lu, Leqi Huang, Ningning Li, Li Luo
The two-component system ActS/ActR plays important roles in bacterial adaptation to abiotic stress, including acid tolerance and oxidant resistance. However, the underlying regulatory mechanism is not clear. In this study, we found that the ActS/ActR system is required for adaptation to oxidative stress by regulating the transcription of the genes actR, katB, gshA and gshB1. The actS and actR mutants were sensitive to low pH and oxidants such as H2O2, oxidized glutathione (GSSG) and sodium nitroprusside (SNP). The expression of actR by using a plasmid rescued the defect of SNP sensitivity for all actS and actR mutants. The expression of actS and actR were suppressed by treatment with H2O2. The expression of actS, actR, oxyR, katA and katB was required for ActS and ActR under normal conditions. The induction of katB, gshA and gshB1 depended on ActS and ActR during treatment with H2O2 and SNP. Our findings revealed that the ActS/ActR system is a key redox regulator in S. meliltoi and provides a new cue to understanding Rhizobium-legume symbiosis.



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Wood-derived-biochar combined with compost or iron grit for in situ stabilization of Cd, Pb, and Zn in a contaminated soil

Abstract

In situ stabilization of Cd, Pb, and Zn in an Austrian agricultural soil contaminated by atmospheric depositions from a smelter plant was assessed with a pine bark chip-derived biochar, alone and in combination with either compost or iron grit. Biochar amendment was also trialed in an uncontaminated soil to detect any detrimental effect. The pot experiment consisted in ten soil treatments (% w/w): untreated contaminated soil (Unt); Unt soil amended with biochar alone (1%: B1; 2.5%: B2.5) and in combination: B1 and B2.5 + 5% compost (B1C and B2.5C), B1 and B2.5 + 1% iron grit (B1Z and B2.5Z); uncontaminated soil (Ctrl); Ctrl soil amended with 1 or 2.5% biochar (CtrlB1, CtrlB2.5). After a 3-month reaction period, the soil pore water (SPW) was sampled in potted soils and dwarf beans were grown for a 2-week period. The SPW Cd, Pb, and Zn concentrations decreased in all amended-contaminated soils. The biochar effects increased with its addition rate and its combination with either compost or iron grit. Shoot Cd and Zn removals by beans were reduced and shoot Cd, Pb, and Zn concentrations decreased to common values in all amended soils except the B1 soil. Decreases in the SPW Cd/Pb/Zn concentrations did not improve the root and shoot yields of plants as compared to the Ctrl soil.

http://ift.tt/2kfRcsf

The role of graphene oxide and graphene oxide-based nanomaterials in the removal of pharmaceuticals from aqueous media: a review

Abstract

In this review paper, the ill effects of pharmaceuticals (PhAs) on the environment and their adsorption on graphene oxide (GO) and graphene oxide-based (GO-based) nanomaterials have been summarised and discussed. The adsorption of prominent PhAs discussed herein includes beta-blockers (atenolol and propranolol), antibiotics (tetracycline, ciprofloxacin and sulfamethoxazole), pharmaceutically active compounds (carbamazepine) and analgesics such as diclofenac. The adsorption of PhAs strictly depends upon the experimental conditions such as pH, adsorbent and adsorbate concentrations, temperature, ionic strength, etc. To understand the adsorption mechanism and feasibility of the adsorption process, the adsorption isotherms, thermodynamics and kinetic studies were also considered. Except for some cases, GO and its derivatives show excellent adsorption capacities for PhAs, which is crucial for their applications in the environmental pollution cleanup.

http://ift.tt/2jl92WM

Additive effects of the herbicide glyphosate and elevated temperature on the branched coral Acropora formosa in Nha Trang, Vietnam

Abstract

The combined effects of the herbicide glyphosate and elevated temperature were studied on the tropical staghorn coral Acropora formosa, in Nha Trang bay, Vietnam. The corals were collected from two different reefs, one close to a polluted fish farm and one in a marine-protected area (MPA). In the laboratory, branches of the corals were exposed to the herbicide glyphosate at ambient (28 °C) and at 3 °C elevated water temperatures (31 °C). Effects of herbicide and elevated temperature were studied on coral bleaching using photography and digital image analysis (new colorimetric method developed here based on grayscale), chlorophyll a analysis, and symbiotic dinoflagellate (Symbiodinium, referred to as zooxanthellae) counts. All corals from the MPA started to bleach in the laboratory before they were exposed to the treatments, indicating that they were very sensitive, as opposed to the corals collected from the more polluted site, which were more tolerant and showed no bleaching response to temperature increase or herbicide alone. However, the combined exposure to the stressors resulted in significant loss of color, proportional to loss in chlorophyll a and zooxanthellae. The difference in sensitivity of the corals collected from the polluted site versus the MPA site could be explained by different symbiont types: the resilient type C3u and the stress-sensitive types C21 and C23, respectively. The additive effect of elevated temperatures and herbicides adds further weight to the notion that the bleaching of coral reefs is accelerated in the presence of multiple stressors. These results suggest that the corals in Nha Trang bay have adapted to the ongoing pollution to become more tolerant to anthropogenic stressors, and that multiple stressors hamper this resilience. The loss of color and decrease of chlorophyll a suggest that bleaching is related to concentration of chloro-pigments. The colorimetric method could be further fine-tuned and used as a precise, non-intrusive tool for monitoring coral bleaching in situ.

http://ift.tt/2kfVhNi

A Systematic Review of Metoidioplasty and Radial Forearm Flap Phalloplasty in Female-to-male Transgender Genital Reconstruction: Is the “Ideal” Neophallus an Achievable Goal?

Introduction: The complex anatomy and function of the native penis is difficult to surgically replicate. Metoidioplasty and radial forearm flap phalloplasty (RFFP) are the 2 most commonly utilized procedures for transgender neophallus construction. Methods: A MEDLINE search for metoidioplasty and RFFP in female-to-male genital reconstruction was performed. Primary outcome measures were subsequently compared. A systematic review was planned in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyse guidelines. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was utilized to evaluate the quality of evidence. Results: Using Population, Intervention, Comparison and Outcomes tool criteria, a total of 188 articles were identified; 7 articles related to metoidioplasty and 11 articles related to RFFP met inclusion criteria. The GRADE quality of evidence was low to very low for all included studies. In studies examining metoidioplasty, the average study size and length of follow-up were 54 patients and 4.6 years, respectively (1 study did not report [NR]). Eighty-eight percent underwent a single-stage reconstruction (0 NR), 87% reported an aesthetic neophallus (3 NR), and 100% reported erogenous sensation (2 NR). Fifty-one percent of patients reported successful intercourse (3 NR), and 89% of patients achieved standing micturition (3 NR). In studies examining RFFP, the average study size and follow-up were 60.4 patients and 6.23 years, respectively (6 NR). No patients underwent single-stage reconstructions (8 NR). Seventy percent of patients reported a satisfactorily aesthetic neophallus (4 NR), and 69% reported erogenous sensation (6 NR). Forty-three percent reported successful penetration of partner during intercourse (6 NR), and 89% achieved standing micturition (6 NR). Compared with RFFP, metoidioplasty was significantly more likely to be completed in a single stage (P

http://ift.tt/2jMmp5F

Congenital Symmastia: A 3-Step Approach

Summary: Congenital symmastia is a medial confluence of the breasts. It is a rare anomaly with few reports in the literature and no standard treatment. In this article, we present a case of congenital symmastia treated by 3 steps: liposuction, fixation of the skin to the chest wall in the area of the intermammary sulcus, and postoperative intermammary compression. A successful result was achieved with normal cleavage between the breasts. So, this is considered the ideal treatment for this condition.

http://ift.tt/2jMn2w2

Two Cases of Adverse Reactions of Hyaluronic Acid–based Filler Injections

Hyaluronic acid (HA) is one of the natural components of the human body with high biocompatibility, biodegradability, and nonimmunogenicity, which makes it the ideal biomedical filling agent currently available. However, for many medical practitioners, HA filler injections remain a relatively new item to carry out. Learning while practicing, it is inevitable to encounter some difficulties and adverse reactions in its application. Here we report two cases of adverse reactions to HA-based filler injections, including anaphylactic reaction on the face and vascular thrombosis after augmentation rhinoplasty with HA filler. In this report, we highlight the management and prevention of the adverse reactions, especially in case 2, because vascular thrombosis is one of the severe complications and injectors should know how to avoid it and how to deal with it, thereby increasing the safety of HA-based procedures.

http://ift.tt/2jMhGkn

A comparison of antibacterial and antibiofilm efficacy of phenothiazinium dyes between Gram positive and Gram negative bacterial biofilm

Publication date: Available online 21 January 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Lama Misba, Sahar Zaidi, Asad U. Khan
BackgroundAntimicrobial photodynamic therapy (APDT) is a process that generates reactive oxygen species (ROS) in presence of photosensitizer, visible light and oxygen which destroys the bacterial cells. We investigated the photoinactivation efficiency of phenothiazinium dyes and the effect of ROS generation on Gram positive and Gram negative bacterial cell as well as on biofilm.Material and MethodsEnterococcus faecalis and Klebsiella pneumonia were incubated with all the three phenothiazinium dyes and exposed to 630nm of light. After PDT, colony forming unit (CFU) were performed to estimate the cell survival fraction. Intracellular reactive oxygen species (ROS) was detected by DCFH-DA. Crystal violet (CV) assay and extracellular polysaccharides (EPS) reduction assay were performed to analyze antibiofilm effect. Confocal laser electron microscope (CLSM) scanning electron microscope (SEM) was performed to assess the disruption of biofilm.Results8log10 reduction in bacterial count was observed in Enterococcus faecalis while 3log10 in Klebsiella pneumoniae. CV and EPS reduction assay revealed that photodynamic inhibition was more pronounced in Enterococcus faecalis. In addition to this CLSM and SEM study showed an increase in cell permeability of propidium iodide and leakage of cellular constituents in treated preformed biofilm which reflects the antibiofilm action of photodynamic therapy.ConclusionWe conclude that Gram-positive bacteria (Enterococcus faecalis) are more susceptible to APDT due to increased level of ROS generation inside the cell, higher photosensitizer binding efficiency and DNA degradation. Phenothiazinium dyes are proved to be highly efficient against both planktonic and biofilm state of cells.



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Positively charged phthalocyanine-arginine conjugates as efficient photosensitizer for photodynamic therapy

Publication date: Available online 21 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Ao Wang, Rongrong Zhou, Lin Zhou, Kang Sun, Jianchun Jiang, Shaohua Wei
Positively charged drugs usually have enhanced water solubility, cellular uptake efficiency and anticancer activity. However, the common quaternized and protonated cationic photosensitizers both have some drawbacks such as needing potentially dangerous agents for preparation and easily being deprotonated in alkaline circumstance. Arginine is unique among the amino acids as its guanidine group has exceptionally high basicity in aqueous solution, which may make it positively charged in a wide range of pH. In this paper, two arginine substituted zinc phthalocyanines (ArgEZnPc and ArgZnPc) were reported. They can be positively charged in the range of pH 5 to 9. Moreover, the photobiological, photochemical properties, subcellular localization, and in vitro anticancer activities of the them were also carried out. The results show that ArgZnPc may be not a good photosensitizer because of its poor photobiological activities though it is positively charged in a wide range of pHs. This may be attributed to the formation of inner salts between guanidine and carboxyl groups of ArgZnPc, which weakens its photobiological and in vitro anticancer activity. While in contrast, ArgEZnPc shows preferential localization in the lysosomes of HeLa cells, exhibits high water solubility, excellent ¹O2 and intracellular reactive oxygen species generation efficiency as well as high in vitro anticancer activity, making it a promising photosensitizer for photodynamic therapy.

Graphical abstract

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Inhibitors of nuclease and redox activity of apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1)

Publication date: Available online 21 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Sergey S. Laev, Nariman F. Salakhutdinov, Olga I. Lavrik
Human apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional protein which is essential in the base excision repair (BER) pathway of DNA lesions caused by oxidation and alkylation. This protein hydrolyzes DNA adjacent to the 5'-end of an apurinic/apyrimidinic (AP) site to produce a nick with a 3'-hydroxyl group and a 5'-deoxyribose phosphate moiety or activates the DNA binding activity of certain transcription factors through its redox function. Studies have indicated a role for APE1/Ref-1 in the pathogenesis of cancer and in resistance to DNA-interactive drugs. Thus, this protein has potential as a target in cancer treatment. As a result, major efforts have been directed to identify small molecule inhibitors against APE1/Ref-1 activities. These agents have the potential to become anticancer drugs. The aim of this review is to present recent progress in studies of all published small molecule APE1/Ref-1 inhibitors. The structures and activities of APE1/Ref-1 inhibitors, that target both DNA repair and redox activities, are presented and discussed. To date, there is an urgent need for further development of the design and synthesis of APE1/Ref-1 inhibitors due to high importance of this protein target.

Graphical abstract

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A stereoselective, catalytic strategy for the in-flow synthesis of advanced precursors of Rasagiline and Tamsulosin

Publication date: Available online 21 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Davide Brenna, Margherita Pirola, Laura Raimondi, Anthony J. Burke, Maurizio Benaglia
The diastereoselective, trichlorosilane-mediate reduction of imines, bearing different and removable chiral auxiliaries, in combination either with achiral bases or catalytic amounts of chiral Lewis bases, was investigated to afford immediate precursors of chiral APIs (Active Pharmaceutical Ingredients). The carbon-nitrogen double bond reduction was successfully performed in batch and in flow mode, in high yields and almost complete stereocontrol. By this metal-free approach, the formal synthesis of rasagiline and tamsulosin was successfully accomplished in micro(meso) flow reactors, under continuous flow conditions. The results of these explorative studies represent a new, important step towards the development of automated processes for the preparation of enantiopure biologically active compounds.

Graphical abstract

http://ift.tt/2jDw5NL

TRIM Family Proteins: Roles in Autophagy, Immunity, and Carcinogenesis

Publication date: Available online 22 January 2017
Source:Trends in Biochemical Sciences
Author(s): Shigetsugu Hatakeyama
Tripartite motif (TRIM) family proteins, most of which have E3 ubiquitin ligase activities, have various functions in cellular processes including intracellular signaling, development, apoptosis, protein quality control, innate immunity, autophagy, and carcinogenesis. The ubiquitin system is one of the systems for post-translational modifications, which play crucial roles not only as markers for degradation of target proteins by the proteasome but also as regulators of protein–protein interactions and of the activation of enzymes. Accumulating evidence has shown that TRIM family proteins have unique, important roles and that their dysregulation causes several diseases classified as cancer, immunological disease, or developmental disorders. In this review we focus on recent emerging topics on TRIM proteins in the regulation of autophagy, innate immunity, and carcinogenesis.



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A Golden Age for Working with Public Proteomics Data

Publication date: Available online 22 January 2017
Source:Trends in Biochemical Sciences
Author(s): Lennart Martens, Juan Antonio Vizcaíno
Data sharing in mass spectrometry (MS)-based proteomics is becoming a common scientific practice, as is now common in the case of other, more mature 'omics' disciplines like genomics and transcriptomics. We want to highlight that this situation, unprecedented in the field, opens a plethora of opportunities for data scientists. First, we explain in some detail some of the work already achieved, such as systematic reanalysis efforts. We also explain existing applications of public proteomics data, such as proteogenomics and the creation of spectral libraries and spectral archives. Finally, we discuss the main existing challenges and mention the first attempts to combine public proteomics data with other types of omics data sets.



http://ift.tt/2k2z95P

Comparison of the local effects of a 600-μm bare fibre at high laser power on lung parenchyma: Nd:YAG laser 1320 vs. 1064 nm

Abstract

Lung metastases are often resected non-anatomically with a laser using a diode-pumped Nd:YAG laser at a wavelength of 1320 nm with a laser output of up to 60 W. Usually the removal of lesions is carried out in contact mode by means of a bare fibre. We compared the local effects of an Nd:YAG laser at a wavelength of 1064 nm with those at a wavelength of 1320 nm using a 600-μm bare fibre in contact mode in an experimental model. The investigations were carried out on porcine lungs freshly withdrawn at the abattoir. The 600-μm laser fibre was fixed vertically in contact with the lung surface on a fibre holder. The fibre holder was connected to a feeding device that advances the laser fibre at constant speeds (5, 10 or 20 mm/s). In each case, two laser powers were examined: 20 and 60 W. The lung lesions produced by the laser fibre were excised for histological examination. After haematoxylin–eosin staining, the depth of the vaporisation and coagulation zones (in μm) from the laser cuts was measured. For each setting, an average value was calculated. The individual groups were compared for significance using a non-parametric Mann–Whitney U test (p < 0.05). At a low speed of the bare fibre of 5 mm/s and a laser output of 20 W, the average depth of the vaporisation zone was 858 ± 3.3 μm (λ = 1064 nm) compared to 766.0 ± 7.5 μm (λ = 1320 nm) (p < 0.01). Upon faster movement (20 mm/s), the extension of the vaporisation zone decreased to 320.3 ± 7.1 μm (λ = 1064 nm). The depth of the vaporisation zone increased significantly at 60 W, both at λ = 1064 and 1320 nm with 1517.0 ± 1.7 μm and 1414.0 ± 4.9 μm, respectively. The extent of the coagulation zone was significantly smaller at 20 W and the low speed of 5 mm/s, namely, 200.4 ± 3.7 μm (λ = 1064 nm) and 224.1 ± 2.8 μm (1320-nm laser). Upon faster movement of the laser fibre at the same output, the extent of the coagulation zone decreased in both groups. At a laser power of 60 W, the extent of the coagulation zone was significantly less with the 1064-nm laser (110.3 ± 2.4 μm) than with the 1320-nm laser (324.8 ± 1.9 μm; p < 0.001). When the laser fibre moves more rapidly, the extent of the coagulation zone decreases further. The Nd:YAG laser with a wavelength of 1320 nm still has the optimal ratio of cutting and coagulation capacity on the resection surface. With the 1064-nm Nd:YAG laser, a higher cutting capacity is associated with a decrease of the coagulation capacity.

http://ift.tt/2jLhNwk

In vivo near-infrared imaging and phototherapy of tumors using a cathepsin B-activated fluorescent probe

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Xiaoqiang Chen, Dayoung Lee, Sungsook Yu, Gyoungmi Kim, Songyi Lee, Yejin Cho, Haengdueng Jeong, Ki Taek Nam, Juyoung Yoon
The development of multifunctional reagents for simultaneous specific near-infrared (NIR) imaging and phototherapy of tumors is of great significance. This work describes the design of a cathepsin B-activated fluorescent probe (CyA-P-CyB) and its applications as an NIR imaging probe for tumor cells and as a phototherapy reagent for tumors. In vitro experiments demonstrated that CyA-P-CyB was activated via the cleavage of a peptide linker by cathepsin B in tumor cells to produce fluorescence in the NIR region based on a FRET mechanism. MTT assays showed that the phototoxicity of CyA-P-CyB toward cells depended on the activity of cathepsin B, and the probe exhibited specific phototoxicity toward tumor cells. CyA-P-CyB was also successfully applied to the in vivo imaging and phototherapy of tumors. Histological analysis indicated that CyA-P-CyB had no cytotoxic effects on seven mouse tissues (lung, liver, heart, kidney, pancreas, spleen and brain) after the CyA-P-CyB treatment and laser irradiation.

Graphical abstract

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Tackling the salinity-pollution nexus in coastal aquifers from arid regions using nitrate and boron isotopes

Abstract

Salinization and nitrate pollution are generally ascertained as the main issues affecting coastal aquifers worldwide. In arid zones, where agricultural activities also result in soil salinization, both phenomena tend to co-exist and synergically contribute to alter groundwater quality, with severe negative impacts on human populations and natural ecosystems' wellbeing. It becomes therefore necessary to understand if and to what extent integrated hydrogeochemical tools can help in distinguishing among possible different salinization and nitrate contamination origins, in order to provide adequate science-based support to local development and environmental protection. The alluvial plain of Bou-Areg (North Morocco) extends over about 190 km² and is separated from the Mediterranean Sea by the coastal Lagoon of Nador. Its surface is covered for more than 60% by agricultural activities, although the region has been recently concerned by urban population increase and tourism expansion. All these activities mainly rely on groundwater exploitation and at the same time are the main causes of both aquifer and lagoon water quality degradation. For this reason, it was chosen as a case study representative of the typical situation of coastal aquifers in arid zones worldwide, where a clear identification of salinization and pollution sources is fundamental for the implementation of locally oriented remedies and long-term management strategies. Results of a hydrogeochemical investigation performed between 2009 and 2011 show that the Bou-Areg aquifer presents high salinity (often exceeding 100 mg/L in TDS) due to both natural and anthropogenic processes. The area is also impacted by nitrate contamination, with concentrations generally exceeding the WHO statutory limits for drinking water (50 mg/L) and reaching up to about 300 mg/L, in both the rural and urban/peri-urban areas. The isotopic composition of dissolved nitrates (δ¹⁵N_NO3 and δ¹⁸O_NO) was used to constrain pollution drivers. The results indicate two main origins for human-induced pollution: (i) manure and septic effluents, especially in urban areas, and (ii) synthetic fertilizers in agricultural areas. In the latter, δ¹⁵N-enriched values highlight a mixture of those sources, possibly related to unbalanced fertilization and agricultural return flow. Boron isotopes (δ¹¹B) were hence studied to further distinguish the nitrate origin in the presence of multiple sources and mixing processes. The results indicate that in the study area, the high geochemical background for B and Cl, associated to the complex water-rock interaction processes, limit the application of the coupled δ¹¹B and δ¹⁵N isotopic systematics to the detection of sources of groundwater pollution. In fact, despite the exceedingly high nitrate contents, the depleted δ¹¹B values that characterize synthetic fertilizers and sewage leakages could not be detected. Therefore, even if in saline groundwater the anthropogenic contribution has a negligible effect in terms of salinity input, with both sewage and irrigation water not very charged, the associated nitrate content fuels up water-rock interaction processes, eventually leading to a mineralization increase.

http://ift.tt/2ja9QAk

Influence of environmental and anthropogenic factors at the bottom sediments in a Doce River tributary in Brazil

Abstract

In developing countries, it is uncommon to find watersheds that have been the object of detailed environmental studies. It makes the assessment of the magnitude of environmental impacts and pollution of these sites difficult. This research demonstrated ways to understand the dynamics of river bottom sediments contamination, even for watersheds with a lack of environmental data. Based on geochemical affinity, we conducted a comprehensive study on the concentration of metals and metalloids. Then, we discussed the probable origin of the concentration of these elements at the bottom sediment along the Matipó River. The Matipó River is an important tributary of the Doce River, which stood out in international headlines because of the mining tailing dam disaster in Mariana, Minas Gerais, in 2015. The bottom sediment samples were taken in 25 stations located along the basin in different seasonal periods. The results showed that copper ( \( \overline{x} \) = 464.7 mg kg⁻¹) and zinc ( \( \overline{x} \) = 287.7 mg kg⁻¹) probably have natural origin, despite of the high concentrations. Lead ( \( \overline{x} \) = 28.0 mg kg⁻¹), chromium ( \( \overline{x} \) = 153.2 mg kg⁻¹), and nickel ( \( \overline{x} \) = 41.8 mg kg⁻¹) also had high concentrations at some collecting stations, and this probably reflected the local natural conditions. The bedrock of the studying basin is dominantly composed of metabasalts and metatonalites interlayered with calcitic and dolomitic metalimestone. On the other hand, the concentration was worrisome in stations near human activities, possibly due to impacts caused by unsustainably agriculture and livestock.

http://ift.tt/2k2oKHh

Symptom burden and dysphagia associated with osteoradionecrosis in long-term oropharynx cancer survivors: A cohort analysis

Publication date: March 2017
Source:Oral Oncology, Volume 66
Author(s): Angela T.T. Wong, Stephen Y. Lai, G. Brandon Gunn, Beth M. Beadle, Clifton D. Fuller, Martha P. Barrow, Theresa M. Hofstede, Mark S. Chambers, Erich M. Sturgis, Abdallah Sherif Radwan Mohamed, Jan S. Lewin, Katherine A. Hutcheson
ObjectiveThe purpose is to examine the relationship between mandibular osteoradionecrosis (ORN) and chronic dysphagia in long-term oropharynx cancer (OPC) survivors, and to determine the perceived symptom burden associated with ORN.Materials and methodsMedical records of 349 OPC patients treated with bilateral IMRT and systemic therapy were reviewed. ORN was graded using a published 4-point classification schema. Patients were considered to have chronic dysphagia if they had aspiration pneumonia, stricture or aspiration detected by fluoroscopy or endoscopy, and/or feeding tube dependence in long-term follow-up ⩾1year following radiotherapy. MD Anderson Symptom Inventory – Head and Neck Module (MDASI-HN) scores were analyzed in a nested cross-sectional survey sample of 118 patients.Results34 (9.7%, 95% CI: 6.8–13.3%) patients developed ORN and 45 (12.9%, 95% CI: 9.6–16.9%) patients developed chronic dysphagia. Prevalence of chronic dysphagia was significantly higher in ORN cases (12/34, 35%) compared to those who did not develop ORN (33/315, 11%, p<0.001). ORN grade was also significantly associated with prevalence of dysphagia (p<0.001); the majority of patients with grade 4 ORN requiring major surgery (6 patients, 75%) were found to have chronic dysphagia. Summary MDASI-HN symptom scores did not significantly differ by ORN grade. Significantly higher symptom burden was reported, however, among ORN cases compared to those without ORN for MDASI-HN swallowing (p=0.033), problems with teeth and/or gums (p=0.016) and change in activity (p=0.015) item scores.ConclusionsORN is associated with excess burden of chronic dysphagia and higher symptom severity related to swallowing, dentition and activity limitations.



http://ift.tt/2j5U8WU

Effects of two grading techniques of zirconia material on the fatigue limit of full-contour 3-unit fixed dental prostheses

Publication date: Available online 21 January 2017
Source:Dental Materials
Author(s): Regina Furbino Villefort, Marina Amaral, Gabriel Kalil Rocha Pereira, Tiago Moreira Bastos Campos, Yu Zhang, Marco Antonio Bottino, Luiz Felipe Valandro, Renata Marques de Melo
ObjectiveThis study evaluated the effects of two grading techniques of zirconia material on the fatigue limit of full-contour 3-unit fixed dental prostheses (FDPs).MethodsPresintered blocks of 3Y-TZP were milled to obtain sixty-nine 3-unit FDPs, which were divided into three groups (n=23). The control group (CTL) was sintered and glazed following manufacturer's instructions. In the two experimental groups presintered FDPs received a surface silica/glass infiltration treatment before the sintering process. Silica sol–gel group (SSG) was graded by the sol–gel processing route, while the glass-zirconia-glass group (GZG) was graded by an enameling technique. Graded groups did not receive a glaze layer after sintering. All FDPs were then luted with a dual-curing resin cement on composite abutments, embedded in polyurethane and stored in water for five days. The initial load of the fatigue test was calculated based on the results of the monotonic testing applied on three specimens of each group. To determine the fatigue limit, 20 samples of each group were subjected to staircase testing (100,000 cycles/5Hz).ResultsThe fatigue limits (in Newtons) were CTL=1607.27, SSG=1824.31, and GZG=2006.57, and the Dixon and Mood test indicated statistically significant differences among groups (95% confidence interval) (GZG > SSG > CTL).SignificanceThe infiltration of silica and glass on bulk zirconia, by two different grading methods, increased the fatigue limits of monolithic zirconia FDPs.



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Crystallization kinetics of syndiotactic polypropylene confined in nanoporous alumina

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Linling Li, Jingwen Liu, Linlin Qin, Chen Zhang, Ye Sha, Jing Jiang, Xiaoliang Wang, Wei Chen, Gi Xue, Dongshan Zhou
Crystalline polymers can exhibit anomalous crystallization behaviors as restricted into nanodomains. Herein, syndiotactic polypropylene (sPP) was infiltrated into nanoporous alumina templates with different pore diameters, and their nonisothermal and isothermal crystallization kinetics were investigated. As located inside nanopores, the crystallization of sPP becomes sluggish. The crystallization temperatures reveal a pronounced cooling rate dependence for sPP in large nanopores. At fast cooling rates, the homogeneous nucleation is dominated. While, at slow cooling rates, the splits of crystallization peaks can be ascribed to fractionated crystallizations initiated by heterogeneous and homogeneous nucleation, respectively. For sPP in small nanopores, the homogeneous nucleation always predominates, which induces less cooling rate effect. In addition, based on the Avrami equation and Lauritzen-Hoffman growth theory, isothermal crystallization experiments indicate that the characteristic crystallization times of sPP under confinement are much longer, and both of the nuclei density and secondary nucleation rate are decreased for sPP confined in nanopores.

Graphical abstract

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Highly-branched cross-linked poly(ethylene oxide) with enhanced ionic conductivity

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Nachiket Paranjape, Praphulla Chandra Mandadapu, Gang Wu, Haiqing Lin
Polymers containing poly(ethylene oxide) (PEO) have been investigated for solid electrolytes for lithium-ion batteries, which are preferred to be amorphous and have flexible polymer chains to achieve high Li ion conductivity. This paper reports ionic conductivity in a series of cross-linked PEOs prepared from poly(ethylene glycol) methyl ether acrylate (PEGMEA, monomer) and poly(ethylene glycol) diacrylate (PEGDA, cross-linker) via photopolymerization. The resulting copolymers contain short PEO side chains and thus high content of amorphous PEO. While the cross-linking enhances mechanical strength for solid electrolytes, the introduction of PEGMEA with methoxyl chain end groups decreases Tg and increases ionic conductivity. The use of acrylate groups for polymerization, instead of methacrylate groups, also yields low Tg and thus high conductivity. The effect of PEGMEA content, salt content, and temperature on the ionic conductivity was thoroughly investigated, and it was satisfactorily described using the Vogel-Fulcher-Tammann (VFT) equation. The effectiveness of PEO-based polymers used for solid electrolytes in advanced lithium batteries was also elucidated based on the VFT equation.

Graphical abstract

http://ift.tt/2k2snwD

Crosslinking of an ethylene-glycidyl methacrylate copolymer with amine click chemistry

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Massimiliano Mauri, Nina Tran, Oscar Prieto, Thomas Hjertberg, Christian Müller
Commonly used crosslinking methods for polyethylenes result in the release of harmful by-products. Here, we demonstrate that an epoxy-bearing polyethylene copolymer, which contains 8 wt% glycidyl methacrylate, can be efficiently crosslinked without by-product formation. Click chemistry based on multifunctional amine curing agents, which carry at least two functional groups separated by a flexible spacer, was used to prepare thermosets. Compounding of the crosslinker and copolymer through extrusion at 120 °C could be carried out without onset of the curing reactions. Careful adjustment of the curing time and temperature, ranging from 20 to 120 min and 160–200 °C, resulted in a high network density of at least 2.8 crosslinks per 1000 carbons at a curing agent stoichiometry of as little as 0.5 wt%.

Graphical abstract

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Iron Mapping in Multiple Sclerosis

Publication date: Available online 20 January 2017
Source:Neuroimaging Clinics of North America
Author(s): Stefan Ropele, Christian Enzinger, Franz Fazekas

Teaser

Increased iron deposition in cerebral deep gray matter has been considered a global marker for neurodegeneration in multiple sclerosis (MS); it scales with disease duration and severity. Iron accumulation in white matter and MS lesions might be more directly related to disease activity and has been discussed as a contributor to the inflammatory and neurodegenerative cascade. New insights into iron and MS are expected from MR imaging. We discuss findings from MR iron mapping proposed. Because of the confounding magnetic properties of myelin, iron mapping in white matter remains an unresolved issue.


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Conductive nanogel-interfaced neural microelectrode arrays with electrically controlled in-situ delivery of manganese ions enabling high-resolution MEMRI for synchronous neural tracing with deep brain stimulation

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Wei-Chen Huang, Yu-Chih Lo, Chao-Yi Chu, Hsin-Yi Lai, You-Yin Chen, San-Yuan Chen
Chronic brain stimulation has become a promising physical therapy with increased efficacy and efficiency in the treatment of neurodegenerative diseases. The application of deep brain electrical stimulation (DBS) combined with manganese-enhanced magnetic resonance imaging (MEMRI) provides an unbiased representation of the functional anatomy, which shows the communication between areas of the brain responding to the therapy. However, it is challenging for the current system to provide a real-time high-resolution image because the incorporated MnCl2 solution through microinjection usually results in image blurring or toxicity due to the uncontrollable diffusion of Mn²⁺. In this study, we developed a new type of conductive nanogel-based neural interface composed of amphiphilic chitosan-modified poly(3,4 -ethylenedioxythiophene) (PMSDT) that can exhibit biomimic structural/mechanical properties and ionic/electrical conductivity comparable to that of Au. More importantly, the PMSDT enables metal-ligand bonding with Mn²⁺ ions, so that the system can release Mn²⁺ ions rather than MnCl2 solution directly and precisely controlled by electrical stimulation (ES) to achieve real-time high-resolution MEMRI. With the integration of PMSDT nanogel-based coating in polyimide-based microelectrode arrays, the post-implantation DBS enables frequency-dependent MR imaging in vivo, as well as small focal imaging in response to channel site-specific stimulation on the implant. The MR imaging of the implanted brain treated with 5-min electrical stimulation showed a thalamocortical neuronal pathway after 36 h, confirming the effective activation of a downstream neuronal circuit following DBS. By eliminating the susceptibility to artifact and toxicity, this system, in combination with a MR-compatible implant and a bio-compliant neural interface, provides a harmless and synchronic functional anatomy for DBS. The study demonstrates a model of MEMRI-functionalized DBS based on functional neural interface engineering and controllable delivery technology, which can be utilized in more detailed exploration of the functional anatomy in the treatment of neurodegenerative diseases.



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Fibroin particle-supported cationic lipid layers for highly efficient intracellular protein delivery

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Woo-Jin Kim, Bong-Soo Kim, Young-Dan Cho, Won-Joon Yoon, Jeong-Hwa Baek, Kyung-Mi Woo, Hyun-Mo Ryoo
Directly delivering therapeutic proteins into cells has promise as an intervention without side effects for protein deficiencies caused by genetic defects. However, as negatively charged macromolecules, proteins require carriers for achieving cellular uptake and maintaining their activity in the cytoplasm. The biodegradable natural polymer silk fibroin has demonstrated outstanding advantages as a protein drug scaffold in vitro and in vivo, but its usage has been limited in the extracellular space because of its negatively charged character. Here, we present an intracellular protein delivery system based on fibroin particles coated with cationic lipid layers, denoted as Fibroplex, the surface charge of which can be modulated. Fibroplex showed higher delivery efficiency than conventional delivery methods as well as long-term cargo release in the cytoplasm without toxicity. Furthermore, in vivo experiments showed that Fibroplex efficiently delivered tyrosinase and horseradish peroxidase, which led to hyper-pigmentation and tumor regression, respectively, suggesting its potential for therapeutic protein applications in hereditary diseases or cancer.



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Aurantiamide Acetate from Baphicacanthus cusia root exhibits Anti-Inflammatory and Anti-viral Effects via inhibition of the NF-κB Signaling Pathway in Influenza A virus-infected Cells

Publication date: Available online 21 January 2017
Source:Journal of Ethnopharmacology
Author(s): Beixian Zhou, Zifeng Yang, Qitong Feng, Xiaoli Liang, Jing Li, Mark Zanin, Zhihong Jiang, Nanshan Zhong
Ethnopharmacological relevanceBaphicacanthus cusia root also names "Nan Ban Lan Gen" has been traditionally used to prevent and treat influenza A virus infections. Here, we identified a peptide derivative, aurantiamide acetate (compound E17), as an active compound in extracts of B. cusia root. Although studies have shown that aurantiamide acetate possesses antioxidant and anti-inflammatory properties, the effects and mechanism by which it functions as an anti-viral or as an anti-inflammatory during influenza virus infection are poorly defined. Here we investigated the anti-viral activity and possible mechanism of compound E17 against influenza virus infection.Materials and MethodsThe anti-viral activity of compound E17 against Influenza A virus (IAV) was determined using the cytopathic effect (CPE) inhibition assay. Viruses were titrated on Madin-Darby canine kidney (MDCK) cells by plaque assays. Ribonucleoprotein (RNP) luciferase reporter assay was further conducted to investigate the effect of compound E17 on the activity of the viral polymerase complex. HEK293T cells with a stably transfected NF-κB luciferase reporter plasmid were employed to examine the activity of compound E17 on NF-κB activation. Activation of the host signaling pathway induced by IAV infection in the absence or presence of compound E17 was assessed by western blotting. The effect of compound E17 on IAV-induced expression of pro-inflammatory cytokines was measured by real-time quantitative PCR and Luminex assays.ResultsCompound E17 exerted an inhibitory effect on IAV replication in MDCK cells but had no effect on avian IAV and influenza B virus. Treatment with compound E17 resulted in a reduction of RNP activity and virus titers. Compound E17 treatment inhibited the transcriptional activity of NF-κB in a NF-κB luciferase reporter stable HEK293 cell after stimulation with TNF-α. Furthermore, compound E17 blocked the activation of the NF-κB signaling pathway and decreased mRNA expression levels of pro-inflammatory genes in infected cells. Compound E17 also suppressed the production of IL-6, TNF-α, IL-8, IP-10 and RANTES from IAV-infected lung epithelial (A549) cells.ConclusionsThese results indicate that compound E17 isolated from B. cusia root has potent anti-viral and anti-inflammatory effects on IAV-infected cells via inhibition of the NF-κB pathway. Therefore, compound E17 could be a potential therapeutic agent for the treatment of influenza.

Graphical abstract

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New aspects on the hepatoprotective potential associated with the antioxidant, hypocholesterolemic and anti-inflammatory activities of Vernonia condensata Baker

Publication date: Available online 21 January 2017
Source:Journal of Ethnopharmacology
Author(s): Jucélia Barbosa da Silva, Renata de Freitas Mendes, Vívian Tomasco, Nícolas de Castro Campos Pinto, Luiz Gustavo de Oliveira, Matheus Nehrer Rodrigues, Danielle Maria de Oliveira Aragão, Jair Adriano Kopke de Aguiar, Maria Silvana Alves, Maria Christina Nogueira Marques Castañon, Antônia Ribeiro, Elita Scio
Ethnopharmacological RelevanceVernonia condensata Baker (Asteraceae) is traditionally used in South American Countries as an anti-inflammatory, analgesic and hepatoprotective.Aim of the studyThis study aimed to investigate the in vivo hepatoprotective and antioxidant, and the in vitro anti-inflammatory activities of the ethyl acetate partition (EAP) from the ethanolic extract of this medicinal plant leaves.Materials and methodsFor the in vivo hepatoprotective activity, rats were pretreated orally for seven days with vehicle, silymarin 100mg/kg or EAP 50, 100 and 200mg/kg. Then, acetaminophen 3g/kg was also orally administrated. Animals were euthanatized 24h after the damage inducement. The levels of the serum enzymes ALT, AST and ALP were determined, as well as the triglycerides, total cholesterol and fractions. The antioxidant activity was evaluated by TBARS assay and by the measurement of glutathione reductase, superoxide dismutase and catalase activities in the rats liver tissue. The in vitro anti-inflammatory assay using Raw 264.7 cell line induced by lipopolysaccharide was conducted to verify EAP ability to inhibit pro-inflammatory cytokines.ResultsEAP was able to inhibit all the acute biochemical alterations caused by acetaminophen overdose. EAP inhibited malondialdehyde formation, maintained the catalase and increased the glutathione reductase activities. Also, EAP decreased NO, IL-6 and TNF-α levels at concentrations from 10 to 20µg/mL. 1,5-dicaffeoylquinic acid was isolated and identified as the major compound in EAP. Apigenin, luteolin, chlorogenic acid were also identified. EAP anti-inflammatory action may be due to its antioxidant activity or its capacity to inhibit the pro-inflammatory cytokines.ConclusionThese results strongly suggested that V. condensata may be useful as a possible therapy against liver damage.

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Hawthorn (Crataegus pinnatifida Bunge) leave flavonoids attenuate atherosclerosis development in apoE knock-out mice

Publication date: Available online 21 January 2017
Source:Journal of Ethnopharmacology
Author(s): Pengzhi Dong, Lanlan Pan, Xiting Zhang, Wenwen Zhang, Xue Wang, Meixiu Jiang, Yuanli Chen, Yajun Duan, Honghua Wu, Yantong Xu, Peng Zhang, Yan Zhu
Ethnopharmacological relevanceHawthorn (Crataegus pinnatifida Bunge) leave have been used to treat cardiovascular diseases in China and Europe. Hawthorn leave flavonoids (HLF) are the main part of extraction. Whether hawthorn leave flavonoids could attenuate the development of atherosclerosis and the possible mechanism remain unknown.Materials and methodsHigh-fat diet (HFD) mixed with HLF at concentrations of 5mg/kg and 20mg/kg were administered to apolipoprotein E (apoE) knock out mice. 16 weeks later, mouse serum was collected to determine the lipid profile while the mouse aorta dissected was prepared to measure the lesion area. Hepatic mRNA of genes involved in lipid metabolism were determined. Peritoneal macrophages were collected to study the impact of HLF on cholesterol efflux, formation of foam cell and the expression of ATP binding cassette transporter A1 (ABCA1). Besides, in vivo reverse cholesterol transport (RCT) was conducted.ResultsHLF attenuated the development of atherosclerosis that the mean atherosclerotic lesion area in en face aortas was reduced by 23.1% (P<0.05). In mice fed with 20mg/kg HLF, Total cholesterol (TC) level was decreased by 18.6% and very low density lipoprotein cholesterol plus low density lipoprotein cholesterol (VLDLc+LDLc) level were decreased by 23.1% whereas high density lipoprotein cholesterol (HDLc) and triglyceride (TG) levels were similar compared to that of the control group. Peroxisome proliferator activated receptor alpha (PPARα) mRNA was increased by 31.2% (P<0.05) and 60.9% (P<0.05) in mice fed with 5mg/kg and 20mg/kg HLF respectively. Sterol regulatory element binding protein-1c (SREBP-1c) was decreased by 59.3% in the group of 20mg/kg. Carnitine palmitoyl transferase 1 (CPT-1) mRNA level of 20mg/kg group was induced 66.7% (P<0.05). Superoxide dismutase 1 and 2 (SOD1 and SOD2) mRNA were induced 25.4% (P<0.05) and 71.4% (P<0.05) while induced by 36.3% (P<0.05) and 73.2% (P<0.05) in group of 20mg/kg. Glutathione peroxidase 3 (Gpx3) mRNA in the group of 20mg/kg was induced by 96.7% (P<0.05). Hepatic hydroxymethylglutaryl CoA reductase (HMG-CoAR) expression was as same level as the control group while LDL receptor (LDLR) mRNA and protein were induced by 84.2% (P<0.05) and 98.8% (P<0.05) in group of 20mg/kg. HLF inhibit the formation of foam cell by 27.9% (P<0.05) in the dosage of 25μg/ml, and 33.3% (P<0.05) in the dosage of 50μg/ml. HLF increased the reverse cholesterol transport (RCT) in vivo.Discussion and conclusionHawthorn leave flavonoids can slow down the development of atherosclerosis in apoE knockout mice via induced expression of genes involved in antioxidant activities, inhibition of the foam cell formation and promotion of RCT in vivo, which implies the potential use in the prevention of atherosclerosis.

Graphical abstract

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Investigations on anti-inflammatory and analgesic activities of Alnus nitida Spach (Endl). stem bark in Sprague Dawley rats

Publication date: Available online 21 January 2017
Source:Journal of Ethnopharmacology
Author(s): Moniba Sajid, Muhammad Rashid Khan, Sayed Afzal Shah, Muhammad Majid, Hammad Ismail, Sonia Maryam, Riffat Batool, Tahira Younis
Ethnopharmacological relevanceStem bark of Alnus nitida (Spach) Endl. (family Betulaceae) is used by local communities in northern areas of Pakistan as a remedy for swelling, injuries and pain. However no pharmacological study of this plant has been reported to confirm these activities. In this study anti-inflammatory and analgesic effect of A. nitida stem bark have been evaluated.MethodsPowder of the stem bark of A. nitida was extracted with methanol (ANBM) and partitioned in escalating polarity to get the n-hexane (ANBH), chloroform (ANBC), ethyl acetate (ANBE) and the residual soluble aqueous (ANBA) fractions. The methanol extract and derived fractions were evaluated for anti-inflammatory activity by using in vitro heat induced albumin denaturation assay and various in vivo assays; carrageenan-induced hind paw edema method, Freunds' complete adjuvant induced arthritis, histamine induced paw edema and xylene induced ear edema in Sprague Dawley rat. The extracts/fractions were also evaluated for analgesic effects by using hot plate analgesic test and acetic acid induced writhing test in rat. The ANBM composition was analyzed by HPLC-DAD and GC-MS analysis.ResultsResults of heat induced albumin denaturation activity indicated that among the extract/fractions ANBC at concentration range of 100 − 500µg/ml remarkably protected the heat induced albumin denaturation. The pretreatment with ANBC significantly reduced the carrageenan induced edema with 90.81±1.6% after 4h, comparing with 86.63±3.42% reduction produced by the reference drug diclofenac potassium. Histopathological alterations of the gastric and hind paw were decreased with the extract/fractions. Furthermore, anti-inflammatory effects of ANBC were evident in Freunds' complete adjuvant induced arthritis, histamine induced paw edema and xylene induced ear edema. The latency time in hot plate analgesic assay with ANBC (61.59±0.38%) after 90min was comparable to standard drug morphine (69.31±2.67%) and aspirin (67.24±2.08%). Similarly ANBC significantly (p < 0.01) inhibited the pain sensation in acetic acid induced writhing test in rat. HPLC-DAD analysis of ANBM indicated the presence of gallic acid, catechin and rutin while the GC-MS analysis of ANBM indicated the presence of 30 compounds predominantly of neophytadiene, 3,7,11,15 tetramethyl-2-hexadecen-1-ol, phytol, vitamin E and linalool.ConclusionThe results of this study suggested that the presence of polyphenols, sterols, terpenoids and other constituents might contributed towards the anti-inflammatory and analgesic activities of the crude methanol extract of A. nitida bark and its derived fractions. This study endorsed the folklore use of A. nitida bark for inflammation related disorders.

Graphical abstract

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Water extract of Helminthostachys zeylanica attenuates LPS-induced acute lung injury in mice by modulating NF-κB and MAPK pathways

Publication date: Available online 21 January 2017
Source:Journal of Ethnopharmacology
Author(s): Chian-Jiun Liou, Yu-Ling Huang, Wen-Chung Huang, Kuo-Wei Yeh, Tzu-Yi Huang, Chwan-Fwu Lin
Ethnopharmacological relevancePrevious studies showed that Helminthostachys zeylanica (L.) Hook. could reduce inflammatory responses in macrophage and brain astrocytes.Aim of the studyIn the present study, we evaluated whether an ethyl acetate extract (HZE) or a water extract (HZW) of H. zeylanica could reduce inflammatory responses in lung epithelial cells and ameliorate lipopolysaccharide (LPS)-induced acute lung injury in mice.MethodsHuman lung epithelial A549 cells were pre-treated with HZE or HZW (1–10μg/mL), then stimulated with LPS. BALB/c mice received oral HZW for 7 consecutive days, then an intratracheal instillation of LPS to induce lung injury.ResultsHZW reduced chemokine and proinflammatory cytokine production in LPS-activated A549 cells. HZW also suppressed ICAM-1 expression and reduced the adherence of acute monocytic leukemia cells to inflammatory A549 cells. HZE had less efficacy than HZW in suppressing inflammatory responses in A549 cells. In vivo, HZW significantly suppressed neutrophil infiltration and reduced the TNF-α and IL-6 levels in bronchoalveolar lavage fluid and serum from LPS-treated mice. HZW also modulated superoxide dismutase activity, glutathione, and myeloperoxidase activity in lung tissues from LPS-treated mice. HZW decreased the phosphorylation of mitogen-activated protein kinase and nuclear factor kappa B, and promoted heme oxygenase-1 expression in inflamed lung tissue from LPS-treated mice.ConclusionOur findings suggested that HZW reduced lung injury in mice by reducing oxidative stress and inflammatory responses. HZW also reduced inflammatory responses in human lung epithelial cells.

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Antiosteoporotic Effect of Hemidesmus indicus Linn. on Ovariectomised Rats

Publication date: Available online 21 January 2017
Source:Journal of Ethnopharmacology
Author(s): Sharad Desai, Parth Babaria, Madhavi Nakarani, Kunal Shah, Archana Paranjape
Pharmacological relevanceRoot of Hemidesmus indicus (L). R. Br., an herbal drug of India is traditionally used to prevent or treat female hormonal disturbance related disorders and assuaging symptoms of menopausal conditions.Aim of the studyLack of scientific data for potential use in bone loss, the present study was undertaken to investigate the effects of ethanol extract of Hemidesmus indicus root for osteoporosis in ovariectomised rats.Materials and MethodsThirty wistar female rats were randomly divided into five groups. One group was sham operated and other four groups were undergone dorsal ovariectomy (OVX). After four weeks of post-operative recovery, three OVX groups, viz. Group1, Group2 and Group3 were treated for ninety days with standard raloxifene (RLX) 1mg/kg/day, Hemidesmus indicus root extract (HIRE) 100mg/kg/day and HIRE 200mg/kg/day respectively. Sham and OVX control groups were fed with equal 1% vehicle volume. Serum and urine biochemistry (alkaline phosphatase, tartrate resistant acid phosphatase, triglyceride, total cholesterol, calcium, phosphorous and hydroxyproline), weight of body, uterus and vagina, femur parameters, three point bending of tibia and fourth lumbar vertebra compression were examined. Furthermore, bone architecture and uterine hypertrophy were examined by histopathological studies.ResultsApplication of HIRE has increased bone strength and restored bone turnover markers such as alkaline phosphatase, tartrate resistant acid phosphatase and hydroxyproline moreover, improved femur parameters indicated mineralized bones, similar to the results observed with raloxifene treatment. Histopathology studies showed fibrocartilaginous proliferation of trabecular bone and absence of uterine hypertrophy.ConclusionThe results strongly suggest that HIRE prevents bone loss in OVX induced osteoporosis without estrogen like side effects. It might be a potential remedy like raloxifene for postmenopausal or estrogen deficiency caused osteoporosis.

Graphical abstract

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Editorial Board

Publication date: February 2017
Source:Free Radical Biology and Medicine, Volume 103





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Chorda tympani nerve management in endoscopic stapes surgery

Publication date: Available online 20 January 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Ahmed Amin Omran, Ahmed Aly Ibrahim, Wael K.A. Hussein, Yasser Osman
ObjectivesTo demonstrate different techniques in manipulating the chorda tympani nerve during endoscopic stapedotomy for otosclerotic patients.MaterialsTwenty patients presented with clinically diagnosed otosclerosis were randomly selected from outpatient ENT clinic in a tertiary referral Hospital over a period of 2years (2013–2015) for endoscopic stapes surgery.MethodsThis prospective study demonstrates different management modalities of chorda tympani nerve in endoscopic stapes surgery according to the endoscopic anatomical relationship between the length of the chorda tympani nerve and the degree of scutum overhanging the oval window niche structures (endoscopic scutum- chorda tympani relationship).ResultsThree management techniques were carried out to deal with chorda tympani based on its endoscopic anatomical relationship with the scutum (no manipulation, upward-displacement, downward-displacement). All patients had significant improvement of postoperative hearing. Only 2 patients were managed by downward displacement technique had postoperative change in taste sensation and tongue numbness that improved over a period of 6months.Conclusiontrans-Canal fully endoscopic stapedotomy provides feasible and safe handling of the chorda tympani nerve with best postoperative taste sensation preservation.



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Vertical supranuclear gaze palsy in a toddler with Niemann-Pick type C

Publication date: Available online 21 January 2017
Source:Pediatric Neurology
Author(s): Tatiana Bremova, Michael Strupp




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Analysis of 22Na using a spectral summation technique on high-volume aerosol samples

Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): I. Hoffman, B. Lewis, P. Chan, K. Ungar
Measurement of cosmogenic ²²Na in daily aerosol samples is often difficult due to low atmospheric production rates. A new technique based upon spectral summation of sequential high-volume aerosol samples to measure ²²Na is described and validated. This summation technique has broad applications to any detection system that produces sequential representative sample measurements in which radioisotopes are just below the detection limit, provided the energy calibration is stable. It is anticipated that a global dataset of this radionuclide will have many important environmental science applications.



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On the divergences in assessment of environmental impacts from ionising radiation following the Fukushima accident

Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): P. Strand, S. Sundell-Bergman, J.E. Brown, M. Dowdall
The accident at the Fukushima-Daiichi Nuclear Power Station on March 11, 2011, led to significant contamination of the surrounding terrestrial and marine environments. Whilst impacts on human health remain the primary concern in the aftermath of such an accident, recent years have seen a significant body of work conducted on the assessment of the accident's impacts on both the terrestrial and marine environment. Such assessments have been undertaken at various levels of biological organisation, for different species, using different methodologies and coming, in many cases, to divergent conclusions as to the effects of the accident on the environment. This article provides an overview of the work conducted in relation to the environmental impacts of the Fukushima accident, critically comparing and contrasting methodologies and results with a view towards finding reasons for discrepancies, should they indeed exist. Based on the outcomes of studies conducted to date, it would appear that in order to avoid the fractured and disparate conclusions drawn in the aftermath of previous accidents, radioactive contaminants and their effects can no longer simply be viewed in isolation with respect to the ecosystems these effects may impact. A combination of laboratory based and field studies with a focus on ecosystem functioning and effects could offer the best opportunities for coherence in the interpretation of the results of studies into the environmental impacts of ionising radiation.



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The possible role of cerium oxide (CeO2) nanoparticles in prevention of neurobehavioral and neurochemical changes in 6-hydroxydopamine-induced parkinsonian disease

Publication date: Available online 20 January 2017
Source:Alexandria Journal of Medicine
Author(s): Maha Abd Elkader Hegazy, Hala Mohamed Maklad, Doaa A. Abd Elmonsif, Fatma Yosry Elnozhy, Malik Ahmad Alqubiea, Fisal Aliwi Alenezi, Obaid Mahdi Al abbas, Mahdi Mana Al abbas
Cerium oxide nanoparticles (CeO2NPs) is an efficient neuroprotective agent and showed promising effects in some neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis. However, the implication of CeO2NPs in Parkinsonism remains to be investigated.The aim of this study was to assess the possible role of CeO2NPs as a neuroprotective agent against the development of behavioral and biochemical changes in rat model of Parkinson's disease. Thirty rats were included and received left intrastriatal injection of either saline (controls, n=10) or 6-hydroxy dopamine (6-OHDA) in untreated group (n=10) and 10 rats were received intraperitoneal injection of low dose CeO2NPs two hours before surgery, and continued once daily for 6 weeks (preventive group). At the end of experimental period, rats were subjected to behavioral assessment and then killed for biochemical analysis of striatal dopamine levels, oxidative stress markers and caspase-3 activity. Results showed that CeO2NPs resulted in partial neuroprotection against disturbances in motor performance. It also partially decreased apoptosis and oxidative stress in preventive group, while it failed to increase striatal dopamine level as compared to untreated rats. The present study verified some neuroprotective effects of CeO2NPs in 6-OHDA-induced Parkinsonian rats through their antioxidant and anti apoptotic effects. Some of these effects persisted till the end of six weeks whereas others declined after three weeks. A larger dose may be needed to produce more valuable effects and to maintain protection for a longer period.



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Prospective comparative study between un-enhanced multidetector computed tomography and ultrasonography in evaluation of acute renal colic

Publication date: Available online 21 January 2017
Source:Alexandria Journal of Medicine
Author(s): Rehab Abdel Rahman El Bakry




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Changes in fMRI activation in anterior hippocampus and motor cortex during memory retrieval after an intense exercise intervention

Publication date: Available online 21 January 2017
Source:Biological Psychology
Author(s): Gerd Wagner, Marco Herbsleb, Feliberto de la Cruz, Andy Schumann, Stefanie Köhler, Christian Puta, Holger W. Gabriel, Jürgen R. Reichenbach, Karl-Jürgen Bär
Strong evidence indicates that regular aerobic training induces beneficial effects on cognitive functions. The present controlled fMRI study was designed to investigate the impact of a short-term intense aerobic exercise on the pattern of functional activation during the retrieval of learned pair-associates in 17 young and healthy male adults compared to 17 matched control subjects. We further aimed to relate putative changes in hippocampal activation to postulated changes in the exercised-induced brain derived neurotrophic factor (BDNF). The supervised exercise program was performed on a bicycle ergometer and lasted six weeks, with three aerobic sessions per week.We found profound improvement of physical fitness in most subjects indicated by the target parameter 'individual anaerobic threshold'. Significant improvements in the cognitive performance were detected in the exercise group, but also in the control group. We observed significant differences in the activation pattern of the left anterior hippocampus during the pair-associates task after the intervention. We could also show a significant positive correlation between changes in exercise-induced BDNF and left anterior as well as right hippocampal activation. Moreover, we observed the brain's motor network to be significantly stronger activated after the exercise intervention. Thus, our results suggest BDNF dependent activation changes of the hippocampus in addition to previously described structural changes after exercise.



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Tumor necrosis factor-alpha inhibitors suppress CCL2 chemokine in monocytes via epigenetic modification

Publication date: March 2017
Source:Molecular Immunology, Volume 83
Author(s): Yi-Ching Lin, Yu-Chih Lin, Ming-Yii Huang, Po-Lin Kuo, Cheng-Chin Wu, Min-Sheng Lee, Chong-Chao Hsieh, Hsuan-Fu Kuo, Chang-Hung Kuo, Wen-Chan Tsai, Chih-Hsing Hung
The treatment of rheumatoid arthritis (RA) with tumor necrosis factor-alpha (TNF-α) inhibitors could lead to adverse effects. Therefore, the identification of downstream therapeutic targets is important. Monocyte chemoattractant protein-1 (MCP-1, also called CCL2) is related to RA disease activity, and epigenetic modifications are hypothesized to regulate gene expression in RA pathogenesis. We studied the effects of two TNF-α inhibitors, etanercept and adalimumab, on CCL2 expression and the potentially associated intracellular mechanisms, including epigenetic regulation. Etanercept and adalimumab decreased CCL2 production in THP-1 cells and human primary monocytes, as detected using enzyme-linked immunosorbent assays, and these changes in the CCL2 levels were independent of the TNF-α levels. Etanercept and adalimumab suppressed mitogen-activated protein kinase (MAPK) phospho-p38, phospho-JNK, phospho-ERK and nuclear factor-κB (NF-κB) phospho-p65, as demonstrated using western blot analyses. The investigation of epigenetic modifications using chromatin immunoprecipitation revealed that etanercept and adalimumab down-regulated acetylation of histone (H)3 and H4 in the CCL2 promoter region by decreasing the recruitment of the NF-κB associated acetyltransferases p300, CBP and PCAF. Etanercept and adalimumab also down-regulated trimethylation of H3K4, H3K27, H3K36 and H3K79 in the CCL2 promoter region by decreasing the expression of the related methyltransferases WDR5 and Smyd2. We demonstrated that TNF-α inhibitors exert immunomodulatory effects on CCL2 expression in human monocytes via MAPKs, NF-κB and epigenetic modifications. These findings broaden the mechanistic knowledge related to TNF-α inhibitors and provide novel therapeutic targets for RA.

Graphical abstract

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