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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Bilateral Tensor Fasciae Suralis Muscles in a Cadaver with Unilateral Accessory Flexor Digitorum Longus Muscle

Muscle variants are routinely encountered in the dissection laboratory and in clinical practice and therefore anatomists and clinicians need to be aware of their existence. Here we describe two different accessory muscles identified while performing educational dissection of a 51-year-old male cadaver. Tensor fasciae suralis, a rare muscle variant, was identified bilaterally and accessory flexor digitorum longus, a more common muscle variant, was present unilaterally. Tensor fasciae suralis and accessory flexor digitorum longus are clinically relevant muscle variants. To our knowledge, the coexistence of tensor fasciae suralis and accessory flexor digitorum longus in the same individual has not been reported in either cadaveric or imaging studies.

http://ift.tt/2jDdcdz

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.



http://ift.tt/2jatnAH

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.



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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.

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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.

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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.



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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

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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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It is important to measure changes in the bone-conduction threshold when evaluating whether FGF-2 can be used to repair blast-induced total or near-total tympanic membrane perforations

We would like to comment on the manuscript entitled "Utility of basic fibroblast growth factor in the repair of blast-induced total or near-total tympanic membrane perforations: A pilot study" by Lou et al. [1]. The authors investigated whether basic fibroblast growth factor (bFGF) could be used to repair blast-induced total or near-total tympanic membrane perforations (TMPs) [1]. The authors concluded that direct application of bFGF was a promising minimally invasive alternative to conventional tympanoplasty, affording a comparable success rate.

http://ift.tt/2iZdLN4

Cochlear duct length–one size fits all?

Recent studies demonstrated the utility of high-resolution computed tomography (HRCT) scans in measuring basal cochlear length and cochlear insertion depths. These studies showed significant variations in the anatomy of the cochlea amongst humans. The aim of our study was to investigate for gender and racial variations in the basal turn length of the human cochlea in an Asian population.

http://ift.tt/2jLPNZv

It is important to measure changes in the bone-conduction threshold when evaluating whether FGF-2 can be used to repair blast-induced total or near-total tympanic membrane perforations

We would like to comment on the manuscript entitled "Utility of basic fibroblast growth factor in the repair of blast-induced total or near-total tympanic membrane perforations: A pilot study" by Lou et al. [1]. The authors investigated whether basic fibroblast growth factor (bFGF) could be used to repair blast-induced total or near-total tympanic membrane perforations (TMPs) [1]. The authors concluded that direct application of bFGF was a promising minimally invasive alternative to conventional tympanoplasty, affording a comparable success rate.

http://ift.tt/2iZdLN4

Cochlear duct length–one size fits all?

Recent studies demonstrated the utility of high-resolution computed tomography (HRCT) scans in measuring basal cochlear length and cochlear insertion depths. These studies showed significant variations in the anatomy of the cochlea amongst humans. The aim of our study was to investigate for gender and racial variations in the basal turn length of the human cochlea in an Asian population.

http://ift.tt/2jLPNZv

MYSM1 deficiency - genotoxic stress-associated bone marrow failure and developmental aberrations

Publication date: Available online 21 January 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Ehsan Bahrami, Maximilian Witzel, Tomas Racek, Jacek Puchałka, Sebastian Hollizeck, Naschla Greif-Kohistani, Daniel Kotlarz, Hans-Peter Horny, Regina Feederle, Heinrich Schmidt, Roya Sherkat, Doris Steinemann, Gudrun Göhring, Brigitte Schlegelbeger, Michael H. Albert, Waleed Al-Herz, Christoph Klein
BackgroundMyb-Like, SWIRM and MPN domains 1 (MYSM1) is a transcriptional regulator mediating histone deubiquitination. Its role in human immunity and hematopoiesis is poorly understood.ObjectivesTo investigate the clinical, cellular and molecular features in two siblings presenting with progressive bone marrow failure, immunodeficiency and developmental aberrations.MethodsWe performed genome-wide homozygosity mapping, whole-exome sequencing (WES) and Sanger sequencing, immunophenotyping studies as well as analysis of genotoxic stress responses. p38 activation, reactive oxygen species (ROS), rate of apoptosis and clonogenic survival and growth in immune and non-immune cells were assessed. Outcome of allogeneic HSCT was monitored.ResultsWe report two patients with progressive bone marrow failure associated with myelodysplastic features, immunodeficiency affecting B-cells and neutrophil granulocytes, and complex developmental aberrations including mild skeletal anomalies, neurocognitive developmental delay, and cataracts. Whole exome sequencing revealed a homozygous premature stop codon mutation in the gene encoding the histone deubiquitinase Myb-Like, SWIRM and MPN Domains 1 (MYSM1). MYSM1-deficient cells are characterized by increased sensitivity to genotoxic stress associated with sustained induction of phosphorylated p38 protein, increased ROS production, and decreased survival upon UV light-induced DNA damage. Both patients were successfully treated using allogeneic hematopoietic stem cell transplantation (HSCT) with sustained reconstitution of hematopoietic defects.ConclusionsWe here show that MYSM1 deficiency is associated with developmental aberrations, progressive BMF with myelodysplastic features, and increased susceptibility to genotoxic stress. HSCT represent a curative therapy for patients with MYSM1 deficiency.

Graphical abstract

Teaser

MYSM1-deficiency causes a rare bone marrow failure syndrome


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Damaging heterozygous mutations in NFKB1 lead to diverse immunological phenotypes

Publication date: Available online 21 January 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Meri Kaustio, Emma Haapaniemi, Helka Göös, Timo Hautala, Giljun Park, Jaana Syrjänen, Elisabet Einarsdottir, Biswajyoti Sahu, Sanna Kilpinen, Samuli Rounioja, Christopher L. Fogarty, Virpi Glumoff, Petri Kulmala, Shintaro Katayama, Fitsum Tamene, Luca Trotta, Ekaterina Morgunova, Kaarel Krjutškov, Katariina Nurmi, Kari Eklund, Anssi Lagerstedt, Merja Helminen, Timi Martelius, Satu Mustjoki, Jussi Taipale, Janna Saarela, Juha Kere, Markku Varjosalo, Mikko Seppänen
BackgroundThe NF-κB signaling pathway is a key regulator of immune responses. Accordingly, mutations in several NF-κB pathway genes cause immunodeficiency.ObjectiveWe sought to identify the cause of disease in three unrelated Finnish kindreds with variable symptoms of immunodeficiency and autoinflammation.MethodsWe applied genetic linkage analysis and next generation sequencing, and functional analyses of NFKB1 and its mutated alleles.ResultsIn all affected individuals, we detected novel heterozygous variants in NFKB1, encoding for p50/p105. Symptoms in variant carriers differed depending on the mutation: Patients harboring a p.I553M variant presented with antibody deficiency, infection susceptibility, and multi-organ autoimmunity. Patients with a p.H67R substitution developed antibody deficiency and suffered from autoinflammatory episodes including aphthae, gastrointestinal disease, febrile attacks, and small vessel vasculitis characteristic of Behcet's disease. Patients with a p.R157X stop-gain experienced hyperinflammatory responses to surgery and showed enhanced inflammasome activation. In functional analyses, the p.R157X variant caused proteasome-dependent degradation of both the truncated and wild-type proteins, leading to a dramatic loss of p50/p105. The p.H67R variant reduced nuclear entry of p50, and showed decreased transcriptional activity in luciferase-reporter assays. The p.I553M mutation, in turn, showed no change in p50 function, but exhibited reduced p105 phosphorylation and stability. Affinity-purification mass spectrometry also demonstrated that both missense variants led to altered protein-protein interactions.ConclusionOur findings broaden the scope of phenotypes caused by mutations in NFKB1, and suggest that a subset of autoinflammatory diseases such as Behcet's disease may be caused by rare monogenic variants in genes of the NF-κB pathway.

Teaser

In addition to antibody deficiency, mutations in NFKB1 may lead to excessive inflammatory response and manifest as Behcet's disease, inflammatory gastrointestinal disease, or severe autoinflammatory postoperative complications.


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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.



http://ift.tt/2jNknCF

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.



http://ift.tt/2jD1lMF

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.

Graphical abstract

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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.



http://ift.tt/2iYtCLL

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.



http://ift.tt/2iYtCLL

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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Management of the clinically node negative neck in squamous cell carcinoma of the maxilla

Squamous cell carcinomas of the maxilla (MSCC) may present with or without lymph node metastasis in the neck. Lymph node involvement is the most important prognostic factor for these malignancies [1–4]. A therapeutic neck dissection, radiotherapy or both, is indicated in case of proven lymph node metastasis in the neck. For MSCC with clinically node negative (N0) neck, a 'watch and wait' strategy for the neck is traditionally followed because the metastatic risk is assumed to be low. However, nowadays this 'watch and wait' strategy has become a matter of debate because the impression arises that occult metastases occur more frequently than previously assumed.

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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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Evidence-based health and clinical informatics: a systematic review on randomized controlled trials

Abstract

Towards the provision of medical research and eHealth services, several Health Information Technology (HIT) platforms are blended with communication and software technologies (i.e. mobile and Web applications, wireless sensor networks, Internet of Things and cloud computing). However, an important research issue is whether and to what degree these technologies are efficiently and effectively integrated into medical practice. Accordingly, this study reviews recent literature on HITs that employ RCTs, which are acknowledged as a reliable solution by the community of health stakeholders. Furthermore, it examines the research efforts in the field and evaluates the relevant functionalities. The literature search strategy was based on PRISMA 2009 Checklist and the CONSORT-EHEALTH Checklist that are two standard methodologies for systematic reviews in Evidence Based Medicine and Health Information Technologies. The analysis of the studies included was performed according to the Cochrane Risk of Bias Assessment Tool. The sources considered in this research include the most common clinical trial registries and academic electronic databases. The studies considered were conducted from 2008 until 2016. The authors considered RCTs having published their results in at least one article. As a result, 55 articles from 42 different journals are considered in this review. The benefits of the HIT delivered interventions are clearly presented in the outcomes of the relevant studies. Significant improvements were observed in the findings of 31 trials from a total of 51 (60.78%) including the acceptance, satisfaction, reliability, usefulness, safety, effectiveness and financial benefit of HITs. The results of this review reveal that HIT and eHealth interventions achieve at least equally reliable and safe outcomes compared with the usual support methods of healthcare. Significantly encouraging results are noticed in interventions employing HIT over several healthcare fields.

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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.

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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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Effect of Mastoid Drilling on Hearing of the Contralateral Normal Ear in Mastoidectomy

Abstract

To evaluate hearing of the contralateral normal ear before and after mastoidectomy in a longitudinal manner and to assess whether the hearing loss is transient or permanent and to find out the duration of temporary hearing loss. This was a clinical longitudinal observational study involving 50 patients with unilateral chronic suppurative otitis media requiring mastoidectomy operation over a period of 18 months after satisfying the inclusion criteria. During the part of the mastoidectomy surgery involving drilling of the mastoid bone, noise levels were recorded at multiple points in the surgery using a digital sound level meter. Postoperatively, beginning from Day 1 to Day 7, PTA and OAE of the contralateral ear were recorded for all patients. The patients were then followed up at 1, 3 and 6 months postoperatively, at which times PTA and OAE were repeated. There is an increase in the absence of High Frequency DPOAEs on the first and second postoperative days, but this increase is higher than that of Low Frequency DPOAEs and gradually returns to normal by 72 h. OAEs were found to be more sensitive at diagnosing and tracking the progress of affected patients. All affected ears only had a temporary postoperative hearing loss, primarily affecting the higher frequencies and returning to normal within 72 h. Drill-generated noise and vibration during mastoidectomy operation is associated with a significant temporary shift in hearing thresholds of the contralateral normal ear in susceptible individuals, affecting the higher frequencies, and is best evaluated using DPOAEs.

http://ift.tt/2iNr5IS

Effect of Mastoid Drilling on Hearing of the Contralateral Normal Ear in Mastoidectomy

Abstract

To evaluate hearing of the contralateral normal ear before and after mastoidectomy in a longitudinal manner and to assess whether the hearing loss is transient or permanent and to find out the duration of temporary hearing loss. This was a clinical longitudinal observational study involving 50 patients with unilateral chronic suppurative otitis media requiring mastoidectomy operation over a period of 18 months after satisfying the inclusion criteria. During the part of the mastoidectomy surgery involving drilling of the mastoid bone, noise levels were recorded at multiple points in the surgery using a digital sound level meter. Postoperatively, beginning from Day 1 to Day 7, PTA and OAE of the contralateral ear were recorded for all patients. The patients were then followed up at 1, 3 and 6 months postoperatively, at which times PTA and OAE were repeated. There is an increase in the absence of High Frequency DPOAEs on the first and second postoperative days, but this increase is higher than that of Low Frequency DPOAEs and gradually returns to normal by 72 h. OAEs were found to be more sensitive at diagnosing and tracking the progress of affected patients. All affected ears only had a temporary postoperative hearing loss, primarily affecting the higher frequencies and returning to normal within 72 h. Drill-generated noise and vibration during mastoidectomy operation is associated with a significant temporary shift in hearing thresholds of the contralateral normal ear in susceptible individuals, affecting the higher frequencies, and is best evaluated using DPOAEs.

http://ift.tt/2iNr5IS

Electroencephalographic characteristics of status epilepticus after cardiac arrest

Publication date: Available online 21 January 2017
Source:Clinical Neurophysiology
Author(s): Sofia Backman, Erik Westhall, Irina Dragancea, Hans Friberg, Malin Rundgren, Susann Ullén, Tobias Cronberg
ObjectiveTo describe the electrophysiological characteristics and pathophysiological significance of electrographic status epilepticus (ESE) after cardiac arrest and specifically compare patients with unequivocal ESE to patients with rhythmic or periodic borderline patterns defined as possible ESE.MethodsRetrospective cohort study of consecutive patients treated with targeted temperature management and monitored with simplified continuous EEG. Patients with ESE were identified and electrographically characterised until 72 hours after ESE start using the standardised terminology of the American Clinical Neurophysiology Society.ResultsESE occurred in 41 of 127 patients and 22 fulfilled the criteria for unequivocal ESE, which typically appeared early and transiently. Three of the four survivors had unequivocal ESE, starting after rewarming from a continuous background. There were no differences between the groups of unequivocal ESE and possible ESE regarding outcome, neuron-specific enolase levels or prevalence of reported clinical convulsions.ConclusionESE is common after cardiac arrest. The distinction between unequivocal and possible ESE patterns was not reflected by differences in clinical features or survival.SignificanceA favourable outcome is seen infrequently in patients with ESE, regardless of using strict or liberal ESE definitions.



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Effect of piroxicam on lipid membranes: Drug encapsulation and gastric toxicity aspects

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): Natalia Wilkosz, Sami Rissanen, Małgorzata Cyza, Renata Szybka, Maria Nowakowska, Alex Bunker, Tomasz Róg, Mariusz Kepczynski
Uptake of piroxicam, a non-steroidal anti-inflammatory drug, from the intestines after oral intake is limited due to its low solubility and its wide use is associated with several side effects related to the gastrointestinal tract. In this study, all-atom molecular dynamics (MD) simulations and fluorescent spectroscopy were employed to investigate the interaction of piroxicam in neutral, zwitterionic, and cationic forms with lipid bilayers composed of phosphatidylcholine, cholesterol, and PEGylated lipids. Our study was aimed to assess the potential for encapsulation of piroxicam in liposomal carriers and to shed more light on the process of gastrointestinal tract injury by the drug. Through both the MD simulations and laser scanning confocal microscopy, we have demonstrated that all forms of piroxicam can associate with the lipid bilayers and locate close to the water-membrane interface. Conventional liposomes used in drug delivery are usually stabilized by the addition of cholesterol and have their bloodstream lifetime extended through the inclusion of PEGylated lipids in the formulation to create a protective polymer corona. For this reason, we tested the effect of these two modifications on the behavior of piroxicam in the membrane. When the bilayer was PEGylated, piroxicam localize to the PEG layer and within the lipid headgroup region. This suggests that PEGylated liposomes are capable of carrying a larger quantity of piroxicam than the conventional ones.

Graphical abstract

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Functional magnetic resonance imaging in dermatology: The skin, the brain and the invisible

Abstract

The skin and brain have a close bi-directional anatomical and functional connection. Historically, the skin-brain axis and the brain-skin axis have been well described. However, brain function in this context has only recently been demystified with the introduction of functional neuroimaging in dermatology. Functional neuroimaging, especially functional magnetic resonance imaging (fMRI), allows indirect visualisation of brain function. This review looks back to the beginnings of functional neuroimaging in dermatology, summarises the currently available dermatology-related fMRI-studies and discusses the potential future role of fMRI as a stratifying tool in clinical dermatology and in the development of novel therapies. According to the main body of research made in this field, the focus is placed on experimental itch studies, which described the brain structures involved in itch processing, the regulation of the scratch response, contagious itch and itch suppression.

This article is protected by copyright. All rights reserved.

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Effect of 6-gingerol on AMPK- NF-κB axis in high fat diet fed rats

Publication date: April 2017
Source:Biomedicine & Pharmacotherapy, Volume 88
Author(s): Reem M. Hashem, Laila A. Rashed, Kamel M.A. Hassanin, Mona H. Hetta, Asmaa O. Ahmed
ObjectivesAdenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in metabolic homeostasis and regulation of inflammatory responses through attenuation of nuclear factor kappa-B (NF-κB), Thus AMPK may be a promising pharmacologic target for the treatment of various chronic inflammatory diseases. We examined the effect of 6-gingerol, an active ingredient of ginger on AMPK-NF-κB pathway in high fat diet (HFD) rats in comparison to fish oil.MethodsProtein levels of AMPK-α1 and phosphorylated AMPK-α1 were measured by western blot while Sirtuin 6 (Sirt-6), resistin and P65 were estimated by RT-PCR, TNF-α was determined by ELISA, FFAs were estimated chemically as well as the enzymatic determination of the metabolic parameters.Results6-Gingerol substantially enhanced phosphorylated AMPK-α1 more than fish oil and reduced the P65 via upregulation of Sirt-6 and downregulation of resistin, and resulted in attenuation of the inflammatory molecules P65, FFAs and TNF-α more than fish oil treated groups but in an insignificant statistical manner, those effects were accompanied by a substantial hypoglycemic effect.ConclusionGingerol treatment effectively modulated the state of inflammatory privilege in HFD group and the metabolic disorders via targeting the AMPK-NF-κB pathway, through an increment in the SIRT-6 and substantial decrement in resistin levels.



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Cutaneous alternariosis in a renal transplant patient successfully treated with posaconazole: Case report and literature review

Publication date: Available online 21 January 2017
Source:Medical Mycology Case Reports
Author(s): Rajinder Bajwa, Amy L. Wojciechowski, Chiu-Bin Hsiao
Cutaneous alternariosis is an uncommon fungal infection that most commonly presents in organ transplant patients on immunosuppressive therapy. There are no clinical trials or guidelines to guide treatment of this condition, however itraconazole is the most commonly used antifungal in published cases. Here we report on a case of cutaneous alternariosis in a renal transplant recipient treated with a newer antifungal, posaconazole. A review of published reports of cutaneous alternariosis since 2008 is also discussed.



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Cranial Nerve Injury After Carotid Endarterectomy: Incidence, Risk Factors, and Time Trends

Publication date: Available online 21 January 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): J.D. Kakisis, C.N. Antonopoulos, G. Mantas, K.G. Moulakakis, G. Sfyroeras, G. Geroulakos
Objective/BackgroundΤo review the incidence of post-carotid endarterectomy (CEA) cranial nerve injury (CNI), and to evaluate the risk factors associated with increased CNI risk.MethodsThe study was a meta-analysis. Pooled rates with 95% confidence intervals (CIs) were calculated for CNIs after primary CEA. Odds ratios (ORs) were calculated for potential risk factors. A fixed-effects model or a random effects model (Mantel–Haenszel method) was used for non-heterogeneous and heterogeneous data, respectively. Meta-regression analysis was performed to examine the influence of publication year upon CNI rate.ResultsTwenty-six articles, published between 1970 and 2015, were included in the meta-analysis, corresponding to 20,860 CEAs. Meta-analysis revealed that the vagus nerve was the most frequently injured cranial nerve (pooled injury rate 3.99%, 95% CI 2.56–5.70), followed by the hypoglossal nerve (3.79%, 95% CI 2.73–4.99). Fewer than one seventh of these injuries are permanent (vagus nerve: 0.57% [95% CI 0.19–1.10]; hypoglossal nerve: 0.15% [95% CI 0.01–0.39]). A statistically significant influence of publication year on the vagus and hypoglossal nerve injury rate was found, with the injury rate having decreased from about 8% to 2% and 1%, respectively, over the last 35 years. Urgent procedures (OR 1.59, 95% CI 1.21–2.10; p = .001), as well as return to the operating room for a neurological event or bleeding (OR 2.21, 95% CI 1.35–3.61; p = .002) were associated with an increased risk of CNI, whereas no statistically significant association was found between CNIs and the type of anaesthesia, the use of a patch, redo operation, and the use of a shunt.ConclusionThe vagus nerve appears to be the most frequently injured cranial nerve after CEA, followed by the hypoglossal nerve, with only a small proportion of these injuries being permanent. The CNI rate has significantly decreased over the past 35 years to a point indicating that CNIs should not be considered a major influencing factor in the decision making process between CEA and stenting.



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6th ESSD Congress Milan 2016 Abstract Book

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In-vitro performance of CAD/CAM-fabricated implant-supported temporary crowns

Abstract

Objectives

The aim of this study was to investigate the in-vitro performance and fracture resistance of a temporary computer-aided designed and computer-aided manufactured polymethylmethacrylate (CAD/CAM-PMMA) material as implant or tooth-supported single crown with respect to the clinical procedure (permanently bonded/temporarily cemented).

Materials and methods

Sixty-four crowns were fabricated on implants or human molar teeth simulating (a) labside procedure on prefabricated titanium-bonding base ([TiBase] implant crown bonded in laboratory, screwed chairside), (b) labside procedure ([LAB] standard abutment and implant crown bonded in laboratory, screwed chairside), (c) chairside procedure ([CHAIR] implant crown bonded to abutment), and (d) reference ([TOOTH] crowns luted on prepared human teeth). Crowns were made of a CAD/CAM-PMMA temporary material (TelioCAD, Ivoclar-Vivadent). For investigating the influence of fixation, half of the crowns were permanently (P) or temporarily (T) bonded. Combined thermal cycling and mechanical loading (TCML) was performed simulating a 5-year clinical situation. Fracture force was determined. Data were statistically analyzed (Kolmogorov-Smirnov test, one-way ANOVA; post hoc Bonferroni, α = 0.05).

Results

All restorations survived TCML without visible failures. Fracture results varied between 3034.3 (Tooth-P) and 1602.9 N (Tooth-T) [TOOTH], 1510.5 (TiBase-P) and 963.6 N (TiBase-T) [TiBase], 2691.1 (LAB-P) and 2064.5 N (LAB-T) [LAB], and 1609.4 (Chair-P) and 1253.0 N (Chair-T) [CHAIR]. Tested groups showed significantly (p < 0.001) different fracture values. Failure pattern was characterized by fractures in mesial-distal, buccal-oral, or mixed (mesial-distal/buccal-oral) directions, with differences for the individual groups.

Conclusions

Temporary CAD/CAM crowns showed no different in-vitro performance but provided different fracture results that depended on cementation, screw channel, and type of abutment.

Clinical relevance

All bonded and screwed PMMA crowns were in a range where clinical application seems not restricted.

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Gingival recessions of lower incisors after proclination by orthodontics alone or in combination with anterior mandibular alveolar process distraction osteogenesis

Abstract

Objectives

The aim of this study was to longitudinally compare periodontal conditions in consecutive patients who had orthodontic treatment with proclination of lower incisors either by orthodontics alone or in combination with anterior mandibular alveolar process distraction osteogenesis (DO).

Materials and methods

Nineteen patients had orthodontic treatment with DO, 18 with extraction of lower premolars (Ex), and 18 without extractions (Nonex). Lateral cephalograms were used to evaluate lower incisor proclination, while study casts and intraoral photographs were used to evaluate labial and lingual gingival recessions before (T1) and at an average of 4.5 years (T2) after treatment.

Results

No differences in labial recessions on lower incisors were present between the patient groups despite greater lower incisor proclination in the Nonex and DO groups. The Ex group showed no new development of lingual recessions in contrast to the Nonex (eight sites; two subjects) and DO groups (seven sites; three subjects). Severe lingual recessions (increased ≥1 mm) were more present in the Nonex group (five sites; two subjects) compared to the Ex group (no sites). Proclination of lower incisors of 10° or more either by orthodontic tooth movement or displacement of the whole alveolar process increased the risk of lingual gingival recessions 17 times. This was not the case with labial gingival recessions.

Conclusions

Orthodontic or surgical proclination of lower incisors beyond a 10° limit increases the risk of inducing lingual gingival recessions.

Clinical relevance

During orthodontic treatment, with or without DO, one should avoid proclining lower incisors more than 10° to decrease the risk of gingival recessions.

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The effect of the Physical Consistency of the Diet on the Bone Quality of the Mandibular Condyle in Rats

Publication date: Available online 20 January 2017
Source:Archives of Oral Biology
Author(s): Shawna Kufley, James Elliot Scott, German Ramirez-Yanez
ObjectiveThis study aimed to analyze how the physical consistency of the diet affects the bone quality at the mandibular condyle.DesignSixty-three Wistar rats were randomly assigned to three groups. Twenty-two animals composed each group and they were fed with either a liquid, soft or hard diet. Seven animals were sacrificed from each group at days 7, 20, and 40 respectively. Their mandibles were removed and scanned at the postero-superior area of the condyle with a micro-CT scan.Resultsshowed a statistically significant difference for the bone mineral density (p <0.01) and total mineral density (p<0.01), when comparing the hard against the liquid group after seven days. After 20days both, the soft and the liquid diet groups, computed a statistically significant difference demonstrating a significant decrease in the measured values for bone mineral density, bone mineral content, total mineral density, and total mineral content. At day 40, the values stayed lower for the soft and liquid diets, even though they did not reach a significant difference.ConclusionsThis study supports the idea that a soft or liquid diet has a negative impact on the bone quality of the mandible, particularly during the periods of more active growing.



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Similarities and Differences between Porcine Mandibular and Limb Bone Marrow Mesenchymal Stem Cells

Publication date: Available online 20 January 2017
Source:Archives of Oral Biology
Author(s): Brandon Lloyd, Boon Ching Tee, Colwyn Headley, Hany Emam, Susan Mallery, Zongyang Sun
ObjectiveResearch has shown promise of using bone marrow mesenchymal stem cells (BMSCs) for craniofacial bone regeneration; yet little is known about the differences of BMSCs from limb and craniofacial bones. This study compared pig mandibular and tibia BMSCs for their in vitro proliferation, osteogenic differentiation properties and gene expression.DesignBone marrow was aspirated from the tibia and mandible of 3-4 month-old pigs (n=4), followed by BMSC isolation, culture-expansion and characterization by flow cytometry. Proliferation rates were assessed using population doubling times. Osteogenic differentiation was evaluated by alkaline phosphatase activity. Affymetrix porcine microarray was used to compare gene expressions of tibial and mandibular BMSCs, followed by real-time RT-PCR evaluation of certain genes.ResultsOur results showed that BMSCs from both locations expressed MSC markers but not hematopoietic markers. The proliferation and osteogenic differentiation potential of mandibular BMSCs were significantly stronger than those of tibial BMSCs. Microarray analysis identified 404 highly abundant genes, out of which 334 genes were matched between the two locations and annotated into the same functional groups including osteogenesis and angiogenesis, while 70 genes were mismatched and annotated into different functional groups. In addition, 48 genes were differentially expressed by at least 1.5-fold difference between the two locations, including higher expression of cranial neural crest-related gene BMP-4 in mandibular BMSCs, which was confirmed by real-time RT-PCR.ConclusionsAltogether, these data indicate that despite strong similarities in gene expression between mandibular and tibial BMSCs, mandibular BMSCs express some genes differently than tibial BMSCs and have a phenotypic profile that may make them advantageous for craniofacial bone regeneration.



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Dental occlusion analysis in the Mesolithic–Neolithic Age, Bronze Age, and Roman to Medieval times in Serbia: Tooth size comparison in skeletal samples

Publication date: Available online 20 January 2017
Source:Archives of Oral Biology
Author(s): Tina Pajević, Branislav Glišić
ObjectiveAnthropological studies have reported that tooth size decreases in the context of diet changes. Some investigations have found a reverse trend in tooth size from the prehistoric to the modern times. The aims of this study were to analyze tooth size in skeletal samples from Mesolithic–Neolithic Age, Bronze Age, and Roman to Medieval times to determine sex differences and establish a temporal trend in tooth size in the aforementioned periods.DesignWell-preserved permanent teeth were included in the investigation. The mesiodistal (MD) diameter of all teeth and buccolingual (BL) diameter of the molars were measured. Effects of sex and site were tested by one-way ANOVA, and the combined effect of these factors was analyzed by UNIANOVA.ResultsSexual dimorphism was present in the BL diameters of all molars and MD diameters of the upper first and the lower third molar. The lower canine was the most dimorphic tooth in the anterior region. The MD diameter of most teeth showed no significant difference between the groups, (sample from: Mesolithic–Neolithic Age-group 1; Bronze Age-group 2; Roman times-group 3; Medieval times-group 4), whereas the BL diameters of the upper second and the lower first molar were the largest in the first group. Multiple comparisons revealed a decrease in the BL diameter of the upper second and the lower first molar from the first to the later groups. Lower canine MD diameter exhibited an increase in the fourth group compared to the second group.ConclusionOn the basis of the MD diameter, a temporal trend could not be observed for most of the teeth. The lower canine exhibited an increase in the MD diameter from the prehistoric to the Medieval times. Changes of BL diameter were more homogeneous, suggesting that the temporal trend of molar size decreased from the Mesolithic–Neolithic to Medieval times in Serbia.



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In vivo magnetic resonance imaging investigating the development of experimental brain metastases due to triple negative breast cancer

Abstract

Triple negative breast cancer (TNBC), when associated with poor outcome, is aggressive in nature with a high incidence of brain metastasis and the shortest median overall patient survival after brain metastasis development compared to all other breast cancer subtypes. As therapies that control primary cancer and extracranial metastatic sites improve, the incidence of brain metastases is increasing and the management of patients with breast cancer brain metastases continues to be a significant clinical challenge. Mouse models have been developed to permit in depth evaluation of breast cancer metastasis to the brain. In this study, we compare the efficiency and metastatic potential of two experimental mouse models of TNBC. Longitudinal MRI analysis and end point histology were used to quantify initial cell arrest as well as the number and volume of metastases that developed in mouse brain over time. We showed significant differences in MRI appearance, tumor progression and model efficiency between the syngeneic 4T1-BR5 model and the xenogeneic 231-BR model. Since TNBC does not respond to many standard breast cancer treatments and TNBC brain metastases lack effective targeted therapies, these preclinical TNBC models represent invaluable tools for the assessment of novel systemic therapeutic approaches. Further pursuits of therapeutics designed to bypass the blood tumor barrier and permit access to the brain parenchyma and metastatic cells within the brain will be paramount in the fight to control and treat lethal metastatic cancer.

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Cell cycle-tailored targeting of metastatic melanoma: challenges & opportunities

Abstract

The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato-oncology from the 'bad guy' to the 'poster child' in oncology. Current targeted therapies are effective; although here is a clear need to develop combination therapies to delay the onset of resistance. Many anti-melanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase-specific drug insensitivity. Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle-mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors. Secondly, if the combination is designed to target different tumor cell sub-populations of a heterogeneous tumor, one drug effective in a particular sub-population should not negatively impact on the other drug targeting another sub-population. In addition to the role of cell cycle stage and progression on standard chemotherapeutics and targeted drugs, we discuss the utilization of cell cycle checkpoint control defects to enhance chemotherapeutic responses or as targets themselves.

We propose that cell cycle-tailored targeting of metastatic melanoma could further improve therapy outcomes and that our real-time cell cycle imaging 3D melanoma spheroid model could be utilized as a tool to measure and design drug scheduling approaches.

This article is protected by copyright. All rights reserved.

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CD4+TCRγδ+FoxP3+cells: An unidentified population of immunosuppressive cells towards disease progression leprosy patients

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Langerhans cell markers CD1a and CD207 are the most rapidly responding genes in lesional psoriatic skin following adalimumab treatment

Abstract

TNFα-, IL-23- and IL-17-targeting drugs are highly effective in the treatment of psoriasis. However, the precise molecular mechanism remains unknown. In psoriatic skin the presence of Langerhans cells (LC) is reduced, but the role of LC is poorly understood. The purpose of this study was to investigate the impact of TNFα and IL-23/IL-17 on the presence of LC in the skin during treatment. Therefore, psoriatic skin was investigated before and after 4 days of adalimumab or ustekinumab treatment. Furthermore, TNFα and IL-17A stimulation was investigated in an ex vivo model of epidermis and dermis from healthy normal skin kept in cultures at an air-liquid interphase for 4 days.

In a gene array analysis we found that the two LC markers, CD1a and CD207, were among the most up- or downregulated genes in psoriatic skin after anti-TNFα therapy. Validation showed that both mRNA expression and protein level followed the same pattern and became significantly upregulated after 4 days of treatment. No changes were seen after ustekinumab treatment. In the ex vivo skin model, a decrease in the CD1a level was seen after TNFα stimulation and it was caused by LC migration from epidermis. No response in LC migration was seen after IL-17A stimulation. Taken together, we demonstrated that changes in the LC level in epidermis precede the histological and clinical changes during adalimumab treatment in psoriatic skin. Furthermore, TNFα plays a prominent role in orchestrating LC migration in the skin. This seems not to be the true for the IL-23/IL-17A pathway.

This article is protected by copyright. All rights reserved.

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