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Τρίτη 20 Ιουνίου 2017

Phytoextraction of Pb, Cr, Ni, and Zn using the aquatic plant Limnobium laevigatum and its potential use in the treatment of wastewater

Abstract

In order to study the bioaccumulation of Pb, Cr, Ni, and Zn and the stress response, the floating aquatic plant Limnobium laevigatum was exposed to increasing concentrations of a mixture of these metals for 28 days, and its potential use in the treatment of wastewater was evaluated. The metal concentrations of the treatment 1 (T1) were Pb 1 μg L−1, Cr 4 μg L−1, Ni 25 μg L−1, and Zn 30 μg L−1; of treatment 2 (T2) were Pb 70 μg L−1, Cr 70 μg L−1, Ni 70 μg L−1, and Zn 70 μg L−1; and of treatment 3 (T3) were Pb 1000 μg L−1, Cr 1000 μg L−1, Ni 500 μg L−1, and Zn 100 μg L−1, and there was also a control group (without added metal). The accumulation of Pb, Cr, Ni, and Zn in roots was higher than in leaves of L. laevigatum, and the bioconcentration factor revealed that the concentrations of Ni and Zn in the leaf and root exceeded by over a thousand times the concentrations of those in the culture medium (2000 in leaf and 6800 in root for Ni; 3300 in leaf and 11,500 in root for Zn). Thus, this species can be considered as a hyperaccumulator of these metals. In general, the changes observed in the morphological and physiological parameters and the formation of products of lipid peroxidation of membranes during the exposure to moderate concentrations (T2) of the mixture of metals did not cause harmful effects to the survival of the species within the first 14 days of exposure. Taking into account the accumulation capacity and tolerance to heavy metals, L. laevigatum is suitable for phytoremediation in aquatic environments contaminated with moderated concentrations of Cr, Ni, Pb, and Zn in the early stages of exposure.



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Investigation of the removal mechanism of Cr(VI) in groundwater using activated carbon and cast iron combined system

Abstract

Zero-valent iron (Fe0) has been widely used for Cr(VI) removal; however, the removal mechanisms of Cr(VI) from aqueous solution under complex hydrogeochemical conditions were poorly understood. In this research, the mixed materials containing cast iron and activated carbon were packed in columns for the treatment of aqueous Cr(VI)-Cr(III) in groundwater with high concentration of Ca2+, Mg2+, HCO3, NO3, and SO42−. We investigate the influences of those ions on Cr(VI) removal, especially emphasizing on the reaction mechanisms and associated precipitations which may lead to porosity loss by using X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) techniques. The results show that the precipitations accumulated on the material surface were (Fe/Cr) (oxy)hydroxide, mixed Fe(III)-Cr(III) (oxy)hydroxides, Fe2O3, CaCO3, and MgCO3. During these reactions, the Cr(VI) was reduced to Cr(III) coupled with the oxidated Fe0 to Fe(II) through the galvanic corrosion formed by the Fe0-C and/or the direct electron transfer between Fe0 and Cr(VI). In addition, Cr(VI) could be reduced by aqueous Fe(II), which dominated the whole removal efficiency. The primary aqueous Cr(III) was completely removed together with Cr(III) reduced from Cr(VI) even when Cr(VI) was detected in the effluent, which meant that the aqueous Cr(III) could occupy the adsorption sites. In general, the combined system was useful for the Cr(VI)-Cr(III) treatment based on galvanic corrosion, and the hardness ions had a negative effect on Cr(VI) removal by forming the carbonates which might promote the passivation of materials and decrease the removal capacity of the system.



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Accumulation properties of polychlorinated biphenyl congeners in Yusho patients and prediction of their cytochrome P450-dependent metabolism by in silico analysis

Abstract

In what has become known as the Yusho incident, thousands of people in western Japan were poisoned by the accidental ingestion of rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds. In this study, we investigated the accumulation patterns of 69 PCB congeners in the blood of Yusho patients in comparison with those of non-exposed controls. The blood samples were collected at medical check-ups in 2004 and 2005. To compare the patterns of PCB congeners, we calculated the concentration ratio of each congener relative to the 2,2′,4,4′,5,5′-hexaCB (CB153) concentration. The concentration ratios of tetra- and penta-chlorinated congeners in the blood of Yusho patients were significantly lower than those of controls. To examine the cytochrome P450 (CYP)-dependent metabolic potential of the 2,3′,4,4′5-pentaCB (CB118), CB153, and 2,3,3′,4,4′5-hexaCB (CB156) congeners, we conducted PCB-CYP (CYP1A1, CYP1A2, CYP2A6, and CYP2B6) docking simulation by in silico analysis. The docking models showed that human CYP1A1, CYP2A6, and CYP2B6 isozymes have the potential to metabolize CB118 and CB153. On the other hand, it was inferred that CB156 is difficult to be metabolized by these four CYP isozymes. These results indicate that CYP1 and CYP2 isozymes may be involved in the characteristic accumulation patterns of PCB congeners in the blood of Yusho patients.



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Revisiting the environmental Kuznets curve and pollution haven hypotheses: MIKTA sample

Abstract

This study aims to examine the validity of the environmental Kuznets curve (EKC) and pollution haven hypotheses in Mexico, Indonesia, South Korea, Turkey, and Australia (MIKTA) countries from 1982 to 2011 by using a panel vector auto regressive (PVAR) model. Empirical findings imply that the EKC hypothesis is rejected by the MIKTA sample. However, PVAR estimations reveal Granger causality from income level, foreign direct investment (FDI) inward, and energy consumption to CO2 emissions. Orthogonalized impulse-response functions are derived from PVAR estimations. According to the analysis results, the response of CO2 emissions to a shock on FDI is positive. These results assert that FDI has a detrimental effect on environmental quality in MIKTA countries which means the pollution haven hypothesis is confirmed by the MIKTA sample. Therefore, MIKTA countries should revise their current economic growth plans to provide sustainable development and also re-organize their legal infrastructure to induce usage of renewable energy sources.



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Test of aerobic TCE degradation by willows ( Salix viminalis ) and willows inoculated with TCE-cometabolizing strains of Burkholderia cepacia

Abstract

Trichloroethylene (TCE) is a widespread soil and groundwater pollutant and clean-up is often problematic and expensive. Phytoremediation may be a cost-effective solution at some sites. This study investigates TCE degradation by willows (S. viminalis) and willows inoculated with three strains of B. cepacia (301C, PR1-31 and VM1330-pTOM), using chloride formation as an indicator of dehalogenation. Willows were grown in non-sterile, hydroponic conditions for 3 weeks in chloride-free nutrient solution spiked with TCE. TCE was added weekly due to rapid loss by volatilization. Chloride and TCE in solution were measured every 2–3 days and chloride and metabolite concentrations in plants were measured at test termination. Based on transpiration, no tree toxicity of TCE exposure was observed. However, trees grown in chloride-free solution showed severely inhibited transpiration. No or very little chloride was formed during the test, and levels of chloride in TCE-exposed trees were not elevated. Chloride concentrations in chloride containing TCE-free nutrient solution doubled within 23 days, indicating active exclusion of chloride by root cell membranes. Only traces of TCE-metabolites were detected in plant tissue. We conclude that TCE is not, or to a limited extent (less than 3%), aerobically degraded by the willow trees. The three strains of B. cepacia did not enhance TCE mineralization. Future successful application of rhizo- and phytodegradation of TCE requires measures to be taken to improve the degradation rates.



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Sediments as a sink for UV filters and benzotriazoles: the case study of Upper Iguaçu watershed, Curitiba (Brazil)

Abstract

Ingredients in home and personal care products, including UV filters and benzotriazoles, are high production volume chemicals extensively used in our daily life, despite several studies revealed their potential eco-toxicity and endocrine-disrupting capacity. Due to some features, such as high lipophilicity, low degradability, and persistence of many of these compounds, sediments can be considered a sink for them in the aquatic environment. In the present study, nine organic UV filters and three benzotriazoles were investigated for the first time in sediments from four urban rivers in Brazil. The contaminants were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results revealed that octocrylene (OC), etylhexyl-methoxycinnamate (EHMC), benzophenone-3 (oxybenzone, BP3), and benzotriazole (BZT) were the predominant compounds adsorbed on the sediments, with concentrations ranging from 5.6 to 322.2 ng g−1 dry weight. The results reported in this work constitute the first data on the accumulation of polar benzotriazoles and lipophilic organic UV filters in sediments from Brazil.



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Removal of polyvinylamine sulfonate anthrapyridone dye by application of heterogeneous electro-Fenton process

Abstract

Diversity and rapidly multiplication of the pollutants incite as to improve the conventional treatments wastewater methods. One of the bottlenecks often faced is the presence into wastewater of organic pollutants with complex structures that requests the design of efficient processes. Thus, this work investigates the removal of polyvinylamine sulfonate anthrapyridone (PSA) dye which complex structure makes difficult its degradation by conventional technologies. For that, a heterogeneous oxidative process using pyrite as sustainable catalyst was designed. Initially, the performance of the system BBD-carbon felt as anode and cathode, respectively for the production of H2O2 was determined in comparison with system boron-doped diamond nickel foam. The carbon felt electrode provided the highest oxidant production, and it was selected for the treatment of the polymeric dye. Several oxidative processes were evaluated, and the best degradation levels were obtained by application of electro-Fenton-pyrite process. In addition, it was determined that dye removal followed a kinetic model of pseudo-first-order achieving the highest efficiency by operation at optimum dosage of pyrite 2 g/L and 200 mA of current intensity. Depending on the optimal experimental conditions, these values lead to a nearly complete mineralization (total organic carbon removal of 95%) after 6 h. Furthermore, the reusability of pyrite was evaluated, by removal of PSA in four cycles.



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Cultivation of freshwater microalgae in biodiesel wash water

Abstract

Biodiesel wash water is a contaminating industrial effluent that must be treated prior to disposal. The use of this effluent as a low-cost alternative cultivation medium for microalgae could represent a viable supplementary treatment. We cultivated 11 microalgae species with potential use for biodiesel production to assess their growth capacities in biodiesel industrial washing waters. Only Monoraphidium contortum, Ankistrodesmus sp., Chlorococcum sp., and one unidentified Chlorophyceae species grew effectively in that effluent. M. contortum showed the highest growth capacity and had the second highest fatty acid content (267.9 mg g−1 of DW), predominantly producing palmitic (20.9%), 7,10,13-hexadecatrienoic (14%), oleic (16.2%), linoleic (10.5%), and linolenic acids (23.2%). In the second phase of the experiment, the microalgae were cultivated in biodiesel wash water at 75% of its initial concentration as well as in WC (control) medium. After 21 days of cultivation, 25.8 and 7.2% of the effluent nitrate and phosphate were removed, respectively, and the chemical oxygen demand was diminished by 31.2%. These results suggest the possibility of cultivating biodiesel producing microalgae in industrial wash water effluents.



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Pulse photoplethysmographic amplitude and heart rate variability during laparoscopic cholecystectomy: A prospective observational study.

BACKGROUND: Surgical stress affects the autonomic nervous system by increasing sympathetic outflow. One method of monitoring sympathetic activity is pulse photoplethysmographic analysis. From this two indices can be derived - autonomic nervous system state (ANSS) and ANSS index (ANSSi). It has recently been claimed that these indices can be used to measure sympathetic activity in anaesthetised patients, but their validity has not yet been demonstrated. OBJECTIVE: To measure changes in pulse photoplethysmographic indices and determine any agreement with autonomic nervous system modulation of the cardiovascular system in healthy study participants during surgery under general anaesthesia. DESIGN: Prospective observational study. SETTING: Single-centre study based at a tertiary care centre in Milan, Italy. PATIENTS: Healthy patients undergoing general anaesthesia for elective laparoscopic cholecystectomy. INTERVENTIONS: ANSS, ANSSi, and heart rate variability (HRV) were analysed at three main times: baseline, after induction of general anaesthesia, and after pneumoperitoneum insufflation. MAIN OUTCOME MEASURES: The magnitude of changes in photoplethysmographic and HRV indices was measured. The agreement between pulse photoplethysmographic and HRV-derived indices was assessed by Bland-Altman plots. RESULTS: In total, 52 patients were enrolled and their data analysed. Both pulse photoplethysmographic and HRV indices changed during the study phases. An agreement was found between ANSSi and low frequency spectral components of HRV [bias 10.2nu, 95% confidence interval (CI) -13 to 33.4], high frequency spectral components of HRV (bias 6.1 nu, 95% CI -16.3-28.6), and low frequency/high frequency ratio (bias 16.1nu, 95% CI -1.4-33.5). The agreement was weaker between ANSSI and HRV indices. CONCLUSION: The study endorses the use of pulse photoplethysmographic indices ANSS and ANSSi as surrogates to estimate changes of autonomic modulation of the cardiovascular system in healthy adults during surgery under general anaesthesia. Orcid ID: http://ift.tt/2tMAaTr. (C) 2017 European Society of Anaesthesiology

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Cardiac cycle efficiency and dicrotic pressure variations: new parameters for fluid therapy: A pilot observational study.

BACKGROUND: During a fluid challenge, the changes in cardiac performance and peripheral circulatory tone are closely related to the position of the ventricle on the Frank-Starling curve. Some patients have a good haemodynamic response to a fluid challenge, others hardly any response. The early haemodynamic effects of a fluid challenge could predict the final response before the entire fluid volume has been administered. OBJECTIVE: To assess whether a multivariate logistic regression model, including pulse pressure variation (PPV), cardiac cycle efficiency (CCE), arterial elastance and the difference between the dicrotic pressure and both systolic and mean arterial pressure (SAP - Pdic and MAP - Pdic) can predict cardiac responsiveness early during a fluid challenge in comparison with the standard procedure described elsewhere. DESIGN: Observational pilot study. SETTING: Elective surgical patients undergoing laparotomy, enrolled in two Italian University Hospitals. PATIENTS: Fifty adult surgical patients, ventilated with a lung protective strategy, were enrolled and data from 46 were analysed. INTERVENTIONS: A fluid challenge consisting of 500 ml of crystalloid infused over 10 min. MAIN OUTCOME MEASURES AND ANALYSIS: The changes in CCE, arterial elastance, SAP - Pdic and MAP - Pdic were compared using analysis of variance. A multivariate logistic regression analysis utilising baseline values and the first minute measuring a variation statistically significant for the considered variables. RESULTS: At baseline, PPV correctly identified 70% of patients (89% of non-responders; 42% of responders). The model, including baseline PPV, [DELTA]CCE and [DELTA]SAP - Pdic, correctly identified the efficiency of fluid challenge in 87% of patients (84.2% of responders; 92.5 of non-responders) after 5 min from fluid challenge infusion. CONCLUSION: In this pilot study conducted in a population of surgical patients mechanically ventilated with a VT less than 8 ml kg-1, a dynamic model of fluid challenge assessment, including PPV, [DELTA]CCE and [DELTA]SAP - Pdic, enhances the prediction of fluid challenge response after 5 min of a 10-min administration. TRIAL REGISTRATION: ACTRN12616001479493. (C) 2017 European Society of Anaesthesiology

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The relative effects of dexmedetomidine and propofol on cerebral blood flow velocity and regional brain oxygenation: A randomised noninferiority trial.

BACKGROUND: Dexmedetomidine constricts cerebral blood vessels without a concomitant reduction in cerebral metabolic oxygen consumption. Its safety as a sedative in patients with neurological diseases thus remains uncertain. OBJECTIVE: Our primary objective was to test the hypothesis that dexmedetomidine is noninferior to propofol as regards cerebral blood flow (CBF) velocity and brain oxygenation. DESIGN: Unblinded randomised trial. SETTING: Cleveland Clinic Hospital, Cleveland, from November 2010 to July 2013. PATIENTS: Forty-four patients scheduled for insertion of a deep-brain stimulating electrodes. INTERVENTIONS: Patients were randomised to receive either dexmedetomidine or propofol sedation during deep-brain stimulating electrode insertion. MAIN OUTCOME MEASURES: Intraoperative CBF velocity was measured with transcranial Doppler, and brain oxygenation was assessed with near-infrared spectroscopy. Noninferiority of dexmedetomidine to propofol was defined as a less than 20% difference in means. RESULTS: Twenty-three patients were given dexmedetomidine and 21 propofol. Baseline characteristics and operative management were similar in each group. Dexmedetomidine was noninferior to propofol on both CBF and brain oxygenation, confirming our primary hypothesis. For cerebral flood flow, the estimated ratio of means (dexmedetomidine/propofol) was 0.94 [90% CI: 0.84 to 1.05], P = 0.011 for noninferiority. For brain oxygenation, the estimated ratio of means was 0.99 [90% CI: 0.96 to 1.02], P

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Comments regarding: Cooper LF, Stanford C, Feine J, McGuire M. Prospective assessment of CAD-CAM zirconia abutment and lithium disilicate crown restorations: 2.4 year results. J Prosthet Dent 2016;116:33-9

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Publication date: Available online 20 June 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Kelvin I. Afrashtehfar, Raphael Freitas de Souza




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Failure torque of ceramic neck titanium implant

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Publication date: Available online 20 June 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Waleed Elshahawy, Raed Ajlouni, Khaldoun Ajlouni, Abdelfattah Sadakah
Statement of problemDental implants are typically made of titanium. However, with the current systems on the market, the implant neck often shows through the gingival tissues as a black or dark gray line and/or as a grayish discoloration of the peri-implant soft tissue.PurposeThe purpose of this in vitro study was to test a new implant design. The key component of this design is the ceramic shell that covers the polished collar of the tissue-level titanium implant and masks its dark color to mimic natural dentition. The main purpose was to determine the maximum torque for fracturing the ceramic shell and compare it with clinical implant insertion torque value.Material and methodsType 4 commercially pure titanium endosseous implants of 3 different diameters (3.3, 4.1, and 4.8 mm) were used. Porcelain was applied in 0.5-mm thickness to the polished collar of each implant. An axial-torsional universal testing machine was used to twist the implants until failure. The data (n=10) were statistically analyzed by ANOVA and the Tukey honest significant difference test (α=.05). The maximum torque for each diameter group was also compared with the optimum clinical implant insertion torque value of 35 Ncm (control) using a 1-sample t test.ResultsNone of the tested groups had a fractured ceramic shell. Instead, the implant carriers fractured at the maximum torque levels. Therefore, the fracture of the implant carriers was selected as the maximum (failure) torque value. A statistical difference was found for the failure torque between the 3.3-mm diameter and the other 2 diameters (P<.001) although no statistical differences were found between the 4.1-mm and 4.8-mm diameters (P=.106). A statistically significant difference was found between the failure torque of any one of the tested groups and the clinical insertion torque (P<.001).ConclusionsThe ceramic shells did not fracture. Instead, the implant carriers fractured at certain torque levels. These levels were sufficiently higher than the clinical torque values.



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Effect of different restorative crown and customized abutment materials on stress distribution in single implants and peripheral bone: A three-dimensional finite element analysis study

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Publication date: Available online 20 June 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Necati Kaleli, Duygu Sarac, Safak Külünk, Özgür Öztürk
Statement of problemIn recent years, the use of resin-matrix ceramics and polyetheretherketone (PEEK) abutments has been suggested to absorb excessive stresses on dental implants. However, only a few studies have evaluated the effect of these materials on stress distribution in implants and peripheral bone structure.PurposeThe purpose of this finite element analysis was to evaluate the biomechanical behaviors of resin-matrix ceramics and PEEK customized abutments in terms of stress distribution in implants and peripheral bone.Material and methodsThree-dimensional (3D) models of a bone-level implant system and a titanium base abutment were created by using the standard tessellation language (STL) data of original implant components. An anatomic customized abutment and a maxillary right second premolar crown were then modeled over the titanium base abutment. A bone block representing the maxillary right premolar area was created, and the implant was placed in the bone block with 100% osseointegration. Six different models were created according to combinations of restoration materials (translucent zirconia [TZI], lithium disilicate glass ceramic [IPS], polymer-infiltrated hybrid ceramic [VTE]), and customized abutment materials (PEEK and zirconia). In each model, the implants were loaded vertically (200 N) and obliquely (100 N). The stress distribution in the crown, implant, and abutments was evaluated through the von Mises stress analysis, and the stress distribution in the peripheral bone was examined through the maximum and minimum principal stress analyses.ResultsThe oblique load resulted in high stress values in the implant components, restorative crown, and cortical bone. Low stress values were observed in the VTE crowns. Zirconia customized abutments exhibited higher stress values than PEEK customized abutments. The stress distributions in the implant and peripheral bone were similar in all models.ConclusionsChanges in restoration and customized abutment material did not affect stress distribution in the implant and peripheral bone.



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Muscle activity and masticatory efficiency with bilateral extension base removable partial dentures with different cusp angles

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Publication date: Available online 20 June 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Mahmoud K. AL-Omiri
Statement of problemWhether masticatory efficiency and electromyographic activity are influenced by type of artificial teeth and food is unclear.PurposeThe purpose of this clinical study was to evaluate the influence of extension base removable partial dentures (RPDs) with different cusp angles: anatomic (33 degrees), semianatomic (20 degrees), and nonanatomic (0 degrees) teeth on masticatory efficiency and muscle activity during the mastication of test foods with different textures.Material and methodsTwelve participants with RPDs were selected to perform masticatory efficiency and electromyographic tests. Surface electromyograms (EMGs) were used to record the activities of the masseter and temporalis muscles during the mastication of different types of test foods. The maximal voltage and duration were measured on the integrated EMG signal in each muscle during food mastication, and the mean reading of both sides was then recorded. Analysis of variance and the Tukey post hoc test were used to perform statistical analyses (α=.05).ResultsThe masticatory efficiency of RPDs with nonanatomic teeth was significantly inferior to that of RPDs with anatomic and semianatomic teeth (P<.05). However, masticatory efficiency did not differ between anatomic and semianatomic teeth (P>.05). Also, muscle activity (according to EMG) with RPDs with NA teeth was significantly higher than that with anatomic and semianatomic teeth (P<.05).ConclusionsRPDs with NA teeth were associated with higher EMG muscle activity and reduced masticatory efficiency than anatomic or semianatomic teeth.



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Experimental evaluation of stress distribution with narrow diameter implants: A finite element analysis

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Publication date: Available online 20 June 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Sezgi Cinel, Ersan Celik, Elcin Sagirkaya, Onur Sahin
Statement of problemNarrow diameter implants were developed to allow placement in narrow alveolar ridges. Clinicians may have concerns about the durability and function of such implants.PurposeThe purpose of this finite element study was to compare the stress values occurring on the implant and at the implant bone interface after the application of the static and dynamic forces on narrow diameter, titanium and titanium-zirconia implants in the maxillary and mandibular second premolar region.Material and methodsTitanium (Ti) and titanium-zirconium (Ti-Zr) narrow diameter implants (3.3 mm in diameter, 10 mm in length) were simulated in the maxillary and mandibular second premolar region, and metal-ceramic crown restorations were designed. Forces of 100 N were applied to crowns in a vertical and oblique (45-degree angle to the long axis) direction. Maximum and minimum principal stresses in the cortical and trabecular bone and the von Mises stresses and fatigue strength of the implants were evaluated with 3-dimensional finite element analysis.ResultsIn vertical and oblique static loading, Ti and Ti-Zr implants showed similar stress distribution within the same jaw models. However, the von Mises stresses in Ti-Zr implants were slightly higher than for Ti implants in all models. In oblique static and dynamic loading, all stresses were found higher than vertical loading, and fatigue failure results were found to be more critical than vertical forces.ConclusionsBased on a numerical simulation, Ti and Ti-Zr alloys can be used successfully as narrow diameter implants in the second premolar area.



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Multidisciplinary approach to oral rehabilitation with dental implants after gunshot injury: A clinical report

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Publication date: Available online 20 June 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Lélis Gustavo Nícoli, Suzane Cristina Pigossi, Raphael Ferreira de Souza Bezerra Araújo, Cláudio Marcantonio, Élcio Marcantonio, Élcio Marcantonio
This clinical report describes a multidisciplinary approach to treat a patient with edentulism and a severe anatomic defect in the mandible caused by a gunshot injury by using an implant-fixed complete dental prosthesis. An immediate loading interim implant-fixed complete dental prosthesis in the mandible associated with a maxillary removable complete denture prosthesis was initially provided to restore the intermaxillary relation. Nasal floor elevation and maxillary sinus augmentation were subsequently performed to increase the maxillary bone volume. Definitive implant-fixed complete dental prostheses were placed in both arches in order to rehabilitate this initially compromised anatomic condition, which ensured patient satisfaction and improvement in masticatory function and esthetics.



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Fracture resistance of CAD-CAM monolithic ceramic and veneered zirconia molar crowns after aging in a mastication simulator

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Publication date: Available online 20 June 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Merve Bankoğlu Güngör, Secil Karakoca Nemli
Statement of problemThe demand for ceramic restorations has increased over the past years, and now various machinable materials can be used for chairside computer-aided design and computer aided manufacturing (CAD-CAM) systems. Limited studies of these new materials make it difficult to evaluate their mechanical performance, advantages, and limitations.PurposeThe purpose of this in vitro study was to investigate the fracture resistance of CAD-CAM monolithic ceramic and veneered zirconia molar crowns after thermomechanical aging.Material and methodsA mandibular first molar tooth was prepared, and 12 different experimental groups were generated (n=10). An aging procedure was performed by subjecting the specimens to 12×105 mechanical cycles and 5000 thermal cycles. Survival analysis was performed according to the thermomechanical aging. The fracture resistance (load at fracture) of all specimens was evaluated with 1-way analysis of variance after the means had been compared using the Tukey honest significant difference test and Weibull distributions of the experimental groups (α=.05).ResultsAccording to the results, the differences between the fracture resistance of the groups were found to be significant. Restorations in the dual network ceramic crown group fractured catastrophically during thermomechanical aging. In all groups, the highest value was found for monolithic zirconia, followed by monolithic lithium disilicate crowns (P<.05). Both of the monolithic crowns made of lithium disilicate derivates and zirconia crowns veneered with lithium disilicate ceramic showed no differences from each other (P>.05). The Weibull modulus (m) ranged from 4.22 to 8.58, and conventionally veneered and overpressed zirconia showed the lowest Weibull modulus values among the tested groups, indicating greater variation of the data.ConclusionsThe highest fracture resistance was observed for yttria-stabilized zirconia crowns, followed by lithium disilicate derivates. Veneered zirconia restorations generally showed lower resistance than these ceramics. The dual network ceramic crowns fractured during thermomechanical aging.



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Titration technique using endoscopy for an oral appliance treatment of obstructive sleep apnea

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Publication date: Available online 20 June 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Kentaro Okuno, Kazuki Ikai, Erika Matsumura-Ai, Takafumi Araie
The degree of mandibular protrusion for an oral appliance (OA) should be customized for each patient with obstructive sleep apnea (OSA). This article describes the mandibular titration technique for OAs to effectively treat OSA by using endoscopy to evaluate the change in the airway at the velopharynx. This technique may minimize the degree of mandible protrusion and contribute to both the efficacy of and compliance with OA therapy.



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Interim rehabilitation of occlusal vertical dimension using a double-crown-retained removable dental prosthesis with polyetheretherketone framework

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Publication date: Available online 20 June 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Sebastian Hahnel, Christian Scherl, Martin Rosentritt
Polyetheretherketone (PEEK) is a polymeric material that has recently been introduced in dentistry and can be used as framework material for fixed and removable dental prostheses. This clinical report describes the fabrication of a double-crown–retained prosthesis with a PEEK framework in a patient with a substantially diminished occlusal vertical dimension. The insertion of the removable dental prosthesis with a PEEK framework resulted in the functional and esthetic rehabilitation of the patient; however, removable dental prostheses fabricated from PEEK should currently be regarded as interim restorations because of the limited available scientific evidence.



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Color masking measurement for ceramic coating of titanium used for dental implants

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Publication date: Available online 20 June 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Khaldoun Ajlouni, Waleed Elshahawy, Raed Ajlouni, Abdelfattah Sadakah
Statement of problemPoor implant placement or thin gingival tissue and progressive bone resorption may lead to the dark metal color showing through the peri-implant soft tissue. Whether the dark color can be adequately masked is unclear.PurposeThe purpose of this in vitro study was to test the color masking effect of porcelain applied on titanium used in fabricating the polished collar of tissue level implants.Material and methodsType 4 commercially pure titanium disks and 5 porcelain dentin shades (A2, A3, B2, C2, and D3) were used. Ten titanium disk specimens per porcelain shade were airborne-particle abraded and ultrasonically cleaned. Porcelain was condensed directly on the specimens, fired, and finished (1200 grit SiC paper). The color (L*a*b* values) of the polished specimens was measured with a reflective spectrophotometer. The specimens were then ground and polished in 0.1 mm increments. Color was measured and ΔE values were calculated at each increment until the thickness at which the ΔE was greater than 3.3 was identified. The data (n=10) were statistically analyzed by ANOVA and the Tukey multiple-comparison test (α=.05).ResultsFor ceramic thicknesses greater or equal to 0.5 mm for the A2, A3, B2, and C2 shades, the ΔE was less than 3.3. This value was 0.4 mm for the D3 shade.ConclusionsThe minimum ceramic thickness required to mask the underlying titanium color is 0.5 mm for all shades except D3, which only needs 0.4 mm. L* decreased with thickness increase. Redness and yellowness increased with thickness increase.



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Development of a 3D printable maxillofacial silicone. Part II: Optimization of moderator and thixotropic agent

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Publication date: Available online 20 June 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Swati K. Jindal, Martyn Sherriff, Mark G. Waters, James E. Smay, Trevor J. Coward
Statement of problemConventionally, maxillofacial prostheses are fabricated by hand carving the missing anatomic defect in wax and creating a mold into which pigmented silicone elastomer is placed. Digital technologies such as computer numerical control milling and 3-dimensional (3D) printing have been used to prepare molds, directly or indirectly, into which a biocompatible pigmented silicone elastomer can be placed.PurposeThe purpose of this in vitro study was to develop a silicone elastomer that could be 3D printed directly without a mold to create facial or body prostheses by varying its composition.Material and methodsThe room temperature vulcanizing silicone composition was divided into 2 components which were mixed 1:1 to initiate polymerization in the printer before printing began. Different types of moderators and thixotropic agents were used, and the base composition was varied to obtain 11 formulations. The specimens were printed and polymerized from these formulations and tested for tear and tensile strength and hardness. Ten readings of the specimens were recorded for tear and tensile strength and 6 for hardness. Results were analyzed using ANOVA (α=.05). Visual assessment of uncured printed specimens was undertaken for 5 formulations to assess any differences in their ability to hold their shape after printing.ResultsThe tear and tensile strength of the 11 formulations with varying moderators, thixotropic agents, and base compositions were statistically similar to each other (P>.05). Five of 11 formulations were chosen for the visual assessment as they had sufficient thixotropic agent to avoid slumping while printing. The specimens showed varied slumping behavior until they polymerized. The filler content was increased in the selected formulation, and the tear and tensile strength of the formulation was increased to 6.138 kNm-1 and 3.836 MPa; these increases were comparable to those of commercial silicones currently used for the fabrication of facial prostheses.ConclusionsThe optimum combination of mechanical properties implies the use of one of the formulations as a suitable material for the 3D printing of facial prostheses.



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Scholar : These new articles for South African Theatre Journal are available online

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Original Articles

Between text and stage: the theatrical adaptations of J.M. Coetzee's Foe
Kareesha Naidoo & Hermann Wittenberg
Pages: 1-16 | DOI: 10.1080/10137548.2017.1327257


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Differential urinary metabolites related with the severity of major depressive disorder

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Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Jian-jun Chen, Chan-juan Zhou, Peng Zheng, Ke Cheng, Hai-yang Wang, Juan Li, Li Zeng, Peng Xie
Major depressive disorder (MDD) is a common mental disorder that affects a person's general health. However, there is still no objective laboratory test for diagnosing MDD. Here, an integrated analysis of data from our previous studies was performed to identify the differential metabolites in the urine of moderate and severe MDD patients. A dual platform approach (NMR spectroscopy and GC–MS) was used. Consequently, 14 and 22 differential metabolites responsible for separating moderate and severe MDD patients, respectively, from their respective healthy controls (HCs) were identified. Meanwhile, the moderate MDD-specific panel (N-Methylnicotinamide, Acetone, Choline, Citrate, vanillic acid and azelaic acid) and severe MDD-specific panel (indoxyl sulphate, Taurine, Citrate, 3-hydroxyphenylacetic acid, palmitic acid and Lactate) could discriminate moderate and severe MDD patients, respectively, from their respective HCs with high accuracy. Moreover, the differential metabolites in severe MDD were significantly involved in three metabolic pathways and some biofunctions. These results showed that there were divergent urinary metabolic phenotypes in moderate and severe MDD patients, and the identified potential urinary biomarkers might be useful for future developing objective diagnostic tests for MDD diagnosis. Our results could also be helpful for researchers to study the pathogenesis of MDD.



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Random survival forest with space extensions for censored data

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Publication date: Available online 20 June 2017
Source:Artificial Intelligence in Medicine
Author(s): Hong Wang, Lifeng Zhou
Prediction capability of a classifier usually improves when it is built from an extended variable space by adding new variables from randomly combination of two or more original variables. However, its usefulness in survival analysis of censored time-to-event data is yet to be verified. In this research, we investigate the plausibility of space extension technique, originally proposed for classification purpose, to survival analysis. By combing random subspace, bagging and extended space techniques, we develop a random survival forest with space extensions algorithm. According to statistical analysis results, we show that the proposed model outperforms or at least comparable to popular survival models such as random survival forest, rotation survival forest, Cox proportional hazard and boosting survival models on well-known benchmark datasets.



http://ift.tt/2sS4z6e

A numerical approach to design dual-scale porosity composite reinforcements with enhanced permeability

Publication date: 5 October 2017
Source:Materials & Design, Volume 131
Author(s): Elena Syerko, Christophe Binetruy, Sébastien Comas-Cardona, Adrien Leygue
Fibrous composite reinforcements with enhanced permeability are of a particular interest for liquid composite molding processes requiring the fibrous preforms to be well impregnated by a viscous polymer. The aim of this work is to study the link between the reinforcement permeability and the geometrical parameters of its architecture, taking into account the internal multi-scale porosity distribution by employing the Brinkman equation. In order to design a reinforcement with the enhanced permeability without degrading mechanical properties of a final composite part, the study is conducted with the condition of fixed and high fiber volume fraction. The Proper Generalized Decomposition method, due to its principle of separation of variables, allowed to efficiently compute the solution of the problem for a range of geometrical parameters at once, as opposed to the classical parametric study. A scale separation criterion for in-plane flow was proposed. It estimates when the microscopic intra-yarn flow can be neglected compared to the mesoscopic inter-yarn flow. The major contributing parameters to the enhancement of both the in-plane and through-thickness permeabilities were identified. Principles established in this study were applied to the design of quasi-unidirectional non-crimp fabrics, where the permeability enhancement was evidenced.

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Micro-mechanical properties and interfacial engineering of SiC fiber reinforced sol-gel fabricated mullite matrix composites

Publication date: 5 October 2017
Source:Materials & Design, Volume 131
Author(s): S. Han, L.W. Yang, H.T. Liu, X. Sun, R. Jiang, W.G. Mao, Z.H. Chen
The toughening mechanisms of a SiC fiber reinforced sol-gel fabricated mullite matrix composites were studied by combining the microstructure, the micro-mechanical properties (especially the interface) and the macro fracture resistance by a bottom-to-up mechanical characterization method (transmission electron microscopy, nanoindentation, fiber push-in, digital image correction, etc.). The results show a chemical-reaction controlled fiber/matrix interface in the as-fabricated composite, leading to pretty strong interfacial shear strength (~537MPa), measured by the fiber push-in tests. Interfacial engineering by chemical vapor deposited pyrocarbon interphase can effectively hinder the interfacial reactions and weaken the interfacial interactions. The low shear strength of the tailored fiber/matrix interface (~155MPa) could trigger the toughening mechanisms like interface debonding, fiber pull-out, etc., when the composite was subjected to external bending stresses. Finally, the fracture toughness of the novel composite was found significantly enhanced from ~0.8MPa√m to ~8.3MPa√m, after the interfacial engineering with pyrocarbon interphase.

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Design and control of microstructure and texture by thermomechanical processing of a multi-phase TiAl alloy

Publication date: 5 October 2017
Source:Materials & Design, Volume 131
Author(s): Petra Erdely, Peter Staron, Emad Maawad, Norbert Schell, Joachim Klose, Helmut Clemens, Svea Mayer
Sheets made of intermetallic γ-TiAl based alloys possess promising engineering properties for lightweight high-temperature applications. Due to the complexity of their manufacturing, however, they are still not fully commercialised. Recently, a manufacturing route has been introduced for β-stabilised γ-TiAl based alloys that is effectively abridged compared to the conventional ingot metallurgy route. The present work explores the impact of each proposed processing stage on a β-solidifying, multi-phase Ti-43.5Al-4Nb-1Mo-0.1B (in at.-%) alloy. Texture measurements using synchrotron radiation were conducted and combined with microstructural analyses. The experiments allowed to fundamentally correlate the processing, which included heat treatment steps for balanced mechanical properties, with the evolution of both microstructure and texture. Thereby, the influences of deformation, recovery and recrystallisation, and phase transformations could be identified. The results reveal several options to optimise the material properties within the cost-effective manufacturing route. One option discussed in depth is the layout of the temperature profile in connection with the exploitation of the prevailing phase transformations. The presented findings are expected to improve the future design of γ-TiAl based sheet manufacturing routes.

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Effect of thermal compensation on microstructure and mechanical properties of electron-beam welded joint for high-Nb containing TiAl/Ti600 alloys

Publication date: 5 October 2017
Source:Materials & Design, Volume 131
Author(s): Ke Han, Houqin Wang, Binggang Zhang, Yuxuan Li, Ting Wang
High-Nb containing TiAl (TNB) and Ti600 alloys are the alternative materials for the tail-nozzle structure of rocket engines because of their low density, high specific strength and high temperature performance. This paper aims to investigate the microstructure evolution and the change in mechanical properties of the TNB/Ti600 electron-beam welded joints after thermal compensation treatment by electron beam defocusing mode. Compared with the electron beam welding of no-thermal compensation treatment, results showed that the cold cracks of the joint could be eliminated effectively by thermal compensation treatment. The microstructure in the fusion zone was composed of fine rod-shaped α-Ti+α2-Ti3Al phase. Moreover, the precipitated phase in heat affected zone on the TNB alloy side increased noticeably. The hardness of fusion zone considerably diminished to 400HV, at the same time both of the tensile strength of the joints at room temperature and 600°C increased substantially, reached 601 and 613MPa respectively, consisting with the evolution of the microstructure of the joint.

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Geometrical and Dimensional Optimization of Sound Absorbing Porous Copper with Cavity

Publication date: 5 October 2017
Source:Materials & Design, Volume 131
Author(s): Xiaocui Yang, Kang Peng, Xinmin Shen, Xiaonan Zhang, Panfeng Bai, Pengjin Xu
Optimization of sound absorbing coefficient of porous copper under a limited dimension is focus of research in the fields of acoustics and mechanics. Through measuring the sound absorbing coefficient based on the standing wave method, 5 groups of experiments are conducted to investigate the sound absorbing property of the porous copper with cavity under a limited dimension of 30mm. There are two options can meet the requirement that the sound absorbing coefficients are larger than 70% in 2000-5000Hz. First is the pure porous copper with thickness of 30mm, and the other is the combination of porous copper with thickness of 25mm and cavity with thickness of 5mm. Based on the modified Johnson-Allard model with correction factor, it can be obtained that theoretical optimal thickness of the pure porous copper is 28.8mm, and the theoretical optimal combination of porous copper and cavity are 22.7mm and 7.3mm. Experimental validations indicate that the two optimal options of the two modes both can meet the sound absorbing requirement. The results will promote the application of porous copper and improve the sound absorbing theory of porous material.

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Immunomodulatory Mechanism of Bushen Huoxue Recipe Alleviates Cyclophosphamide-Induced Diminished Ovarian Reserve in Mouse Model

Publication date: Available online 21 June 2017
Source:Journal of Ethnopharmacology
Author(s): Cong Huang, Kunkun Song, Wenwen Ma, Jiahui Ding, Zhuo Chen, Mingmin Zhang
Ethnopharmacological relevanceBushen Huoxue recipe (BHR) is a Chinese herbal prescription composed of ten herbs and it is widely used for the treatment of diminished ovarian reserve (DOR). This study investigates the potentially beneficial effects and underlying mechanism of BHR on a cyclophosphamide (CTX) induced model of DOR in mice.Materials and methodsGranules of BHR were first subjected to high performance liquid chromatography (HPLC) to determine the exact ingredients within the mixture. We then induced DOR in mice by injecting them with 90mg/kg of CTX. Following the single intraperitoneal injection, mice then received either saline or BHR for 21 days. To assess the effects of BHR on DOR, we examined splenic and ovarian morphology, estrous cycle duration, ovarian index, follicle number, body weight, and concentration of serum E2 and FSH. To explore the immunological mechanism behind the effects, mouse splenocytes were isolated in order to analyze the proportion of CD4+, CD8+ T cells and Th1, Th17 and Treg subsets by flow cytometry. The serum levels of IFN-γ, TNF-α, IL-4, IL-17A, IL-6 and IL-10 were detected using Cytometric Bead Array (CBA). Additionally, the mRNA expression levels of T-bet, RORγt and Foxp3 were measured with quantitative real-time PCR.ResultsOur results show that following treatment with BHR in DOR mice, several measures showed significant improvement. The morphology of the ovary and spleen, estrous cycle duration, body weight, ovarian index, and serum levels of E2 and FSH recovered to approximately normal levels and the loss of follicles at all stages was significantly attenuated. Furthermore, the elevated proportions of CD4+ T cells, Th1, Th17, Treg subsets and the increased serum levels of IFN-γ, TNF-α, IL-17A, IL-6 and IL-10 as well as the mRNA expressions of T-bet, RORγt and Foxp3 in DOR mice were significantly decreased.ConclusionsOur results show that BHR is a promising candidate to treat DOR mice and this beneficial effect may be mediated through the downregulation of augmented autoimmunity.

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Pine needle extract prevents hippocampal memory impairment in acute restraint stress mouse model

Publication date: Available online 19 June 2017
Source:Journal of Ethnopharmacology
Author(s): Jin-Seok Lee, Hyeong-Geug Kim, Hye-Won Lee, Won-Yong Kim, Yo-Chan Ahn, Chang-Gue Son
Ethnopharmacological relevanceThe Pinus densiflora leaf has been traditionally used to treat mental health disorders as a traditional Chinese medicine. Here we examined the ethnopharmacological relevance of pine needle on memory impairment caused by stress.Aim of the studyTo elucidate the possible modulatory actions of 30% ethanolic pine needle extract (PNE) on stress-induced hippocampal excitotoxicity, we adopted an acute restraint stress mouse model.Materials and methodsMice were orally administered with PNE (25, 50, or 100mg/kg) or ascorbic acid (100mg/kg) for 9 days, and were then subjected to restraint stress (6h/day) for 3 days (from experimental day 7 to 9). To evaluate spatial cognitive and memory function, the Morris water maze was performed during experimental days 5 to 9.ResultsRestraint stress induced the memory impairment (the prolonged escape latency and cumulative path-length, and reduced time spent in the target quadrant), and these effects were significantly prevented by PNE treatment. The levels of corticosterone and its receptor in the sera/hippocampus were increased by restraint stress, which was normalized by PNE treatment. Restraint stress elicited the hippocampal excitotoxicity, the inflammatory response and oxidative injury as demonstrated by the increased glutamate levels, altered levels of tumor necrosis factor (TNF)-α and imbalanced oxidant-antioxidant balance biomarkers. Two immunohistochemistry activities against glial fibrillary acidic protein (GFAP)-positive astrocytes and neuronal nuclei (NeuN)-positive neurons supported the finding of excitotoxicity especially in the cornu ammonis (CA)3 region of the hippocampus. Those alterations were notably attenuated by administration of PNE.ConclusionsThe above findings showed that PNE has pharmacological properties that modulate the hippocampal excitotoxicity-derived memory impairment under severe stress conditions.

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Cysteine-stabilised peptide extract of Morinda lucida (Benth) leaf exhibits antimalarial activity and augments antioxidant defense system in P. berghei-infected mice

Publication date: Available online 20 June 2017
Source:Journal of Ethnopharmacology
Author(s): Joseph O. Adebayo, Kayode E. Adewole, Antoniana U. Krettli
Ethnopharmacological relevanceCysteine-stabilised peptides (CSP) are majorly explored for their bioactivities with applications in medicine and agriculture. Morinda lucida leaf is used indigenously for the treatment of malaria; it also contains CSP whose role in the antimalarial activity of the leaf has not been evaluated.Aim of the studyThis study was therefore performed to evaluate the antimalarial activity of partially purified cysteine-stabilised peptide extract (PPCPE) of Morinda lucida leaf and its possible augmentation of the antioxidant systems of liver and erythrocytes in murine malaria.Materials and methodsPPCPE was prepared from Morinda lucida leaf. The activity of PPCPE was evaluated in vitro against Plasmodium falciparum W2 and its cytotoxicity against a BGM kidney cell line. PPCPE was also evaluated for its antimalarial activity and its effects on selected liver and erythrocyte antioxidant parameters in P. berghei NK65-infected mice.ResultsPPCPE was not active against P. falciparum W2 (IC50: >50µg/ml) neither was it cytotoxic (MLD50: >1000µg/ml). However, PPCPE was active against P. berghei NK65 in vivo, causing 51.52% reduction in parasitaemia at 31.25mg/Kg body weight on day 4 post-inoculation. PPCPE significantly reduced (P < 0.05) malondialdehyde concentrations in the liver and erythrocyte at higher doses compared to untreated controls. PPCPE increased glutathione concentration and activities of glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase in a dose-dependent manner, which was significant (P < 0.05) at higher doses compared to the untreated controls.ConclusionThe results suggest that PPCPE may require bioactivation in vivo in order to exert its antimalarial effect and that PPCPE may augment the antioxidant defense system to alleviate the reactive oxygen species-mediated complications of malaria.

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Salvia miltiorrhiza Bunge (Danshen) extract attenuates permanent cerebral ischemia through inhibiting platelet activation in rats

Publication date: Available online 20 June 2017
Source:Journal of Ethnopharmacology
Author(s): Yu-xiang Fei, Si-qi Wang, Li-jian Yang, Yan-ying Qiu, Yi-ze Li, Wen-yuan Liu, Tao Xi, Wei-rong Fang, Yun-man Li
Ethnopharmacological relevanceDanshen is a crude herbal drug isolated from dried roots of Salvia miltiorrhiza Bunge. This plant is widely used in oriental medicine for the treatment of cardiovascular and cerebrovascular diseases. The supercritical CO2 extract from Danshen (SCED) (57.85%, 5.67% and 4.55% for tanshinone IIA, tanshinone I and cryptotanshinone respectively) was studied in this article, whose potential molecular mechanism remains unclear, especially in anti-thrombosis.Aim of the studyThe present study was designed to observe the protective effect of SCED on ischemic stroke in rats and to explore the underlying anti-thrombosis mechanism.Materials and methodsFollowing induction of cerebral ischemia in rats by permanent middle cerebral artery occlusion (pMCAO). Neurological defect score, cerebral blood flow, infarct size, and brain edema were measured to evaluate the injury. Arteriovenous shunt thrombosis model and adenosine 5'-diphosphate (ADP) induced acute pulmonary embolism model were conducted to estimate the antithrombotic effect of SCED. In order to investigate the effects of SCED on platelet aggregation, rat platelet-rich-plasma (PRP) were incubated with SCED prior to the addition of the stimuli (ADP or 9, 11-dideoxy-11α, 9α-epoxymethanoprostaglandin F2α (U46619)). Aggregation was monitored in a light transmission aggregometer. Inhibitory effect of SCED on thromboxane A2 (TXA2) release was detected by ELISA kit. Phospholipase C (PLC)/ Protein kinase C (PKC) signaling pathway was analyzed by a Western blot technique. The effect of the SCED was also studied in vivo on bleeding time in mice.ResultsSCED improved the neurological defect score, increased cerebral blood flow, reduced infarct size and alleviated brain edema in rats exposed to pMCAO. After administration of SCED, thrombosis formation in arteriovenous shunt was inhibited and recovery time in pulmonary embolism was shortened. The inhibitory effect of SCED on platelet activation was further confirmed by TXB2 ELISA kit and Western blot analysis of PLC/PKC signaling pathway.ConclusionsSCED attenuates cerebral ischemic injury. The possible mechanism is that SCED inhibits thrombosis formation, platelet aggregation and activation of PLC/PKC pathway. On this basis, this new extract could be a promising agent to inhibit thrombosis formation and protect against cerebral ischemia injury.

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Ginsenoside Rg1 alleviates corticosterone-induced dysfunction of gap junctions in astrocytes

Publication date: Available online 20 June 2017
Source:Journal of Ethnopharmacology
Author(s): Cong-Yuan Xia, Shi-Feng Chu, Shuai Zhang, Yan Gao, Qian Ren, Yu-Xia Lou, Piao Luo, Man-Tong Tian, Zhi-Qi Wang, Guo-Hua Du, Yoshihisa Tomioka, Tohru Yamakuni, Yi Zhang, Zhen-Zhen Wang, Nai-Hong Chen
Ethnopharmacological relevanceGinsenoside Rg1 (Rg1), one of the major bioactive ingredients of Panax Ginseng C. A. Mey, has neuroprotective effects in animal models of depression, but the mechanism underlying these effects is still largely unknown.Aim of the studyGap junction intercellular communication (GJIC) dysfunction is a potentially novel pathogenic mechanism for depression. Thus, we investigated that whether antidepressant-like effects of Rg1 were related to GJIC.Materials and MethodsPrimary rat prefrontal cortical and hippocampal astrocytes cultures were treated with 50μM CORT for 24hours to induce gap junction damage. Rg1 (0.1, 1, or 10μM) or fluoxetine (1μM) was added 1hour prior to CORT treatment. A scrape loading and dye transfer assay was performed to identify the functional capacity of gap junctions. Western blot was used to detect the expression and phosphorylation of connexin43 (Cx43), the major component of gap junctions.ResultsTreatment of primary astrocytes with CORT for 24hours inhibited GJIC, decreased total Cx43 expression, and increased the phosphorylation of Cx43 at serine368 in a dose-dependent manner. Pre-treatment with 1μM and 10μM Rg1 significantly improved GJIC in CORT-treated astrocytes from the prefrontal cortex and hippocampus, respectively, and this was accompanied by upregulation of Cx43 expression and downregulation of Cx43 phosphorylation.ConclusionThese findings provide the first evidence indicating that Rg1 can alleviate CORT-induced gap junction dysfunction, which may have clinical significance in the treatment of depression.

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Maerua angolensis stem bark extract reverses anxiety and related behaviours in zebrafish—involvement of GABAergic and 5-HT systems

Publication date: Available online 20 June 2017
Source:Journal of Ethnopharmacology
Author(s): Charles Kwaku Benneh, Robert Peter Biney, Priscilla Kolibea Mante, Augustine Tandoh, Donatus Wewura Adongo, Eric Woode
Ethnopharmacological relevanceMaerua angolensis DC (Capparaceae) has been employed in the management of several central nervous system (CNS) disorders including anxiety. This study evaluated the anxiolytic effects of the petroleum ether/ethyl acetate fraction stem bark extract and its possible mechanism(s) using zebrafish anxiety models.MethodsAdult zebrafish, tested in the novel tank and light dark tests, have shown by previous authors to be sensitive to the anxiolytic effects of known anxiolytic drugs. Adult zebrafish were treated with M. angolensis extract, fluoxetine, desipramine, and diazepam followed by testing in the novel tank and light dark tests. We further assessed the effect of the extract on anxiety after inducing an anxiogenic phenotype using the ethanol-withdrawal and chronic unpredictable stress (CUS) tests. The anxiolytic effect was further investigated after pretreatment with flumazenil, granisetron, cyproheptadine, methysergide and pizotifen.ResultsM. angolensis extract, similar to fluoxetine and desipramine, demonstrated significant anxiolytic behaviour at doses that did not reduce locomotor activity significantly. Similar anxiolytic effects were recorded in the ethanol withdrawal-induced anxiety test. Furthermore, the anxiogenic effects induced by the CUS paradigm were significantly reversed by treatment M. angolensis extract and fluoxetine. The anxiolytic effects of M. angolensis extract were however reversed after pre-treatment with flumazenil, granisetron, cyproheptadine, methysergide and pizotifen.ConclusionsTaken together, this suggests that the petroleum ether/ ethyl acetate fraction of M. angolensis possesses significant anxiolytic activity, which could partly be accounted for by an interaction with the serotoninergic system and the GABAA receptor.

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Investigation of the component in Artemisia annua L. leading to enhanced antiplasmodial potency of artemisinin via regulation of its metabolism

Publication date: Available online 19 June 2017
Source:Journal of Ethnopharmacology
Author(s): Tian-Yu Cai, Yun-Rui Zhang, Jian-Bo Ji, Jie Xing
Ethnopharmacological relevanceThe chemical matrix of the herb Artemisia annua L. (A. annua), from which artemisinin (QHS) is isolated, can enhance both the bioavailability and efficacy of QHS. However, the exact mechanism of this synergism remains unknown. The biotransformation of QHS and potential "enzyme inhibitors" in plant matrix could be of great importance in understanding the improved efficacy of QHS in A. annua, which has been limited to the synergism with flavonoid components.Aim of the studyTo investigate the component in A. annua extracts (MAE) leading to enhanced antiplasmodial potency of QHS via regulation of its metabolism. The efficacy of QHS in combination with the synergistic component was also evaluated.Materials and methodsThe total MAE extract and its three MAE fractions (MAE-I eluted using 3% methanol, MAE-II eluted using 50% methanol and MAE-III eluted using 85% methanol) were obtained from dry plant materials and prepared after lyophilization. The pharmacokinetic profiles of QHS and its major phase I metabolite monohydroxylated artemisinin (QHS-M) were investigated in healthy rats after a single oral administration of QHS in each MAE extract. Major components isolated from the target MAE fraction were evaluated for their enzyme inhibition. The antimalarial activity of QHS in combination with the potential synergistic component against Plasmodium falciparum was studied in vivo (murine Plasmodium yoelii). The recrudescence and survival time of infected mice were also recorded after drug treatment.ResultsCompared to pure QHS, a 2-fold increase in QHS exposure (AUC and Cmax) was found in healthy rats after a single oral dose of QHS in the total MAE extract or its fraction MAE-III. In addition, metabolic biotransformation of QHS to the metabolite QHS-M (mediated by CYP3A) was inhibited by MAE or MAE-III. Among nine major components isolated from MAE-III (five sesquiterpenenes, three flavonoids and one phenolic acid), only arteannuin B (AB) showed an inhibition of CYP3A4 (IC50 1.2 μM). The synergism between QHS and AB was supported using in vivo antiplasmodial assay and a pharmacokinetic study in mice. Unfortunately, the synergism cannot reduce the rate of recrudescence.ConclusionsAB was one of main contributors in A. annua leading to enhanced antiplasmodial potency of QHS via regulation of its metabolism. The final recrudescence indicated the careful use of A. annua for malaria treatment unless additional contributing components or antiplasmodial mechanism were found.

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Comparative prevalence of Escherichia coli carrying virulence genes and class 1 and 2 integrons in sub-tropical and cool temperate freshwater

Abstract

Aquatic environments are now recognized secondary habitat of potentially pathogenic Escherichia coli. In this study, PCR-based analyses were used to determine the phylogenetic composition and frequency of occurrence of eight clinically significant virulence genes (VGs) in E. coli isolates from sub-tropical Brisbane and cool temperate Tasmania freshwater in Australia. In Brisbane, non-commensal E. coli isolates belonging to the B2 and D phylogenetic group were dominant (72%). A significantly higher number (P < 0.05) of E. coli carrying VGs were detected in the sub-tropical freshwaters compared to the cool temperate water. Furthermore, diarrheagenic pathotype (EHEC) was also observed in the sub-tropical freshwater. The genes east1 and eaeA were significantly more common (P < 0.00001) than other VGs. The eaeA gene which codes for intimin protein along with toxin genes east1, stx 1 , stx 2 , and LT1 were mostly detected in phylogenetic groups B2 and D. The ANOVA results also suggested a statistically significant difference (P < 0.016) between the VGs carried by phylogenetic groups B2 and D. Class 1 integrase (intl1) and class 2 integrase (intl2) genes were detected in 38 (24.83%) and 23 (15.03%) of E. coli isolates, respectively. The Gretna site (Tasmania) with known fecal input from bovine and ovine sources had the highest number of E. coli carrying intl1 (29%) and intl2 (13%) genes. In addition, class 2 integron was more commonly detected in the phylogenetic group B2. The results of this study highlight the need to better understand sources and reasons for the high prevalence of E. coli carrying clinically significant VGs in a sub-tropical environment and its public health implications.



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Household water insecurity and its cultural dimensions: preliminary results from Newtok, Alaska

Abstract

Using a relational approach, I examine several cultural dimensions involved in household water access and use in Newtok, Alaska. I describe the patterns that emerge around domestic water access and use, as well as the subjective lived experiences of water insecurity including risk perceptions, and the daily work and hydro-social relationships involved in accessing water from various sources. I found that Newtok residents haul water in limited amounts from a multitude of sources, both treated and untreated, throughout the year. Household water access is tied to hydro-social relationships predicated on sharing and reciprocity, particularly when the primary treated water access point is unavailable. Older boys and young men are primarily responsible for hauling water, and this role appears to be important to male Yupik identity. Many interviewees described preferring to drink untreated water, a practice that appears related to cultural constructions of natural water sources as pure and self-purifying, as well as concerns about the safety of treated water. Concerns related to the health consequences of low water access appear to differ by gender and age, with women and elders expressing greater concern than men. These preliminary results point to the importance of understanding the cultural dimensions involved in household water access and use. I argue that institutional responses to water insecurity need to incorporate such cultural dimensions into solutions aimed at increasing household access to and use of water.



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Biocontrol of the wheat pathogen Zymoseptoria tritici using cyclic lipopeptides from Bacillus subtilis

Abstract

Innovation toward ecofriendly plant protection products compatible with sustainable agriculture and healthy food is today strongly encouraged. Here, we assessed the biocontrol activity of three cyclic lipopeptides from Bacillus subtilis (mycosubtilin, M; surfactin, S; fengycin, F) and two mixtures (M + S and M + S + F) on wheat against Zymoseptoria tritici, the main pathogen on this crop. Foliar application of these biomolecules at a 100-mg L−1 concentration on the wheat cultivars Dinosor and Alixan, 2 days before fungal inoculation, provided significant reductions of disease severity. The best protection levels were recorded with the M-containing formulations (up to 82% disease reduction with M + S on Dinosor), while S and F treatments resulted in lower but significant disease reductions. In vitro and in planta investigations revealed that M-based formulations inhibit fungal growth, with half-maximal inhibitory concentrations of 1.4 mg L−1 for both M and M + S and 4.5 mg L−1 for M + S + F, thus revealing that the observed efficacy of these products may rely mainly on antifungal property. By contrast, S and F had no direct activity on the pathogen, hence suggesting that these lipopeptides act on wheat against Z. tritici as resistance inducers rather than as biofungicides. This study highlighted the efficacy of several lipopeptides from B. subtilis to biocontrol Z. tritici through likely distinct and biomolecule-dependent modes of action.



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Editorial Board

Publication date: July 2017
Source:Free Radical Biology and Medicine, Volume 108, Supplement 1





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L-5 Global vitamin status – perspectives for nutrition

Publication date: July 2017
Source:Free Radical Biology and Medicine, Volume 108, Supplement 1
Author(s): Manfred Eggersdorfer
Vitamins are essential for life and optimal health. We focused on vitamin E as key vitamin and reviewed the published literature reporting vitamin E intake levels and serum concentration to obtain a global overview of vitamin E status. Dietary recommendations are established in many countries around the world and refer to the role of vitamin E in preserving the integrity of the cell membrane.A search in the Pubmed/Medline database focused on population based studies published between January 1st 2000 and July 30th 2012 and resulted in 176 articles referring to 132 single studies with reported intake and /or serum concentration. Applying a Recommended Daily Allowance (RDA) of 15 mg/d, 82% and 61% of mean and median data points were below the RDA and EAR. Several prospective observational studies suggest a α-tocopherol concentration of 30 µmol/L and above to have beneficial effects on human health. Of the reported study populations and subpopulations, only 21% reached this threshold globally.A significant scientific and medical consensus exists on the long-term impact on public health of appropriate levels of micronutrient throughout the life course to foster health.



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L-1 OCC/SFRRE 2017 Invited Lectures Abstracts

Publication date: July 2017
Source:Free Radical Biology and Medicine, Volume 108, Supplement 1
Author(s): Tobias Dick
Redox signaling is a process by which endogenous oxidants, derived from metabolism, reversibly modify particular thiols on particular proteins to change their functional behavior in an adaptive manner. However, the molecular mechanisms of redox signaling remain largely unknown. In particular, specificity and efficiency of redox signaling remain largely unexplained. The now emerging solution to this conundrum is that redox signaling is mediated and channeled by protein-to-protein redox relay chains. There is growing evidence that H2O2 signals are relayed through thiol peroxidases to neighboring proteins within supramolecular assemblies. Evidence further suggests that so far we may have just glimpsed the 'tip of the iceberg', in that redox relay chains are ubiquitous and may also operate for reactive nitrogen and sulfur species.



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L-3 The silver lining of cerebrosterol in Alzheimer’s disease: the involvement of sirtuin 1 in neuroprotection

Publication date: July 2017
Source:Free Radical Biology and Medicine, Volume 108, Supplement 1
Author(s): Paola Gamba, Gabriella Testa, Erica Staurenghi, Simona Gargiulo, Giuseppe Poli, Gabriella Leonarduzzi
Altered cholesterol metabolism in the brain is implicated both in the initiation and in the progression of Alzheimer's disease (AD), and hypercholesterolemia is a potential risk factor. In particular, oxidized cholesterol, in the form of oxysterols, is believed to be one of the main triggers of AD. Oxysterols can accumulate in the brain, where they can behave as friends or foes: they cause neuron dysfunction and degeneration and contribute to neuroinflammation and amyloidogenesis, but they can also be neuroprotective.One of the main oxysterols most closely involved in AD pathogenesis is 24-hydroxycholesterol (24OH), also called cerebrosterol. The levels of 24OH are markedly reduced in the brain during AD progression, and it is likely that its reduction may accelerate the disease development, considering that it's known from literature that 24OH may have neuroprotective effects. Moreover, the loss of 24OH proceeds in parallel with the reduction of sirtuin 1 (SIRT1), a deacetylase promoting neuroprotection. We demonstrated that 24OH activates the neuroprotective axis ROS/SIRT1/PGC1a in neuroblastoma cells, thus favoring Tau deacetylation and preventing Tau hyperphosphorylation. Thus, it would be clinically important to prevent the loss of 24OH in the brain, in order to stimulate long upon the expression of SIRT1 with the consequent delay of Tau pathology.



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L-2 Selenium and selenoproteins in redox signaling

Publication date: July 2017
Source:Free Radical Biology and Medicine, Volume 108, Supplement 1
Author(s): Anna P. Kipp
The European population is only suboptimally supplied with the essential trace element selenium. Different selenium species either modify the cellular redox status directly or have indirect effects after incorporation into selenoproteins. In the past years, we have been working on the role of glutathione peroxidases such as GPx2. In addition, consequences of a suboptimal selenium status have been studied in mice indicating that redox-regulated pathways including Nrf2, Wnt, and NF-kB are modified under such conditions. Especially the up-regulation of antioxidant Nrf2 target genes might be an attempt to compensate for the reduced expression of selenoproteins. It is well accepted that cancer cells are characterized by substantial differences in maintaining and regulating their redox status in comparison to normal cells. Cancer cells highly depend on antioxidant enzymes and thus profit from a high selenium supply. On the contrary, a suboptimal selenium status increases the risk to develop a tumor. Depending on the tumor model, also GPx2 can act anti- and pro-carcinogenic. Using a 3D culture model, we started to elucidate which cell types within multicellular spheroids have a high basal and inducible activity of redox-regulated transcription factors. Based on that, we aim to understand better, how redox signaling and thus the selenium status contribute to tumorigenesis.



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L-4 Protein oxidation: Beyond the cell

Publication date: July 2017
Source:Free Radical Biology and Medicine, Volume 108, Supplement 1
Author(s): Michael J. Davies
Proteins are major targets for oxidants due to their abundance and high rate constants for reaction. For isolated proteins, we now have a reasonable understanding of both the chemistry that occurs, and its structural and functional consequences. With highly-reactive oxidants both side-chain and backbone damage can be detected, whereas with less reactive species more selective damage is observed, primarily at the side-chains of Cys, Met, Trp, Tyr and His. For cellular proteins, a similar pattern can be observed. Much of this damage is repaired, or removed rapidly via protein catabolism. Outside the cell, the situation is somewhat different. Extracellular proteins, and particularly matrix protein, are often highly abundant (e.g. elastin comprises ~50% of arteries by dry mass) and are relatively poorly protected against damage. Many of these proteins are long-lived and can accumulate high levels of modification during ageing and disease. Most of these proteins have low levels of Cys and Met residues resulting in altered extents and types of damage. Of particular note are the high levels of cystine (i.e. disulfides) present in some structural proteins. Recent data indicate that some of these are particularly susceptible to oxidation, with this resulting in structural, functional and mechanical changes, with consequences for tissue integrity and the function of adherent cells.



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L-6 Vitamin E deficiency causes a metabolic reprogramming dysregulating cellular energy homeostasis

Publication date: July 2017
Source:Free Radical Biology and Medicine, Volume 108, Supplement 1
Author(s): Maret G. Traber, Melissa McDougall, Jaewoo Choi, Hye-Kyeong Kim, Gerd Bobe, J. Frederik Stevens, Enrique Cadenas, Robert Tanguay
Vitamin E (α-tocopherol, VitE) was discovered in 1922 because it prevented rat fetal resorption. We investigated the mechanisms causing lethality using targeted metabolomic analyses of zebrafish VitE-deficient embryos daily from 1 to 5 days by which time 80% experienced increased morbidity or mortality. VitE deficiency caused lipid peroxidation of docosahexaenoic acid (DHA), depleted DHA-containing phospholipids, especially phosphatidylcholine, and depleted choline. It also increased NADPH oxidation, leading to glucose depletion by shunting it to the pentose phosphate pathway. VitE deficiency caused impairment of oxygen consumption and energy homeostasis. The observed morbidity outcomes could be attenuated by glucose injection into VitE-deficient embryos at developmental day one. Thus, embryonic VitE deficiency in vertebrates leads to a metabolic reprogramming that adversely affects methyl donor status and cellular energy homeostasis with lethal outcomes.



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Publication date: July 2017
Source:Acta Oecologica, Volume 82





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Glycyrrhetic acid, but not glycyrrhizic acid, strengthened entecavir activity by promoting its subcellular distribution in the liver via efflux inhibition

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): Qianying Chen, Hongzhu Chen, Wenjie Wang, Jiali Liu, Wenyue Liu, Ping Ni, Guowei Sang, Guangji Wang, Fang Zhou, Jingwei Zhang
Entecavir (ETV) is a superior nucleoside analogue used to treat hepatitis B virus (HBV) infection. Although its advantages over other agents include low viral resistance and the elicitation of a sharp decrease in HBV DNA, adverse effects such as hepatic steatosis, hepatic damage and lactic acidosis have also been reported. Glycyrrhizin has long been used as hepato-protective medicine. The clinical combination of ETV plus glycyrrhizin in China displays better therapeutic effects and lower rates of liver damage. However, there is little evidence explaining the probable synergistic mechanism that exists between these two drugs from a pharmacokinetics view. Here, alterations in the plasma pharmacokinetics, tissue distribution, subcellular distribution, and in vitro and in vivo antiviral activity of ETV after combination with glycyrrhizic acid (GL) were analysed to determine the synergistic mechanisms of these two drugs. Specific efflux transporter membrane vesicles were also used to elucidate their interactions. The primary active GL metabolite, glycyrrhetic acid (GA), did not affect the plasma pharmacokinetics of ETV but promoted its accumulation in hepatocytes, increasing its distribution in the cytoplasm and nucleus and augmenting the antiviral efficiency of ETV. These synergistic actions were primarily due to the inhibitory effect of GA on MRP4 and BCRP, which transport ETV out of hepatocytes. In conclusion, GA interacted with ETV at cellular and subcellular levels in the liver through MRP4 and BCRP inhibition, which enhanced the antiviral activity of ETV. Our results partially explain the synergistic mechanism of ETV and GL from a pharmacokinetics view, providing more data to support the use of these compounds together in clinical HBV treatment.

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Molecular Dynamics as a tool for in silico screening of skin permeability

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): Paolo Rocco, Francesco Cilurzo, Paola Minghetti, Giulio Vistoli, Alessandro Pedretti
Prediction of skin permeability can have manifold applications ranging from drug delivery to toxicity prediction. Along with the semi-empirical or mechanistic models proposed in the last decades, Molecular Dynamics simulations have recently become a fruitful tool for investigating membrane permeability, in particular as they allow the involved mechanisms to be modelled at a molecular level. Despite their significant structural complexity, Molecular Dynamics simulations can also be utilized to study permeation through the lipid matrix that characterizes the stratum corneum. In this work, Steered Molecular Dynamics simulations are performed on a suitably developed stratum corneum lipid matrix model. Regardless of their actual tortuous path within the stratum corneum, the permeants, taken from a Fully Validated dataset of 80 compounds of known permeability coefficient, are moved through the bilayer along its normal. This allows the exploration of all the possible conformational and physicochemical constraints the molecule experiences when moving through the bilayer. The so performed Steered Molecular Dynamics simulations are then utilized to extract the corresponding lipophilicity and diffusion parameters as computed by subdividing the entire path in 18 regions of different polarity and composition. Correlative analyses showed that the water-lipids interface is the best performing region and that significant enhancements can be gained by including parameters accounting for the temperature effect. Taken together, the developed models possess an enhanced predictive power compared to the existing equations and statistics are approaching the best possible results, given the uncertainty in the utilized permeability data.

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Importance of N- and C-terminal residues of substance P 1–7 for alleviating allodynia in mice after peripheral administration

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): Anna Skogh, Anna Lesniak, Fabienne Z. Gaugaz, Richard Svensson, Gunnar Lindeberg, Rebecca Fransson, Fred Nyberg, Mathias Hallberg, Anja Sandström
The heptapeptide SP1–7 (1, Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7) is the major bioactive metabolite formed after proteolytic processing of the neuropeptide substance P (SP, Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7-Phe8-Gly9-Leu10-Met11-NH2). The heptapeptide 1 frequently exhibits opposite effects to those induced by SP, such as exerting antinociception, or attenuating thermal hyperalgesia and mechanical allodynia. The heptapeptide SP1–7 amide (2, Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7-NH2) is often more efficacious than 1 in experimental pain models. We have now assessed the anti-allodynic outcome after systemic administration of 2 and a series of Ala-substituted and truncated analogues of 2, in the spared nerve injury (SNI) mice model and the results obtained were correlated with in vitro plasma stability and permeability measurements. It is herein demonstrated that an intact Arg1 in SP1–7 amide analogues is fundamental for retaining a potent in vivo effect, while Lys3 of 2 is less important. A displacement with Ala1 or truncation rendered the peptide analogues either inactive or with a significantly attenuated in vivo activity. Thus, the pentapeptide SP3–7 amide (7, t1/2=11.1 min) proven to be the major metabolite of 2, demonstrated an in vivo effect itself although considerably less significant than 2 in the SNI model. Intraperitoneal administration of 2 in a low dose furnished the most powerful anti-allodynic effect in the SNI model of all the analogous evaluated, despite a fast proteolysis of 2 in plasma (t1/2=6.4 min). It is concluded that not only the C-terminal residue, that we previously demonstrated, but also the N-terminal with its basic side chain, are important for achieving effective pain relief. This information is of value for the further design process aimed at identifying more drug-like SP1–7 amide related peptidomimetics with pronounced anti-allodynic effects.

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siRNA delivery system based on magnetic nanovectors: Characterization and stability evaluation

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): Mohammed Abdelrahman, Laurence Douziech Eyrolles, Suad Y. Alkarib, Katel Hervé-Aubert, Sanaa Ben Djemaa, Hervé Marchais, Igor Chourpa, Stephanie David
Gene therapy and particularly small interfering RNA (siRNA) is a promising therapeutic method for treatment of various human diseases, especially cancer. However the lack of an ideal delivery system limits its clinical applications. Effective anticancer drug development represents the key for translation of research advances into medicines. Previously we reported, the optimization of magnetic siRNA nanovectors (MSN) formulation based on superparamagnetic iron oxide nanoparticles (SPION) and chitosan for systemic administration.This work aimed at using rational design to further optimize and develop MSN. Therefore, formulated MSN were first purified, then their physical and chemical properties were studied mainly through capillary electrophoresis. 95% of siRNA was found enclosed within the purified MSN (pMSN). pMSN showed colloidal stability at pH 7.4, effective protection of siRNA against ribonuclease degradation up to 24 hours and few siRNA release (less than 10%) at pH 7.4. These findings push toward further evaluation studies in vitro and/or in vivo, indicating the appropriateness of pMSN for cancer theranostics.

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Comparison of liposomal drug formulations for transdermal iontophoretic drug delivery

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): K. Malinovskaja-Gomez, S. Espuelas, M.J. Garrido, J. Hirvonen, T. Laaksonen
This study was aimed to evaluate the in vitro transdermal direct/pulsed current iontophoretic delivery of an amphiphilic model compound from various lipid vesicle-encapsulated formulations compared to free-drug formulation. Conventional, pegylated, ultradeformable liposomes (transfersomes) and ethosomes loaded with a negatively charged drug diclofenac sodium (DS) were prepared and characterized. All the liposomes possessed an average size of ≈100–150nm and negative zeta potential. No changes in colloidal stability were detected after 8h incubation of any vesicle formulation under constant or pulsed iontophoretic current. DS was released from all the liposome formulations with a similar, limited rate (≈50% in 24h), leading therefore to significantly lower transdermal fluxes across full-thickness porcine skin compared to the respective free drug formulation. From the tested lipid vesicle formulations, the transfersomes resulted in the highest passive flux and the ethosomes in the highest iontophoretic flux under direct constant current treatment. Higher negative surface charge of the vesicle led to better transport efficiency due to the higher mobility of the drug carrier under electric field. Pulsed current iontophoresis had no advantage over constant current treatment in combination with any type of lipid vesicular nanocarriers, in contrast to what has been described earlier with drug-loaded polymeric nanocarriers.

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β2-adrenergic receptor-mediated in vitro regulation of human hepatic drug transporter expression by epinephrine

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): Abdullah Mayati, Amélie Moreau, Claire Denizot, Bruno Stieger, Yannick Parmentier, Olivier Fardel
The catecholamine epinephrine is known to repress expression of hepatic drug metabolizing enzymes such as cytochromes P-450. The present study was designed to determine whether epinephrine may also target expression of main hepatic drug transporters, that play a major role in liver detoxification and are commonly coordinately regulated with drug detoxifying enzymes. Treatment of primary human hepatocytes with 10μM epinephrine for 24h repressed mRNA expression of various transporters, such as the sinusoidal influx transporters NTCP, OATP1B1, OATP2B1, OAT2, OAT7 and OCT1 and the efflux transporters MRP2, MRP3 and BSEP, whereas it induced that of MDR1, but failed to alter that of BCRP. Most of these changes in transporter mRNA levels were also found in epinephrine-exposed human highly-differentiated hepatoma HepaRG cells, which additionally exhibited reduced protein expression of OATP2B1 and MRP3, increased expression of P-glycoprotein and decreased transport activity of NTCP, OATPs and OCT1. Epinephrine effects towards transporter mRNA expression in human hepatocytes were next shown to be correlated to those of the selective β2-adrenoreceptor (ADR) agonist fenoterol, of the adenylate cyclase activator forskolin and of the cAMP analogue 8-bromo-cAMP. In addition, the non-selective β-ADR antagonist carazolol and the selective β2-ADR antagonist ICI-118,551, unlike the α-ADR antagonist phentolamine, suppressed epinephrine-mediated repressions of transporter mRNA expression. Taken together, these data indicate that epinephrine regulates in vitro expression of main hepatic drug transporters in a β2-ADR/adenylate cyclase/cAMP-dependent manner. Hepatic drug transport appears therefore as a target of the β2-adrenergic system, which may have to deserve attention for drugs interacting with β2-ADRs.

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Protective effects of flavonoids against Alzheimer’s disease-related neural dysfunctions

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Mahsa Bakhtiari, Yunes Panahi, Javad Ameli, Behrad Darvishi
Senile ages of human life is mostly associated with developmental of several neurological complicated conditions including decreased cognition and reasoning, increased memory loss and impaired language performance. Alzheimer's disease (AD) is the most prevalent neural disorder associated with dementia, consisting of about 70% of dementia reported cases. Failure of currently approved chemical anti-AD therapeutic agents has once again brought up the idea of administering naturally occurring compounds as effective alternative and/or complementary regimens in AD treatment. Polyphenol structured neuroprotecting agents are group of biologically active compounds abundantly found in plants with significant protecting effects against neural injuries and degeneration. As a subclass of this family, Flavonoids are potent anti-oxidant, anti-inflammatory and signalling pathways modulatory agents. Phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen activated protein kinase (MAPK) pathways are both affected by Flavonoids. Regulation of pro-survival transcription factors and induction of specific genes expression in hippocampus are other important anti AD therapeutic activities of Flavonoids. These agents are also capable of inhibiting specific enzymes involved in phosphorylation of tau proteins including β-secretases, cyclin dependent kinase 5 and glycogen synthase. Other significant anti AD effects of Flavonoids include neural rehabilitation and lost cognitive performance recovery. In this review, first we briefly describe the pathophysiology and important pathways involved in pathology of AD and then describe the most important mechanisms through which Flavonoids demonstrate their significant neuroprotective effects in AD therapy.



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Study of intestinal anti-inflammatory activity of Phoenix loureiroi Kunth (Arecaceae) fruit

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Rajan Murugan, Shanmugam Saravanan, Thangaraj Parimelazhagan
Phoenix loureiroi Kunth belongs to the family Arecaceae, the fruits are widely consumed by Kurumba and Irula tribes of Tamil Nadu (India) and also used to cure intestinal related diseases in folklore medicine. Therefore, in vivo animal studies were evaluated to confirm the prevention of inflammatory bowel disease (IBD) with the treatment of this plant fruits. The IBD was studied in Wistar albino rats by indomethacin (s.c.), acetic acid (i.c.) and dextran sulfate sodium (DSS) induced models. The diseases parameters such as macroscopic, microscopic features, serum biomarkers levels, haematological profile, biochemical and antioxidant levels were determined. The fruit extract (50, 100 and 200mg/kg) treated enterocolitis rats significantly retain their body weight, organ weight, stool consistency, macroscopic score, histology, haematological parameters, antioxidative enzyme levels and also reduce the serum marker levels and myeloperoxidase (MPO) activity compared to prednisolone (2mg/kg) and sulfasalazine (50mg/kg) drugs. In conclusion, regular consumption of P. loureiroi fruit may prevent IBD and strongly support the folklore use of fruit in the treatment of intestinal ailments.

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