|
Παρασκευή 13 Απριλίου 2018
Scholar : These new articles for Spanish Journal of Finance and Accounting / Revista Española de Financiación y Contabilidad are available online
Haloperidol ameliorates androgen-induced behavioral deficits in developing male rats
The purpose of present study was to infer the potential effects of testosterone increase in some male-based childhood-onset neuropsychiatric disorders, such as Tourette syndrome. Thus, the influence of early postnatal androgen exposure upon the neurobehaviors and its possible neural basis were investigated in the study. Male pup rats received consecutive 14-day testosterone propionate (TP) subcutaneous injection from postnatal day (PND) 7. The TP treatment produced the hyperactive motor behavior and grooming behavior as well as the increased levels of dopamine, tyrosine hydroxylase and dopamine transporter in the mesodopaminergic system and the elevated levels of serotonin in the nucleus accumbens, without affecting the levels of glutamate, -aminobutyric acid, norepinephrine and histamine in the caudate putamen and nucleus accumbens of PND21 and PND49 rats. Dopamine D2 receptor antagonist haloperidol was administered to the early postnatal TP-exposed PND21 and PND49 male rats 30 min prior to open field test. Haloperidol significantly ameliorated the motor behavioral and grooming behavioral defects induced by early postnatal TP exposure. The results demonstrated that early postnatal androgen exposure significantly disturbed the brain activity of developing male rats via enhancing the mesodopaminergic activity. It was suggested that abnormal increments of testosterone levels during the early postnatal development might be a potential risk factor for the incidence of some male-based childhood-onset neuropsychiatric disorders by affecting the mesodopaminergic system.
https://ift.tt/2vbllPL
Clusterin deficiency induces lipid accumulation and tissue damage in kidney
Clusterin is a secretory glycoprotein that is involved in multiple physiopathological processes, including lipid metabolism. Previous studies have shown that clusterin prevents hepatic lipid accumulation via suppression of sterol regulatory element-binding protein (SREBP) 1. In this study, we examined the role of clusterin in renal lipid accumulation in clusterin-knockout mice and NRK52e tubular epithelial cells. Clusterin deficiency increased the expression of SREBP1 and its target genes and decreased malonyl-CoA decarboxylase protein levels in the kidney. Expression of the endocytic receptor, megalin, and scavenger receptor class A was increased in clusterin-deficient mice. Functional analysis of lipid metabolism also revealed that lipid uptake and triglyceride synthesis were increased and fatty acid oxidation was reduced, leading to increased lipid accumulation in clusterin-deficient mice. These phenomena were accompanied by mesangial expansion, fibrosis and increased urinary protein-to-creatinine ratio. High-fat feeding aggravated these clusterin deficiency-induced pathological changes. Clusterin knockdown in NRK52e cells increased lipogenic gene expression and lipid levels, whereas overexpression of clusterin by treatment with adenovirus or recombinant clusterin protein suppressed lipogenic gene expression and lipid levels. Transforming growth factor-beta 1 (TGFB1) expression increased in the kidney of clusterin-deficient mice and suppression of TGFB1 in NRK52e cells suppressed lipid accumulation. These results suggest that clusterin deficiency induces renal lipid accumulation by dysregulating the expression of lipid metabolism-related factors and TGFB1, thereby leading to chronic kidney disease. Hence, clusterin may serve as a therapeutic target for lipid-induced chronic kidney disease.
https://ift.tt/2JGgBoI
Muscarinic M2 receptor promotes vasopressin synthesis in mice supraoptic nuclei
Muscarinic acetylcholine receptors have been suggested to be implicated in arginine–vasopressin secretion because intracerebroventricular muscarinic agonist administration induces arginine–vasopressin release into the circulation. Although which subtype is involved in the regulation of arginine–vasopressin secretion is unclear, M2 receptors have been reported to be highly expressed in the hypothalamus. In the present study, M2 receptor-knockout mice were used to elucidate whether M2 receptor regulates arginine–vasopressin synthesis in the paraventricular nuclei and supraoptic nuclei of the hypothalamus. The number of arginine–vasopressin-immunoreactive neurons in M2 receptor-knockout mice was significantly decreased in the supraoptic nuclei, but not in the paraventricular nuclei compared with wild-type mice. Plasma arginine–vasopressin level in M2 receptor-knockout mice was also significantly lower than in the wild-type mice. Urinary volume and frequency as well as water intake in M2 receptor-knockout mice were significantly higher than those in wild-type mice. The V2 vasopressin receptor expression in kidneys of M2 receptor-knockout mice was comparable with that of wild-type mice, and increased urination in M2 receptor-knockout mice was significantly decreased by administration of desmopressin, a specific V2 receptor agonist, suggesting that V2 receptors in the kidneys of M2 receptor-knockout mice are intact. These results suggest that M2 receptors promote arginine–vasopressin synthesis in the supraoptic nuclei and play a role in the regulation and maintenance of body fluid.
https://ift.tt/2vblra3
Scholar : These new articles for Journal of Architectural Conservation are available online
|
Corneal and conjunctival drug permeability: Systematic comparison and pharmacokinetic impact in the eye
Publication date: 1 July 2018
Source:European Journal of Pharmaceutical Sciences, Volume 119
Author(s): Eva Ramsay, Eva M. del Amo, Elisa Toropainen, Unni Tengvall-Unadike, Veli-Pekka Ranta, Arto Urtti, Marika Ruponen
On the surface of the eye, both the cornea and conjunctiva are restricting ocular absorption of topically applied drugs, but barrier contributions of these two membranes have not been systemically compared. Herein, we studied permeability of 32 small molecular drug compounds across an isolated porcine cornea and built a quantitative structure-property relationship (QSPR) model for the permeability. Corneal drug permeability (data obtained for 25 drug molecules) showed a 52-fold range in permeability (0.09–4.70 × 10−6 cm/s) and the most important molecular descriptors in predicting the permeability were hydrogen bond donor, polar surface area and halogen ratio. Corneal permeability values were compared to their conjunctival drug permeability values. Ocular drug bioavailability and systemic absorption via conjunctiva were predicted for this drug set with pharmacokinetic calculations. Drug bioavailability in the aqueous humour was simulated to be <5% and trans-conjunctival systemic absorption was 34–79% of the dose. Loss of drug across the conjunctiva to the blood circulation restricts significantly ocular drug bioavailability and, therefore, ocular absorption does not increase proportionally with the increasing corneal drug permeability.
Graphical abstract
https://ift.tt/2JIPMjt
The impact of CYP2B6 polymorphisms on the interactions of efavirenz with lumefantrine: Implications for paediatric antimalarial therapy
Publication date: 1 July 2018
Source:European Journal of Pharmaceutical Sciences, Volume 119
Author(s): Zaril Zakaria, Raj K.S. Badhan
Lumefantrine is a widely used antimalarial in children in sub-Saharan Africa and is predominantly metabolised by CYP3A4. The concomitant use of lumefantrine with the antiretroviral efavirenz, which is metabolised by CYP2B6 and is an inducer of CYP3A4, increases the risk of lumefantrine failure and can result in an increased recrudescence rate in HIV-infected children. This is further confounded by CYP2B6 being highly polymorphic resulting in a 2–3 fold higher efavirenz plasma concentration in polymorphic subjects, which enhances the potential for an efavirenz-lumefantrine drug-drug interaction (DDI). This study developed a population-based PBPK model capable of predicting the impact of efavirenz-mediated DDIs on lumefantrine pharmacokinetics in African paediatric population groups, which also considered the polymorphic nature of CYP2B6. The validated model demonstrated a significant difference in lumefantrine target day 7 concentrations (Cd7) in the presence and absence of efavirenz and confirmed the capability of efavirenz to initiate this DDI. This was more apparent in the *6/*6 compared to *1/*1 population group and resulted in a significantly lower (P < 0.001) lumefantrine Cd7. A prospective change in dosing schedule from 3-days to 7-days resulted in a greater number of *6/*6 subjects (28–57%) attaining the target Cd7 across age bands (0.25–13 years), with the greatest increase evident in the 1–4 year old group (3-day: 1%; 7-day: 28%).
Graphical abstract
https://ift.tt/2vcdm51
Investigating the role of ion-pair strategy in regulating nicotine release from patch: Mechanistic insights based on intermolecular interaction and mobility of pressure sensitive adhesive
Publication date: 1 July 2018
Source:European Journal of Pharmaceutical Sciences, Volume 119
Author(s): Qiaoyun Li, Xiaocao Wan, Chao Liu, Liang Fang
The aim of this study was to prepare a drug-in-adhesive patch of nicotine (NIC) and use ion-pair strategy to regulate drug delivery rate. Moreover, the mechanism of how ion-pair strategy regulated drug release was elucidated at molecular level. Formulation factors including pressure sensitive adhesives (PSAs), drug loading and counter ions (C4, C6, C8, C10, and C12) were screened. In vitro release experiment and in vitro transdermal experiment were conducted to determine the rate-limiting step in drug delivery process. FT-IR and molecular modeling were used to characterize the interaction between drug and PSA. Thermal analysis and rheology study were conducted to investigate the mobility variation of PSA. The optimized patch prepared with NIC-C8 had the transdermal profile fairly close to that of the commercial product (p > 0.05). The release rate constants (k) of NIC, NIC-C4 and NIC-C10 were 21.1, 14.4 and 32.4, respectively. Different release rates of NIC ion-pair complexes were attributed to the dual effect of ion-pair strategy on drug release. On one hand, ion-pair strategy enhanced the interaction between drug and PSA, which inhibited drug release. On the other hand, using ion-pair strategy improved the mobility of PSA, which facilitated drug release. Drug release behavior was determined by combined effect of two aspects above. These conclusions provided a new idea for us to regulate drug release behavior from patch.
Graphical abstract
https://ift.tt/2JIPp8z
Encapsulation of trans-aconitic acid in mucoadhesive microspheres prolongs the anti-inflammatory effect in LPS-induced acute arthritis
Publication date: 1 July 2018
Source:European Journal of Pharmaceutical Sciences, Volume 119
Author(s): Diego Pinto de Oliveira, Gabriela Guimarães Augusto, Nathália Vieira Batista, Vivian Louise S. de Oliveira, Diêgo Santos Ferreira, Mateus Araújo Castro e Souza, Christian Fernandes, Flávio Almeida Amaral, Mauro Martins Teixeira, Rodrigo Maia de Pádua, Mônica Cristina Oliveira, Fernão Castro Braga
trans-Aconitic acid (TAA) is the main constituent of the leaves from the medicinal plant Echinodorus grandiflorus, used to treat different inflammatory diseases. TAA induces a potent but short-lasting biological response, credited to its high polarity and unfavorable pharmacokinetics. Here we developed, characterized and evaluated the anti-inflammatory activity of mucoadhesive microspheres loaded with TAA. Seven batches of mucoadhesive microspheres were prepared by the emulsification/solvent evaporation method, employing different proportions of TAA and Carbopol 934 or/and hydroxypropylmethylcellulose. All batches were characterized for their particle medium size, polydispersity index and entrapment percentage. The batch coded F3c showed highest entrapment percentage and was characterized by infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analyses (TGA) and zeta potential. The anti-inflammatory activity of F3c was assessed in a model of acute arthritis induced by injection of LPS in the knee joint of Swiss mice. The granulometric analyses indicated heterogeneous size distribution for F3c. SEM characterization indicated microspheres with slightly irregular shape and rough surface. Results from ATR-FTIR and thermal analyses (DSC and TGA) pointed out absence of incompatibility between the components of the formulation; thermal events related to the constituents were isolated and randomly located, suggesting amorphous distribution of TAA in the formulation matrix. The zeta potential of the formulations varied from −30 to −34 mV, which may contribute to good stability. When given orally to mice, F3c induced a prolonged anti-inflammatory response by reducing total cell count and neutrophilic accumulation in the joint cavity even when given 48 and 36 h before the stimulus, respectively, in comparison to free TAA (up to 24 and 6 h, respectively). Therefore, the encapsulation of TAA in mucoadhesive microspheres provided its sustained release, indicating that this drug delivery system is a potential agent to treat inflammatory diseases by regulating cell influx.
Graphical abstract
https://ift.tt/2vcHOMo
Investigation of the physical and chemical characteristics of rural solid waste in China and its spatiotemporal distributions
Abstract
Despite governmental efforts toward the development of policies, funds, and technologies, the inherent characteristics of rural solid waste (RSW) discharge have led to great difficulties in RSW pollution control. However, establishing a realistic management strategy requires greater knowledge of RSW generation. Therefore, the RSW of 72 typical towns and villages from 12 provinces of China was analyzed for physicochemical characteristics, as well as its spatiotemporal distribution. The largest proportion of kitchen waste, coal ash, plastic, and paper of RSW was 33.70% ± 17.87%, 26.50% ± 17.61%, 13.48% ± 5.68%, and 10.75% ± 5.75%, respectively, in 2015. Although RSW had the potential for composting, it was still necessary to pay special attention to heavy metals pollution of RSW. The spatiotemporal distributions of RSW components were extremely non-homogenous, and significant variations existed in the kitchen residue, coal ash, plastic, and paper because of differences in economic growth, climatic changes, dietary habits, energy consumption structure, and consumer preferences. No obvious differences in RSW components were observed between villages and market towns. Overall, RSW treatment and management approaches should be considered based on local conditions of RSW generation.
https://ift.tt/2HyHXMW
Scholar : Aging, Neuropsychology, and Cognition, Volume 25, Issue 3, May 2018 is now available online on Taylor & Francis Online
|
Detection of high GS risk group prostate tumors by diffusion tensor imaging and logistic regression modelling
Source:Magnetic Resonance Imaging, Volume 50
Author(s): Gokhan Ertas
PurposeTo assess the value of joint evaluation of diffusion tensor imaging (DTI) measures by using logistic regression modelling to detect high GS risk group prostate tumors.Materials and methodsFifty tumors imaged using DTI on a 3 T MRI device were analyzed. Regions of interests focusing on the center of tumor foci and noncancerous tissue on the maps of mean diffusivity (MD) and fractional anisotropy (FA) were used to extract the minimum, the maximum and the mean measures. Measure ratio was computed by dividing tumor measure by noncancerous tissue measure. Logistic regression models were fitted for all possible pair combinations of the measures using 5-fold cross validation.ResultsSystematic differences are present for all MD measures and also for all FA measures in distinguishing the high risk tumors [GS ≥ 7(4 + 3)] from the low risk tumors [GS ≤ 7(3 + 4)] (P < 0.05). Smaller value for MD measures and larger value for FA measures indicate the high risk. The models enrolling the measures achieve good fits and good classification performances (R2adj = 0.55–0.60, AUC = 0.88–0.91), however the models using the measure ratios perform better (R2adj = 0.59–0.75, AUC = 0.88–0.95). The model that employs the ratios of minimum MD and maximum FA accomplishes the highest sensitivity, specificity and accuracy (Se = 77.8%, Sp = 96.9% and Acc = 90.0%).ConclusionJoint evaluation of MD and FA diffusion tensor imaging measures is valuable to detect high GS risk group peripheral zone prostate tumors. However, use of the ratios of the measures improves the accuracy of the detections substantially. Logistic regression modelling provides a favorable solution for the joint evaluations easily adoptable in clinical practice.
https://ift.tt/2IRhRnG
Quantitative electroencephalography as a marker of cognitive fluctuations in dementia with Lewy bodies and an aid to differential diagnosis
Publication date: June 2018
Source:Clinical Neurophysiology, Volume 129, Issue 6
Author(s): Myrto Stylianou, Nicholas Murphy, Luis R. Peraza, Sara Graziadio, Ruth Cromarty, Alison Killen, John T. O' Brien, Alan J. Thomas, Fiona E.N. LeBeau, John-Paul Taylor
ObjectiveWe investigated for quantitative EEG (QEEG) differences between Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) patients and healthy controls, and for QEEG signatures of cognitive fluctuations (CFs) in DLB.MethodsWe analysed eyes-closed, resting state EEGs from 18 AD, 17 DLB and 17 PDD patients with mild dementia, and 21 age-matched controls. Measures included spectral power, dominant frequency (DF), frequency prevalence (FP), and temporal DF variability (DFV), within defined EEG frequency bands and cortical regions.ResultsDLB and PDD patients showed a leftward shift in the power spectrum and DF. AD patients showed greater DFV compared to the other groups. In DLB patients only, greater DFV and EEG slowing were correlated with CFs, measured by the clinician assessment of fluctuations (CAF) scale. The diagnostic accuracy of the QEEG measures was 94% (90.4–97.9%), with 92.26% (80.4–100%) sensitivity and 83.3% (73.6–93%) specificity.ConclusionAlthough greater DFV was only shown in the AD group, within the DLB group a positive DFV – CF correlation was found. QEEG measures could classify DLB and AD patients with high sensitivity and specificity.SignificanceThe findings add to an expanding literature suggesting that EEG is a viable diagnostic and symptom biomarker in dementia, particularly DLB.
https://ift.tt/2qwjaRc
Metabolite Depletion Affects Flux Profiling of Cell Lines
Publication date: Available online 12 April 2018
Source:Trends in Biochemical Sciences
Author(s): A. Nilsson, J.R. Haanstra, B. Teusink, J. Nielsen
Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation.
https://ift.tt/2vgnqu0
Comparative microstructural analysis of bone osteotomies after cutting by computer-assisted robot-guided laser osteotome and piezoelectric osteotome: an in vivo animal study
Abstract
Most industrial laser applications utilize computer and robot assistance, for guidance, safety, repeatability, and precision. In contrast, medical applications using laser systems are mostly conducted manually. The advantages can be effective only when the system is coupled to a robotic guidance, as operating by hand does not reach the required accuracy. We currently developed the first laser osteotome which offers preoperative planning based on CT data, robot guidance, and a precise execution of the laser cuts. In an animal trial, our system was used to create a grid pattern of the same depth on the inner layer of parietal bone in 12 adult sheep. The same bone cuts were done with piezoelectric osteotome on the contralateral side. The micro-CT and histological analysis showed more new mineralized bone in the laser group compared to the piezoelectric group. As well, a cutting pattern with especially a constant osteotomy depth in the laser group was demonstrated. The here presented autonomous osteotomy tool shows not only an advantage in early bone healing stage but additionally sharp bone cuts with a very high accuracy and freely selectable design cuts.
https://ift.tt/2H0A5CQ
Comparison of gingival depigmentation with Er,Cr:YSGG laser and surgical stripping, a 12-month follow-up
Abstract
Gingival melanin hyperpigmentation is an esthetic concern for many individuals. In this study, we compared the standard surgical removal method with two different Er,Cr:YSGG laser settings in order to find the best treatment method. In 33 dental arches, the following three treatment groups were comparatively evaluated: (1) surgical stripping, (2) removal with laser setting 1 (4.5 W, 50 Hz, 100% water, 80% air, 60 μs, 800 μm Tip; MZ8), and (3) laser setting 2 (2.5 W, 50 Hz, 20% water, 40% air, 700 μs, 800 μm Tip; MZ8). We comparatively evaluated pain, patient satisfaction and wound healing, treatment time, and the amount of bleeding. Re-pigmentation was evaluated after 1 and 12 months by Hedin and Dummet pigmentation scores. Laser setting 1 had the best results regarding pain and patient satisfaction, although not statistically significant (P > 0.05). Wound healing results were better using lasers compared to surgical stripping (P < 0.05). Laser setting 1 was a faster procedure with mild amounts of bleeding. The least amount of bleeding was seen with laser setting 2. After 1 month, only two cases of the laser setting 2-treated areas showed an isolated pigmented area in the papilla; at 12 months, the mean Hedin indexes were still less than 2 and mean Dummett index less than 1 in all treatment techniques, with the lowest scores seen in the laser setting 1 sites. Based on our results, Er,Cr:YSGG laser can be more convenient for gingival depigmentation compared to surgical blade. Although not statistically significant, laser setting 1 with shorter pulse duration and higher water spray showed better overall results. However, laser setting 2, with longer pulse duration and less water spray, resulted in better coagulative effects and can be used to control bleeding wherever necessary in clinical practice.
https://ift.tt/2Hw1q0u
Emergency material allocation with time-varying supply-demand based on dynamic optimization method for river chemical spills
Abstract
Aiming to minimize the damage caused by river chemical spills, efficient emergency material allocation is critical for an actual emergency rescue decision-making in a quick response. In this study, an emergency material allocation framework based on time-varying supply-demand constraint is developed to allocate emergency material, minimize the emergency response time, and satisfy the dynamic emergency material requirements in post-accident phases dealing with river chemical spills. In this study, the theoretically critical emergency response time is firstly obtained for the emergency material allocation system to select a series of appropriate emergency material warehouses as potential supportive centers. Then, an enumeration method is applied to identify the practically critical emergency response time, the optimum emergency material allocation and replenishment scheme. Finally, the developed framework is applied to a computational experiment based on south-to-north water transfer project in China. The results illustrate that the proposed methodology is a simple and flexible tool for appropriately allocating emergency material to satisfy time-dynamic demands during emergency decision-making. Therefore, the decision-makers can identify an appropriate emergency material allocation scheme in a balance between time-effective and cost-effective objectives under the different emergency pollution conditions.
https://ift.tt/2GUOynE
Effect of biochar derived from barley straw on soil physicochemical properties, crop growth, and nitrous oxide emission in an upland field in South Korea
Abstract
This study was conducted to investigate soil quality, Chinese cabbage growth, and N2O emission after biochar application in an upland field in South Korea. Each of the barley straw biochar (BC, applied at 10 ton ha−1), inorganic fertilizer (IF, applied at N-P-K = 320–78–198 kg ha−1), and BC + IF treatment areas were separated by a control (Cn) treatment area. Soils treated with BC and BC + IF treatments had lower bulk density and higher porosity than those in the Cn treatment areas. Soil chemical properties (pH, TN, Avail. P2O5, and CEC) after biochar addition were improved. In particular, soil pH and CEC related to crop nutrient availability were significantly increased in BC areas compared to those in Cn and IF areas. Fresh weights of Chinese cabbage grown under BC, IF, and BC + IF treatment conditions increased by 64.9, 78.4, and 112.0%, respectively, over that in the Cn treatment area. Total nutrient (TN, TP, and K) uptakes among the treatment areas were, in declining order, BC + IF (14.51 g plant−1) > IF > BC > Cn. More interestingly, the BC application had a positive effect on growth of Chinese cabbage under IF application conditions, and there was a tight relationship between the effect of BC application on Chinese cabbage growth and that of agronomic IF application efficiency. Compared to the IF results, total N2O flux was lower with BC (flux decreased by 60.6%) or BC + IF (flux decreased by 22.3%) treatments. These results indicate that Chinese cabbage yield, when cultivated in soil conditions such as those in an upland field in South Korea, can be increased by application of BC or a combination of BC and IF.
https://ift.tt/2quONea
Panel estimation for renewable and non-renewable energy consumption, economic growth, CO 2 emissions, the composite trade intensity, and financial openness of the commonwealth of independent states
Abstract
This article investigates the long-run and causal linkages between economic growth, CO2 emissions, renewable and non-renewable (fossil fuels) energy consumption, the Composite Trade Intensity (CTI) as a proxy for trade openness, and the Chinn-Ito index as a proxy for financial openness for a panel of the Commonwealth of Independent States (CIS) region including Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Turkmenistan, Ukraine, and Uzbekistan over the period of 1992–2015. It is the first time that CTI and the Chinn-Ito indexes are used in an economic-pollution model. Employing three panel unit root tests, panel cointegration estimation methods (DOLS and FMOLS), and two panel causality tests, the main empirical results provided evidence for the bidirectional long-run relationship between all the variables in all 12 sampled countries except for economic growth-renewable energy use linkage. The findings of causality tests indicated that there is a unidirectional short-run panel causality running from economic growth, financial openness, and trade openness to CO2 emissions and from fossil fuel energy consumption to renewable energy use.
https://ift.tt/2GUOrse
A spontaneous binge-like eating model in mice using unpredictable once weekly access to palatable diets
Source:Appetite, Volume 126
Author(s): Michelle Murphy, Dorieka J. Dijkstra, Jacqueline S. Duncan, Graham W. Horgan, Julian G. Mercer
Many pre-clinical models of binge-like eating involve predictable, scheduled, access to a palatable diet high in fat (HF), where access may be preceded by anticipatory behaviour. Here, to introduce spontaneity into the binge-type consumption of palatable diets, mice were allowed 2 h access on a random day once per week and at a random time within an 8 h window either side of the transition from dark phase to light phase. Despite normal intake of a stock diet prior to unpredictable access to HF diet, mice immediately initiated a substantial eating episode when presented with HF diet. Following this consumption, compensatory hypophagia was observed relative to stock diet-fed controls, and cumulative energy intakes converged. There were no effects of HF diet on body weight or body composition over a 12-week period. Binge-like consumption was also observed on unpredictable access to the complete liquid diet, chocolate Ensure, but not with a 10% sucrose solution. Binge-like responses to unpredictable access to HF diet or Ensure were similar in male and female mice, although there were effects of sex on caloric consumption from stock diet in the compensatory period following palatable diet intake, with higher intakes in females. The timing of the 2h access period relative to light phase transition affected intake of palatable diets, but less robustly than the equivalent effect on stock diet intake during the same timed periods – the diurnal patterning of energy intake was diet sensitive. The large spontaneous binge-like consumption on unpredictable access to either solid or liquid palatable diets in mice of either sex offers the potential to combine these attributes with other manipulations where a developing obesity is part of the binge-like eating phenotype.
https://ift.tt/2Hwlu30
A mind cleared by walnut oil: The effects of polyunsaturated and saturated fat on extinction learning
Source:Appetite, Volume 126
Author(s): Holly C. Miller, Dieter Struyf, Pascale Baptist, Boushra Dalile, Lukas Van Oudenhove, Ilse Van Diest
The treatment of anxiety-based psychopathology often hinges upon extinction learning. Research in nutritional neuroscience has observed that the regular consumption of perilla oil (50% alpha-linolenic acid (ALA)) facilitates extinction learning in rats (Yamamoto et al., 1988). However, acute facilitation of extinction learning by oils rich in ALA has not been reported for rats or humans, though the acute consumption of rapeseed oil (10% ALA) has been observed to improve cognitive processing speed in humans (Jones, Sünram-Lea, & Wesnes, 2012). For this reason, the present laboratory work examined the effects of adding walnut oil (12% ALA) to a chocolate milkshake on the acquisition, generalization, and extinction of a fear-based prediction in young adults. It compared performance between subjects. The other participants consumed a similar milkshake with either an equicaloric amount of cream (saturated fat), or with no added fat (control). Acquisition and generalization of the fear-based prediction were similar for all groups. However, those who consumed walnut oil extinguished most rapidly and profoundly. Implications for extinction learning are discussed.
https://ift.tt/2GZ3aOV
The effect of sugar-sweetened beverage price increases and educational messages on beverage purchasing behavior among adults
Source:Appetite, Volume 126
Author(s): Miranda R. Blake, Emily Lancsar, Anna Peeters, Kathryn Backholer
There is a paucity of evidence regarding the impact of sugar sweetened beverage (SSB) price increases on beverage consumption, using individual-level data, for the population overall and for different socioeconomic groups. This study aimed to predict the impact of altered beverage prices and educational messages on consumer purchasing behavior. 2020 adults representative of the Australian population by age, gender and income completed a discrete choice experiment online in 2016. Each subject completed 20 choice scenarios in a hypothetical convenience store setting where subjects chose between seven SSB and non-SSB beverage options or a no beverage option. Beverage prices and volumes varied between scenarios. Half of participants (n = 1012) were randomly exposed to an educational poster discouraging SSB consumption prior to completing choice scenarios. We used discrete choice models to predict purchases under several policy proposals, overall and for income and SSB consumption frequency sub-groups. Compared to baseline prices, a 10% SSB price increase was predicted to reduce SSB purchases by 15.0% [95%CI -15.2, −14.7], and increase purchases of non-SSBs by +11.0% [95%CI 10.8, 11.2] and no beverage by +15.5% [95%CI 15.1, 15.9]. Effects were greater with a 20% SSB price increase. Across all policy scenarios, the highest income quintile had a similar absolute and slightly greater relative decrease in SSB purchases compared to the lowest quintile. Educational poster exposure reduced SSB choice for all groups, with a greater reduction in the lower compared to higher income group, and additively increased response to price changes. Our results support the use of population-wide SSB pricing and educational interventions to reduce demand across all income groups.
https://ift.tt/2HwlgJc
A biopsychosocial model of body image, disordered eating, and breastfeeding among postpartum women
Source:Appetite, Volume 126
Author(s): Rachel F. Rodgers, Jennifer L. O'Flynn, Althea Bourdeau, Emily Zimmerman
BackgroundThe aim of the current study was to test a biopsychosocial model of body image, eating, and feeding attitudes among postpartum women. Specifically, the model predicted that desired weight-loss, depressive symptoms, and body surveillance would predict body dissatisfaction and appearance-related barriers to breastfeeding, which in turn would predict maternal disordered eating and breastfeeding self-efficacy.MethodsData from 151 women, mean age = 32.77 (4.47) years, who provided complete data in response to an online survey were analyzed.ResultsPath analysis revealed that after minor modifications, the biopsychosocial model was a good fit to the data. Desired weight-loss, depressive symptoms, and body surveillance were associated with higher levels of disordered eating and lower levels of breastfeeding self-efficacy directly, as well as indirectly through body dissatisfaction and appearance-related barriers to breastfeeding.ConclusionFindings provide support for an integrated biopsychosocial model of body image concerns, and eating and feeding attitudes among postpartum women as well as highlighting the need for additional support around body image, eating, and breastfeeding following childbirth. Our study has clinical implications for healthcare providers working with new mothers and can be used to inform postpartum psychoeducation efforts addressing breastfeeding, weight loss expectations and body image concerns.
https://ift.tt/2GZVw6E
Scholar : African Studies, Volume 77, Issue 2, June 2018 is now available online on Taylor & Francis Online
|
Scholar : These new articles for Asian Security are available online
|
Institutional Interventional Radiology Symposium Increases Medical Student Interest and Identifies Target Recruitment Candidates
Publication date: Available online 12 April 2018
Source:Current Problems in Diagnostic Radiology
Author(s): Mina S. Makary, Anand Rajan, Rose J. Miller, Eric D. Elliott, James W. Spain, Gregory E. Guy
ObjectivesTo assess and raise medical student interest in Interventional Radiology (IR); and to evaluate student response across gender, level of training, and surgical vs non-surgical specialty interest.Materials and MethodsAll Ohio medical students were invited to an IR Symposium held by a large academic medical center in central Ohio. The program encompassed didactic lectures, hands-on simulation models, and a networking luncheon with faculty, trainees, and industry partners. All attendees completed an anonymous, 5-point-Likert scaled survey pre- and post- attending the event to assess their awareness of IR as a specialty, understanding of the current training pathways, and level of interest.ResultsA total of 46 participants (M:F 60:40%, MS1–53%, MS2–36%, MS3–11%) attended the symposium. The cohort demonstrated increased interest in pursuing a career in IR following the symposium (4.12 vs 3.70, p<.001). Students with an interest in a non-surgical specialty showed an increased interest in IR (4.20 vs 3.68, p<.001), whereas surgically-oriented students did not demonstrate a significant increase (4.00 vs 3.71, p=0.375). No statistically significant differences were noted across gender or level of training. The symposium experience significantly increased understanding of the IR training pathways (4.51 vs 2.94, p<.001). Students rated lectures (57%) and endovascular simulators (41%) as the most useful experiences.ConclusionsThis study demonstrated the role of symposia in improving medical student awareness of IR and training pathways. Findings were validated across gender and training level, and identified the subset of students with nonsurgical interests as most responsive to such intervention and potential recruitment.
https://ift.tt/2GZRtHu
Structured Head and Neck CT Angiography Reporting Reduces Resident Revision Rates
Publication date: Available online 12 April 2018
Source:Current Problems in Diagnostic Radiology
Author(s): Tucker F. Johnson, Waleed Brinjikji, Derrick A. Doolittle, Alex A. Nagelschneider, Brian T. Welch, Amy L. Kotsenas
This resident-driven quality improvement project was undertaken to assess the effectiveness of structured reporting to reduce revision rates for afterhours reports dictated by residents. The first part of the study assessed baseline revision rates for head and neck CT angiography (CTA) exams dictated by residents during afterhours call. A structured report was subsequently created based on templates on the RSNA informatics reporting website and critical findings that should be assessed for on all CTA exams. The template was made available to residents through the speech recognition software for all head and neck CTA exams for a duration of two months. Report revision rates were then compared with and without use of the structured template. The structured template was found to reduce revision rates by approximately 50% with 10/41 unstructured reports revised and 2/17 structured reports revised. Based on our experience, we believe that structured reporting can help reduce reporting errors, particularly in term of typographical errors, train residents to evaluate complex exams in a systematic fashion, and assist them in recalling critical findings on these exams.
https://ift.tt/2HAZ1Ss
Exploring experimental autoimmune optic neuritis using multimodal imaging
Source:NeuroImage, Volume 175
Author(s): Praveena Manogaran, Christine Walker-Egger, Marijana Samardzija, Conny Waschkies, Christian Grimm, Markus Rudin, Sven Schippling
BackgroundNeuro-axonal injury is a key contributor to non-reversible long-term disability in multiple sclerosis (MS). However, the underlying mechanisms are not yet fully understood. Visual impairment is common among MS patients, in which episodes of optic neuritis (ON) are often followed by structural retinal damage and sustained functional impairment. Alterations in the optic nerve and retina have also been described in experimental autoimmune encephalomyelitis (EAE), a rodent model of MS. Thus, investigating structural anterior visual pathway damage may constitute a unique model for assessing mechanisms and temporal sequence of neurodegeneration in MS. We used a multimodal imaging approach utilizing optical coherence tomography (OCT) and diffusion tensor imaging (DTI) to explore the mechanisms and temporal dynamics of visual pathway damage in the animal model of MS.Methods7 EAE-MOG35-55 and 5 healthy female C57BL/6J mice were used in this study. Ganglion cell complex (GCC) thickness was derived from an OCT volume scan centred over the optic nerve head, while the structure of the optic nerve and tracts was assessed from DTI and co-registered T2-weighted sequences performed on a 7T MRI scanner. Data was acquired at baseline, disease onset, peak of disease and recovery. Linear mixed effect models were used to account for intra-subject, inter-eye dependencies, group and time point. Correlation analyses assessed the relationship between GCC thickness and DTI parameters. Immunofluorescence staining of retina and optic nerve sections was used to assess distribution of marker proteins for microglia and neurodegeneration (nerve filaments).ResultsIn EAE mice, a significant increase in GCC thickness was observed at disease onset (p < 0.001) followed by a decrease at recovery (p < 0.001) compared to controls. The EAE group had significant GCC thinning at recovery compared to all other time points (p < 0.001 for each). Signal increase on T2-weighted images around the optic nerves indicative of inflammation was seen in most of the EAE mice but in none of the controls. A significant decrease in axial diffusivity (AD) and increase in radial diffusivity (RD) values in EAE optic nerves (AD: p = 0.02, RD: p = 0.01) and tract (AD: p = 0.02, RD: p = 0.006) was observed compared to controls. GCC at recovery was positively correlated with AD (optic nerve: rho = 0.74, p = 0.04, optic tract: rho = 0.74, p = 0.04) and negatively correlated with RD (optic nerve: rho = −0.80, p = 0.02, optic tract: rho = −0.75, p = 0.04). Immunofluorescence analysis indicated the presence of activated microglia in the retina and optic nerves in addition to astrocytosis and axonal degeneration in the optic nerve of EAE mice.ConclusionOCT detected GCC changes in EAE may resemble what is observed in MS-related acute ON: an initial phase of swelling (indicative of inflammatory edema) followed by a decrease in thickness over time (representative of neuro-axonal degeneration). In line with OCT findings, DTI of the visual pathway identifies EAE induced pathology (decreased AD, and increased RD). Immunofluorescence analysis provides support for inflammatory pathology and axonal degeneration. OCT together with DTI can detect retinal and optic nerve damage and elucidate to the temporal sequence of neurodegeneration in this rodent model of MS in vivo.
https://ift.tt/2vbXpMb
Representation of steady-state visual evoked potentials elicited by luminance flicker in human occipital cortex: An electrocorticography study
Source:NeuroImage, Volume 175
Author(s): Benjamin Wittevrongel, Elvira Khachatryan, Mansoureh Fahimi Hnazaee, Evelien Carrette, Leen De Taeye, Alfred Meurs, Paul Boon, Dirk Van Roost, Marc M. Van Hulle
Despite the widespread use of steady-state visual evoked potentials (SSVEPs) elicited by luminance flicker in clinical and research settings, their spatial and temporal representation in the occipital cortex largely remain elusive. We performed intracranial-EEG recordings in response to targets flickering at frequencies from 11 to 15 Hz using a subdural electrode grid covering the entire right occipital cortex of a human subject, and we were able to consistently locate the gazed stimulus frequency at the posterior side of the primary visual cortex (V1). Peripheral flickering, undetectable in scalp-EEG, elicited activations in the interhemispheric fissure at locations consistent with retinotopic maps. Both foveal and peripheral activations spatially coincided with activations in the high gamma band. We detected localized alpha synchronization at the lateral edge of V2 during stimulation and transient post-stimulation theta band activations at the posterior part of the occipital cortex. Scalp-EEG exhibited only a minor occipital post-stimulation theta activation, but a strong transient frontal activation.
https://ift.tt/2qtT7Lw
Scholar : New articles have been published for Journal of Natural History, Volume 52, Issue 17-18
|
Proteomic and toxinological characterization of the venom of the South African Ringhals cobra Hemachatus haemachatus
Publication date: Available online 12 April 2018
Source:Journal of Proteomics
Author(s): Andrés Sánchez, María Herrera, Mauren Villalta, Daniela Solano, Álvaro Segura, Bruno Lomonte, José María Gutiérrez, Guillermo León, Mariángela Vargas
The protein composition and toxinological profile of the venom of the African spitting elapid Hemachatus haemachatus (Ringhals) were characterized by bottom-up proteomics and functional in vitro and in vivo assays. Venom is composed of abundant three-finger toxins (3FTxs; 63.3%), followed by phospholipases A2 (PLA2s; 22.8%), snake venom metalloproteinases (SVMPs 7.1%), cysteine-rich secretory proteins (CRISPs; 4.1%) and Kunitz type protease inhibitors (KTPIs; 1.5%). 3FTxs are the main responsible for lethality and myotoxicity in mice and in vitro anticoagulant activity. In contrast to closely related spitting species, whose venom 3FTxs induces dermonecrosis, the 3FTxs of H. haemachatus did not induce dermonecrotic activity. The venom showed in vitro PLA2 activity, and most likely PLA2s contribute to some extent in venom lethality, as judged by partial reduction in toxicity after inhibition of their catalytic activity. Despite its relatively high content of SVMPs, compared to most elapids, the venom of H. haemachatus did not exert hemorrhagic effect, proteolytic activity on azocasein or defibrinogenating activity. Toxicovenomic characterization of H. haemachatus venom revealed that RP-HPLC fractions with higher abundance of 3FTxs presented lethal activity, while fractions with high content of PLA2s did not, underscoring the role of 3FTxs in the pathophysiology caused by this venom.Biological significanceThe proteomic composition and toxinological profile of the venom of Ringhals snake, Hemachatus haemachatus, a cobra-like spitting snake endemic to southern Africa, were investigated. In vitro, Ringhals venom showed anticoagulant and phospholipase A2 activities, but was devoid of proteolytic activity on azocasein. In mice, venom induced lethality and myotoxicity, but no local hemorrhage or dermonecrosis. The lack of dermonecrotic activity is in sharp contrast to venoms of closely related spitting cobras which present a similar relative abundance of 3FTxs but are potently dermonecrotic. 3FTxs, the most abundant protein family in the venom, are predominantly responsible for toxic effects. PLA2 enzyme inactivation experiments suggest that H. haemachatus venom lethality is not dependent on PLA2s, but instead is more related to neurotoxic or cardiotoxic 3FTxs. The characterization of this venom, based on proteomic and toxicovenomic approaches, is useful for more in depth studies associated with biogeography, phylogeny, toxinology and antivenom efficacy towards the venom of this species, and its association with related elapids.
Graphical abstract
https://ift.tt/2v6uVDA
Systematic analysis of the cerebrospinal fluid proteome of fibromyalgia patients
Publication date: Available online 12 April 2018
Source:Journal of Proteomics
Author(s): Payam Emami Khoonsari, Sravani Musunri, Stephanie Herman, Camilla I. Svensson, Lars Tanum, Torsten Gordh, Kim Kultima
Fibromyalgia (FM) is a syndrome characterized by widespread muscular pain, fatigue and functional symptoms, which is known to be difficult to diagnose as the various symptoms overlap with many other conditions. Currently, there are no biomarkers for FM, and the diagnosis is made subjectively by the clinicians. We have performed shotgun proteomics on cerebrospinal fluid (CSF) from FM patients and non-pain controls to find potential biomarker candidates for this syndrome. Based on our multivariate and univariate analyses, we found that the relative differences in the CSF proteome between FM patients and controls were moderate. Four proteins, important to discriminate FM patients from non-pain controls, were found: Apolipoprotein C-III, Galectin-3-binding protein, Malate dehydrogenase cytoplasmic and the neuropeptide precursor protein ProSAAS. These proteins are involved in lipoprotein lipase (LPL) activity, inflammatory signaling, energy metabolism and neuropeptide signaling.SignificanceFibromyalgia is present in as much as 2% of the population, causing pain, stiffness, and tenderness of the muscles. Upon accurate diagnostic, nonpharmacological and pharmacological therapies can be used to alleviate pain and manage other symptoms. However, lack of objective, universal applicable diagnostic criteria as well as vague and diffused symptoms, have made diagnosis difficult. In this context, our findings can shed light on potential value of CSF proteome for objectively diagnosing FM.
Graphical abstract
https://ift.tt/2HfMIgD
Proteomic identification of virulence-related factors in young and aging C. elegans infected with Pseudomonas aeruginosa
Publication date: Available online 12 April 2018
Source:Journal of Proteomics
Author(s): Christina D. King, Daljeet Singh, Kyle Holden, Annie B. Govan, Scott A. Keith, Arjumand Ghazi, Renã A.S. Robinson
The molecular mechanisms that distinguish immunosenescence from general age-related decline are poorly understood. We addressed this by exposing Day 1 and Day 5 adults of Caenorhabditis elegans to Pseudomonas aeruginosa strain PA01, an opportunistic pathogen. Day 5 adult C. elegans exhibited greater vulnerability to infection as compared to Day 1 C. elegans. Using TMT6-plex isobaric labeling and reductive dimethylation, we identified 55 proteins whose levels were altered following infection of Day 1 and Day 5 adults. Proteins whose levels changed in response to infection at both ages were strongly enriched for locomotory functions underscoring the importance of pathogen avoidance mechanisms. In Day 1 C. elegans, proteins with reproductive functions were highly enriched, whereas, Day 5 worms showed elevated levels of factors representing stress response pathways such as unfolded protein response (UPR) and metabolic functions. We also found that PA01 infection is associated with elevated protein carbonylation, an irreversible marker for oxidative stress. We explored the function of UNC-60, a cytoskeletal protein whose levels were changed by both age and infection, and found that mutants of unc-60 have reduced lifespan. Overall, our data provide novel insights into the relationship between age and immunosenescence in metazoans.SignificanceThere are gaps in our knowledge pertaining to how aging influences an organism's response to pathogen exposure. In C. elegans, pathogen exposure to P. aeruginosa PA01 results in shortened lifespan, which is more pronounced in Day 5, compared to Day 1 adult worms. The proteome has age-specific responses to this exposure, and notably affects development, reproduction, metabolism, protein folding/unfolding, locomotion, and response to stress. This study addresses the molecular links between aging and immunosenescence in invertebrates.
Graphical abstract
https://ift.tt/2vaXm3b
Overexpression of CTRP3 protects against sepsis-induced myocardial dysfunction in mice
Source:Molecular and Cellular Endocrinology
Author(s): Wen-Ying Wei, Zhen-Guo Ma, Ning Zhang, Si-Chi Xu, Yu-Pei Yuan, Xiao-Feng Zeng, Qi-Zhu Tang
C1q/tumor necrosis factor-related protein-3 (CTRP3) shows striking homologies of genomic structure to the adiponectin. In this study, we aimed to investigate the protective role of CTRP3 against sepsis-induced cardiomyopathy. Here, we overexpressed CTRP3 in myocardium by direct intramyocardial injection and constructed a model of lipopolysaccharide (LPS)-induced sepsis in mice. Our results demonstrated that cardiac-specific overexpression of CTRP3 remarkably attenuated myocardial dysfunction and increased the phosphorylation level of AMPKα during LPS-induced sepsis. The anti-inflammatory effects of CTRP3, as determined by decreased mRNA levels of TNF-α, IL-6 and a lower protein expression of phosphorylated NF-κB p65 and IκBα, was detected in mice following LPS treatment. Additionally, CTRP3 suppressed cardiac apoptosis induced by LPS in mice as indicated by terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining and western blot for Cleaved-caspase3, Bax and Bcl-2. In conclusion, CTRP3 could protect against sepsis-induced myocardial dysfunction in mice. The cardioprotective effects of CTRP3 might be mediated by activating AMPKα signaling pathway and blunting inflammatory response and apoptosis.
https://ift.tt/2Hjn8XW
New technologies to uncover the molecular basis of disorders of sex development
Source:Molecular and Cellular Endocrinology
Author(s): Hayk Barseghyan, Emmanuèle C. Délot, Eric Vilain
The elegant developmental biology experiments conducted in the 1940s by French physiologist Alfred Jost demonstrated that the sexual phenotype of a mammalian embryo depended whether the embryonic gonad develops into a testis or not. In humans, anomalies in the processes that regulate development of chromosomal, gonadal or anatomic sex result in a spectrum of conditions termed Disorders/Differences of Sex Development (DSD). Each of these conditions is rare, and understanding of their genetic etiology is still incomplete. Historically, DSD diagnoses have been difficult to establish due to the lack of standardization of anatomical and endocrine phenotyping procedures as well as genetic testing. Yet, a definitive diagnosis is critical for optimal management of the medical and psychosocial challenges associated with DSD conditions.The advent in the clinical realm of next-generation sequencing methods, with constantly decreasing price and turnaround time, has revolutionized the diagnostic process. Here we review the successes and limitations of the genetic methods currently available for DSD diagnosis, including Sanger sequencing, karyotyping, exome sequencing and chromosomal microarrays. While exome sequencing provides higher diagnostic rates, many patients still remain undiagnosed. Newer approaches, such as whole-genome sequencing and whole-genome mapping, along with gene expression studies, have the potential to identify novel DSD-causing genes and significantly increase total diagnostic yield, hopefully shortening the patient's journey to an accurate diagnosis and enhancing health-related quality-of-life outcomes for patients and families.
https://ift.tt/2vdi6Ye
Next generation neuro-oncology
Source:European Journal of Cancer, Volume 96
Author(s): Michael Weller
Neuro-oncology has evolved as a growing, but still small, highly specialised and multidisciplinary field at the interface of several diagnostic and therapeutic disciplines. The major challenge in the field of primary tumours is to translate the almost unique progress in deciphering the highly complex molecular genetic nature of many primary brain tumours, notably glioblastoma, into advances that allow for clinical benefit for affected patients. Furthermore, metastases to the central nervous system are an increasingly prevalent complication in many systemic cancers. Their diagnosis and management require major expertise, notably with consideration of several new systemic therapy options, such as targeted therapy and immuno-oncology approaches. These new treatments contribute to challenges within the third major domain of neuro-oncology, the diagnosis, treatment and prevention of nervous system toxicity of old and new anti-cancer treatments. All these considerations strongly argue for the development of specialised centres of excellence to improve care for patients with brain tumour across Europe.
https://ift.tt/2GX3o90
Corrigendum to “An association study of established breast cancer reproductive and lifestyle risk factors with tumour subtype defined by the prognostic 70-gene expression signature (MammaPrint®)” [Eur J Cancer 75 (April 2017) 5–13]
Source:European Journal of Cancer
Author(s): M. Makama, C.A. Drukker, E.J.Th. Rutgers, L. Slaets, F. Cardoso, M.A. Rookus, K. Tryfonidis, L.J. Van't Veer, M.K. Schmidt
https://ift.tt/2HuMi3v
Stimulation-induced reversed plus-minus syndrome: Insights into eyelid physiology
Source:Brain Stimulation
Author(s): Derrick Soh, Musleh Algarni, Agnes Wong, Andres M. Lozano, Alfonso Fasano
https://ift.tt/2GYQo2V
Erratum
Publication date: Available online 12 April 2018
Source:Journal of the American Academy of Dermatology
https://ift.tt/2IQJLA2
Editorial Board
Source:Gene Expression Patterns, Volume 28
https://ift.tt/2v6h2oW
Effective cancer immunotherapy in mice by polyIC-imiquimod complexes and engineered magnetic nanoparticles
Publication date: July 2018
Source:Biomaterials, Volume 170
Author(s): Ana Isabel Bocanegra Gondan, Ane Ruiz-de-Angulo, Aintzane Zabaleta, Nina Gómez Blanco, Beatriz Macarena Cobaleda-Siles, María Jesús García-Granda, Daniel Padro, Jordi Llop, Blanca Arnaiz, María Gato, David Escors, Juan C. Mareque-Rivas
Encouraging results are emerging from systems that exploit Toll like receptor (TLR) signaling, nanotechnology, checkpoint inhibition and molecular imaging for cancer immunotherapy. A major remaining challenge is developing effective, durable and tumour-specific immune responses without systemic toxicity. Here, we report a simple and versatile system based on synergistic activation of immune responses and direct cancer cell killing by combined TLR ligation using polyIC as TLR3 and imiquimod (R837) as TLR7 agonist, in combination with the model antigen ovalbumin (OVA) and phospholipid micelles loaded with zinc-doped iron oxide magnetic nanoparticles (MNPs). The combination of TLR agonists triggered a strong innate immune response in the lymph nodes (LNs) without systemic release of pro-inflammatory cytokines. The vaccines showed excellent efficacy against aggressive B16-F10 melanoma cells expressing OVA, which was improved with immune checkpoint abrogation of the immunosuppressive programmed death-ligand 1 (PD-L1) at the level of the cancer cells. By magnetic resonance (MR) and nuclear imaging we could track the vaccine migration from the site of injection to LNs and tumour. Overall, we show this synergistic TLR agonists and their combination with MNPs and immune checkpoint blockade to have considerable potential for preclinical and clinical development of vaccines for cancer immunotherapy.
Graphical abstract
https://ift.tt/2ISfcdv
-
Ειδοποίηση Μελετητή:[ ωτα ] [HTML] Gender, identity and material: Film screening C Brand - 2017 ftypM4V *M4V M4A mp42isom*a┌moovlmvhd...
-
Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
