Activation of Wnt/β-catenin signaling is involved in hair growth-promoting effect of 655-nm red light and LED in in vitro culture model

Abstract

Activation of the Wnt/β-catenin signaling pathway plays an important role in hair follicle morphogenesis and hair growth. Recently, low-level laser therapy (LLLT) was evaluated for stimulating hair growth in numerous clinical studies, in which 655-nm red light was found to be most effective and practical for stimulating hair growth. We evaluated whether 655-nm red light + light-emitting diode (LED) could promote human hair growth by activating Wnt/β-catenin signaling. An in vitro culture of human hair follicles (HFs) was irradiated with different intensities of 655-nm red light + LED, 21 h7 (an inhibitor of β-catenin), or both. Immunofluorescence staining was performed to assess the expression of β-catenin, GSK3β, p-GSK3β, and Lef1 in the Wnt/β-catenin signaling. The 655-nm red light + LED not only enhanced hair shaft elongation, but also reduced catagen transition in human hair follicle organ culture, with the greatest effectiveness observed at 5 min (0.839 J/cm²). Additionally, 655-nm red light + LED enhanced the expression of β-catenin, p-GSK3β, and Lef1, signaling molecules of the Wnt/β-catenin pathway, in the hair matrix. Activation of Wnt/β-catenin signaling is involved in hair growth-promoting effect of 655-nm red light and LED in vitro and therefore may serve as an alternative therapeutic option for alopecia.

http://ift.tt/2sLJOdc

Progressive osseous heteroplasia caused by a mosaic gnas mutation

Abstract

Progressive osseous heteroplasia (POH, OMIM#166350) is an "ultrarare" genetic condition characterized by plaque-like heterotopic ossification, beginning in infancy in the dermis and subsequently progressing to involve deep connective tissues such as muscles and joints, sometimes resulting in loss of mobility ¹. It is usually associated with paternal inheritance of an inactivating mutation at the GNAS gene but in some patients (around 30% of cases) with identical clinical characteristics of POH no mutations have been detected ². On the other hand, the same mutation on the paternal allele can be responsible for pseudopseudohypoparathyroidism (PPHP, OMIM#612463), or, if maternally inherited, pseudohypoparathyroidism type 1A (PHP1A, OMIM#103580) ^.

This article is protected by copyright. All rights reserved.

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Accuracy of adrenal computed tomography in predicting the unilateral subtype in young patients with hypokalaemia and elevation of aldosterone in primary aldosteronism

Summary

Context

The current Endocrine Society Guideline suggests that patients aged <35 years with marked primary aldosteronism (PA) and unilateral adrenal lesions on adrenal computed tomography (CT) scan may not need adrenal vein sampling (AVS) before proceeding to unilateral adrenalectomy. This suggestion is, however, based on the data from only one report in the literature.

Objective

We sought to determine the accuracy of CT findings in young PA patients who had unilateral adrenal disease on CT with hypokalaemia and elevation of aldosterone.

Design and Patients

We retrospectively studied 358 PA patients (n=30, aged <35 years; n=39, aged 35-40 years; n=289, aged ≥40 years) with hypokalaemia and elevation of aldosterone and unilateral disease on CT who had successful AVS.

Main outcome measure

Accuracy of CT findings determined by AVS findings and/or surgical outcomes in patients aged <35 years.

Results

Concordance of the diagnosis between CT and AVS was 90% (27/30) in patients aged <35 years, 79% (31/39) in patients aged 35-40 years, and 69% (198/289) in those aged ≥40 years (Trend for p<0.01). Surgical benefit was confirmed in three patients aged <35 years and in three patients aged 35-40 years with available surgical data who had discordance between CT and AVS findings. Collectively, the diagnostic accuracy of CT findings was 100% (30/30) if aged <35 years and 87% (34/39) if aged 35-40 years.

Conclusion

PA patients aged <35 years with hypokalaemia and elevation of aldosterone and unilateral disease on adrenal CT could be spared AVS.

This article is protected by copyright. All rights reserved.

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Copeptin role in polyuria-polydipsia syndrome (PPS) differential diagnosis and reference range in paediatric age

Summary

Objective

Plasma arginine-vasopressin (AVP) analysis can help in the differential diagnosis of the polyuria-polydipsia syndrome (PPS), even if such investigation is hampered by technical difficulties, conversely to its surrogate copeptin. This study aims to enlarge the existing data on normal copeptin levels in childhood, to evaluate the correlation between copeptin, serum sodium and plasma and urine osmolality, and to assess the utility of the copeptin analysis in the diagnostic work-up of PPS in the paediatric age.

Patients and methods

Plasma copeptin levels were evaluated in 53 children without AVP disorders (control population), in 12 hypopituitaric children and in 15 patients with PPS after water deprivation test (WDT).

Results

Mean basal copeptin levels were 5.2±1.56 (range 2.4-8.6 pmol/L) in the control population, 2.61±0.49 pmol/L in the hypopituitaric children with complete diabetes insipidus (CDI) (p=0.04), and 6.21±1.17 pmol/L in the hypopituitaric patients without DI (p=0.02). After WDT, among 15 naïve polyuric/polydipsic children copeptin values greater than 20 pmol/liter allowed to identify nephrogenic diabetes insipidus (NDI), concentrations below 2.2 pmol/liter complete central DI (CCDI) and between 5-20 pmol/l primary polydipsia (PP). Copeptin cut-off level of 3.5 pmol/l distinguished CDI from PP, with a sensitivity and specificity of 75% and 83.3%, respectively.

Conclusion

Copeptin evaluation holds promises as a diagnostic tool in paediatric PPS; its interpretation might be useful to promptly distinguish NDI, even avoiding the WDT need.

This article is protected by copyright. All rights reserved.

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Heterozygous aggrecan variants are associated with short stature and brachydactyly: Description of 16 probands and a review of the literature

Summary

Objective

Mutations in the aggrecan gene (ACAN) have been identified in two autosomal dominant skeletal dysplasias, Spondyloepiphyseal dysplasia, Kimberley type (SEDK) and osteochondritis dissecans, as well as in a severe recessive dysplasia, Spondyloepimetaphyseal dysplasia, aggrecan type. Next generation sequencing (NGS) has aided the identification of heterozygous ACAN mutations in individuals with short stature, minor skeletal defects and mild facial dysmorphisms, some of whom have advanced bone age (BA), poor pubertal spurt and early growth cessation as well as precocious osteoarthritis.

Design & methods

Clinical and genetic characterization of 16 probands with heterozygous ACAN variants, 14 with short stature and mild skeletal defects (group 1) and two with SEDK (group 2). Subsequently, we reviewed the literature to determine the frequency of the different clinical characteristics in ACAN positive individuals.

Results

A total of 16 ACAN variants were located throughout the gene, six pathogenic mutations and 10 variants of unknown significance (VUS). Interestingly, brachydactyly was observed in all probands. Probands from group 1, with a pathogenic mutation tended to be shorter and 60% had an advanced BA compared to 0% in those with a VUS. A higher incidence of coxa valga was observed in individuals with a VUS (37% v 0%). Nevertheless, other features were present at similar frequencies.

Conclusions

ACAN should be considered as a candidate gene in patients with short stature and minor skeletal defects, particularly those with brachydactyly, and in patients with spondyloepiphyseal dysplasia. It is also important to note that advanced BA and osteoarticular complications are not obligatory conditions for aggrecanopathies/aggrecan-associated dysplasias.

This article is protected by copyright. All rights reserved.

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Sorption of benzene derivatives onto a humic acid-zeolitic tuff adduct

Abstract

The sorption of some benzene derivatives: o-xylene, toluene, phenol, benzyl alcohol, resorcinol and hydroquinone onto a zeolitic tuff-humic acid adduct (PCT-ImHA) was analysed by batch technique at 25 °C and neutral pH. PCT-ImHA was prepared by binding leonardite-extracted humic acids (HA) to a zeolitic tuff sample rich in phillipsite and chabazite and enriched with Ca²⁺ by cation exchange (Ca-PCT). The HA calcium salts were gently mixed with wet Ca-PCT; then, the mixture was heated at 330 °C for 1.5 h. An adduct with almost 2% of HA was obtained. The experimental data were well fitted by the Langmuir adsorption isotherm and showed that saturation capacity (q_Max) increased with the octanol-water repartition coefficient (K_O-W). The comparison with previous data on sorption onto immobilised HA highlights that q_Max values for PCT-ImHA are far higher than the sum of the contributions of the two separate components.

http://ift.tt/2omw8Qw

Clinical efficacy of oral administration of finasteride at a dose of 2.5 mg/day in women with female pattern hair loss

Abstract

Female pattern hair loss (FPHL) presents with diffuse thinning over the mid-frontal scalp, for which various treatment modalities have been tried. Although currently, oral 5 α-reductase inhibitors such as finasteride are being used, their clinical efficacy remains controversial. We retrospectively investigated 544 premenopausal or postmenopausal patients with FPHL who were prescribed finasteride at a dose of 2.5 mg/day. Our study excluded patients with a follow-up period of < 3 months and patients who were prescribed other FPHL treatment modalities including topical minoxidil. Finally, 112 patients were evaluated based on their medical records and clinical photographs. Based on assessment using the Ludwig scale at the time of their initial visit, among 112 patients studied, 59 patients were classified as belonging to grade I, 47 were grade II, and 6 were grade III. Using global photographs, we found that 33 (29.5%) of the 112 patients studied showed slight improvement, 73 (65.2%) showed significant improvement, whereas no change was recorded in 6 (5.4%). We could demonstrate efficacy of administration of finasteride at a dose of 2.5 mg/day for patients with FPHL and also found that finasteride has a better effect on hair growth when patients had a lower Ludwig score and an older age at onset

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The efficacy of botulinum neurotoxin A in the treatment of plaque psoriasis

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pH-Dependent production of himeic acid A and its non-enzymatic conversions to himeic acids B and C

Publication date: Available online 20 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Ayako Katsuki, Hikaru Kato, Yurika Tahara, Makoto Hashimoto, Isao Fujii, Sachiko Tsukamoto
The fungus Aspergillus japonicus MF275 produces himeic acid A (1), containing a 4-pyrone ring, along with its congeners, himeic acids B (2) and C (3). During culture, 1 was gradually converted to 3, the corresponding 4-pyridone derivative. A study of the relationship between the culture pH and the fungal metabolites showed that a decrease from pH 6.5 to pH 2 is essential for production of 1, while a subsequent increase to pH 5 is necessary for production of 3. In addition, we revealed that 1 was non-enzymatically converted to 3 by the incorporation of an ammonium nitrogen atom in a pH 5 buffer, and that 1 was converted to 2 at a conversion ratio of 50% during incubation in MeOH for five days.

Graphical abstract

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Design, synthesis and biological evaluation of novel 7-azaspiro[3.5]nonane derivatives as GPR119 agonists

Publication date: Available online 20 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Daisuke Matsuda, Madoka Kawamura, Yohei Kobashi, Fumiyasu Shiozawa, Youichirou Suga, Keiko Fusegi, Shinichi Nishimoto, Kayo Kimura, Masako Miyoshi, Noriko Takayama, Hiroyuki Kakinuma, Norikazu Ohtake
The design and synthesis of a novel class of 7-azaspiro[3.5]nonane GPR119 agonists are described. In this series, optimization of the right piperidine N-capping group (R²) and the left aryl group (R³) led to the identification of compound 54g as a potent GPR119 agonist. Compound 54g showed a desirable PK profile in Sprague-Dawley (SD) rats and a favorable glucose lowering effect in diabetic rats.

Graphical abstract

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Comparison of stratum corneum thickness between two proposed methods of calculation using Raman spectroscopic depth profiling of skin water content

Abstract

Background/purpose

The stratum corneum (SC) is the most important layer for the barrier function of skin, so investigation of the SC is very important in cosmetic and medical research. Here, we calculated the SC thickness using the depth profile of the skin's water concentration based on previously described methods, and then compared the results.

Methods

Seven Korean women in their 30s participated in this study. Raman spectroscopy was used to measure the in vivo depth profile of skin water concentration. A total of 21 areas were measured at forearm. Microsoft Excel 2007 was used to calculate SC thickness based on the slope and intersection methods.

Results

The slope method and the intersection method gave a forearm SC thickness calculated at 21.3 ± 2.6 μm and 17.6 ± 2.8 μm, respectively. There was a significant difference between the two calculation methods but the two methods showed strong correlation of SC thickness results (r = .899).

Conclusion

Although there was a difference in calculated SC thickness of about 20% between the two methods, these results reveal that the two SC thickness calculation methods using Raman spectroscopy were suitable for measuring SC thickness, a finding consistent with other published results.

http://ift.tt/2FhkWNc

Enlarged Size and Impaired Elastic Properties of the Ascending Aorta are Associated with Endothelial Dysfunction and Elevated Plasma Matrix Metalloproteinase-2 Level in Patients with Bicuspid Aortic Valve

Publication date: Available online 20 February 2018
Source:Ultrasound in Medicine & Biology
Author(s): Yi-Bin Wang, Yang Li, You-Bin Deng, Ya-Ni Liu, Jun Zhang, Jie Sun, Ying Zhu, Li Li, Qiao-Ying Tang, Wei Zhou
The aim of this study was to test whether enlarged size and impaired elastic properties of the ascending aorta are associated with impaired endothelial function and increases in plasma matrix metalloproteinase (MMP)-2 concentrations in patients with bicuspid aortic valve (BAV) without significant valvular dysfunction. The size and the elasticity of the ascending aorta and the flow-mediated vasodilation (FMD) in the brachial artery in response to hyperemia were evaluated with 2-D echocardiography and high-frequency linear ultrasound in 42 patients with BAV without significant valvular dysfunction and 30 age- and sex-matched healthy controls. In the BAV group, diastolic ascending aortic diameter (AoD) (32.1 ± 8.1 mm vs. 25.3 ± 3.6 mm, p < 0.001) and aortic stiffness index (8.0 ± 5.3 vs. 4.0 ± 1.8, p < 0.001) were significantly higher, and aortic strain (7.4 ± 3.6% vs. 11.1 ± 3.0%, p < 0.001) and aortic distensibility (7.4 ± 4.1 × 10⁻⁶cm²/dyn vs. 11.1 ± 4.3 × 10⁻⁶cm²/dyn, p < 0.001) were significantly lower than those in the control group. The BAV group also had lower FMD (6.5 ± 2.2% vs. 11.9 ± 2.7%, p < 0.001) and higher plasma MMP-2 levels (226.7 ± 55.0 ng/mL vs. 177.0 ± 45.3 ng/mL, p < 0.001) compared with the control group. In the BAV group, AoD, aortic strain, aortic stiffness index and aortic distensibility significantly correlated with FMD and MMP-2 (all p < 0.05). The multivariable linear regression analysis further indicated that FMD and MMP-2 were independently associated with AoD (β = −1.1, p = 0.005, and β = 0.09, p < 0.001, respectively). These findings suggest that enlarged size and impaired elastic properties of the ascending aorta are associated with endothelial dysfunction and elevated plasma MMP-2 level in patients with BAV without significant valvular dysfunction. FMD and plasma MMP-2 level are the significant and independent predictors of dilation of the ascending aorta in patients with BAV.



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American Heart Association Precision Medicine Platform.

Author: Kass-Hout, Taha A. MD, MS; Stevens, Laura M. BS; Hall, Jennifer L. PhD

Page: 647-649

http://ift.tt/2sDes8A

Upper Limits of Aerobic Power and Performance in Heart Transplant Recipients: Legacy Effect of Prior Endurance Training.

Author: Haykowsky, Mark J. PhD; Halle, Martin MD; Baggish, Aaron MD

Page: 650-652

http://ift.tt/2ERTnMS

Genetic Predisposition to High Blood Pressure and Lifestyle Factors: Associations With Midlife Blood Pressure Levels and Cardiovascular Events.

Author: Pazoki, Raha MD, PhD; Dehghan, Abbas MD, PhD; Evangelou, Evangelos PhD; Warren, Helen PhD; Gao, He PhD; Caulfield, Mark MD, PhD; Elliott, Paul MD, PhD; Tzoulaki, Ioanna PhD

Page: 653-661

http://ift.tt/2EK6z71

Hypertension, Genes, and Environment: Challenges for Prevention and Risk Prediction.

Author: Cooper, Richard MD

Page: 662-664

http://ift.tt/2sHuJcT

Value of Progression of Coronary Artery Calcification for Risk Prediction of Coronary and Cardiovascular Events: Result of the HNR Study (Heinz Nixdorf Recall).

Author: Lehmann, Nils PhD *,; Erbel, Raimund MD *,; Mahabadi, Amir A. MD; Rauwolf, Michael MD; Mohlenkamp, Stefan MD; Moebus, Susanne PhD; Kalsch, Hagen MD; Budde, Thomas MD; Schmermund, Axel MD; Stang, Andreas MD; Fuhrer-Sakel, Dagmar MD; Weimar, Christian MD; Roggenbuck, Ulla CRA; Dragano, Nico PhD; Jockel, Karl-Heinz PhD; on behalf of the Heinz Nixdorf Recall Study Investigators; Meinertz, T.; Bode, C.; de Feyter, P.J.; Guntert, B.; Gutzwiller, F.; Heinen, H.; Hess, O.; Klein, B.; Lowel, H.; Reiser, M.; Schmidt, G.; Schwaiger, M.; Steinmuller, C.; Theorell, T.; Willich, S.N.; Bode, C.; Berger, K.; Figulla, H.R.; Hamm, C.; Hanrath, P.; Kopcke, W.; Ringelstein, B.; Dichgans, M.; Zeiher, A.

Page: 665-679

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Coronary Artery Calcium: If Measuring Once Is Good, Is Twice Better?.

Author: Khera, Amit MD, MSc; Greenland, Philip MD

Page: 680-683

http://ift.tt/2sJsohu

Frequency, Predictors, and Impact of Combined Antiplatelet Therapy on Venous Thromboembolism in Patients With Symptomatic Atherosclerosis.

Author: Cavallari, Ilaria MD; Morrow, David A. MD, MPH; Creager, Mark A. MD; Olin, Jeffrey MD; Bhatt, Deepak L. MD, MPH; Steg, P. Gabriel MD; Storey, Robert F. MD, PhD; Cohen, Marc MD; Scirica, Benjamin S. MD; Piazza, Gregory MD, MS; Goodrich, Erica L. MS; Braunwald, Eugene MD; Sabatine, Marc S. MD, MPH; Bonaca, Marc P. MD, MPH

Page: 684-692

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Prognostic Value of Follow-Up Hemodynamic Variables After Initial Management in Pulmonary Arterial Hypertension.

Author: Weatherald, Jason MD; Boucly, Athenais MD; Chemla, Denis MD, PhD; Savale, Laurent MD, PhD; Peng, Mingkai PhD; Jevnikar, Mitja MD; Jais, Xavier MD; Taniguchi, Yu MD, PhD; O'Connell, Caroline MD; Parent, Florence MD; Sattler, Caroline MD; Herve, Philippe MD; Simonneau, Gerald MD; Montani, David MD, PhD; Humbert, Marc MD, PhD; Adir, Yochai MD *,; Sitbon, Olivier MD, PhD *,,,

Page: 693-704

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Assessing Prognosis of Pulmonary Arterial Hypertension in the Therapeutic Era: Importance of Serial Hemodynamic Measurements.

Author: Rubin, Lewis J. MD

Page: 705-706

http://ift.tt/2EK6sbB

Opposing Actions of Fibroblast and Cardiomyocyte Smad3 Signaling in the Infarcted Myocardium.

Author: Kong, Ping PhD *,; Shinde, Arti V. PhD *,; Su, Ya MD; Russo, Ilaria PhD; Chen, Bijun PhD; Saxena, Amit PharmD, PhD; Conway, Simon J. PhD; Graff, Jonathan M. MD, PhD; Frangogiannis, Nikolaos G. MD

Page: 707-724

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Developing a Clinical Approach to Air Pollution and Cardiovascular Health.

Author: Hadley, Michael B. MD, MScPH; Baumgartner, Jill PhD; Vedanthan, Rajesh MD, MPH

Page: 725-742

http://ift.tt/2ETwVTn

Broad[horizontal ellipsis] Narrow[horizontal ellipsis] Broad QRS Tachycardia.

Author: Ballesteros, Gabriel MD; Menendez, Diego MD; Ramos, Pablo MD; Garcia-Bolao, Ignacio MD, PhD

Page: 743-746

http://ift.tt/2sJhHvj

Impact of Coronary Remodeling on Fractional Flow Reserve.

Author: Collet, Carlos MD; Katagiri, Yuki MD; Miyazaki, Yosuke MD, PhD; Asano, Taku MD; Sonck, Jeroen MD; van Geuns, Robert-Jan MD, PhD; Andreini, Daniele MD, PhD; Bittencourt, Marcio S. MD, PhD; Kitslaar, Pieter MSc; Tenekeciouglu, Erhan MD; Tijssen, Jan G.P. PhD; Piek, Jan J. MD, PhD; de Winter, Robbert J. MD, PhD; Cosyns, Bernard MD, PhD; Rogers, Campbell MD; Zarins, Christopher K. MD, PhD; Taylor, Charles PhD; Onuma, Yoshinobu MD, PhD; Serruys, Patrick W. MD, PhD

Page: 747-749

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Proefferocytic Therapy Promotes Transforming Growth Factor-[beta] Signaling and Prevents Aneurysm Formation.

Author: Kojima, Yoko MD, PhD; Werner, Norna MD; Ye, Jianqin MD, PhD; Nanda, Vivek PhD; Tsao, Noah; Wang, Ying PhD; Flores, Alyssa M. BS; Miller, Clint L. PhD; Weissman, Irving MD; Deng, Hongping MD, PhD; Xu, Baohui MD, PhD; Dalman, Ronald L. MD; Eken, Suzanne M. MD, PhD; Pelisek, Jaroslav PhD; Li, Yuhuang MD, PhD; Maegdefessel, Lars MD, PhD; Leeper, Nicholas J. MD

Page: 750-753

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Letter by Jin-shan and Xue-bin Regarding Article, "Physiology of Angina and Its Alleviation With Nitroglycerin: Insights From Invasive Catheter Laboratory Measurements During Exercise".

Author: Jin-shan, He MD; Xue-bin, Li MD

Page: 754

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Response by Asrress et al to Letter Regarding Article, "Physiology of Angina and Its Alleviation With Nitroglycerin: Insights From Invasive Catheter Laboratory Measurements During Exercise".

Author: Asrress, Kaleab N. PhD; Williams, Rupert PhD; Lockie, Timothy PhD; Khawaja, Muhammed Z. PhD; Patterson, Tiffany MBBS; Arri, Satpal MBBS; De Silva, Kalpa PhD; Perera, Divaka MD; Marber, Michael S. PhD; Redwood, Simon R. MD

Page: 755-756

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Letter by Galyfos and Filis Regarding Article, "Effect of Obesity and Underweight Status on Perioperative Outcomes of Congenital Heart Operations in Children, Adolescents, and Young Adults: An Analysis of Data From the Society of Thoracic Surgeons Database".

Author: Galyfos, George MD, PhD; Filis, Konstantinos MD, PhD

Page: 757-758

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Response by O'Byrne et al to Letter Regarding Article, "Effect of Obesity and Underweight Status on Perioperative Outcomes of Congenital Heart Operations in Children, Adolescents, and Young Adults: An Analysis of Data From the Society of Thoracic Surgeons Database".

Author: O'Byrne, Michael L. MD, MSCE; Jacobs, Jeffrey P. MD; Jacobs, Marshall L. MD; Jonas, Richard A. MD

Page: 759

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Correction to: Efficacy and Safety of a Pharmaco-Invasive Strategy With Half-Dose Alteplase Versus Primary Angioplasty in ST-Segment-Elevation Myocardial Infarction: EARLY-MYO Trial (Early Routine Catheterization After Alteplase Fibrinolysis Versus Primary PCI in Acute ST-Segment-Elevation Myocardial Infarction).

Author:

Page: e29

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Comparison between male and female rats in a model of self-administration of a chocolate-flavored beverage: Behavioral and neurochemical studies

Publication date: 15 May 2018
Source:Behavioural Brain Research, Volume 344
Author(s): Andrea Contini, Fabrizio Sanna, Paola Maccioni, Giancarlo Colombo, Antonio Argiolas
The existence of sex differences was studied in a rat model of operant self-administration of a chocolate-flavored beverage (CFB), which possesses strong reinforcing properties and is avidly consumed by rats. Whether these differences occurred concomitantly to changes in extracellular dopamine in the dialysate obtained from the nucleus accumbens, was assessed by intracerebral microdialysis. Male, ovariectomized and intact female rats showed similar self-administration profiles, with minor differences in both acquisition and maintenance phases. Intact females self-administered larger amounts of CFB, when expressed per body weight, than males and ovariectomized females, in spite of similar values of lever-responding, latency to the first lever-response and consumption efficiency (a measure of rat's licking effectiveness) in males, ovariectomized and intact females and no difference in breakpoint value and number of lever-responses emerged when males, ovariectomized and intact females were exposed to a progressive ratio schedule of reinforcement. Intracerebral microdialysis revealed a slight but significant increase in dopamine activity in the shell of the nucleus accumbens of male rats when compared to intact female rats during CFB self-administration. The above differences may be caused by the hormonal (mainly estradiol) fluctuations that occur during the estrus cycle in intact females. Accordingly, in intact females CFB self-administration and dopamine activity were found to fluctuate across the estrus cycle, with lower parameters of CFB self-administration and lower dopamine activity in the Proestrus and Estrus phases vs. the Metestrus and Diestrus phases of the cycle.



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Development of novel tasks for studying view-invariant object recognition in rodents: Sensitivity to scopolamine

Publication date: 15 May 2018
Source:Behavioural Brain Research, Volume 344
Author(s): Krista A. Mitchnick, Cassidy E. Wideman, Andrew E. Huff, Daniel Palmer, Bruce L. McNaughton, Boyer D. Winters
The capacity to recognize objects from different view-points or angles, referred to as view-invariance, is an essential process that humans engage in daily. Currently, the ability to investigate the neurobiological underpinnings of this phenomenon is limited, as few ethologically valid view-invariant object recognition tasks exist for rodents. Here, we report two complementary, novel view-invariant object recognition tasks in which rodents physically interact with three-dimensional objects. Prior to experimentation, rats and mice were given extensive experience with a set of 'pre-exposure' objects. In a variant of the spontaneous object recognition task, novelty preference for pre-exposed or new objects was assessed at various angles of rotation (45°, 90° or 180°); unlike control rodents, for whom the objects were novel, rats and mice tested with pre-exposed objects did not discriminate between rotated and un-rotated objects in the choice phase, indicating substantial view-invariant object recognition. Secondly, using automated operant touchscreen chambers, rats were tested on pre-exposed or novel objects in a pairwise discrimination task, where the rewarded stimulus (S+) was rotated (180°) once rats had reached acquisition criterion; rats tested with pre-exposed objects re-acquired the pairwise discrimination following S+ rotation more effectively than those tested with new objects. Systemic scopolamine impaired performance on both tasks, suggesting involvement of acetylcholine at muscarinic receptors in view-invariant object processing. These tasks present novel means of studying the behavioral and neural bases of view-invariant object recognition in rodents.



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Graded 6-OHDA-induced dopamine depletion in the nigrostriatal pathway evokes progressive pathological neuronal activities in the subthalamic nucleus of a hemi-parkinsonian mouse

Publication date: 15 May 2018
Source:Behavioural Brain Research, Volume 344
Author(s): Sunghee Estelle Park, Kang-Il Song, Hyungmin Kim, Seok Chung, Inchan Youn
Recent studies have established methods for establishing a rodent model that mimics progressive stages of human Parkinson's disease (PD), via injection of graded doses of 6-hydroxydopamine (6-OHDA) into regions within the nigrostriatal pathway. However, the electrophysiological characteristics of the subthalamic nucleus (STN) in this model have not been fully elucidated in this model. This study aimed to investigate changes in the neuronal activity of the STN in a graded mouse model of PD. Increasing doses of 6-OHDA were unilaterally injected into the medial forebrain bundle (MFB) to produce a hemi-parkinsonian mouse model, mimicking early, moderate, advanced, and severe stages of human PD. Mice treated with higher doses of 6-OHDA demonstrated significantly lower rates of use of the impaired (contralateral) forelimb during wall contact, relative to sham mice. The STN firing rate was significantly increased in groups with >75% dopaminergic cell loss in the substantia nigra pars compacta (SNc), whereas little increase was observed in groups with partial lesions of the SNc, relative to the sham group. In addition, firing patterns of the STN in groups treated with higher doses of 6-OHDA became more irregular and exhibited burst-like patterns of activity, with dominant slow wave oscillations in the frequency range of 0.3–2.5 Hz. Our results demonstrated a strong correlation between neuronal activities in the STN and dopamine depletion in the nigrostriatal pathway, which can be manipulated by variation of 6-OHDA doses.



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Destruction of noradrenergic terminals increases dopamine concentration and reduces dopamine metabolism in the medial prefrontal cortex

Publication date: 15 May 2018
Source:Behavioural Brain Research, Volume 344
Author(s): Rita Gálosi, Zoltán Petykó, Veronika Kállai, Attila Tóth, Tamás Ollmann, László Péczely, Anita Kovács, Beáta Berta, László Lénárd
Effects of destroyed noradrenergic (NE) innervation in the medial prefrontal cortex (mPFC) were examined on dopamine (DA) content and metabolism. Six-hydroxy-DOPA (6-OHDOPA) or 6-hydroxy-dopamine (6-OHDA) in combination with a potent DA reuptake inhibitor GBR 12935 or 6-OHDA were injected bilaterally into the mPFC in separate groups of animals. In addition, GBR 12935 or vehicle was injected into the mPFC in two other groups of animals as control experiments. NE and DA concentrations from postmortem tissue of the mPFC were measured using HPLC with electrochemical detection. In addition, extracellular NE, DA and DOPAC levels were determined using in vivo microdialysis after the 6-OHDA lesion in combination with GBR 12935 pretreatment in the mPFC. Using reverse microdialysis of alpha-2-adrenoreceptor antagonist yohimbine, we tested the remaining activity of NE innervation and the extracellular concentration of DA and DOPAC. NE and DA concentrations from postmortem tissue of the mPFC showed that 6-OHDOPA lesion reduced NE concentration to 76%, which was a non-significant alteration, however it enhanced significantly DA concentration to 186% compared to vehicle. After 6-OHDA lesion with GBR 12935 pretreatment, concentration of NE significantly decreased to 51% and DA level increased to 180%. 6-OHDA lesion without GBR 12635 pretreatment decreased NE concentration to 23% and DA concentration to 67%. In the microdialysis experiment, after 6-OHDA lesion with GBR 12935 pretreatment, extracellular NE levels were not detectable, whereas extracellular DA levels were increased and DOPAC levels were decreased compared to controls. Reverse microdialysis of yohimbine demonstrated that the residual NE innervation was able to increase NE level and DA levels, but DOPAC concentration remained low after lesion of the NE terminals. These findings suggest that the damage of NE innervation in the mPFC may alter extracellular DA level due to a reduced DA clearance.



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Editorial Board

Publication date: March 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 177





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Vitamin D3 supplementation decreases a unique circulating monocyte cholesterol pool in patients with type 2 diabetes

Publication date: March 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 177
Author(s): Amy E. Riek, Jisu Oh, Isra Darwech, Veronica Worthy, Xiaobo Lin, Richard E. Ostlund, Rong M. Zhang, Carlos Bernal-Mizrachi
Cross-sectional studies indicate consistent associations between low 25(OH)D concentration and increased risk of cardiovascular disease (CVD), but results of randomized control trials (RCTs) are mixed. However, the majority of the RCTs do not focus on type 2 diabetics, potentially obscuring the effects of vitamin D in this population. In vitro 1,25(OH)2D3 downregulates macrophage cholesterol deposition, but the in vivo effects are unknown. To explore potential mechanisms of the effects of vitamin D on CVD risk in patients with type 2 diabetes, we isolated monocytes in a subset of 26 patients from our RCT of diabetics with baseline serum 25(OH)D <25ng/mL randomized to vitamin D3 4000 IU/day or placebo for 4 months. Upon enrollment, the mean 25(OH)D level was 17ng/mL, which increased to 36ng/mL after vitamin D and remained unchanged in the placebo group. Before randomization, groups demonstrated similar mean hemoglobin A1c and plasma lipids levels, none of which was significantly altered by vitamin D supplementation. Moreover, assessment of oxidized LDL uptake in monocytes cultured in the patient's own serum before vs. after treatment resulted in >50% reduction in the vitamin D group with no change in the placebo group. This was mediated through suppression of endoplasmic reticulum stress and scavenger receptor CD36 protein expression. The reduction in monocyte cholesterol uptake was reflected in a 19% decrease in total monocyte cholesterol content. Interestingly, cross-sectional analysis of circulating monocytes from vitamin D-deficient vs. sufficient diabetic patients revealed 8-fold higher cholesteryl ester content, confirming the capacity of these monocytes to uptake and carry cholesterol in the circulation. This study identifies a unique circulating cholesterol pool within monocytes that is modulated by vitamin D and has the potential to contribute to CVD in type 2 diabetes.



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Deletion of JNK2 prevents vitamin-D-deficiency-induced hypertension and atherosclerosis in mice

Publication date: March 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 177
Author(s): Jisu Oh, Amy E. Riek, Rong M. Zhang, Samantha A.S. Williams, Isra Darwech, Carlos Bernal-Mizrachi
The c-Jun N-terminal kinase 2 (JNK2) signaling pathway contributes to inflammation and plays a key role in the development of obesity-induced insulin resistance and cardiovascular disease. Macrophages are key cells implicated in these metabolic abnormalities. Active vitamin D downregulates macrophage JNK activation, suppressing oxidized LDL cholesterol uptake and foam cell formation and promoting an anti-inflammatory phenotype. To determine whether deletion of JNK2 prevents high blood pressure and atherosclerosis known to be induced by vitamin D deficiency in mice, we generated mice with knockout of JNK2 in a background susceptible to diet-induced atherosclerosis (LDLR^−/−). JNK2^−/− LDLR^−/− and LDLR^−/− control mice were fed vitamin D-deficient chow for 8 weeks followed by vitamin D-deficient high fat diet (HFD) for 10 weeks and assessed before and after HFD. There was no difference in fasting glucose, cholesterol, triglycerides, or free fatty acid levels. However, JNK2^−/− mice, despite vitamin D-deficient diet, had 20–30mmHg lower systolic (SBP) and diastolic (DBP) blood pressure before HFD compared to control mice fed vitamin D-deficient diets, with persistent SBP differences after HFD. Moreover, deletion of JNK2 reduced HFD-induced atherosclerosis by 30% in the proximal aorta when compared to control mice fed vitamin D-deficient diets. We have previously shown that peritoneal macrophages obtained from LDLR^−/− mice fed vitamin D-deficient HFD diets have higher foam cell formation compared to those from mice on vitamin D-sufficient HFD. The increased total cellular cholesterol and modified cholesterol uptake in macrophages from mice on vitamin D-deficient HFD were blunted by deletion of JNK2. These data suggest that JNK2 signaling activation is necessary for the atherosclerosis and hypertension induced by vitamin D deficiency.



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Vitamin D prevents lipid accumulation in murine muscle through regulation of PPARγ and perilipin-2 expression

Publication date: March 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 177
Author(s): Jiarong Li, Milton Mihalcioiu, Lifeng Li, Mahvash Zakikhani, Anne Camirand, Richard Kremer
Vitamin D plays an important role in regulation of skeletal muscle tone and contraction. Serum vitamin D status is linked to muscle power and force in adolescent girls, and vitamin D deficiency is associated with myopathies in children and poorer physical performance in the elderly. We previously reported that vitamin D deficiency is linked to a significant increase in muscle fatty infiltration in healthy young women, and studies in patients with neuromuscular disorders also associate muscle weakening and lipid content. In order to better understand the link between vitamin D status and skeletal muscle lipid metabolism, we compared the effect of a low (25IU/kg) or normal (1000IU/kg) vitamin D3 diet on muscle fat in female FVB mice maintained in a room without UVB lighting to minimize endogenous vitamin D production. Animals on low vitamin D diet displayed lower circulating 25(OH)D levels and a dramatic increase (287±52% compared to normal diet, p<0.0001) in lipid deposition in skeletal muscle accompanied by muscle fiber disorganization. Lipid droplet staining increased by 242±23% (p<0.0001) in low vitamin D diet, and lipid droplet coat protein perilipin-2 and nuclear receptor transcription factor PPARγ expression levels were increased compared to mice fed the normal vitamin D diet: average staining for PLIN2: 0.22±0.08 (25IU/kg diet) vs 0.10±0.02 (1000IU/kg). Average staining for PPARγ: 0.24±0.06 (25IU/kg diet) vs 0.07±0.04 (1000IU/kg) p<0.0001. Tissue mass spectrometry imaging revealed major differences in muscle phospholipids profile depending on diet. In vitro, 1,25(OH)2D3 treatment of 3T3-L1 pre-adipocytes inhibited appearance of lipid droplets by 79±9.3%, and caused a 80±10% and 25±8% (p=0.001) reduction in PPARγ and perilipin-2 mRNA levels (by qPCR) compared to control cells. In summary, we report here the first in vivo model illustrating the important structural muscle fiber disorganization and fat accumulation inside and outside muscle fibers that accompany vitamin D deficiency. Furthermore, we show that the underlying mechanisms involve PPARγ and perilipin-2.

Graphical abstract

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Vitamin D status in relation to physical performance, falls and fractures in the Longitudinal Aging Study Amsterdam: A reanalysis of previous findings using standardized serum 25-hydroxyvitamin D values

Publication date: March 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 177
Author(s): N.M. Van Schoor, M.W. Heymans, P. Lips
The Longitudinal Aging Study Amsterdam (LASA) is an ongoing prospective cohort study in a representative sample of Dutch older persons. In previous LASA studies, lower serum 25-hydroxyvitamin D (25(OH)D) values, as assessed by a competitive protein binding assay or radioimmunoassay, have been associated with decreased physical functioning, falls and fractures. Recently, serum 25(OHD) values in LASA were standardized using the Vitamin D Standardization Program (VDSP) protocol as part of the European ODIN project. In the current manuscript, the influence of standardizing serum 25(OH)D values will be discussed using the associations with physical functioning, falls and fractures as examples.



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Kinetics, isotherms, and thermodynamic studies of lead, chromium, and cadmium bio-adsorption from aqueous solution onto Picea smithiana sawdust

Abstract

Lead (Pb), chromium (Cr), and cadmium (Cd) removal capacity of sawdust (Picea smithiana) from aqueous solution was investigated by conducting batch experiments. Thermodynamic parameters, like change in standard free energy (ΔG^Θ), enthalpy (ΔH^Θ) and entropy (ΔS^Θ) during bio-adsorption process were estimated using the Van't Hoff equation. The maximum metals adsorption was observed at pH 8, 20 g L⁻¹ bio-adsorbent and at 60 min of contact time. The metal adsorption kinetics was examined by fitting the pseudo-first-order as well as four forms of pseudo-second-order kinetic models. Type 1 pseudo-second-order equation described adsorption kinetics better than others. Langmuir model and Freundlich equations were used for calculation of sorption parameters. The Langmuir maximum adsorption capacity of Pb, Cr, and Cd was 6.35, 3.37, and 2.87 mg g⁻¹ at room temperature, respectively. The values of the separation factor (RL) were in between 0 and 1, indicating that bio-adsorption was favorable. Thermodynamics study revealed that the Pb, Cr, and Cd uptake reactions were endothermic and spontaneous. Results of the study asserted that the removal of heavy metal ions from aqueous solution is viable and the sawdust could be used in the treatment of effluents from industries, thereby reducing the level of water pollution.

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Computer-Aided Surgical Simulation in Head and Neck Reconstruction: A Cost Comparison among Traditional, In-House, and Commercial Options

J reconstr Microsurg
DOI: 10.1055/s-0037-1621735

Background Computer-aided surgical simulation (CASS) has redefined surgery, improved precision and reduced the reliance on intraoperative trial-and-error manipulations. CASS is provided by third-party services; however, it may be cost-effective for some hospitals to develop in-house programs. This study provides the first cost analysis comparison among traditional (no CASS), commercial CASS, and in-house CASS for head and neck reconstruction. Methods The costs of three-dimensional (3D) pre-operative planning for mandibular and maxillary reconstructions were obtained from an in-house CASS program at our large tertiary care hospital in Northern Virginia, as well as a commercial provider (Synthes, Paoli, PA). A cost comparison was performed among these modalities and extrapolated in-house CASS costs were derived. The calculations were based on estimated CASS use with cost structures similar to our institution and sunk costs were amortized over 10 years. Results Average operating room time was estimated at ten hours, with an average of two hours saved with CASS. The hourly cost to the hospital for the operating room (including anesthesia and other ancillary costs) was estimated at $4,614/hour. Per case, traditional cases were $46,140, commercial CASS cases were $40,951, and in-house CASS cases were $38,212. Annual in-house CASS costs were $39,590. Conclusions CASS reduced operating room time, likely due to improved efficiency and accuracy. Our data demonstrate that hospitals with similar cost structure as ours, performing greater than 27 cases of 3D head and neck reconstructions per year can see a financial benefit from developing an in-house CASS program.
[...]

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Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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The GRP78/BiP inhibitor HA15 synergizes with mitotane action against adrenocortical carcinoma cells through convergent activation of ER stress pathways

Publication date: Available online 20 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Carmen Ruggiero, Mabrouka Doghman-Bouguerra, Cyril Ronco, Rachid Benhida, Stéphane Rocchi, Enzo Lalli
Many types of cancer cells present constitutively activated ER stress pathways because of their significant burden of misfolded proteins coded by mutated and rearranged genes. Further increase of ER stress by pharmacological intervention may shift the balance towards cell death and can be exploited therapeutically. Recent studies have shown that an important component in the mechanism of action of mitotane, the only approved drug for the medical treatment of adrenocortical carcinoma (ACC), is represented by activation of ER stress through inhibition of the SOAT1 enzyme and accumulation of toxic lipids. Here we show that HA15, a novel inhibitor of the essential ER chaperone GRP78/BiP, inhibits ACC H295R cell proliferation and steroidogenesis and is able to synergize with mitotane action. These results suggest that convergent activation of ER stress pathways by drugs acting via different mechanisms represents a valuable therapeutic option for ACC.



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Foods with increased protein content: A qualitative study on European consumer preferences and perceptions

Publication date: 1 June 2018
Source:Appetite, Volume 125
Author(s): Marija Banovic, Liisa Lähteenmäki, Anne Arvola, Kyösti Pennanen, Denisa E. Duta, Monika Brückner-Gühmann, Klaus G. Grunert
Foods with increased protein content have rapidly become one of the fastest-growing product categories targeting image- and health-focused consumers. However, it is not clear whether consumers really understand the difference between 'inherently rich in protein' and 'artificially increased protein'. This study used a qualitative focus group approach to investigate the consumer preferences and perceptions of foods with increased protein content among mixed-age and older population in four European countries. In total fifty-two participants were involved in the study. Understanding of the concept of foods with 'increased protein' content was limited. Both older and mixed-age participants could not differentiate between natural sources of protein and foods with increased protein content, no matter whether foods with animal or plant proteins were mentioned. Older participants expressed more scepticism towards foods with increased protein content than mixed-age participants. The combination of protein type and food carrier closer to conventional foods received more acceptance among both older and mixed-age participants. Future use and acceptance of foods with increased protein content will depend on the extent to which consumer concerns about incorporating additional protein into a diet can be responded.



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Healthy and sustainable diets: Community concern about the effect of the future food environments and support for government regulating sustainable food supplies in Western Australia

Publication date: 1 June 2018
Source:Appetite, Volume 125
Author(s): Amelia J. Harray, Xingqiong Meng, Deborah A. Kerr, Christina M. Pollard
ObjectiveTo determine the level of community concern about future food supplies and perception of the importance placed on government regulation over the supply of environmentally friendly food and identify dietary and other factors associated with these beliefs in Western Australia.DesignData from the 2009 and 2012 Nutrition Monitoring Survey Series computer-assisted telephone interviews were pooled. Level of concern about the effect of the environment on future food supplies and importance of government regulating the supply of environmentally friendly food were measured. Multivariate regression analysed potential associations with sociodemographic variables, dietary health consciousness, weight status and self-reported intake of eight foods consistent with a sustainable diet.SettingWestern Australia.SubjectsCommunity-dwelling adults aged 18–64 years (n = 2832).ResultsSeventy nine per cent of Western Australians were 'quite' or 'very' concerned about the effect of the environment on future food supplies. Respondents who paid less attention to the health aspects of their diet were less likely than those who were health conscious ('quite' or 'very' concerned) (OR = 0.53, 95% CI [0.35, 0.8] and 0.38 [0.17, 0.81] respectively). The majority of respondents (85.3%) thought it was 'quite' or 'very' important that government had regulatory control over an environmentally friendly food supply. Females were more likely than males to rate regulatory control as 'quite' or 'very' important' (OR = 1.63, 95% CI [1.09, 2.44], p = .02). Multiple regression modeling found that no other factors predicted concern or importance.ConclusionsThere is a high level of community concern about the impact of the environment on future food supplies and most people believe it is important that the government regulates the issue. These attitudes dominate regardless of sociodemographic characteristics, weight status or sustainable dietary behaviours.



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Title Page

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1





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Table of Contents

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1





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Editorial Board

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1





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CME Overview

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1





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The future is finally here: Advances in the treatment of atopic dermatitis

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): Matthew J. Zirwas




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Dupilumab: A review of its use in the treatment of atopic dermatitis

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): Melinda J. Gooderham, H. Chih-ho Hong, Panteha Eshtiaghi, Kim A. Papp
Atopic dermatitis (AD) is a chronic, pruritic immune-mediated inflammatory dermatosis characterized by a T helper 2 (Th2) immune response phenotype and may be associated with systemic inflammation. Dupilumab is an interleukin 4 (IL-4) receptor α-antagonist that inhibits IL-4 and IL-13 signaling through blockade of the shared IL-4α subunit. Blockade of IL-4/13 is effective in reducing Th2 response. Dupilumab has recently been approved in the United States and Europe for the treatment of adult patients with moderate-to-severe AD. Clinical trials have shown that adults with moderate-to-severe AD who receive weekly or biweekly dupilumab injections have significantly improved clinical and patient-reported outcomes, including Eczema Area Severity Index, SCORing Atopic Dermatitis, Dermatology Life Quality Index, and itch Numeric Rating Scale scores. Concomitant use of topical corticosteroids along with dupilumab results in a greater improvement in signs and symptoms of AD than with use of dupilumab alone. Biomarker analyses show that dupilumab modulates the AD molecular signature and other Th2-associated biomarkers. Common adverse events reported in the clinical trials were nasopharyngitis, upper respiratory tract infection, injection site reactions, skin infections, and conjunctivitis. These were mild-to-moderate in nature, and overall rates of adverse events occurred with similar frequency between the treatment and placebo groups. There were no significant serious safety concerns identified in phase III clinical trials. Dupilumab, as monotherapy or with concomitant use of topical corticosteroids, can significantly improve clinical outcomes and quality of life in patients suffering from moderate-to-severe AD. Ongoing studies of dupilumab will help determine the clinical efficacy and safety profile of its long-term use.



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New therapies for atopic dermatitis: Additional treatment classes

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): Paras P. Vakharia, Jonathan I. Silverberg
BackgroundA wide array of miscellaneous agents is being studied for the treatment of atopic dermatitis (AD), including targeted topical, oral systemic, and biologic agents.ObjectiveTo review the known efficacy and safety to date for such agents being studied for the treatment of AD.MethodsA nonsystematic review of the literature was performed. PubMed and ClinicalTrials.gov were searched for studies assessing agents not described previously for the treatment of AD. Randomized controlled trials were primarily sought, but other study types were also included if they contained pertinent data. Agents are presented by mechanism of action, with analysis of mechanism of action and data regarding efficacy and safety in patients with AD.ResultsData regarding the following agents are presented: omiganan (an antimicrobial peptide), tapinarof (a nonsteroidal anti-inflammatory agent), PR022 (hypochlorous acid), asimadoline (a κ-opioid agonist), DS107 (dihomo-γ-linolenic acid), ZPL-389 (a histamine H4 receptor antagonist), secukinumab (an interleukin 17A inhibitor), and fezakinumab (interleukin 22 inhibitor).LimitationsLimited clinical data exist for many of the described agents.ConclusionsAs recent research has improved our understanding of AD pathogenesis, various agents with unique mechanisms of action have been studied for the treatment of AD. Many of these hold great therapeutic promise for AD, and continued research and development is warranted.



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Monoclonal antibodies against interleukin 13 and interleukin 31RA in development for atopic dermatitis

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): Carsten R. Hamann, Jacob P. Thyssen
The interleukin 13 (IL-13) and IL-31 cytokines and inflammatory pathways have been identified as important for the pathophysiology of atopic dermatitis (AD). Monoclonal antibodies against IL-13 have been studied for the treatment of asthma since 2011. More recently, 2 phase 2 trials have been completed with these antibodies in AD treatment. In both trials, significant reductions of Eczema Area and Severity Index scores were seen. IL-31 is thought to play a role transmitting itch sensation to the central nervous system, and blocking IL-31 activity reduces itch in patients with AD. One phase 2 trial has been completed for a humanized antibody against IL-31 receptor alpha, which is 1 subunit of the IL-31 receptor complex. This study showed significant dose-dependent reductions in pruritus, Eczema Area and Severity Index scores, and markers of sleep quality. Initial clinical trials for monoclonal antibodies against IL-13 and IL-31 receptor A all show promise, although long-term safety and efficacy data are lacking. Nevertheless, these medications will likely play a role in the treatment of moderate-to-severe AD.



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Phosphodiesterase 4 inhibitors

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): Rema Zebda, Amy S. Paller
Historically, drugs available for treating atopic dermatitis (AD) have been limited to topical corticosteroids and topical calcineurin inhibitors, with systemic immunosuppressants and phototherapy reserved for severe AD. Despite their efficacy and infrequent adverse events, phobia about the use of topical steroids and calcineurin inhibitors has limited their use. More targeted options with fewer systemic and cutaneous side effects are needed for treating AD. Phosphodiesterase 4 (PDE4) is involved in the regulation of proinflammatory cytokines via the degradation of cyclic adenosine monophosphate. PDE4 activity is increased in the inflammatory cells of patients with AD, leading to increased production of proinflammatory cytokines and chemokines. Targeting PDE4 reduces the production of these proinflammatory mediators in AD. Both topical and oral PDE4 inhibitors have a favorable safety profile. Crisaborole 2% ointment, a topical PDE4, is now US Food and Drug Administration–approved for children older than 2 years and adults in the treatment of AD. Crisaborole 2% ointment shows early and sustained improvement in disease severity and pruritus and other AD symptoms, with burning and/or stinging upon application as the only related adverse event. Other PDE4 inhibitors are currently in trials with promising efficacy and safety.



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Emerging therapies for atopic dermatitis: JAK inhibitors

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): David G. Cotter, David Schairer, Lawrence Eichenfield
The Janus kinase–signal transducer and activator of transcription pathway is a conserved master regulator of immunity and myeloproliferation. Advanced understanding of this pathway has led to development of targeted inhibitors of Janus kinases (Jakinibs). As a class, JAK inhibitors effectively treat a multitude of hematologic and inflammatory diseases. Given such success, use of JAK inhibitors for mitigation of atopic dermatitis is under active investigation. Herein, we review the evolving data on the safety and efficacy of JAK inhibitors in treatment of atopic dermatitis. Although it is still early in the study of JAK inhibitors for atopic dermatitis, evidence identifies JAK inhibitors as effective alternatives to conventional therapies. Nonetheless, multiple large safety and efficacy trials are needed before widespread use of JAK inhibitors can be advocated for atopic dermatitis.



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Emerging therapies for atopic dermatitis: TRPV1 antagonists

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): Jonathan G. Bonchak, Robert A. Swerlick
Transient receptor potential (TRP) ion channels are important mediators of somatosensory signaling throughout the body. Our understanding of the contribution of TRPs to a multitude of cutaneous physiologic processes has grown substantially in the past decade. TRP cation channel subfamily V member 1 (TRPV1), one of the better-understood members of this large family of ion channels, affects multiple pathways involved in pruritus. Further, TRPV1 appears to play a role in maintaining skin barrier function. Together, these properties make TRPV1 a ripe target for new therapies in atopic dermatitis. Neurokinin antagonists may affect similar pathways and have been studied to this effect. Early trials data suggest that these therapies are safe, but assessment of their efficacy in atopic dermatitis is pending as we await publication of phase II and III clinical trials data.



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T-cell inhibitors for atopic dermatitis

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): W. James Tidwell, Joseph F. Fowler
The management of atopic dermatitis is changing with the development of novel biologic agents to target specific molecules in the inflammatory cascade. Following the ability of dupilumab has proved its ability to act on the interleukin 4 receptor in treating atopic dermatitis. Thymic stromal lymphopoietin monoclonal antibody (AMG157/MEDI9929) and OX40 blocking antibody (GBR 830) were developed by targeting the same pathway as dupilumab further upstream. The clinical data on the efficacy for these drugs are not yet known. There is some early evidence that AMG157/MEDI9929 attenuates most measures of allergen-induced asthmatic responses. However, there are no public data on its ability to treat atopic dermatitis. In a phase 2a study, GBR 830 showed at least a 50% reduction in the Eczema Area and Severity Index scores of 17 of 23 patients, but it was not sufficiently powered for identification of statistical differences between GBR 830 versus placebo. Although there is potential for these 2 drugs to greatly improve the management of severe atopic dermatitis, significant clinical trials have not yet been completed to prove efficacy, and there are not yet any available phase 3 clinical trials, which are needed to truly evaluate their efficacy in affecting T-cells.



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Emerging therapies for atopic dermatitis: The prostaglandin/leukotriene pathway

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): Daniel A. Yanes, Joy L. Mosser-Goldfarb
The role of leukotrienes and prostaglandins in development of atopy has been prototypically established in studies of asthma pathogenesis. Likewise, both in vitro and in vivo studies of atopic dermatitis have demonstrated that these molecules maintain important pathophysiologic roles. Thus, it follows that targeted therapies against these molecules may be promising in management of atopic dermatitis. Montelukast has had questionable efficacy in patients with atopic dermatitis, whereas small pilots using zileuton did have some clinically significant improvement. There are several agents in development that target leukotrienes and/or prostaglandins as well, including OC000459, Q301, and ZPL-521. In atopic dermatitis, OC000459 did not demonstrate efficacy in clinical trials, and the efficacy of the other 2 agents remains to be seen. Should these medications prove promising, these topical agents may play a future role in chronic maintenance therapy and flare prophylaxis in atopic dermatitis, as antileukotriene therapy does in asthma.



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Editorial Board and Contents

Publication date: March 2018
Source:Trends in Endocrinology & Metabolism, Volume 29, Issue 3





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Taking Aim at Glycolysis with CDK8 Inhibitors

Publication date: Available online 20 February 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Robert P. Fisher
Dependence on glycolysis under aerobic conditions, a frequent metabolic derangement in cancer cells, suggests a therapeutic opportunity. Now, through chemical genetics, CDK8, a kinase associated with the Mediator transcriptional coactivator complex, has emerged as an upstream inducer of glycolysis and a possible target for anticancer drug discovery.



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Brain Feeding Circuits after Roux-en-Y Gastric Bypass

Publication date: Available online 20 February 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Mohammed K. Hankir, Florian Seyfried, Alexander D. Miras, Michael A. Cowley
Metabolic surgical procedures, such as Roux-en-Y gastric bypass (RYGB), uniquely reprogram feeding behavior and body weight in obese subjects. Clinical neuroimaging and animal studies are only now beginning to shed light on some of the underlying central mechanisms. We present here the roles of key brain neurotransmitter/neuromodulator systems in food choice, value, and intake at various stages after RYGB. In doing so, we elaborate on how known signals emanating from the reorganized gut, including peptide hormones and microbiota products, impinge on newly mapped homeostatic and hedonic brain feeding circuits. Continued progress in the rapidly evolving field of metabolic surgery will inform the design of more effective weight-loss compounds.



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Generalization and maintenance of functional communication training for individuals with developmental disabilities: A systematic and quality review

Publication date: Available online 19 February 2018
Source:Research in Developmental Disabilities
Author(s): Leslie Neely, Elaina Garcia, Brooke Bankston, Andrew Green
BackgroundFunctional communication training (FCT) is considered an evidence-based practice for treating problem behavior in individuals with developmental disabilities (e.g. autism, intellectual disabilities, down syndrome, etc.). However, there is little known on how to sustain behavioral change following FCT interventions. This systematic and quality review synthesizes the current literature base evaluating the maintenance and generalization of behavioral effects following FCT.MethodA systematic review identified 37 studies that met the pre-set inclusion criteria. Those studies were summarized in terms of: (a) generalization dimension, (b) generalization assessment design, (c) maintenance assessment design, (d) maintenance and generalization teaching strategy, and (e) latency to maintenance probes. All studies employed single-case research designs and were evaluated using the What Works Clearinghouse pilot single-case research standards (Kratochwill et al., 2013) as adapted by Maggin, Briesch, and Chafouleas (2013). Maintenance and generalization data were evaluated using a researcher-developed rubric based on the WWC standards.Results and discussionResults indicate that 30 studies met standards or met standards with reservations while only six studies also met all of the maintenance and generalization standards. Of the six studies, five did not implement any additional strategies beyond the contacting natural contingencies that is inherent in the FCT intervention. Implications for future research and practice are discussed.



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Functional richness: Overview of indices and underlying concepts

Publication date: February 2018
Source:Acta Oecologica, Volume 87
Author(s): G. Legras, N. Loiseau, J.-C. Gaertner
Functional richness, currently defined as the amount of niche space occupied by the species within a community, is one of the three major components of functional diversity. Different indices have been developed in order to quantify this component. However, the range of indices available for assessing functional richness, often mathematically complex and based on different rationales, can cause confusion for field ecologists and lead to misinterpretation of the results obtained. In this context, we have provided the first study exclusively focused on the comparison of the definitions, advantages and drawbacks of a large set of functional richness indices. The first part of this work is focused on four indices (FDP&G, FRic, TOP and N-hypervolumes indices) that are currently the most commonly used for assessing functional richness. We have completed our study by including recently developed indices that enable us to take into account the intraspecific trait variability (i.e. FRim index and TDP framework), because there is currently a growing scientific consensus regarding the necessity of including this aspect in the assessment of the functional diversity of communities.We demonstrate that although authors have argued that their index describes the functional richness, each of them describes only part of it, and this part may strongly differ from one index to another. Rather than advocating the general use of a single index and/or systematically avoiding others, our study highlights the need for selecting indices in close relation with the context, the available data and the aims of each study. Such a strategy is an essential preliminary step for preventing misunderstanding and artefactual controversies. Along these lines, we propose some guidelines to help users in selecting the most appropriate indices according both to the facet of functional richness on which they wish to focus and to the characteristics of the available data.



http://ift.tt/2sOMdnR

Below and above-ground carbon distribution along a rainfall gradient. A case of the Zambezi teak forests, Zambia

Publication date: February 2018
Source:Acta Oecologica, Volume 87
Author(s): Justine Ngoma, Eddy Moors, Bart Kruijt, James H. Speer, Royd Vinya, Emmanuel N. Chidumayo, Rik Leemans
Understanding carbon (C) stocks or biomass in forests is important to examine how forests mitigate climate change. To estimate biomass in stems, branches and roots takes intensive fieldwork to uproot, cut and weigh the mass of each component. Different models or equations are also required. Our research focussed on the dry tropical Zambezi teak forests and we studied their structure at three sites following a rainfall gradient in Zambia. We sampled 3558 trees at 42 plots covering a combined area of 15ha. Using data from destructive tree samples, we developed mixed-species biomass models to estimate above ground biomass for small (<5 cm diameter at breast height (DBH, 1.3 m above-ground)) and large (≥5 cm DBH) trees involving 90 and 104 trees respectively, that belonged to 12 species. A below-ground biomass model was developed from seven trees of three species (16–44 cm DBH) whose complete root systems were excavated. Three stump models were also derived from these uprooted trees. Finally, we determined the C fractions from 194 trees that belonged to 12 species. The analysis revealed that DBH was the only predictor that significantly correlated to both above-ground and below-ground biomass. We found a mean root-to-shoot ratio of 0.38:0.62. The C fraction in leaves ranged from 39% to 42%, while it varied between 41% and 46% in wood. The C fraction was highest at the Kabompo site that received the highest rainfall, and lowest at the intermediate Namwala site. The C stocks varied between 15 and 36 ton C ha⁻¹ and these stocks where highest at the wetter Kabompo site and lowest at the drier Sesheke site. Our results indicate that the projected future rainfall decrease for southern Africa, will likely reduce the C storage potential of the Zambezi teak forests, thereby adversely affecting their mitigating role in climate change.



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Qualitative aspects of the effectiveness of Culpeo foxes (Lycalopex culpaeus) as dispersers of Prosopis alba (Fabaceae) in a Bolivian dry valley

Publication date: February 2018
Source:Acta Oecologica, Volume 87
Author(s): D.E. Maldonado, A.P. Loayza, E. Garcia, L.F. Pacheco
Foxes disperse several plant species in arid and semi-arid environments, but their effectiveness as dispersal agents still remains unclear. In this study, we examined qualitative components of the effectiveness of L. culpaeus as a disperser of P. alba seeds in an inter-Andean dry valley of La Paz, Bolivia. Specifically, we determined seed deposition microhabitats, and the probabilities of germination, seed removal and seedling recruitment in these microhabitats. Additionally, we assessed the effect of gut-passage on P. alba germination. We collected 159 scats, which contained a total of 3402 endocarps fragments. Foxes dispersed seeds into two microhabitats: open areas and under woody vegetation, but more frequently in the former. The probability of germination did not differ between gut-passed and control seeds, but control seeds germinated faster than gut-passed ones. The likelihood of removal was greater for endocarps fragments in open microhabitats than under woody vegetation. Only a small percentage of the seeds in each microhabitat germinated, but none survived more than a week. We conclude that although the Culpeo fox can defecate intact P. alba seeds, it does not provide effective dispersal services.



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Meetings Calendar

Rejuvenation Research Feb 2018, Vol. 21, No. 1: 77-84.


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Longevity Escape Velocity Medicine: A New Medical Specialty for Longevity?

Rejuvenation Research Feb 2018, Vol. 21, No. 1: 1-2.


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ATP Synthase, a Target for Dementia and Aging?

Rejuvenation Research Feb 2018, Vol. 21, No. 1: 61-66.


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Commentary on Some Recent Theses Relevant to Combating Aging: February 2018

Rejuvenation Research Feb 2018, Vol. 21, No. 1: 70-76.


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Validated Living Worldwide Supercentenarians, Living and Recently Deceased: February 2018

Rejuvenation Research Feb 2018, Vol. 21, No. 1: 67-69.


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Development and characterization of DNA aptamers against florfenicol: Fabrication of a sensitive fluorescent aptasensor for specific detection of florfenicol in milk

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): Atefeh Sarafan Sadeghi, Mohammad Mohsenzadeh, Khalil Abnous, Seyed Mohammad Taghdisi, Mohammad Ramezani
Specific ssDNA aptamers for the antibiotic florfenicol (FF) were developed from an enriched nucleotide library using magnetic beads-based SELEX (Systematic Evolution of Ligands by EXponential enrichment) technique with high-binding affinity. After 12 rounds of selection, thirty-six sequences were obtained that were then divided into five major families, according to the primary sequence similarity. Binding affinity analyses of three fluorescently tagged aptamers belonging to different families demonstrated that the dissociation constants (Kd) were in the low nanomolar range (Kd = 52.78–211.4 nmol L⁻¹). Furthermore, to verify the potential application of the aptamers, a fluorescent aptasensor was fabricated for detecting the FF residue in raw milk samples based on the energy transfer between graphene oxide as the acceptor and fluorescently tagged FF-specific aptamer as the donor. Under optimal conditions, the aptasensor displayed a wide linear range from 5 to 1200 nmol L⁻¹ and a detection limit of 5.75 nmol L⁻¹ with excellent selectivity in milk. The recovery rate in the milk was between 101% ± 0.14% and 110% ± 2.8%, indicating high accuracy. This fluorescent aptasensor possessed considerable potential for rapid analysis of FF in raw milk because of its simplicity of detection. Moreover, the interaction between the aptamer and FF was studied using molecular modeling.

Graphical abstract

http://ift.tt/2CA9Vn3

Dual-target recognition sandwich assay based on core-shell magnetic mesoporous silica nanoparticles for sensitive detection of breast cancer cells

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): Weiwei Wang, Suqin Liu, Chengjie Li, Yan Wang, Chao Yan
A novel dual-target recognition sandwich strategy for selective capture and detection of MCF-7 breast cancer cells based on core-shell magnetic mesoporous silica (Fe3O4@nSiO2@mSiO2@apt) nanoparticles was developed. Fe3O4@nSiO2@mSiO2@apt nanoparticles, which were prepared by a layer-by-layer method and were used for the first time to capture cancer cells, have large surface areas, particularly accessible mesochannels, and good biocompatibility, enabling aptamers to be compactly anchored onto the surface of the core-shell magnetic nanoparticles. A mucin 1 protein (MUC1)-targeted Fe3O4@nSiO2@mSiO2@apt nanoparticle was used as an affinity magnetic isolate material to capture target MCF-7 cells selectively and to reduce interference through affinity interaction between the anti-MUC1 aptamer and the MUC1 protein over-expressed on the surface of the MCF-7 cells. Meanwhile, a folate receptor (FR)-targeted affinity fluorescent probe (FA-BSA-FITC) was developed by coupling folic acid and FITC to the surface of BSA, enabling high sensitivity, selective fluorescent labeling of FR over-expressed MCF-7 cells. A dual-target recognition sandwich assay was developed based on the MUC1-targeted magnetic nanoparticles and the FR-targeted fluorescent probes. Under optimum conditions, a quantitative assay of MCF-7 cells was achieved with a dynamic range of 10²–10⁵ cells/mL (R² = 0.9991). This assay showed high specificity and sensitivity to the target MCF-7 cells. Finally, the proposed strategy could be extended to detect MCF-7 cells in human plasma and whole blood with a recovery range of 86.1–104.0% and a RSD range of 1.2–8.4%, respectively. This indicates that the dual-target recognition method developed in this research exhibits good selectivity, anti-interference capability, and reliability even in plasma and whole blood samples and is more suitable for complex samples than previous targeted assays. Therefore, the approach proposed here may have great potential for early breast cancer diagnosis.

Graphical abstract

http://ift.tt/2EFz066

Nanoparticle-Enhanced Laser Induced Breakdown Spectroscopy for the noninvasive analysis of transparent samples and gemstones

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): C. Koral, M. Dell'Aglio, R. Gaudiuso, R. Alrifai, M. Torelli, A. De Giacomo
In this paper, Nanoparticle-Enhanced Laser Induced Breakdown Spectroscopy is applied to transparent samples and gemstones with the aim to overcome the laser induced damage on the sample. We propose to deposit a layer of AuNPs on the sample surface by drying a colloidal solution before ablating the sample with a 532 nm pulsed laser beam. This procedure ensures that the most significant fraction of the beam, being in resonance with the AuNP surface plasmon, is mainly absorbed by the NP layer, which in turn results the breakdown to be induced on NPs rather than on the sample itself. The fast explosion of the NPs and the plasma induction allow the ablation and the transfer in the plasma phase of the portion of sample surface where the NPs were placed. The employed AuNPs are prepared in milliQ water without the use of any chemical stabilizers by Pulsed Laser Ablation in Liquids (PLAL), in order to obtain a strict control of composition and impurities, and to limit possible spectral interferences (except from Au emission lines). Therefore with this technique it is possible to obtain, together with the emission signal of Au (coming from atomized NPs), the emission spectrum of the sample, by limiting or avoiding the direct interaction of the laser pulse with the sample itself. This approach is extremely useful for the elemental analysis by laser ablation of high refractive index samples, where the laser pulse on an untreated surface can otherwise penetrate inside the sample, generate breakdown events below the superficial layer, and consequently cause cracks and other damage. The results obtained with NELIBS on high refractive index samples like glasses, tourmaline, aquamarine and ruby are very promising, and demonstrate the potentiality of this approach for precious gemstones analysis.

Graphical abstract

http://ift.tt/2CAxbBp

Rapid and robust analytical protocol for E. coli STEC bacteria subspecies differentiation using whole cell MALDI mass spectrometry

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): Kevin Mclean, Javier Palarea-Albaladejo, Carol G. Currie, Lisa H.J. Imrie, Erin D.T. Manson, Douglas Fraser-Pitt, Frank Wright, Colin J. Alexander, Kevin G.J. Pollock, Lesley Allison, Mary Hanson, David G.E. Smith
Whole cell MALDI is regularly used for the identification of bacteria to species level in clinical Microbiology laboratories. However, there remains a need to rapidly characterize and differentiate isolates below the species level to support outbreak management. We describe the implementation of a modified preparative approach for MALDI-MS combined with a custom analytical computational pipeline as a rapid procedure for subtyping Shigatoxigenic E. coli (STEC) and accurately identifying strain-specifying biomarkers. The technique was able to differentiate E. coli O157:H7 from other STEC. Within O157 serotype O157:H7 isolates were readily distinguishable from Sorbitol Fermenting O157 isolates. Overall, nine homogeneous groups of isolates were distinguished, each exhibiting distinct profiles of defining mass spectra features. This offers a robust analytical tool useable in reference/diagnostic public health scenarios.

Graphical abstract

http://ift.tt/2GvjKoS

Two-dimensional liquid chromatography consisting of twelve second-dimension columns for comprehensive analysis of intact proteins

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): Jiangtao Ren, Matthew A. Beckner, Kyle B. Lynch, Huang Chen, Zaifang Zhu, Yu Yang, Apeng Chen, Zhenzhen Qiao, Shaorong Liu, Joann J. Lu
A comprehensive two-dimensional liquid chromatography (LCxLC) system consisting of twelve columns in the second dimension was developed for comprehensive analysis of intact proteins in complex biological samples. The system consisted of an ion-exchange column in the first dimension and the twelve reverse-phase columns in the second dimension; all thirteen columns were monolithic and prepared inside 250 µm i.d. capillaries. These columns were assembled together through the use of three valves and an innovative configuration. The effluent from the first dimension was continuously fractionated and sequentially transferred into the twelve second-dimension columns, while the second-dimension separations were carried out in a series of batches (six columns per batch). This LCxLC system was tested first using standard proteins followed by real-world samples from E. coli. Baseline separation was observed for eleven standard proteins and hundreds of peaks were observed for the real-world sample analysis. Two-dimensional liquid chromatography, often considered as an effective tool for mapping proteins, is seen as laborious and time-consuming when configured offline. Our online LCxLC system with increased second-dimension columns promises to provide a solution to overcome these hindrances.

Graphical abstract

http://ift.tt/2EICGnS

A compact and low-cost laser induced fluorescence detector with silicon based photodetector assembly for capillary flow systems

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): Xuhui Geng, Meng Shi, Haijing Ning, Chunbo Feng, Yafeng Guan
A compact and low-cost laser induced fluorescence (LIF) detector based on confocal structure for capillary flow systems was developed and applied for analysis of Her2 protein on single Hela cells. A low-power and low-cost 450 nm laser diode (LD) instead of a high quality laser was used as excitation light source. A compact optical design together with shortened optical path length improved the optical efficiency and detection sensitivity. A superior silicon based photodetector assembly was used for fluorescence detection instead of a photomultiplier (PMT). The limit of detection (LOD) for fluorescein sodium was 3 × 10^–12 M or 165 fluorescein molecules in detection volume measured on a homemade capillary electroosmotic driven (EOD)-LIF system, which was similar to commercial LIFs. Compared to commercial LIFs, the whole volume of our LIF was reduced to 1/2–1/3, and the cost was less than 1/3 of them.

Graphical abstract

http://ift.tt/2Cy5MQI

An electrochemical immunosensor for cardiac Troponin I using electrospun carboxylated multi-walled carbon nanotube-whiskered nanofibres

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): Babak Rezaei, Ahmad Mousavi Shoushtari, Mohammad Rabiee, Lokman Uzun, Wing Cheung Mak, Anthony P.F. Turner
A sandwich-type nanostructured immunosensor based on carboxylated multi-walled carbon nanotube (CMWCNT)-embedded whiskered nanofibres (WNFs) was developed for detection of cardiac Troponin I (cTnI). WNFs were directly fabricated on glassy carbon electrodes (GCE) by removing the sacrificial component (polyethylene glycol, PEG) after electrospinning of polystyrene/CMWCNT/PEG nanocomposite nanofibres, and utilised as a transducer layer for enzyme-labeled amperometric immunoassay of cTnI. The whiskered segments of CMWCNTs were activated and utilised to immobilise anti-cTnT antibodies. It was observed that the anchored CMWCNTs within the nanofibres were suitably stabilised with excellent electrochemical repeatability. A sandwich-type immuno-complex was formed between cTnI and horseradish peroxidase-conjugated anti-cTnI (HRP-anti-cTnI). The amperometric responses of the immunosensor were studied using cyclic voltammetry (CV) through an enzymatic reaction between hydrogen peroxide and HRP conjugated to the secondary antibody. The nanostructured immunosensor delivered a wide detection range for cTnI from the clinical borderline for a normal person (0.5–2ngmL⁻¹) to the concentration present in myocardial infarction patients (> 20ngmL⁻¹), with a detection limit of ~ 0.04ngmL⁻¹. It also showed good reproducibility and repeatability for three different cTnI concentration (1, 10 and 25ngmL⁻¹) with satisfactory relative standard deviations (RSD). Hence, the proposed nanostructured immunosensor shows potential for point-of-care testing.

Graphical abstract

http://ift.tt/2GvAzjC

A simple and economical spectrofluorimetric alternative for Al routine analysis in seafood

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): José A. López-López, Carlos Borrego-Corchado, Manuel P. Mánuel, Estrella Espada-Bellido
A simple and economical spectrofluorimetric alternative for aluminium determination in bivalve mollusks based on the fluorescent blue-green colour complex between Al(III) and salicylaldehyde picolinoylhydrazone (SAPH) has been studied. The factors that are most likely to affect were optimized with a Box-Behnken design. Optimum conditions were: pH 6.6, 0.9 mol L⁻¹ acetic acid/acetate buffer, 3.0 mmol L⁻¹ SAPH, and 50% ethanol. Detection and quantitation limits were found to be 2.7 μg L⁻¹ and 9.1 μg L⁻¹, respectively. The upper limit of application was assessed through the limit of linearity which was set as 300 μg L⁻¹. Intra-day repeatability and inter-day repeatability were evaluated showing an excellent precision for the fluorescence method (both < 5%). The method was sensitive enough for the satisfactory determination of aluminium in several bivalve mollusk samples both fresh and canned seafood. The results showed that commercial fresh wild products presented the smallest Al concentration (6–27 mg per 100 g dry weight), while bivalves preserved in cans the concentration was considerably higher (75 mg per 100 g dry weight). Thus, differences between Al concentration related to processing were identified. The study shows a simple, cost-effective and reliable tool for routine aluminium determination in seafood for food quality control.

Graphical abstract

http://ift.tt/2Hwmwvr

An overview of the main foodstuff sample preparation technologies for tetracycline residue determination

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): Michael Pérez-Rodríguez, Roberto Gerardo Pellerano, Leonardo Pezza, Helena Redigolo Pezza
Tetracyclines are widely used for both the treatment and prevention of diseases in animals as well as for the promotion of rapid animal growth and weight gain. This practice may result in trace amounts of these drugs in products of animal origin, such as milk and eggs, posing serious risks to human health. The presence of tetracycline residues in foods can lead to the transmission of antibiotic-resistant pathogenic bacteria through the food chain. In order to ensure food safety and avoid exposure to these substances, national and international regulatory agencies have established tolerance levels for authorized veterinary drugs, including tetracycline antimicrobials. In view of that, numerous sensitive and specific methods have been developed for the quantification of these compounds in different food matrices. One will note, however, that the determination of trace residues in foods such as milk and eggs often requires extensive sample extraction and preparation prior to conducting instrumental analysis. Sample pretreatment is usually the most complicated step in the analytical process and covers both cleaning and pre-concentration. Optimal sample preparation can reduce analysis time and sources of error, enhance sensitivity, apart from enabling unequivocal identification, confirmation and quantification of target analytes. The development and implementation of more environmentally friendly analytical procedures, which involve the use of less hazardous solvents and smaller sample sizes compared to traditional methods, is a rapidly increasing trend in analytical chemistry. This review seeks to provide an updated overview of the main trends in sample preparation for the determination of tetracycline residues in foodstuffs. The applicability of several extraction and clean-up techniques employed in the analysis of foodstuffs, especially milk and egg samples, is also thoroughly discussed.

Graphical abstract

http://ift.tt/2GruXqv

High-throughput quantification of sodium saccharin in foods by ambient flame ionization mass spectrometry

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): Zhongquan Li, Fang Zhang, Junbo Zhao, Xiaopan Liu, Xiuping Chen, Yue Su, Yinlong Guo
Ambient flame ionization (AFI) coupled with triple quadrupole tandem mass spectrometry was developed for quantitative analysis of sodium saccharin (SAC) in various food samples. Typically, the micro-flame by the combustion of n-butane provided a heating zone for fast desorption and ionization of analytes in milliseconds. Then high ion abundance of analyte could be produced in a short time, which made AFI-MS possess a very high sensitivity for SAC detection and was particularly appropriate for the quantification in multiple reaction monitor (MRM) mode. Liquid samples were introduced into outer flame using dip-it tips in order to facilitate a rapid and high-throughput analysis. Saccharin-d4 was used as the internal standard to compensate for the variations of the ion intensities. With a minimal sample preparation, a linear range of 4–100 μg/mL was developed with all linear relationships of different matrices (including coke, juice, liquors, sunflower seeds and sweetmeats) greater than 0.992. Recoveries for coke and apple matrices were ranged from 88.4% to 108.9% at the concentration of 5, 20, 80 μg/mL and the limits of detection (LODs) were in the range of 0.12–0.21 μg/mL. Furthermore, the feasibility of this method was exhibited by the quantification analysis of SAC in seventeen real samples. These results indicated that AFI-MS was a valuable strategy for rapid screening detection and precise quantification analysis of SAC in food.

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http://ift.tt/2CyysZT

Untargeted screening of phase I metabolism of combretastatin A4 by multi-tool analysis

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): Karol Jaroch, Paulina Zofia Goryńska, Krzysztof Goryński, Tomasz Stefański, Barbara Bojko
The aim of the current study was to apply different strategies for generation of metabolites of combretastatin A4 (CA4) and subsequent identification of the unknown products of phase I metabolism. CA4 is a potent anti-tubulin agent currently undergoing clinical trials. The multi-tool analytical approach was based on electrochemistry (EC), in silico predictions, and in vitro studies with the use of rat liver microsomes. With the latter, two different analytical sample preparation methods were applied: protein precipitation and solid phase microextraction, both hyphenated to the liquid chromatography-high-resolution mass spectrometry platform (LC-HRMS). The EC was coupled directly to HRMS. Conventional techniques using enzyme fractions pooled from human or animals remain a method of choice for determinations of phase I of drug metabolism, EC and in silico methods, which enable determinations of metabolism patterns, are in turn considered to have great potential as fast alternatives to in vitro assays. While individual findings attained via employment of these four methods showed high similarity in relation to generated metabolic pathways for CA4, each method was found to provide unique features not identified with other approaches. In this paper, these differences are reviewed in view of potential artifacts and true metabolite production via various metabolism patterns under different experimental conditions. In addition, the reliability, applicability, MS compatibility issues, and potential of each of these technologies are discussed.

Graphical abstract

http://ift.tt/2FiAr7H

Renewable chemiluminescence optosensors based on implementation of bead injection principle with multicommutation

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): Juan C. Domínguez-Romero, Bienvenida Gilbert-López, Miriam Beneito-Cambra, Antonio Molina-Díaz
In this work, the implementation of Bead Injection with multicommutation-based flow systems is reported. A surface renewable chemiluminescence (CL) flow sensor is presented based on the use of CL reaction of luminol with H2O2. Dowex 1 × 8 beads with immobilized luminol onto them were injected in the flow system by means of a six-port rotary valve and were accommodated into a 1 mm optical glass flow cell placed just in front of the rectangular photosensor window with the same size than the cell wall. Automatic computer-controlled manipulation of both reagents and sample solutions was undertaken using a multicommutated flow system which comprises five three-way solenoid valves, a home-made electronic interface and a Java-written software. Once the chemiluminescence signal was registered, sensing beads were automatically discarded out with a six-port rotary valve without needing to reverse or stop the flow. As a proof of concept and example, the enhancement of the chemiluminescence signal produced by Co(II) on the luminol-H2O2 reaction in alkaline medium was used for illustrating this implementation determining vitamin B12 in pharmaceutical preparations (after mineralization for releasing Co(II)). The analytical performance of the approach was satisfactory, showing a linear dynamic range from 1.7 to 50 µg L⁻¹, a detection limit of 0.5 µg L⁻¹, RSD (%) of 5.3%, with a sampling frequency of 11 h⁻¹. The proposed approach was applied to different samples and the results were consistent with those obtained with a reference method based on ICP-MS. Based on the same reaction (or re-configuring the system to accommodate it to reaction requirements) the approach can also be applied to the determination of other metal ions such as Cr(III) and Fe(II) and appropriately extended to molecules of bioanalytical interest based e.g. in CL immunoassays, given its versatility.

Graphical abstract

http://ift.tt/2EFoj3m

A novel strategy for discriminating marine oils by using the positional distribution (sn-1, sn-2, sn-3) of omega-3 polyunsaturated fatty acids in triacylglycerols

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): Pedro Araujo, Ephrem Tilahun, Yingxu Zeng
A novel strategy for discriminating genuine and adulterated marine oils is proposed. The strategy consists of i) determining the stereospecific distribution (sn-1, sn-2 and sn-3) of omega 3 polyunsaturated fatty acids (ω−3 PUFA) on the backbone of triacylglycerols by using liquid chromatography tandem mass spectrometry; ii) transforming the qualitative stereospecific information into quantitative data by means of a novel strategy; iii) analyzing the transformed data by principal component analysis. The proposed strategy was tested on pure oils (seal, salmon, cod liver, sandeel, blue whiting, herring), a mixture of blue whiting, herring, sandeel and Norway pout and some intentionally adulterated oils. In addition, some published krill oil data were analyzed to confirm the reliability of the new approach.

Graphical abstract

http://ift.tt/2GxACeN

A new electrochemical immunoassay for prion protein based on hybridization chain reaction with hemin/G-quadruplex DNAzyme

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): Xiaoyu Li, Junjing Li, Caixia Zhu, Xiaohua Zhang, Jinhua Chen
In this work, a new electrochemical immunosensor was developed for prion protein assay based on hybridization chain reaction (HCR) with hemin/G-quadruplex DNAzyme for signal amplification. In this amplification system, the hemin/G-quadruplex DNAzyme simultaneously mimicked the biocatalytic functions for H2O2 reduction and L-cysteine oxidation. In the presence of L-cysteine, the hemin/G-quadruplex catalyzed the oxidation of L-cysteine to L-cystine. At the same time, H2O2 was produced under the oxygen condition. Then, the hemin/G-quadruplex could quickly catalyze the reduction of H2O2, mimicking the catalytic performance of horseradish peroxidase (HRP). Under the optimal conditions, the immunosensor showed a wide linear response range from 0.5 pg/mL to 100 ng/mL with the low detection limit of 0.38 pg/mL (3σ). By changing the specific antibody, this strategy could be easily extended to detect the infectious isoform of prion (PrP^Sc) and other proteins. Based on its good analytical performance, the developed method shows great potential applications in diagnosis of prion diseases at presymptomatic stage and bioanalysis.

Graphical abstract

http://ift.tt/2CyymBv

Covalent functionalization of MoS2 nanosheets synthesized by liquid phase exfoliation to construct electrochemical sensors for Cd (II) detection

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): Xiaorong Gan, Huimin Zhao, Kwok-Yin Wong, Dang Yuan Lei, Yaobin Zhang, Xie Quan
Surface functionalization is an effective strategy in the precise control of electronic surface states of two-dimensional materials for promoting their applications. In this study, based on the strong coordination interaction between the transition-metal centers and N atoms, the surface functionalization of few-layer MoS2 nanosheets was successfully prepared by liquid phase exfoliation method in N, N-dimethylformamide (DMF), 1-methyl-2-pyrrolidinone, and formamide. The cytotoxicity of surface-functionalized MoS2 nanosheets was for the first time evaluated by the methylthiazolyldiphenyl-tetrazoliumbromide assays. An electrochemical sensor was constructed based on glass carbon electrode (GCE) modified by MoS2 nanosheets obtained in DMF, which exhibits relatively higher sensitivity to Cd²⁺ detection and lower cytotoxicity against MCF-7 cells. The mechanisms of surface functionalization and selectively detecting Cd²⁺ were investigated by density functional theory calculations together with various spectroscopic measurements. It was found that surface-functionalized MoS2 nanosheets could be generated through Mo-N covalent bonds due to the orbital hybridization between the 5 s orbitals of Mo atoms and the 2p orbitals of N atoms of the solvent molecules. The high selectivity of the sensor is attributed to the coordination reaction between Cd²⁺ and O donor atoms of DMF adsorbed on MoS2 nanosheets. The robust anti-interference is ascribed to the strong binding energy of Cd²⁺ and O atoms of DMF. Under the optimum conditions, the electrochemical sensor exhibits highly sensitive and selective assaying of Cd²⁺ with a measured detection limit of 0.2 nM and a linear range from 2 nM to 20 μM.

Graphical abstract

http://ift.tt/2HyiK4P

Fabrication of Pd-decorated TiO2/MoS2 ternary nanocomposite for enhanced benzene gas sensing performance at room temperature

Publication date: 15 May 2018
Source:Talanta, Volume 182
Author(s): Dongzhi Zhang, Chuanxing Jiang, Xiaoyan Zhou
A high-performance benzene gas sensor based on Pd-decorated TiO2/MoS2 ternary nanocomposite was demonstrated in this paper. The morphologies, microstructures and composition of the Pd-TiO2/MoS2 nanocomposite were sufficiently examined by X-ray diffraction (XRD), energy dispersive spectrometer (EDS), scanning electron microscopy (SEM), transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS), confirming its successful preparation and reasonability. The benzene-sensing performances of the Pd-TiO2/MoS2 sensor were investigated upon exposure to various concentrations of benzene vapor from 100 ppb to 100 ppm at room temperature. The experimental results showed that the sensor has a high response, short response-recovery time, good repeatability and selectivity toward benzene gas, which is largely superior to that of the pure TiO2 and MoS2 sensors. In addition, the influence of Pd loading in the nanocomposite on the benzene-sensing was investigated. The sensing mechanism of the Pd-TiO2/MoS2 sensor was attributed to the synergistic effect of the ternary nanostructures, combining the modulation of potential barrier with electron transfer. This work indicates that the synthesized Pd-TiO2/MoS2 ternary nanocomposite is an excellent candidate for constructing high-performance benzene sensor for various applications.

Graphical abstract

http://ift.tt/2EH7ogY