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Σάββατο 17 Σεπτεμβρίου 2016
Scholar : These new articles for International Journal of Heritage Studies are available online
Lactate dehydrogenase inhibitors can reverse inflammation induced changes in colon cancer cells
Publication date: 1 January 2017
Source:European Journal of Pharmaceutical Sciences, Volume 96
Author(s): Marcella Manerba, Lorenza Di Ianni, Marzia Govoni, Marinella Roberti, Maurizio Recanatini, Giuseppina Di Stefano
The inflammatory microenvironment is an essential component of neoplastic lesions and can significantly impact on tumor progression. Besides facilitating invasive growth, inflammatory cytokines were also found to reprogram cancer cell metabolism and to induce aerobic glycolysis.Previous studies did not consider the possible contribution played in these changes by lactate dehydrogenase (LDH). The A isoform of LDH (LDH-A) is the master regulator of aerobic glycolysis; it actively reduces pyruvate and causes enhanced lactate levels in tumor tissues. In cancer cells, lactate was recently found to directly increase migration ability; moreover, when released in the microenvironment, it can facilitate matrix remodeling. In this paper, we illustrate that treatment of human colon adenocarcinoma cells with TNF-α and IL-17, two pro-inflammatory cytokines, modifies LDH activity, causing a shift toward the A isoform which results in increased lactate production. At the same time, the two cytokines appeared to induce features of epithelial-mesenchymal transition in the treated cells, such as reduction of E-cadherin levels and increased secretion of metalloproteinases. Noteworthy, oxamate and galloflavin, two inhibitors of LDH activity which reduce lactate production in cells, were found to relieve the inflammation-induced effects.These results suggest LDH-A and/or lactate as common elements at the cross-road between cancer cell metabolism, tumor progression and inflammation. At present, LDH inhibitors suitable for clinical use are actively searched as possible anti-proliferative agents; our data lead to hypothesize for these compounds a wider potential in anticancer treatment.
Graphical abstract
http://ift.tt/2cELf3C
Evaluate the ability of PVP to inhibit crystallization of amorphous solid dispersions by density functional theory and experimental verify
Publication date: 1 January 2017
Source:European Journal of Pharmaceutical Sciences, Volume 96
Author(s): Bing Wang, Dandan Wang, Shan Zhao, Xiaobin Huang, Jianbin Zhang, Yan Lv, Xiaocen Liu, Guojun Lv, Xiaojun Ma
In this study, we used density functional theory (DFT) to predict polymer-drug interactions, and then evaluated the ability of poly (vinyl pyrrolidone) (PVP) to inhibit crystallization of amorphous solid dispersions by experimental-verification. Solid dispersions of PVP/resveratrol (Res) and PVP/griseofulvin (Gri) were adopted for evaluating the ability of PVP to inhibit crystallization. The density functional theory (DFT) with the B3LYP was used to calculate polymer-drug and drug-drug interactions. Fourier transform infrared spectroscopy (FTIR) was used to confirm hydrogen bonding interactions. Polymer-drug miscibility and drug crystallinity were characterized by the modulated differential scanning calorimetry (MDSC) and X-ray powder diffraction (XRD). The release profiles were studied to investigate the dissolution advantage. DFT results indicated that EPVP-Res>ERes-Res (E: represents hydrogen bonding energy). A strong interaction was formed between PVP and Res. In addition, Fourier transform infrared spectroscopy (FTIR) analysis showed hydrogen bonding formed between PVP and Res, but not between PVP and Gri. MDSC and XRD results suggested that 70–90wt% PVP/Res and PVP/Gri solid dispersions formed amorphous solid dispersions (ASDs). Under the accelerated testing condition, PVP/Res dispersions with higher miscibility quantified as 90/10wt% were more stable than PVP/Gri dispersions. The cumulative dissolution rate of 90wt% PVP/Res dispersions still kept high after 90days storage due to the strong interaction. However, the cumulative dissolution rate of PVP/Gri solid dispersions significantly dropped because of the recrystallization of Gri.
Graphical abstract
http://ift.tt/2cEJX8K
Scholar : African Journal of Aquatic Science, Volume 41, Issue 3, September 2016 is now available online on Taylor & Francis Online
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Scholar : These new articles for Aphasiology are available online
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Scholar : Culture, Theory and Critique, Volume 57, Issue 3, November 2016 is now available online on Taylor & Francis Online
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Scholar : These new articles for Criminal Justice Studies are available online
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Scholar : These new articles for Contemporary Music Review are available online
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Scholar : These new articles for Anxiety, Stress, & Coping are available online
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Scholar : These new articles for Archives of Agronomy and Soil Science are available online
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Visceral Manipulation and Endometriosis
Publication date: Available online 16 September 2016
Source:Journal of Bodywork and Movement Therapies
Author(s): Matt Wallden
http://ift.tt/2d7SMcv
A Case Study Utilizing Myofascial Release, Acupressure and Trigger Point Therapy to Treat Bilateral “Stringhalt” in A 12 Year Old Akhal-Teke Horse
Publication date: Available online 16 September 2016
Source:Journal of Bodywork and Movement Therapies
Author(s): Tammy Brockman
"Stringhalt" is a horse condition that causes one or both hind legs to spasm when walking, trotting or backing. The condition is thought to be related to a neurological cause from either plant toxicity or peripheral nerve injury. The prognosis is poor and the horse's performance and quality of life can be affected. Treatment has included surgically cutting the digital extensors with varied results.The objective of the study is to utilize soft tissue release via acupressure, trigger point and myofascial release to decrease symptoms of stringhalt.The case study is a 12 year old Akhal-Teke horse of excellent pedigree. In 2011, she was caught in barbed wire overnight and sustained lacerations to the bone in her hindlimbs. Shortly after the injury the horse was placed in a stall for several months and was unable to walk or run, developing stringhalt. Currently, her condition is aggravated by stress and alleviated by certain types of massage (myofascial, acupressure, and trigger point release). The incidence of stringhalt occurs every 3-5 minutes, with more frequent and severe symptoms on the right hindlimb. The horse is unable to run or back up.Six 1 to 1 ½ hour bi-weekly treatments were performed. The treatments consisted of myofascial release at the cervical, sacrum and iliums, acupressure of the bladder meridian (including c-spine, t-spine, L-spine, and hamstring), and trigger point release of the iliacus. The stringhalt symptoms were monitored for 30 minutes prior to each of the 6 treatment sessions.After 6 treatments, the horse was observed running and standing in a position that promotes hip extension. She has not been able to do either since the injury. The frequency and severity of the spasms have decreased to every 10-20 minutes. The horse's owners report that her disposition, stress and quality of life are much improved.The results suggest that myofascial release, acupressure and trigger point therapy may be utilized to provide a positive treatment outcome in the case of stringhalt. However, please note that the scope of practice varies by state and special training is needed to work with the equine population.
http://ift.tt/2cgcSkq
Selection and characterization of single domain antibodies against human CD20
Source:Molecular Immunology, Volume 78
Author(s): Jinny L. Liu, Dan Zabetakis, Ellen R. Goldman, George P. Anderson
CD20 is a membrane protein with four integral membrane regions and a large extracellular loop between residues 142 and 187, which serves as a target binding region for rituximab (RTX) and most other anti-CD20 monoclonal antibodies. It is highly expressed in B-lymphoma cells and B lymphocytes and often serves as a target for immunotherapy. In this study, we developed single domain antibodies (sdAbs) for the sensitive detection of CD20. To achieve this, an immune sdAb library was prepared from llamas immunized with a fusion between the large loop from CD20 and Hoc, a highly antigenic protein from the T4 bacteriophage, (CD20-Hoc). By subtracting binders to recombinant Hoc during the biopanning, potential anti-CD20 sdAbs were selected, sequenced, and characterized for their binding affinity to CD20-Hoc fusion versus Hoc. Twenty five clones grouped into three different families based on CDR3 sequence were identified as potential CD20 binders. The binding kinetics of representative sdAbs from each class and RTX were evaluated by surface plasmon resonance (SPR). Most of the sdAbs that were evaluated show binding affinities to CD20-Hoc in the nM range, and class A sdAbs, exhibited ≥40-fold increase in affinity for CD20-Hoc versus Hoc. When the binding of the sdAbs to CD20 on SU-DHL-4 cells was evaluated by flow cytometry, only class A sdAbs displayed strong binding to CD20 and recognized DHL cells in a concentration dependent manner.
http://ift.tt/2cgb4YU
IL-27 suppresses SKOV3 cells proliferation by enhancing STAT3 and inhibiting the Akt signal pathway
Source:Molecular Immunology, Volume 78
Author(s): Zhu Zhang, Bin Zhou, Kui Zhang, Yaping Song, Lin Zhang, Mingrong Xi
Ovarian cancer continues to be the most lethal gynecologic malignancy worldwide. IL-27 is a novel member of the IL-12 cytokine family. The aim of this study was to investigate the effects of IL-27 on the ovarian cystadenocarcinoma cell line SKOV3 and determine possible mechanisms underlying its effect. We stably transfected an IL-27 plasmid, empty vector, IL-27 shRNA or negative control into SKOV3 cells. Cell proliferative activity was evaluated using a WST-1 cell proliferation assay kit. Cell viability was quantified by measurements of lactate dehydrogenase release. The mRNA levels of nine genes were tested by q-PCR. Western blotting was used to verify apoptosis and signal pathways. We found that the IL-27 plasmid significantly enhanced cytotoxicity and inhibited the proliferation of SKOV3 cells. Caspase-3 protein was augmented by IL-27 plasmid and abated by IL-27 shRNA. The incremental expression of IL-27 activated the STAT3 pathway and attenuated the Akt pathway. The over-expression of IL-27 could significantly upregulate a series of antitumor cytokines including IL-6, IL-12 and interferon-γ and down-regulate protumor factors such as TLR4 and NF-κB1. Our data show that IL-27 has direct antitumor capacity in ovarian cancer cells via enhancing apoptosis by inducing the STAT3 pathway and restraining the Akt pathway.Précis: IL-27 enhanced the cytotoxicity and suppressed the proliferation of ovarian cancer cells by activating STAT3 and inhibiting the Akt signal pathway. IL-27 plays an important role in antitumor activity against epithelial ovarian cancer.
http://ift.tt/2cedBOe
Scholar : These new articles for Aging & Mental Health are available online
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Narratives of children with high-functioning autism spectrum disorder: A meta-analysis
Publication date: December 2016
Source:Research in Developmental Disabilities, Volume 59
Author(s): Inmaculada Baixauli, Carla Colomer, Belén Roselló, Ana Miranda
BackgroundThe aim of this meta-analysis was to analyze the narrative performance of children and adolescents with high-functioning Autism Spectrum Disorders (ASD) in terms of microstructure, macrostructure and internal state language.MethodA systematic literature search yielded 24 studies that met the predetermined inclusion criteria. Effect sizes for each study were calculated for eight variables and analyzed using a random effects model. Intellectual ability, age and type of narrative were considered as potential moderators.ResultsResults revealed that the children with ASD performed significantly worse than their peers on all the variables considered.ConclusionsFindings are discussed taking into account the main explanatory psychological autism theories. Implications for intervention and orientations for future research are suggested.
http://ift.tt/2cQSHro
p16 expression as a prognostic and predictive marker in high-grade localized osteosarcoma of the extremities: an analysis of 357 cases
Publication date: December 2016
Source:Human Pathology, Volume 58
Author(s): Alberto Righi, Marco Gambarotti, Marta Sbaraglia, Andrea Sisto, Stefano Ferrari, Angelo P. Dei Tos, Piero Picci
The potential prognostic and predictive value of p16 in high-grade localized osteosarcoma of the extremities has been recently investigated in small series of cases, and the results from different studies were somewhat controversial. A retrospective immunohistochemical analysis of p16 expression was performed in a series of 357 patients, included in different neoadjuvant chemotherapy protocols from 1986 to 2010, to explore its potential prognostic and predictive value. Immunohistochemistry was performed with a commercially available p16 monoclonal mouse antibody. Follow-up data were available in all cases with a median of 120 months. Positivity for p16 was detected in 70.6% (252/357) of cases. The p16 expression did not differ by age, sex, tumor site, histologic subtype, tumor volume, surgical margin, serum alkaline phosphatase levels, and lactate dehydrogenase levels. In the different chemotherapy protocols included, the incidence of p16 expression was similar. The absence of p16 expression was significantly associated with an adverse disease-free survival (P=.04) and overall survival (P=.05) when compared with the presence of p16 expression. At the multivariate Cox regression analysis, p16 expression lost its prognostic significance. Multivariate logistic regression analysis showed that as p16 expression was the only statistically significant parameter to predict the pathological response to neoadjuvant chemotherapy treatment with an odds ratio of 3.025 (P<.001) for "good" chemotherapy response. Our data indicate that the negative expression of p16 is associated with a reduced rate of good response to primary chemotherapy and to a worse probability of survival, although it was not confirmed as an independent prognostic biomarker after multivariate analysis.
http://ift.tt/2cQSrIO
Work stress and satisfaction in relation to personality profiles in a sample of Dutch anaesthesiologists: A questionnaire survey.
http://ift.tt/2cEiaDV
Incidence and severity of chronic pain after caesarean section: A systematic review with meta-analysis.
http://ift.tt/2cRhRsx
Impact of age on anaesthesiologists' competence: A narrative review.
http://ift.tt/2cRhv5l
Modelling of the optimal bupivacaine dose for spinal anaesthesia in ambulatory surgery based on data from systematic review.
http://ift.tt/2cEj4jH
T cell subpopulations in juvenile idiopathic arthritis and their modifications after biotherapies
Source:Autoimmunity Reviews
Author(s): Laura Maggi, Lorenzo Cosmi, Gabriele Simonini, Francesco Annunziato, Rolando Cimaz
Inflammatory T cells are thought to be central to the pathogenesis of juvenileidiopathicarthritis. In particular, recentevidencehasunderlined the importance of a balance between Th17 and Tregcells. Severalmechanismshave come to light that control thisreciprocalrelationship.Moreover, ithasbeenshownthat in certainconditions Th17 cells can shifttoward a non classic Th1 phenotype. Anti-rheumaticbiologictherapiesmayinterfere with thesemechanisms and re-establish immune tolerance.
http://ift.tt/2cxSpWA
The industrial food additive microbial transglutaminase, mimics the tissue transglutaminase and is immunogenic in celiac disease patients
Source:Autoimmunity Reviews
Author(s): T. Matthias, P. Jeremias, S. Neidhöfer, A. Lerner
Microbial transglutaminase (mTg) is capable of cross-linking numerous molecules. It is a family member of human tissue transglutaminase (tTg), involved in CD. Despite declarations of mTg industrial use safety, direct evidence for immunogenicity of the enzyme is lacking.The serological activity of mTg, tTg, gliadin complexed mTg (mTg neo-epitope) and gliadin complexed tTg (tTg neo-epitope) were studied in: 95 pediatric celiac patients (CD), 99 normal children (NC) 79 normal adults (NA) and 45 children with nonspecific abdominal pain (AP). Sera were tested by ELISAs, detecting IgA, IgG or both IgA and IgG (check): AESKULISA® tTg (tTg), AESKULISA® tTg New Generation (tTg neo-epitope (tTg-neo)), microbial transglutaminase (mTg) and mTg neo-epitope (mTg-neo). Marsh criteria were used for the degree of intestinal injury. Parallel, mTg and tTg neo-epitopes were purified by asymmetric field flow fractionation, confirmed by multi light scattering and SDS-page, and analyzed on the adult CD and controls group by competition ELISAs.No sequence homology but active site similarity were detected on alignment of the 2 Tgs. Comparing pediatric CD patients with the 2 normal groups: mTg-neo IgA, IgG and IgA+IgG antibody activities exceed the comparable mTg ones (p<0.0001). All mTg-neo and tTg-neo levels were higher (p<0.001). tTg IgA and IgG+IgA were higher than mTg IgA and IgA+IgG (p<0.0001). The levels of tTg-neo IgA/IgG were higher than tTg IgA/IgG (p<0.0001). The sequential antibody activities reflecting best the increased intestinal damage were: tTg-neo check>tTg-neo IgA≥mTg-neo IgG>tTg-neo IgG>mTg-neo check > mTg-neo IgA. Taken together, tTg-neo check, tTg-neo IgA and mTg-neo IgG correlated best with intestinal pathology (r2=0.6454, r2=0.6165,r2=0.5633 p<0.0001, p<0.0001, p<0.0001, respectively). Purified mTg-neo IgG and IgA showed an increased immunoreactivity compared to single mTg and gliadin (p<0.001) but similar immunoreactivity to the tTg-neo IgG and IgA ELISA. Using a competition ELISA, the mTg neo-epitopes and tTg neo-epitopes have identical outcomes in CD sera both showing a decrease in optical density of 55±6%, (p<0.0002).mTg is immunogenic in children with CD and by complexing to gliadin its immunogenicity is enhanced. Anti-mTg-neo-epitope IgG antibodies correlate with intestinal damage to a comparable degree as anti-tTg-neo IgA. mTg and tTg display a comparable immunopotent epitope. mTg-neo IgG is a new marker for CD. Further studies are needed to explore the pathogenic potential of anti-mTg antibodies in CD.
http://ift.tt/2cwsKkg
Statin-associated autoimmune myopathy: A distinct new IFL pattern can increase the rate of HMGCR antibody detection by clinical laboratories
Source:Autoimmunity Reviews
Author(s): M Alvarado-Cardenas, A Marin, MA Martínez, L Martínez, I Pinal-Fernandez, M Labrador-Horrillo, E Balada, X Mundet-Tuduri, L Gonzalez-Mera, J Casademont, E Martínez Acebes, PJ Moreno, C Juarez, JM Grau-Junyent, R Pujol-Borrell, A Selva-O'Callaghan
Background and objectiveStatin-associated autoimmune myopathy (SAAM) with anti-HMGCR antibodies has recently been described. Several specific immunoassays are in use to detect HMGCR antibodies. In the course of systematic autoantibody screening we recognized a new distinct IFL staining pattern on rat liver sections that regularly coincided with anti-HMGCR antibodies. In this study we investigated whether this new IFL pattern is specifically associated to statin-associated autoimmune myopathy and corresponds to anti-HMGCR antibodies.Patients and methodsTwenty-three patients positive for anti-HMGCR antibodies (14 diagnosed with SAAM) were investigated for anti-HMGCR antibodies by two ELISA assays and confirmed by immmunoblot. HMGCR associated liver IFL pattern (HALIP) was detected by indirect IFL and the reactivity against HMGCR was confirmed by immunoabsorption using purified human HMGCR antigen. 90 patients with other autoimmune diseases and 45 non-autoimmune statin treated patients were studied as controls.Results21 out of 23 (91%) anti-HMGCR positive patients were HALIP positive. The staining was completely and specifically removed by immunoabsorption with human purified HMGCR. None of the control sera from autoimmune patients or non-autoimmune statin treated subjects was positive for HALIP. Statistical concordance between HALIP and anti-HMGCR antibody specific tests was 98.7%, kappa 0.95.ConclusionsA new and distinct IFL staining pattern (HALIP) is associated to HMGCR associated myopathy. Absorption and concordance studies indicate that the antigen recognized in the liver by HALIP is HMGCR or a closely related protein. Awareness of this new pattern can help to detect HMGCR autoantibodies in statin treated patients tested for autoimmune serology.
http://ift.tt/2cxUoKi
Plant materials for gastrointestinal diseases used in Chawang District, Nakhon Si Thammarat Province, Thailand
Publication date: 24 December 2016
Source:Journal of Ethnopharmacology, Volume 194
Author(s): Oratai Neamsuvan, Thanchanok Phumchareon, Wanisa Bunphan, Wayanan Kaosaeng
Ethnopharmacological relevanceIn Thailand, gastrointestinal diseases have occurred since the past, consequently healers know well how to use herbs for treatment. Currently, some groups of Thai people continue to be interested in treating diseases by herbs. Therefore, the aims of this study were to (1) compile a list of species of medicinal plants and their source, (2) document the diseases treated and their frequency of citation, (3) record the parts used, methods of preparation and route of administration of traditional medicines, and (4) compare the folk knowledge to that in other relevant reports.Materials and methodsTen folk healers were included in the study. Semi-structured interviews were used to compile data, namely plant parts used, preparation, route of administration and properties. The data were analyzed by interpretation and descriptive statistics.ResultsSixty-two species in 28 families were identified. The most used plants (11 species) were grouped in Zingiberaceae. The highest level of relative frequency of citation (RFC) was found in Zingiber officinale Roscoe (1.0). Most plants were applied for treating constipation. Powder was the most common preparation form of folk drug. A total of 174 use lists were recorded, however, more than two thirds were reported as new uses in this study.ConclusionA literature review revealed that the remaining 37 species for pharmacological activities and 42 species for toxicity should be further studied to validate the folk use of these medicinal resource.
Graphical abstract
http://ift.tt/2d1IFaf
Ginsenosides attenuate d-galactose- and AlCl3-inducedspatial memory impairment by restoring the dysfunction of the neurotransmitter systems in the rat model of Alzheimer's disease
Publication date: 24 December 2016
Source:Journal of Ethnopharmacology, Volume 194
Author(s): Yan Zhang, Zifeng Pi, Fengrui Song, Zhiqiang Liu
Ethnopharmacological relevancePanax ginseng C.A.Mey. is a traditional Chinese herbal medicine, which has been used to treat Alzheimer's disease (AD) for thousands of years. Ginsenoside is one of the major compounds found in P. ginseng. This study aimed to explore the attenuation of spatial memory impairment by ginsenosides and its correlation with restoring the dysfunction of the neurotransmitter systems in AD model rats to understand the mechanism underlying the anti-AD effect of P. ginseng.Materials and methodsIn this study, the AD model was established by combining d-galactose (d-gal) with AlCl3 (Al) for 60 days. From day 30, the ginsenosides group was intragastrically administered with ginsenosides for 30 days. The ethology of rats was tested through the Morris water maze test(MWM). Histopathological changes in the hippocampus of rats were observed through hematoxylin and eosin staining. The expressions of amyloid β peptide (Aβ) and phospho-tau (p-tau) in the hippocampus and cortex of rats were detected by immunohistochemistry. A liquid chromatography–mass spectrometry assay was used to measure neurotransmitter concentrations in the hippocampus, cortex, and blood.ResultsGinsenosides could significantly decrease the escape latency time and the average latency time in the place navigation test and increase the times of crossing the platform area, the percentage of residence time, and the distance in the original platform quadrant in the spatial probe test. Ginsenosides could repair the damage of the hippocampus and reduce the expressions of Aβ and p-tau. Ginsenosides could also increase γ-aminobutyric acid, acetylcholine, and dopamine levels and decrease glutamate and aspartic acid levels in the hippocampus and cortex and increase glycine and serotonin levels in the blood.ConclusionsAfter effectively administrated, ginsenosides attenuate d-gal- and Al-induced spatial memory impairment. The possible mechanism of the beneficial effect is restoring the dysfunction of various neurotransmitters.
Graphical abstract
http://ift.tt/2d1Jjo4
The antioxidant transcription factor Nrf2 contributes to the protective effect of mild thermotolerance (40°C) against heat shock-induced apoptosis
Source:Free Radical Biology and Medicine, Volume 99
Author(s): Audrey Glory, Diana A. Averill-Bates
The exposure of cells to low doses of stress induces adaptive survival responses that protect cells against subsequent exposure to toxic stress. The ability of cells to resist subsequent toxic stress following exposure to low dose heat stress at 40°C is known as mild thermotolerance. Mild thermotolerance involves increased expression of heat shock proteins and antioxidants, but the initiating factors in this response are not understood. This study aims to understand the role of the Nrf2 antioxidant pathway in acquisition of mild thermotolerance at 40°C, and secondly, whether the Nrf2 pathway could be involved in the protective effect of thermotolerance against heat-shock (42°C)-induced apoptosis. During cell preconditioning at 40°C, protein expression of the Nrf2 transcription factor increased after 15–60min. In addition, levels of the Nrf2 targets MnSOD, catalase, heme oxygenase-1, glutamate cysteine ligase and Hsp70 increased at 40°C. Levels of these Nrf2 targets were enhanced by Nrf2 activator oltipraz and decreased by shRNA targeting Nrf2. Levels of pro-oxidants increased after 30–60min at 40°C. Pro-oxidant levels were decreased by oltipraz and increased by knockdown of Nrf2. Increased Nrf2 expression and catalase activity at 40°C were inhibited by the antioxidant PEG-catalase and by p53 inhibitor pifithrin-α. These results suggest that mild thermotolerance (40°C) increases cellular pro-oxidant levels, which in turn activate Nrf2 and its target genes. Moreover, Nrf2 contributes to the protective effect of thermotolerance against heat-shock (42°C)-induced apoptosis, because Nrf2 activation by oltipraz enhanced thermotolerance, whereas Nrf2 knockdown partly reversed thermotolerance. Improved knowledge about the different protective mechanisms that mild thermotolerance can activate is crucial for the potential use of this adaptive survival response to treat stress-related diseases.
http://ift.tt/2cwm59T
Sensitive detection and estimation of cell-derived peroxynitrite fluxes using fluorescein-boronate
Source:Free Radical Biology and Medicine
Author(s): Natalia Rios, Lucía Piacenza, Madia Trujillo, Alejandra Martínez, Verónica Demicheli, Carolina Prolo, María Noel Álvarez, Gloria V. López, Rafael Radi
The specific and sensitive detection of peroxynitrite (ONOO‒/ONOOH) in biological systems is a great challenge due to its high reactivity towards several biomolecules. Herein, we validated the advantages of using fluorescein-boronate (Fl-B) as a highly sensitive fluorescent probe for the direct detection of peroxynitrite under biologically-relevant conditions in two different cell models. The synthesis of Fl-B was achieved by a very simply two-step conversion synthetic route with high purity (> 99 %) and overall yield (∼ 42%). Reactivity analysis of Fl-B with relevant biological oxidants including hydrogen peroxide (H2O2), hypochlorous acid (HOCl) and peroxynitrite were performed. The rate constant for the reaction of peroxynitrite with Fl-B was 1.7 x 106 M-1s-1, a million times faster than the rate constant measured for H2O2 (k = 1.7 M-1s-1) and 2,700 faster than HOCl (6.2 x 102 M-1s-1) at 37° C and pH 7.4. The reaction of Fl-B with peroxynitrite was significant even in the presence of physiological concentrations of CO2, a well-known peroxynitrite reactant. Experimental and simulated kinetic analyses confirm that the main oxidation process of Fl-B takes place with peroxynitrite itself via a direct bimolecular reaction and not with peroxynitrite-derived radicals. Fl-B was successfully applied for the detection of endogenously- generated peroxynitrite by endothelial cells and in macrophage-phagocyted parasites. Moreover, the generated data allowed estimating the actual intracellular flux of peroxynitrite. For instance, ionomycin-stimulated endothelial cells generated peroxynitrite at a rate of ∼ 0.1 μM s-1, while immunostimulated macrophages do so in the order of ∼ 1 μM s-1 inside T. cruzi-infected phagosomes. Fl-B revealed not to be toxic in concentrations up to 1 mM for 24 h. Cellular peroxynitrite detection was achieved by conventional laboratory fluorescence-based methods including flow cytometry and epi-fluorescence microscopy. Fl-B was shown to be more sensitive than the coumarin boronate due to a higher molar absorption coefficient and quantum yield. Overall, our results show that Fl-B is a kinetically selective and highly sensitive probe for the direct detection of cell-derived peroxynitrite.
http://ift.tt/2cxNPHM
Interactions between neurokinin B and kisspeptin in mediating estrogen feedback in healthy women
The Journal of Clinical Endocrinology &Metabolism, Early Release.
http://ift.tt/2ckO6hw
Diabetic Ketoacidosis without Diabetes
The Journal of Clinical Endocrinology &Metabolism, Early Release.
http://ift.tt/2cGK54v
Adhesion G-protein coupled receptor G1 (ADGRG1/GPR56) and pancreatic β-cell function
The Journal of Clinical Endocrinology &Metabolism, Early Release.
http://ift.tt/2ckNzwe
Impact of completion axillary lymph node dissection in patients with breast cancer and isolated tumour cells or micrometastases in sentinel nodes
Source:European Journal of Cancer, Volume 67
Author(s): G. Houvenaeghel, J.M. Boher, F. Reyal, M. Cohen, J.R. Garbay, J.M. Classe, R. Rouzier, S. Giard, C. Faure, H. Charitansky, C. Tunon de Lara, E. Daraï, D. Hudry, P. Azuar, P. Gimbergues, R. Villet, P. Sfumato, E. Lambaudie
BackgroundOmission of completion axillary lymph node dissection (ALND) is a standard practice in patients with breast cancer (BC) and negative sentinel nodes (SNs) but has shown insufficient evidence to be recommended in those with SN invasion.MethodsA retrospective analysis of a cohort of patients with BC and micrometastases (Mic) or isolated tumour cells (ITCs) in SN. Factors associated with ALND were identified, and patients with ALND were matched to patients without ALND. Overall survival (OS) and recurrence-free survival (RFS) were estimated in the overall population, in Mic and in ITC cohorts.FindingsAmong 2009 patients analysed, 1390 and 619 had Mic and ITC in SN, respectively. Factors significantly associated with ALND were SN status, histological type, age, number of SN harvested and absence of adjuvant chemotherapy. After a median follow-up of 60.4 months, ALND omission was independently associated with reduced OS (hazard ratio [HR] 2.41, 90 confidence interval [CI] 1.36–4.27, p = 0.0102), but not with increased RFS (HR 1.21, 90 CI 0.74–2.0, p = 0.52) in the overall population. In matched patients, the increased risk of death in case of ALND omission was found only in the Mic cohort (HR 2.88, 90 CI 1.46–5.69), not in the ITC cohort. The risk of recurrence was also significantly increased in the subgroup of matched Mic patients (HR 1.56, 90 CI 0.90–2.73).InterpretationA separate analysis of Mic and ITC groups, matched for the determinants of ALND, suggested that patients with Mic had increased recurrence rates and shorter OS when ALND was not performed. Our results are consistent with those of previous studies for patients with ITC but not for those with Mic. Randomised controlled clinical trials are still warranted to show with a high level of evidence if ALND can be safely omitted in patients with micrometastatic disease in SN.
http://ift.tt/2cEnsRx
Neutrophil-to-lymphocyte ratio as a prognostic marker in locally advanced nasopharyngeal carcinoma: A pooled analysis of two randomised controlled trials
Source:European Journal of Cancer, Volume 67
Author(s): Melvin Lee Kiang Chua, Sze Huey Tan, Grace Kusumawidjaja, Ma Than Than Shwe, Shie Lee Cheah, Kam Weng Fong, Yoke Lim Soong, Joseph Tien Seng Wee, Terence Wee Kiat Tan
PurposeTo assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with International Union Against Cancer (UICC)–staged III/IVA,B nasopharyngeal carcinoma (NPC), who were enrolled into two randomised controlled trials of concurrent/adjuvant chemotherapy when added to radiotherapy (SQNP01), and induction chemotherapy when added to chemoradiotherapy (NCC0901).Material and methodsA post hoc analysis of pooled cohorts from SQNP01 (N = 221) and NCC0901 (N = 172) was performed. We employed a threshold of pre-treatment NLR = 3.0 (median) to stratify patients. Survival outcomes were compared using log-rank test. Multivariable Cox regression analyses were performed to assess association between NLR and overall survival (OS), disease-free survival (DFS), distant metastasis–free survival (DMFS), and locoregional recurrence–free survival (LRFS).ResultsHigh NLR (≥3.0) was associated with advanced T-status (p = 0.002), N-status (p = 0.002), overall UICC stage (p = 0.004), and high pre-treatment Epstein–Barr virus DNA titre (p = 0.001). High NLR was not associated with OS (0.94 [0.67–1.32], p = 0.7), DFS (0.98 [0.73–1.33], p = 0.9), DMFS (1.02 [0.66–1.57], p = 0.9), and LRFS (1.37 [0.84–2.22], p = 0.2) on univariable and multivariable analyses, while conventional clinical indices (T-status, N-status, and overall UICC stage) were prognostic of clinical outcomes. High NLR also did not predict for a treatment effect with the experimental arms in both trials.ConclusionOur pooled analyses that were confined to a homogenous patient population of locally advanced NPC do not suggest that NLR adds prognostic value to conventional clinical indices in identifying patients with unfavourable disease.
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Associations between childhood height and morphologically different variants of melanoma in adulthood
Source:European Journal of Cancer, Volume 67
Author(s): Kathrine Damm Meyle, Michael Gamborg, Lisbet Rosenkrantz Hölmich, Jennifer Lyn Baker
Aim of the studyMelanoma subtypes have different aetiological characteristics. Child height is positively associated with adult melanoma; however, a clarification of associations with specific melanoma variants is necessary for an improved understanding of risk factors underlying the histologic entities. This study investigated associations between childhood height and future development of cutaneous melanoma variants.MethodA cohort study of 316,193 individuals from the Copenhagen School Health Records Register, with measured heights at ages 7–13 years who were born from 1930 to 1989. Melanoma cases were identified via linkage to the national Danish Cancer Registry and subdivided into subtypes. Cox proportional hazards regressions were performed.ResultsA total of 2223 cases of melanoma distributed as 60% superficial spreading melanoma (SSM), 27.5% melanoma not otherwise specified (NOS), 8.5% nodular melanoma (NM), and 2% lentigo maligna melanoma (LMM). The remaining rare melanoma forms were not analysed. Childhood height was positively and significantly associated with SSM, melanoma NOS, and NM, but not LMM, in adulthood. Per height z-score at age 13 years, the hazard ratios were 1.20 (95% confidence intervals [CI]: 1.13–1.27) for SSM, 1.19 (95% CI: 1.09–1.29) for melanoma NOS, and 1.21 (95% CI: 1.04–1.41) for NM. Further, growth patterns were linked to the melanoma variants with persistently tall children having an increased risk of developing SSM, melanoma NOS, or NM.ConclusionChildhood height is positively associated with the majority of the melanoma variants. These results suggest that the underlying processes contributing to childhood height and growth patterns interconnect early-life events with the predisposition to melanomagenesis in adulthood.
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Retrolaminar Migration of Intraocular Silicone Oil.
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Ειδοποίηση Μελετητή:[ ωτα ] [HTML] Gender, identity and material: Film screening C Brand - 2017 ftypM4V *M4V M4A mp42isom*a┌moovlmvhd...
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
