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Τετάρτη 18 Απριλίου 2018
Scholar : Shakespeare, Volume 14, Issue 1, April 2018 is now available online on Taylor & Francis Online
Thymol attenuates the worsening of atopic dermatitis induced by Staphylococcus aureus membrane vesicles
Source:International Immunopharmacology, Volume 59
Author(s): Hyo Il Kwon, Na Hee Jeong, So Hyun Jun, Joo Hee Son, Shukho Kim, Hyejin Jeon, Sun Chul Kang, Sang Hyun Kim, Je Chul Lee
Staphylococcus aureus membrane vesicles (MVs) aggravate atopic dermatitis (AD) through the delivery of bacterial effector molecules to host cells and the stimulation of inflammatory responses. This study investigated the inhibitory effect of thymol, a phenolic monoterpene found in essential oils derived from plants, on the worsening of AD induced by S. aureus MVs both in vitro and in vivo. The sub-minimal inhibitory concentrations of thymol disrupted S. aureus MVs. Intact S. aureus MVs induced the expression of pro-inflammatory cytokine (interleukin (IL)-1β, IL-6, and tumor necrosis factor-α) and chemokine (IL-8 and monocyte chemoattractant protein-1) genes in cultured keratinocytes, whereas thymol-treated S. aureus MVs did not stimulate the expression of these genes. Topical application of thymol-treated S. aureus MVs or treatment with thymol after intact S. aureus MVs to AD-like skin lesions diminished the pathology of AD. This included decreases in epidermal/dermal thickness and infiltration of eosinophils/mast cells, and inhibited expression of pro-inflammatory cytokine and chemokine genes in mouse AD model. Moreover, thymol significantly suppressed the Th1, Th2, and Th17-mediated inflammatory responses in AD-like skin lesions induced by S. aureus MVs, and reduced the serum levels of immunoglobulin (Ig) G2a, mite-specific IgE, and total IgE. In summary, thymol disrupts S. aureus MVs and suppresses inflammatory responses in AD-like skin lesions aggravated by S. aureus MVs. Our results suggest that thymol is a possible candidate for the management of AD aggravation induced by S. aureus colonization or infection in the lesions.
https://ift.tt/2HGcp7D
A population-based examination of the co-occurrence and functional correlates of chronic pain and generalized anxiety disorder
Source:Journal of Anxiety Disorders
Author(s): Brian Csupak, Jordana L. Sommer, Eric Jacobsohn, Renée El-Gabalawy
ObjectivesThis study aimed to: 1) Establish the prevalence of co-occurring chronic pain conditions (i.e., arthritis, back pain, and migraines) and generalized anxiety disorder (GAD), and 2) Examine levels of pain severity, disability, and work absenteeism among comorbid chronic pain conditions and GAD.MethodsData were analyzed from the 2012 Canadian Community Health Survey–Mental Health (CCHS-MH; N = 25,113). Chi-square analyses assessed whether significant differences existed in pain severity in those with comorbid chronic pain and GAD versus pain conditions alone. Multivariable regressions examined the association between comorbid chronic pain and GAD with functional outcomes.ResultsThe weighted prevalence of GAD among those with chronic migraines, arthritis and back pain was 6.9%, 4.4%, and 6.1% respectively, compared to 2.6% among the entire sample. Severity of pain was increased among those with comorbid chronic pain and GAD compared with chronic pain conditions alone. Migraine was the only pain condition that was significantly associated with disability in our most stringent adjustment model. After controlling for other psychiatric disorders, comorbid GAD and chronic pain was not associated with work absenteeism.ConclusionChronic pain is common among the Canadian population and is associated with substantial disability. Results demonstrated that GAD is prevalent among chronic pain conditions, and comorbidity is associated with greater pain severity. GAD in the context of migraines, in particular, may represent an important treatment target to reduce disability.
https://ift.tt/2J59fd3
“No pain, No gain” still true with immunotherapy: When the finger shows the moon, look at the moon!
Publication date: Available online 17 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): G. Milano, F. Innocenti, B. Lacarelle, J. Ciccolini
There is a rising evidence that the proverbial statement "No pain, No gain" first coined at the light of pioneering clinical experiences with canonical chemotherapy still holds true in the era of modern treatments of cancer. This close relationship between the occurrence of specific drug-related toxicity and treatment outcome has been confirmed since then with a large variety of treatments, ranging from cytotoxics, hormonotherapy, targeted therapy and much interestingly even with the latest immune checkpoint inhibitors. In the current context of precision medicine, and along with the constant quest for identifying predictive biomarkers, close monitoring of treatment-related toxicities could therefore be convenient to help predicting therapeutic response, but presents several caveats. The purpose of this review is to briefly describe these relationships across the different treatments, to comment on possible underlying mechanisms and to comment on possible strategies aiming at exploiting this relationship while keeping the maximal safety ensured in patients with cancer. In particular, this review will investigate on how drug exposure along with germinal and somatic genetic issues does impact on the "No Pain, No Gain" aphorism, and why the temptation to use treatment-related toxicities as a cheap and convenient way to predict clinical outcome or to adapt dosing should be resisted. We do advocate instead for developing comprehensive genomic support along with extensive biomathematical modeling to better customize dosing and shift towards a new "No Pain, Maximal Gain" paradigm.
Graphical abstract
https://ift.tt/2qFTmCo
Effects of growth hormone on pregnancy rates of patients with thin endometrium
Abstract
Purpose
To investigate whether growth hormone (GH) could improve pregnancy rates of patients with thin endometrium by clinical study and laboratory experiments.
Materials and methods
Ninety-three patients were randomized to either the GH-received group (40) or the routine exogenous administration of estrogens control group (53) for clinical study. The human endometrial carcinoma cell line RL95-2 was used for testing the role of GH with Western blot and real-time PCR by exposure to various concentrations of GH (0.1 nM,1 nM,10 nM,100 nM).
Results
Patients treated with GH had a significantly (P < 0.05) greater endometrium thickness on day 3 (7.87±0.72 vs 6.34±0.86), higher implantation rates (24.4% vs 10.5%) and greater clinical pregnancy rates (42.5% vs 18.9%) compared with the control group. No adverse events were associated with the use of GH. Administration of GH significantly up-regulated the expression of VEGF, ItgB3 and IGF-I expression in RL95-2 cells at both mRNA and protein levels (P < 0.05). AG490, an inhibitor of JAK2, nearly completely inhibited the up-regulative effect of GH through the JAK2-STAT5 pathway, and GH-induced effects could be mediated through autocrine IGF-I together with its hepatic counterpart. IGF-I mRNA was detected in the RL95-2 cells.
Conclusion
GH may improve pregnancy outcomes of patients with thin endometrium who undergo frozen embryo transfer by acting on human endometrial cells to promote proliferation and vascularization and to up-regulate receptivity-related molecular expression.
https://ift.tt/2qGbYmK
Childhood obesity: how long should we wait to predict weight?
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
https://ift.tt/2vp2Ver
A tandem mass tag (TMT) proteomic analysis during the early phase of experimental pancreatitis reveals new insights in the disease pathogenesis
Publication date: Available online 17 April 2018
Source:Journal of Proteomics
Author(s): Violeta García-Hernández, Carmen Sánchez-Bernal, Domitille Schvartz, José J. Calvo, Jean-Charles Sanchez, Jesús Sánchez-Yagüe
Changes in the protein expression occurring within the initiation phase of acute pancreatitis (AP) might be vital in the development of this complex disease. However, the exact mechanisms involved in the onset of AP remains elusive and most of our knowledge about the pathobiology of AP comes from animal models. We performed in a rat pancreatitic model a high-throughput shotgun proteomic profiling of the soluble and whole membrane fractions from the pancreas during the early phase of cerulein (Cer)-induced AP. We identified 997 proteins, of which 353 were significantly different (22, 276 or 55 in both, the soluble or the membrane fractions, respectively). Gene Ontology and KEGG PATHWAY analyses revealed that these proteins were implicated in molecular mechanisms relevant to AP pathogenesis, including vesicle-mediated and protein transport, lysosomal and mitochondrial impairment or proteolysis. Numerous metabolic processes were downregulated apparently to reduce energy consumption, and a remarkable increase in inflammatory and stress responses was also highlighted. The proteomic data were verified by immunoblotting of 11 and 7 different soluble or membrane-associated proteins, either novel (VPS29 and MCTS1) or known factors in AP. Also, our first observation of the imbalance of some COP proteins during AP early phase deserves further characterization.Biological significanceAP is one of the most important pathological inflammatory states of the exocrine pancreas but its pathophysiology remains incompletely understood, especially the early acinar events. Proteomic analysis of pancreatic subcellular fractions simplifies protein maps and helps in the identification of new protein alterations and biomarkers characterizing pancreatic tissue damage. Our shotgun approach has not been previously used to profile the early proteomic alterations of the disease, which are considered crucial for its development and for the founding of clinical procedures. Furthermore, our subcellular fractionation protocol allowed us to detect changes in membrane proteins so far overlooked in the proteomic study of AP.Accordingly, using TMT proteomics and bioinformatic tools, we were able to detect significant changes in protein expression related to many pathobiological pathways of acute pancreatitis as from the early phase of the disease. To our knowledge, some of these changes, such as the imbalance of some COP proteins, have never been described in this disease.
Graphical abstract
https://ift.tt/2HGvDKp
“No pain, No gain” still true with immunotherapy: When the finger shows the moon, look at the moon!
Publication date: Available online 17 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): G. Milano, F. Innocenti, B. Lacarelle, J. Ciccolini
There is a rising evidence that the proverbial statement "No pain, No gain" first coined at the light of pioneering clinical experiences with canonical chemotherapy still holds true in the era of modern treatments of cancer. This close relationship between the occurrence of specific drug-related toxicity and treatment outcome has been confirmed since then with a large variety of treatments, ranging from cytotoxics, hormonotherapy, targeted therapy and much interestingly even with the latest immune checkpoint inhibitors. In the current context of precision medicine, and along with the constant quest for identifying predictive biomarkers, close monitoring of treatment-related toxicities could therefore be convenient to help predicting therapeutic response, but presents several caveats. The purpose of this review is to briefly describe these relationships across the different treatments, to comment on possible underlying mechanisms and to comment on possible strategies aiming at exploiting this relationship while keeping the maximal safety ensured in patients with cancer. In particular, this review will investigate on how drug exposure along with germinal and somatic genetic issues does impact on the "No Pain, No Gain" aphorism, and why the temptation to use treatment-related toxicities as a cheap and convenient way to predict clinical outcome or to adapt dosing should be resisted. We do advocate instead for developing comprehensive genomic support along with extensive biomathematical modeling to better customize dosing and shift towards a new "No Pain, Maximal Gain" paradigm.
Graphical abstract
https://ift.tt/2qFTmCo
Comparative study of remediation of Cr(VI)-contaminated soil using electrokinetics combined with bioremediation
Abstract
The purpose of this research is to design a new bioremediation-electrokinetic (Bio-EK) remediation process to increase treatment efficiency of chromium contamination in soil. Upon residual chromium analysis, it is shown that traditional electrokinetic-PRB system (control) does not have high efficiency (80.26%) to remove Cr(VI). Bio-electrokinetics of exogenous add with reduction bacteria Microbacterium sp. Y2 and electrokinetics can enhance treatment efficiency Cr(VI) to 90.67% after 8 days' remediation. To optimize the overall performance, integrated bio-electrokinetics were designed by synergy with 200 g humic substances (HS) into the systems. According to our results, Cr(VI) (98.33%) was effectively removed via electrokinetics. Moreover, bacteria and humic substances are natural, sustainable, and economical enhancement agents. The research results indicated that the use of integrated bio-electrokinetics is an effective method to remediate chromium-contaminated soils.
https://ift.tt/2qGp6r3
Effects of 1,540-nm Fractional Nonablative Erbium and 2,940-nm Fractional Ablative Erbium on p53 Epidermal Expression After 3 months: A Split-Face Interventional Study
https://ift.tt/2J4OLBb
Review of historical aquatic toxicity and bioconcentration data for the brominated flame retardant tetrabromobisphenol A (TBBPA): effects to fish, invertebrates, algae, and microbial communities
Abstract
This paper summarizes the historical and recent research on the aquatic toxicology and bioconcentration potential of tetrabromobisphenol A (TBBPA), a major flame retardant in electronics. Historical studies on TBBPA are presented in detail, and are compared with more recent research. The historical studies have not been published to date, though they were pivotal in regulatory assessments by the European Union, Canada, and the USA. These assessments have enabled the use of TBBPA as a flame retardant in electronic applications, to the present. The studies were conducted under a Test Rule by the US Environmental Protection Agency in 1987, and were sponsored by member companies of the North American Flame Retardants Alliance (NAFRA) through the American Chemistry Council. The studies were conducted under Good Laboratory Practice procedures, and include 6 acute toxicity tests of TBBPA with fish, invertebrates, algae, and microbes, eight chronic tests, and three bioconcentration studies with fish and invertebrates. Methods and empirical data for each study are detailed in an electronic supplement. Results of the NAFRA studies are compared with recent findings on TBBPA toxicity. Molluscan shell growth may be uniquely sensitive to TBBPA, more sensitive than chronic fish or crustacean toxicity endpoints. Several of the NAFRA studies and several independent studies have reported toxicities exceeding the empirical water solubility limits of TBBPA (in the range of 2.0 mg/L depending on pH). The validity of these results is discussed.
https://ift.tt/2qFh2rk
Τρίτη 17 Απριλίου 2018
Effects of single- and double-layered resorbable membranes and platelet-rich fibrin on bone healing
Abstract
Objectives
Research has been ongoing on achieving optimum bone healing in the reconstruction of bone loss. Clinically, soft tissue migration into the already existing bone defects is the leading cause of unfavourable bone healing. Platelet-rich fibrin, a recent material that is used to promote bone healing, was compared with single- and double-layered resorbable collagen membranes to determine whether a healing protocol which increases patient comfort is possible.
Materials and methods
Sixty adult female Sprague-Dawley rats were used. The rats were divided into five main groups as a sacrification group, a control group, and three experimental groups. The bone defects experimental group 1 were covered with a single-layer collagen membrane, and experimental group 2 were covered with the double-layered collagen membrane. Defects on the experimental group 3 were covered with platelet-rich fibrin membranes which were derived from the sacrification group. The animals in the main groups were also divided into eight subgroups arranged by sacrification periods on day 7 and day 28.
Results
Statistical analysis of our study revealed that new bone formation in experimental group 3 was significantly higher than in other groups. Fibrosis was found to be lower in experimental group 3 than in any other group. No significant differences were found between experimental group 1 and the control group.
Conclusion
Platelet-rich fibrin, which can be used as an autologous membrane which promotes bone healing, yields better clinical result compared to collagen membranes.
Clinical relevance
Histopathologic evaluation has been carried out regarding the effect of platelet-rich fibrin and collagen membranes applied on bone recovery. Our objective is to contribute to barrier membrane studies that continue to guide and accelerate bone recovery.
https://ift.tt/2ETl7wh
Effect of bleaching agent extracts on murine macrophages
Abstract
Objectives
The aim of this study was to evaluate the cytotoxicity and the influence of bleaching agents on immunologically cell surface antigens of murine macrophages in vitro.
Materials and methods
RAW 264.7 cells were exposed to bleaching gel extracts (40% hydrogen peroxide or 20% carbamide peroxide) and different H2O2 concentrations after 1 and 24-h exposure periods and 1-h exposure and 23-h recovery. Tests were performed with and without N-acetyl cysteine (NAC) and buthionine sulfoximine (BSO). Cell viability was determined by MTT assay. The expression of surface markers CD14, CD40, and CD54 with and without LPS stimulation was detected by flow cytometry, while the production of TNF-α was measured by ELISA. Statistical analysis was performed using the Mann-Whitney U test (α = 0.05).
Results
Extracts of bleaching agents were cytotoxic for cells after a 1-h exposure; cells could not recover after 24 h. This effect can be mitigated by the antioxidant NAC and increased by BSO, an inhibitor of glutathione (GSH) synthesis. LPS stimulated expression of all surface markers and TNF-α production. Exposure to bleaching agent extracts and H2O2 leads to a reduction of TNF-α, CD14, and CD40 expression, while the expression of CD54 was upregulated at non-cytotoxic concentrations. Whereas NAC reduced this effect, it was increased in the presence of BSO.
Conclusions
Extracts of bleaching agents were irreversibly cytotoxic to macrophages after a 1-h exposure. Only the expression of CD54 was upregulated. The reactions are mediated by the non-enzymatic antioxidant GSH.
Clinical relevance
The addition of an antioxidant can downregulate unfavorable effects of dental bleaching.
https://ift.tt/2JTVy1Z
Lack of association between ENAM gene polymorphism and dental caries in primary and permanent teeth in Czech children
Abstract
Objectives
The enamelin gene (ENAM) polymorphism (rs12640848) was recently associated with dental caries in primary teeth in Polish children. The aims of the present study were to prove this association in primary dentition and to find a possible effect of this variant on caries development in permanent dentition in Czech children.
Materials and methods
This study comprised 905 Czech children. Totally, 187 children aged 2–6 years with primary dentition [78 healthy subjects (with decayed/missing/filled teeth, dmft = 0) and 109 patients with early childhood caries (ECC; dmft ≥ 1)] were included in this case-control study. In addition, 177 subjects aged 13–15 years without caries (DMFT = 0) and 541 children with dental caries (DMFT ≥ 1) in permanent dentition were selected from the ELSPAC study. Genotype determination of the ENAM polymorphism (rs12640848) was based on the TaqMan method.
Results
No significant differences in the allele or genotype frequencies between the caries-free children and those affected by dental caries were observed in both primary and permanent dentitions.
Conclusions
Lack of association between the ENAM polymorphism (rs12640848) and dental caries in Czech children was detected.
Clinical relevance
Although ENAM is considered as a candidate gene for dental caries, the presence of the ENAM variant (rs12640848) cannot be used as a risk factor of this multifactorial disease in the Czech population.
https://ift.tt/2EVN32w
Evaluation of the interface between gutta-percha and two types of sealers using scanning electron microscopy (SEM)
Abstract
Objectives
The aim of the present study was to evaluate the adaptation of a calcium silicate bioceramic (BC) sealer with either BC or conventional gutta-percha compared with that of AH Plus sealer in different root canal sections.
Materials and methods
Seventy-two extracted mandibular premolars were divided randomly into six groups. After standardised chemomechanical preparation, four groups were obturated with the BC sealer and BC gutta-percha or conventional gutta-percha, and the other two groups were obturated with AH Plus sealer and conventional gutta-percha either in lateral compaction or in a single cone technique. Each root was sectioned into three sections. An impression was made from each section, and replicas were then made for scanning electron microscopy (SEM) analysis. Areas and interfacial gaps were identified using image analysis software. In addition to descriptive and explorative data analyses, linear regression analysis was performed.
Results
All specimens had measurable interfacial gaps. Significantly fewer gaps were found between conventional gutta-percha and sealer compared to those observed when using the BC gutta-percha (p < 0.001). However, minor interfacial gaps between sealer and dentin were observed with the BC sealer (p = 0.04). The technique of obturation in different root canal sections did not significantly affect the sealer adaptability.
Conclusion
The type of gutta-percha as well as the sealer had a noticeable impact on the adaptability.
Clinical relevance
Different obturation techniques will result in similar outcomes. However, within the limitations of the study, there seems to be no advantage in using the BC gutta-percha.
https://ift.tt/2JSGTEa
Prevention of coronal discoloration induced by regenerative endodontic treatment in an ex vivo model
Abstract
Objectives
The aim of this study was to assess the effect of sealing the pulp chamber walls with a dentin-bonding agent (DBA) on prevention of discoloration induced by regenerative endodontic procedures (REPs) in an ex vivo model.
Materials and methods
Ninety-six bovine incisors were prepared and randomly divided into two groups. In one group, the pulp chamber walls were sealed with DBA before placement of triple antibiotic paste (TAP) containing minocycline inside the root canals, but in the other group, DBA was not applied. After 4 weeks, the root canals were filled with human blood and each group was then randomly divided into four subgroups (n = 12) according to the endodontic cements placed over the blood clot (ProRoot MTA, OrthoMTA, RetroMTA, or Biodentine). The color changes (∆E) were measured at different steps. The data were analyzed using t test and two-way ANOVA.
Results
The specimens in which dentinal walls of pulp chamber were sealed with DBA showed significantly less coronal discoloration at each step of regenerative treatment (p < 0.001). However, application of DBA did not completely prevent the clinically perceptible coronal color change. Sealing the blood clot with different endodontic cements did not result in significant difference in coronal discoloration (p > 0.05).
Conclusions
Sealing the pulp chamber walls before insertion of TAP decreased coronal discoloration following REP using different endodontic cements but did not prevent it.
Clinical relevance
Discoloration of teeth undergoing REPs is an unfavorable outcome. Considering the significant contribution of TAP containing minocycline to the coronal tooth discoloration even after sealing the pulp chamber walls, the revision of current guidelines in relation to the use of TAP with minocycline might need to be revised.
https://ift.tt/2EWkvWL
Oral cancer radiotherapy affects enamel microhardness and associated indentation pattern morphology
Abstract
Objectives
The aim of this study is to determine the effects of in vitro and in vivo high-dose radiotherapy on microhardness and associated indentation pattern morphology of enamel.
Materials and methods
The inner, middle, and outer microhardness of enamel was evaluated using three experimental groups: control (non-radiated); in vitro irradiated; in vivo irradiated. In vitro specimens were exposed to simulated radiotherapy, and in vivo specimens were extracted teeth from oral cancer patients previously treated with radiotherapy. Indentations were measured via SEM images to calculate microhardness values and to assess the mechanomorphological properties of enamel before and after radiotherapy.
Results
Middle and outer regions of enamel demonstrated a significant decrease in microhardness after in vitro and in vivo irradiation compared to the control group (p < 0.05). Two indentation patterns were observed: pattern A—presence of microcracks around indent periphery, which represents local dissipation of deformation energy; pattern B—clean, sharp indents. The percentage of clean microindentation patterns, compared to controls, was significantly higher following in vitro and in vivo irradiation in all enamel regions. The highest percentage of clean microindentations (65%) was observed in the in vivo irradiated group in the inner region of enamel near the dentin-enamel junction.
Conclusions
For the first time, this study shows that in vitro and in vivo irradiation alters enamel microhardness. Likewise, the indentation pattern differences suggest that enamel may become more brittle following in vitro and in vivo irradiation.
Clinical relevance
The mechanomorphological property changes of enamel following radiation may be a contributory component of pathologic enamel delamination following oral cancer radiotherapy.
https://ift.tt/2JSfh22
Development of a novel bioactive glass for air-abrasion to selectively remove orthodontic adhesives
Abstract
Objectives
To develop a novel, bioactive glass for removing residual orthodontic adhesive via air-abrasion, following bracket debonding, and to evaluate its effectiveness against a proprietary bioactive glass 45S5(Sylc™)-air-abrasion, and a slow-speed tungsten carbide (TC) bur.
Materials and methods
Three glasses were prepared and their bioactivity was proved. One novel glass (QMAT3) was selected due to its appropriate hardness, lower than that of enamel/45S5(Sylc™). Sixty extracted human premolars were randomly assigned to adhesive removal using: (a) QMAT3-air-abrasion, (b) 45S5(Sylc™)-air-abrasion, and (c) TC bur, which were further subdivided (n = 10) based on the adhesive used (Transbond XT™ or Fuji Ortho LC™). Enamel roughness was assessed using scanning electron microscopy (SEM) and non-contact profilometry before bracket bonding, after removing residual adhesive following bracket debonding and after polishing.
Results
QMAT3 formed apatite faster (6 h) than 45S5(Sylc™) (24 h) in Tris solution. QMAT3-air-abrasion gave the lowest enamel roughness (Ra) after removing the adhesives. SEM images showed a pitted, roughened enamel surface in the TC bur group and to a lesser extent with 45S5(Sylc™), while a virtually smooth surface without any damage was observed in the QMAT3-air-abrasion group. The time taken for adhesive removal with QMAT3 was comparable to 45S5(Sylc™) but was twice as long with the TC bur.
Conclusions
QMAT3-air-abrasion is a promising technique for selective removal of adhesives without inducing tangible enamel damage.
Clinical relevance
A novel bioactive glass has been developed as an alternative to the use of TC burs for orthodontic adhesive removal.
https://ift.tt/2EVx9pc
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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...
