Publication date: 14 April 2017
Source:Behavioural Brain Research, Volume 323
Author(s): Mingming Qi, Heming Gao, Guangyuan Liu
This study aimed to investigate the effect of acute psychological stress on response inhibition and its electrophysiological correlates using a dual-task paradigm. Acute stress was induced by a primary task (mental arithmetic task), which consisted of a stress block and a control block. Response inhibition was measured using a secondary task (Go/NoGo task). In each trial, a Go/NoGo stimulus was presented immediately after the mental arithmetic task. The results revealed increased subjective stress and negative affect for the stress relative to control block, suggesting that the mental arithmetic task triggered a reliable stress response. ERPs locked to the Go/NoGo stimuli revealed that decreased P2 and increased N2 components were evoked for the stress block compared to the control block. These results demonstrated that acute psychological stress alters the response inhibition process by reducing the early selective attention process and enhancing the cognitive control process.
http://ift.tt/2jV0Woe
Τετάρτη 1 Φεβρουαρίου 2017
Effect of acute psychological stress on response inhibition: An event-related potential study
Up-regulation of SIRT6 in the hippocampus induced rats with depression-like behavior via the block Akt/GSK3β signaling pathway
Source:Behavioural Brain Research, Volume 323
Author(s): Qiang Mao, Xue Gong, Chanjuan Zhou, Zhe Tu, Libo Zhao, Ling Wang, Xinfa Wang, Lu Sun, Jinjun Xia, Bin Lian, Jianjun Chen, Jun Mu, Deyu Yang, Peng Xie
Major depression is the leading cause of disability worldwide, which is associated with diverse alterations in brain such as neuro-inflammation, synaptic dysfunction, and cognitive deficit. Accumulating evidences suggest sirtuins (SIRTs) are involved in brain developmental disorders, metabolic diseases and play a key role in cognition and synaptic plasticity, yet the role in mood regulation remains controversial. Hence, Western blotting and RT-qPCR were used to investigate whether SIRTs (SIRT1–7) expression levels were altered in the hippocampus of rats, which followed 5 weeks of chronic unpredictable mild stress (CUMS) treatment, the results showed depressive-like behaviors: like body weight, forced swim test and sucrose preference test and SIRT6 was a significant increase in the hippocampal of CUMS rats. Furthermore, via a lentivirus-mediated transfection in hippocampal neurons, we aimed to detect how SIRT6 influence the function of hippocampus. The SIRT6 overexpression significantly inhibited expressions of proteins and/or phosphoproteins (e.g AKT, p-AKT, P-GSK3β), decreased the ratios of p-GSK3β/GSK3β and p-Akt/Akt in the primary hippocampus neurons. Thus, our data indicates that SIRT6 is involved in the modulation of depressive-like behaviors and affects the survival and synaptic plasticity of hippocampal neuron via inhibitory activation of Akt-GSK3β signaling.
http://ift.tt/2jXmjHR
Brain-specific knockin of the pathogenic Tubb5 E401K allele causes defects in motor coordination and prepulse inhibition
Publication date: 14 April 2017
Source:Behavioural Brain Research, Volume 323
Author(s): Martin W. Breuss, Andi H. Hansen, Lukas Landler, David A. Keays
The generation, migration, and differentiation of neurons requires the functional integrity of the microtubule cytoskeleton. Mutations in the tubulin gene family are known to cause various neurological diseases including lissencephaly, ocular motor disorders, polymicrogyria and amyotrophic lateral sclerosis. We have previously reported that mutations in TUBB5 cause microcephaly that is accompanied by severe intellectual impairment and motor delay. Here we present the characterization of a Tubb5 mouse model that allows for the conditional expression of the pathogenic E401K mutation. Homozygous knockin animals exhibit a severe reduction in brain size and in body weight. These animals do not show any significant impairment in general activity, anxiety, or in the acoustic startle response, however, present with notable defects in motor coordination. When assessed on the static rod apparatus mice took longer to orient and often lost their balance completely. Interestingly, mutant animals also showed defects in prepulse inhibition, a phenotype associated with sensorimotor gating and considered an endophenotype for schizophrenia. This study provides insight into the behavioral consequences of tubulin gene mutations.
http://ift.tt/2jUY2jo
Effects of repeated treatment with a delta opioid receptor agonist KNT-127 on hyperemotionality in olfactory-bulbectomized rats
Source:Behavioural Brain Research, Volume 323
Author(s): Leo Gotoh, Akiyoshi Saitoh, Misa Yamada, Hideaki Fujii, Hiroshi Nagase, Mitsuhiko Yamada
We previously demonstrated that a single treatment of a non-peptidic delta opioid receptor agonist, KNT-127, has an antidepressant-like effect in rodents in the forced swim test. Here we evaluated the effect of repeated administration of the potential antidepressant KNT-127 in an olfactory-bulbectomized (OBX) rat model. Male Wistar rats (8–12 weeks old) underwent olfactory bulbectomy. From 14days after surgery each was weighed and administered either KNT-127 (3mgkg−1/day), the selective serotonin reuptake inhibitor (SSRI) fluoxetine (10mgkg−1/day), or vehicle, daily for 14 days. Hyperemotionality was measured on days 3, 5, 7, 10, and 14. Repeated administration of KNT-127 significantly decreased total and individual hyperemotionality scores (attack, startle, struggle and fight) over the entire period. Conversely, fluoxetine did not show any significant effect on days 3, 5, 7, or 14 but significantly reduced the total score on day 10. The inhibitory effects of KNT-127 were greater than those of fluoxetine. The KNT-127 and control groups both gained weight, while the fluoxetine group lost weight. Our results suggest that KNT-127 is a potential lead compound for antidepressant therapy, with high efficacy, a relatively rapid onset of therapeutic effect, and without the possible adverse effects of weight loss caused by SSRIs.
http://ift.tt/2jX5sFc
Renoprotective and antioxidative effects of methanolic Paederia foetida leaf extract on experimental diabetic nephropathy in rats
Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): M.P. Borgohain, L. Chowdhury, S. Ahmed, N. Bolshette, K. Devasani, T.J. Das, A. Mohapatra, M. Lahkar
Ethnopharmacological relevancePaederia foetida Linn. (Family: Rubiaceae) is widely used as a natural remedy for diabetes mellitus by the Nepali and Lepcha tribes of Sikkim and Darjeeling Himalayan region. The plant is administered to a diabetic individual in the form of leaf infusion for 2–3 weeks. Therefore, we investigated the effects of methanolic leaf extract of Paederia foetida (MEPF) on alloxan (ALX) induced diabetic renal oxidative stress and NF-kB dependent renoinflammatory events in rat.MethodEffects of MEPF on blood glucose, glomerular filtration rate (GFR), serum and oxidative stress markers were evaluated in ALX induced diabetic wistar rats. Enzyme linked immunosorbent assay (ELISA) was carried out to estimate serum IL-6, IL-1β, TNF-α and renal tissue NF-kB p65 levels. MEPF treatment was given to the diabetic rats at a dose of 250 and 500mg/kg body weight (b.w.).Results & discussionMEPF treatment significantly reduced hyperglycaemia, serum creatinine, blood urea nitrogen (BUN), bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TRIGs), and total cholesterol (TCHOL) levels in the diabetic rats, whereas it significantly restored GFR and serum albumin level. The activity of enzymatic and non-enzymatic antioxidant machineries was remarkably augmented by MEPF treatment. Likewise, it also significantly lowered lipid peroxidation which was evidenced by decreased concentration of thiobarbituric reactive substances (malondialdehyde, MDA) in the renal tissue of treated diabetic groups. Moreover, MEPF treated animals exhibited low serum concentrations of IL-6, IL-1β and TNF-α compared to the diabetic control rats. It showed a dose dependent inhibition of NF-kB activation in the diabetic kidney, but the effects were more prominent at a dose of 500mg/kg. Histopathological examinations also confirmed its nephroprotective action during diabetes.ConclusionMEPF treatment mitigates oxidative stress and suppresses renal inflammation via inhibition of NF-kB in diabetic kidney in early progressive diabetic nephropathy.
Graphical abstract
http://ift.tt/2jV3oLo
Rehmanniae Radix in osteoporosis: A review of traditional Chinese medicinal uses, phytochemistry, pharmacokinetics and pharmacology
Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Chenyue Liu, Rufeng Ma, Lili Wang, Ruyuan Zhu, Haixia Liu, Yubo Guo, Baosheng Zhao, Shangang Zhao, Jinfa Tang, Yu Li, Jianzhao Niu, Min Fu, Dongwei Zhang, Sihua Gao
Ethnopharmacological relevanceEmerging clinical usage and pharmacological effects have been achieved in using Rehmanniae Radix either singly or in combination with other herbs to treat skeletal diseases in traditional Chinese medicine (TCM) in the recent years. This study is aimed to provide a comprehensive review about the historical TCM interpretation of the action of Rehmanniae Radix in osteoporosis, its usage in clinical trials and osteoporotic models, its main phytochemical constituents, and its pharmacokinetics.Materials and methodsSeveral databases included PubMed, China Knowledge Resource Integrated Database, China Science and Technology Journal Database, National Science and Technology Library and the Web of Science Database were consulted to locate the publications pertaining to Rehmanniae Radix. The initial inquiry was conducted for the presence of the following terms combinations in the abstracts: Rehmanniae Radix, Dihuang, phytochemistry, pharmacokinetics, osteoporosis, bone, osteoclast and osteoblast. About 330 research papers and reviews were consulted.ResultsIn TCM, Rehmanniae Radix exerts the anti-osteoporotic effect via regulating the functions of kidney and liver as well as improving blood circulation. 107 clinical trials are identified that used Rehmanniae Radix in combination with other herbs to treat post-menopausal, senile and secondary osteoporosis. Most of the clinical trials are characterized by high efficacy and no obvious adverse effects. However, the efficacies of these clinical trials are limited because of small patient sample size, short treatment duration and poor clinical design. In addition, TCM herbs under the clinical study are not clear because of a lack of standardization and authentication. The pharmacokinetics data demonstrate that the ingredients of Rehmanniae Radix are widely distributed after administration, and that catalpol and ajugol as well as acetoside are supposed to be the active constituents. More than 140 individual compounds have been currently isolated from this plant and reported to show pleiotropic effects on various diseases. Rehmanniae Radix displays bone protecting features in the osteoporosis models via the delicate balance between osteoclastogenesis and osteoblastogenesis through single herb extracts and its isolated compounds.ConclusionsThe successful inclusion of Rehmanniae Radix in clinical trials and preclinical studies for the management of osteoporosis has attracted rising attentions for identifying potential anti-osteoporotic candidates from this plant and clinical existing TCM formulas, which will further speed up anti-osteoporosis drug discovery processes. Properly designed and well controlled prospective studies are still needed to further demonstrate bone protective actions and safe use of this herb and its ingredients
Graphical abstract
http://ift.tt/2jV1BpF
Reverse ethnopharmacology and drug discovery
Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Marco Leonti, Gary I. Stafford, Maja Dal Cero, Stefano Cabras, Maria Eugenia Castellanos, Laura Casu, Caroline S. Weckerle
Ethnopharmacological relevanceEthnopharmacological investigations of traditional medicines have made significant contributions to plant-derived drugs, as well as the advancement of pharmacology. Drug discovery from medicinal flora is more complex than generally acknowledged because plants are applied for different therapeutic indications within and across cultures. Therefore we propose the concept of "reverse ethnopharmacology" and compare biomedical uses of plant taxa with their ethnomedicinal and popular uses and test the effect of these on the probability of finding biomedical and specifically anticancer drugs.Materials and methodsFor this analysis we use data on taxonomy and medical indications of plant derived biomedical drugs, clinical trial, and preclinical trial drug candidates published by Zhu et al. (2011) and compare their therapeutic indications with their ethnomedicinal and popular uses as reported in the NAPRALERT® database. Specifically, we test for increase or decrease of the probability of finding anticancer drugs based on ethnomedicinal and popular reports with Bayesian logistic regression analyses.ResultsAnticancer therapy resulted as the most frequent biomedicinal indication of the therapeutics derived from the 225 drug producing higher plant taxa and showed an association with ethnomedicinal and popular uses in women's medicine, which was also the most important popular use-category. Popular remedies for dysmenorrhoea, and uses as emmenagogues, abortifacients and contraceptives showed a positive effect on the probability of finding anticancer drugs. Another positive effect on the probability of discovering anticancer therapeutics was estimated for popular herbal drugs associated with the therapy of viral and bacterial infections, while the highest effect was found for popular remedies used to treat cancer symptoms. However, this latter effect seems to be influenced by the feedback loop and divulgence of biomedical knowledge on the popular level.ConclusionWe introduce the concept of reverse ethnopharmacology and show that it is possible to estimate the probability of finding biomedical drugs based on ethnomedicinal uses. The detected associations confirm the classical ethnopharmacological approach where a popular remedy for disease category X results in a biomedical drug for disease category X but does also point out the existence of cross-over relationships where popular remedies for disease category X result in biomedical therapeutics for disease category Y (Zhu et al., 2011).
Graphical abstract
http://ift.tt/2jUZ8LM
Yupingfeng Powder relieves the immune suppression induced by dexamethasone in mice
Publication date: Available online 1 February 2017
Source:Journal of Ethnopharmacology
Author(s): Yuhua Li, Bin Zheng, Huajie Tian, Xiaotao Xu, Yang Sun, Qibing Mei, Xiaotian Lin, Li Liu
Ethnopharmacological relevance:Yupingfeng Powder (YPF), a Chinese medical formula, is used traditionally for allergic diseases and characterized by reducing allergy relapse. In the present study, we attempted to investigate the effect of YPF on the immunity of mice and the possible mechanisms.Materials and methods:An immunosuppressive mice model induced by Dexamethasone (Dex) was used. Blood samples, spleen and thymus were collected. Then, hematology parameters and organ weight were measured; Phenotypic analyses (CD4+/CD8+) of lymphocytes were performed using a flow cytometer; Phagocytosis of peritoneal macrophages were evaluated by particle tracers; Spleen lymphocytes were isolated, whose proliferation and apoptosis were assessed. NK cells' cytotoxicity was determined using the LDH release assay.Results:YPF could ameliorate weight loss and improve low thymus and spleen coefficients caused by Dex. Treatment with YPF made decreased lymphocytic activity of Dex-treated mice back to normal and inhibited Dex-induced apoptosis of lymphocytes. YPF increased the Dex caused low proportion of CD4+/CD8+, and upregulated Dex-reduced NK cells' activity.Conclusion:The series of experiments demonstrated that YPF could exert immune regulation and enhance immunity of immunosuppressive mice through adjusting nonspecific and cellular immunity. The results would provide a basis for clinical application of YPF.
Graphical abstract
http://ift.tt/2jUTvNU
Topical treatments of Saussurea costus root and Thuja orientalis L. synergistically alleviate atopic dermatitis-like skin lesions by inhibiting protease-activated receptor-2 and NF-κB signaling in HaCaT cells and Nc/Nga mice
Publication date: Available online 1 February 2017
Source:Journal of Ethnopharmacology
Author(s): Hye Jeong Yang, Min Jung Kim, Suna Kang, Na Rang Moon, Da Sol Kim, Na Ra Lee, Kang Sung Kim, Sunmin Park
Ethnopharmacological relevanceThe root of Saussurea costus (Aucklandia lappa Decne, Aucklandiae Radix, SC) and Thuja orientalis L. (TOL) have been traditionally used as anti-inflammatory agents in Korea. However, they have not been studied for the efficacy of atopic dermatitis (AD) treatment, a chronic inflammatory skin disease. We investigated the efficacy of topical applications with 1,3-butyleneglycol extracts of SC and TOL to alleviate the symptoms of AD.Materials and methodsHaCaT cells and the dorsal skin of Nc/Nga mice had a local exposure of house mite extracts and 2,4-dinitrochlorobenzene (DNCB), respectively. After lesions developed, we topically applied 1,3-butylen glycol (vehicle; control), SC (30%), TOL (30%), or SC (15%)+TOL (15%) to the skin lesions for 5 weeks. The normal-control was not exposed to DNCB. The skin thickness, mast cell infiltration, serum immunoglobulin E (IgE) and IgG1 and gene expressions of interleukin (IL)−4, IL-13, and IFN-γ in the dorsal skin and HaCaT cells were measured.ResultsChlorogenic acid (129.6±10.2μg/g) for SC and catechin and apigenin (93.4±13.2 and 16.9±1.3μg/g, respectively) for TOL were used as indicator compounds for the strength of the extracts. SC+TOL decreased the expression of protease-activated receptor-2 and ICAM-1 and the release of TNF-α and IL-6 in HaCaT cells activated by 3ug/mL house mite extracts in comparison to either of SC or TOL alone. In Nc/Nga mice challenged with DNCB, SC+TOL synergistically attenuated clinical symptoms of AD such as erythema, hemorrhage, edema, excoriation and dryness in the dorsal skin better than either SC or TOL alone. Histological analysis of the dorsal skin also showed that SC+TOL treatment significantly and additively decreased the inflammatory cellular infiltrate, including mast cells and eosinophils in comparison to either of SC or TOL. SC+TOL also decreased serum IgE and IgG1 levels and the expression of IFN-γ, IL-4, and IL-13 mRNA in dorsal skin in DNCB-treated Nc/Nga mice.ConclusionSC+TOL relieved the symptoms of AD by reducing pro-inflammatory activity and over-activated immune responses. These data suggest that SC+TOL may be an effective alternative intervention for the management of AD.
Graphical abstract
http://ift.tt/2jV4Zka
Anti-ulcer Effect and Potential Mechanism of Licoflavone by Regulating Inflammation Mediators and Amino Acid Metabolism
Publication date: Available online 31 January 2017
Source:Journal of Ethnopharmacology
Author(s): Yi Yang, Shuai Wang, Yong-rui Bao, Tian-jiao Li, Guan-lin Yang, Xin Chang, Xian-sheng Meng
Ethnopharmacological relevanceGlycyrrhiza is the dry root and rhizome of the leguminous plant, Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L., which was firstly cited in Shennong's Herbal Classic in Han dynasty and was officially listed in the Chinese Pharmacopoeia, has been widely used in China during the past millennia. Licoflavone is the major component of Glycyrrhiza with anti-ulcer activity. The present study is based on clarifying the anti-ulcer effect of licoflavone, aiming at elucidating the possible molecule mechanisms of its action for treating gastric ulcer rats induced by acetic acid.Materials and methodsRats were divided into 7 groups, and drugs were administered from on the day after the onset of gastric ulcer (day 3) until day 11 of the experiment once daily continuously. The plasma were analyzed by high-performance liquid chromatography combined with time-of-flight masss pectrometry (HPLC/ESI-TOF-MS), significant different metabolites were investigated to explain its therapeutic mechanism. Furthermore, quantitative real time polymerase chain reaction (RT-PCR) analysis was performed to detect the expression of RNA in stomach tissue for verifying the above results.ResultsLicoflavone can effectively cure the gastric ulcer, particularly the middle dose group. According to the statistical analysis of the plasma different metabolites from each groups and the expression of genes in tissues, sixteen significant different metabolites, including histamine, tryptophan, arachidonic acid, phingosine-1-phosphate etc., contributing to the treatment of gastric ulcer were discovered and identified. In RT-PCR analysis, the results of the expression of RNA were corresponded with what we discovered.ConclusionsOur study indicated licoflavone plays the role of treating gastric ulcer by regulating inflammation mediators and amino acid metabolism. We demonstrated that metabolomics technology combined with gene technology is a useful tool to search different metabolites and to dissect the potential mechanisms of traditional Chinese medicine (TCM) in treating gastric ulcer.
Graphical abstract
http://ift.tt/2jX59tX
Laparoscopic sleeve gastrectomy: Everything the radiologist needs to know
Publication date: Available online 31 January 2017
Source:Clinical Imaging
Author(s): Tulay Ekinci, Marjorie W. Stein, Fernanda S. Mazzariol, Ellen L. Wolf
Obesity has become an epidemic in the United States, and bariatric surgery is being increasingly performed for its management. There has been an increased number of laparoscopic sleeve gastrectomies performed for the treatment of morbid obesity due to its efficacy and lower complication rate compared to other bariatric surgical techniques. The authors discuss the surgical technique, review the imaging of normal and complicated sleeve gastrectomy, and highlight radiographic pitfalls.
http://ift.tt/2kgBJFz
IMMUNOEXPRESSION OF GADD45β IN THE MYOCARDIUM OF NEWBORNS EXPERIENCING PERINATAL HYPOXIA
Publication date: Available online 31 January 2017
Source:Pathology - Research and Practice
Author(s): Mona Adalgisa Simões, Francisco Cesar Pabis, Ana Karyn Ehrenfried de Freitas, Marina Luise Viola de Azevedo, Daiane Cristine Martins Ronchi, Lucia de Noronha
AimAmong the several organs affected by perinatal hypoxia, the heart plays a central role, with cell death caused mainly by apoptosis. One of the biomarkers most often linked to hypoxia-derived apoptosis of cardiomyocytes in animals is Gadd45β. From the published literature, Gadd45β is proposed as a biomarker of hypoxia-induced lesion in cardiomyocytes, both in vitro, as well as in animal models. Our study suggests that this protein can be used as an early biomarker of cell damage in neonate's cardiomyocytes (humans specimens), a process that can ultimately lead to apoptosis. The aim is to determine levels of tissue immunoexpression of the Gadd45β biomarker in myocardium samples of newborns affected by hypoxia, and to correlate these results with clinical and anatomopathologic data.MethodsMyocardium samples from the left ventricle of newborns were used. The samples were collected from 78 autopsies performed in neonates of both genders, with hypoxia (Apgar score at five minutes below 6 and/or pH below 7.2 and/or autopsy with anatomopathological signs of hypoxia), who had died within the first day of life. All samples were organized in Tissue Microarray. Immunohistochemistry analysis, using anti-Gadd45β as the primary antibody, was performed on 3 multi-sample histological slides. There was no correlation between Gadd45β tissue immunoexpression and neonatal weight (p=0.93), gestational age (p=0.16), Apgar score at first minute (p=0.914), Apgar score at five minutes (p=0.988) and arterial blood pH (p=0.542). There was a relation between Gadd45β tissue immunoexpression and survival (p=0.02). The maximum peak of Gadd45β tissue immunoexpression was 8.43% HPF (high power field) and was observed around of six hours of life.ConclusionGadd45β could be a suitable biomarker of cardiomyocytes apoptosis in newborns experiencing hypoxia in the first day of life, as its highest tissue immunoexpression around at the first six hours after birth.
http://ift.tt/2jCQWis
Clinicopathological and molecular features of a large cohort of gastrointestinal stromal tumors (GISTs) and review of the literature: BRAF mutations in KIT/PDGFRA wildtype GISTs are rare events
Publication date: Available online 1 February 2017
Source:Human Pathology
Author(s): Sebastian Huss, Hlen Pasternack, Michaela Angelika Ihle, Sabine Merkelbach-Bruse, Birthe Heitkötter, Wolfgang Hartmann, Marcel Trautmann, Heidrun Gevensleben, Reinhard Büttner, Hans-Ulrich Schildhaus, Eva Wardelmann
In KIT/PDGFRA wild-type gastrointestinal stromal tumors (wt-GISTs), BRAF mutations are regarded as alternative pathogenic event driving tumorigenesis. In our study, we aimed at analyzing a large cohort (n=444) of GISTs for BRAF mutations using molecular and immunohistochemical methods. More than 3000 GIST samples from caucasian patients were available in our GIST and Sarcoma Registry NRW. Of these, we selected 172 wt-GISTs to evaluate the frequency of BRAF mutations. Furthermore, 272 GISTs with a representative KIT and PDGFRA mutational status were selected. BRAF mutational status was evaluated by high resolution melting analysis, Sanger sequencing, and VE1-immunohistochemistry. A BRAF mutation (p.V600E) was found in 7 cases (3.9%) of the wt-GIST cohort. In two cases multiple synchronous tumors harbored the same somatic BRAF mutation. VE1 immunohistochemical staining had a sensitivity of 81.8% and a specificity of 97.5% to detect BRAF p.V600E mutations. Analyzing our cases and the cases reported in the literature (n=37), the percentage of intermediate and high risk BRAF-mutated wt-GISTs (17/31; 54.8%) was comparable to that recorded for large GIST cohorts irrespective of the mutational status. BRAF mutations are rare events in wt-GISTs, and VE1 immunohistochemistry appears to be a valuable pre-screening tool for the detection of BRAF p.V600E mutations. BRAF mutations in GISTs do not seem to have a prognostic value per se. However, as BRAF inhibition represents a therapeutic option to control disease, we suggest the assessment of the BRAF mutational status, especially in the setting of advanced GIST disease.
http://ift.tt/2jWM22Z
Transforming Growth Factor-β- and Interleukin-13-Producing Mast Cells Are Associated with Fibrosis in Bone Marrow
Publication date: Available online 31 January 2017
Source:Human Pathology
Author(s): Shoko Nakayama, Taiji Yokote, Nobuya Hiraoka, Toshikazu Akioka, Uta Nishiwaki, Takuji Miyoshi, Kazuki Iwaki, Ayami Fumimoto, Yuki Masuda, Jun Hatooka, Mayumi Fujimoto, Yasuichiro Nishimura, Motomu Tsuji
Although bone marrow fibrosis is a lethal condition, its underlying mechanism is not fully understood. This study aimed to investigate the pathogenesis of fibrosis in the bone marrow through histological examination of mast cell infiltration and the expression of fibrosis-associated cytokines. We analyzed 22 bone marrows with fibrosis [eight primary myelofibrosis (PMF), five post-essential thrombocythemia (ET) myelofibrosis (MF), and nine myelodysplastic syndrome (MDS) with bone marrow fibrosis (BMF)]. Immunohistochemical and immunofluorescence staining were performed using anti-mast cell tryptase, interleukin (IL)-13, transforming growth factor-beta (TGF-β), CD34, and CD42b antibodies. The number of mast cells in bone marrows with fibrosis was significantly higher than that in controls (P<.0001 for all cases with fibrosis vs control, P=.0470 for PMF vs control, P<.0001 post- ET MF vs control, and P=.0005 for MDS with BMF vs control). Moreover, bone marrows with higher fibrotic grades exhibited greater amounts of infiltrating mast cells. Mast cells were positive for TGF-β and IL-13 in bone marrows with fibrosis of all three groups. Megakaryocytes were negative for TGF-β in post-ET and MDS with BMF, but some megakaryocytes in PMF were weakly positive for TGF-β. Megakaryocytes were negative for IL-13 in all three groups. Blasts were negative for both TGF-β and IL-13 in all three groups. Thus, TGF-β- and IL-13-producing mast cells might be key players in the development of bone marrow fibrosis. Therefore, mast cells could be potential therapeutic targets for the treatment of bone marrow fibrosis.
http://ift.tt/2kV3PFM
Transformation of prostatic adenocarcinoma to well differentiated neuroendocrine tumor after hormonal treatment
Publication date: Available online 31 January 2017
Source:Human Pathology
Author(s): Syed Gilani, Charles C. Guo, Elsa M Li-Ning, Curtis Pettaway, Patricia Troncoso
Carcinoid tumor of the prostate is extremely rare. Here we report a unique case of prostate cancer that underwent complete transformation from conventional adenocarcinoma to carcinoid-like tumor shortly after androgen deprivation treatment (ADT). The patient was a 59years old man who presented with lower urinary tract symptoms. His biopsy specimen demonstrated a high-grade prostatic adenocarcinoma with mixed acinar and ductal features. After ADT for 6months, the patient underwent radical prostatectomy. The post-ADT tumor showed monotonous neoplastic cells with fine granular chromatin forming rosette-like structures, resembling a carcinoid tumor. No residual conventional adenocarcinoma was present. On immunostain, the tumor cells were diffusely positive for synaptophysin and chromogranin and negative for prostate specific antigen (PSA) and prostein. Thus the carcinoid-like tumor represented complete transformation from prostatic adenocarcinoma to well differentiated neuroendocrine tumor after ADT. This unique case highlights the important role of ADT in neuroendocrine differentiation of prostate cancer.
http://ift.tt/2jWZsMz
The nerve: A fragile balance between physiology and pathophysiology
Regarding nerves as simple cables and electrical conduits is a gross error that does not allow us to understand the anomalies and disorders observed postoperatively. Instead, nerves should be seen as a living tissue of which physiological regulation is as complex as that of the blood–brain barrier. This review describes the basic structure and functions of this blood–nerve barrier and highlights the mechanisms of its breakdown and the resultant disorders. For clinical practice, it is important to note that the diffusion of molecules from the perineurium or from the blood is very limited, and so the blood–nerve barrier is a major pharmacologic barrier. Any stress upon neural physiological balance, particularly the terminal vascular blood supply, will induce the classic inflammatory cascade. Due to the complexity of the vascular system, nerve ischaemia will occur more quickly when the terminal blood supply is compromised. This blood supply can adapt in a variety of ways but when these possibilities of adaptation are exceeded, tissue ischaemia may be more extensive. Also, even after the initial injury has subsided, inflammation can cause a secondary insult. This could be particularly important in some patients with subclinical neuropathy.http://ift.tt/2kR0tnH
Smartphone-based behavioural intervention alleviates children's anxiety during anaesthesia induction: A randomised controlled trial
BACKGROUND: Preoperative anxiety negatively influences children's anaesthetic and surgical experience, and results in postoperative complications, such as emergence delirium and behavioural changes. Nonpharmacological management using alternative therapies that alleviate psychological stress can be as important as pharmacological ones in reducing children's anxiety. Nevertheless, their validity as an effective anxiety-reducing strategy in children remains controversial. OBJECTIVE(S): To verify whether nonpharmacological strategies, that is, leaflet and distraction with smartphone application presented to parents/guardians and children, respectively, were effective in preventing children's anxiety during anaesthesia induction. DESIGN: Randomised clinical trial. SETTING: A tertiary care teaching hospital. PATIENTS: In total, 84 children (aged 4 to 8 years; American Society of Anesthesiologists I and II) undergoing minor-to-moderate elective surgical procedures and their parents/guardians. INTERVENTIONS: Children were randomised into four groups: control group, in which the parent/guardian was verbally informed about the anaesthetic procedure; the informed group, in which the parent/guardian was also provided with an information leaflet about the anaesthetic procedure; the smartphone group, in which the parent/guardian was verbally informed and the child received a smartphone application to play with while in the holding area before entering the operating room and the smartphone and informed group, in which the parent/guardian also received an information leaflet and the child, a smartphone application to play with while in the holding area before entering the operating room. MAIN OUTCOME MEASURES: Children's anxiety at two time points: in the holding area of the surgical centre and in the operating room during induction of anaesthesia by facemask. RESULTS: Median (IQR) anxiety levels were greater at time point operating room for children in the control group (55.0; range: 30.0 to 68.4) than in the other groups: informed group, 28.4 (23.4 to 45.0); smartphone group, 23.4 (23.4 to 30.0); smartphone and informed group, 23.4 (23.4 to 25.9). CONCLUSION: The behavioural distraction strategies using smartphones were effective in preventing an increase in children's anxiety during anaesthesia induction. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02246062.http://ift.tt/2kQXmw8
Double-injection technique assisted by a nerve stimulator for ultrasound-guided supraclavicular brachial plexus block results in better distal sensory–motor block: A randomised controlled trial
BACKGROUND: To evaluate the efficacy of a nerve stimulator when used with ultrasound-guided double injection in supraclavicular brachial plexus block. OBJECTIVES: We hypothesised that targeting the inferior trunk of the plexus guided by a nerve stimulator would obtain a higher success rate of ulnar nerve blockade than the traditional double-injection technique. DESIGN: A blinded randomised controlled study. SETTING: Conducted at the University Hospital from October 2015 to January 2016. PATIENTS: Ninety patients undergoing upper extremity surgery were randomised into two equal groups. INTERVENTIONS: Patients were randomly allocated to a modified double-injection group (MDI group) or a traditional double-injection group (DI group). All patients received 23 ml of a 1 : 1 mixture of 2% lidocaine and 1% ropivacaine during ultrasound-guided supraclavicular brachial plexus block. In the MDI group (n = 45), half the volume was deposited within the brachial plexus sheath guided by ultrasound, next to the inferior trunk and verified by nerve stimulation; the remaining volume was deposited in the main neural cluster. In the double-injection group (n = 45), the first half volume was deposited on ultrasound guidance alone. Sensory–motor blockade of the musculocutaneous, median, radial, ulnar nerves and surgical anaesthesia, performance time, number of needle passes and complications were recorded. MAIN OUTCOME MEASURES: The success rate of complete sensory block of the ulnar nerve within 15 min after local anaesthetic injection. RESULTS: Compared with the DI group the MDI group had higher success rates of complete sensory block of the ulnar nerve (93 vs 67%, P = 0.002) and complete anaesthesia (80 vs 56%, P = 0.014) at 15 min, whereas the average performance time was significantly longer (5.08 ± 1.41 vs 4.10 ± 0.64 min, P http://ift.tt/2kQYjEV
Novel needle guide reduces time to perform ultrasound-guided femoral nerve catheter placement: A randomised controlled trial
BACKGROUND: Ultrasound-guided nerve blocks have become the standard when performing regional nerve blocks in anaesthesia. Infiniti Plus (CIVCO Medical Solutions, Kalona, Iowa, USA) is a needle guide that has been recently developed to help clinicians in performing ultrasound-guided nerve blocks. OBJECTIVES: We tested the hypothesis that femoral nerve catheter placement carried out with the Infiniti Plus needle guide will be quicker to perform than without the Infiniti Plus. Secondary aims were to assess whether the Infiniti Plus needle guide decreased the number of block attempts and also whether it improved needle visibility. DESIGN: A randomised, controlled trial. SETTING: Cleveland Clinic, Cleveland, Ohio, USA. PATIENTS: We enrolled adult patients having elective total knee arthroplasty with a femoral nerve block and femoral nerve catheter. Patients, who were pregnant or those who had preexisting neuropathy involving the surgical limb, coagulopathy, infection at the block site or allergy to local anaesthetics were excluded. INTERVENTIONS: Patients were randomised into two groups to receive the ultrasound-guided femoral nerve catheter placement with or without the Infiniti Plus needle guide. MAIN OUTCOME MEASURES: The time taken to place the femoral nerve catheter, the number of attempts, the success rate and needle visibility were recorded. We used an overall α of 0.05 for both the primary and secondary analyses; the secondary analyses were Bonferroni corrected to control for multiple comparisons. RESULT: The median (interquartile range Q1 to Q3) time to perform the femoral nerve catheter placement was 118 (100 to 150) s with Infiniti Plus and 177 (130 to 236) s without Infiniti Plus. Infiniti Plus significantly reduced the time spent performing femoral nerve catheterisation, with estimated ratio of means [(95% confidence interval), P value] of 0.67 [(0.60 to 0.75), P http://ift.tt/2jUOrZG
The effect of prior tetanic stimulation on train-of-four monitoring in paediatric patients: A randomised open-label controlled trial
BACKGROUND: In clinical research, neuromuscular monitoring must present a stable response for a period of 2 to 5 min before administration of a neuromuscular blocking agent. The time required to reach this stable response may be shortened by applying a 5-s tetanic stimulus. OBJECTIVES: The aim of this study was to test whether tetanic stimulation interferes with onset and recovery times after a single dose of rocuronium 0.6 mg kg−1 followed by spontaneous recovery. DESIGN: A randomised, open-label, controlled trial. SETTING: A single-centre trial, study period from January 2014 to July 2015. PATIENTS: Fifty children aged 2 to 11 years scheduled for elective paediatric surgery. INTERVENTION: Patients were randomly allocated to receive either tetanic stimulation (group T) or not (group C) before calibration of the neuromuscular monitor. MAIN OUTCOME MEASURES: Onset and recovery times. Initial and final T1 height, time to obtain initial T1 height stability and monitor settings were also analysed. RESULTS: There was no significant difference in mean onset time [(C: 57.5 (± 16.9) vs. T: 58.3 (± 31.2) s; P = 0.917]. Mean times to normalised train-of-four (TOF) ratios of 0.7, 0.8 and 0.9 were significantly shorter in the tetanic stimulation group [C: 40.1 (±7.9) vs. T: 34.8 (±10) min; P = 0.047, C: 43.8 (±9.4) vs. T: 37.4 (±11) min; P = 0.045 and C: 49.9 (±12.2) vs. T: 41.7 (±13.1) min; P = 0.026, respectively]. The mean time required for T1 height stabilisation was similar in the two groups [C: 195.0 (± 203.0) vs. T: 116.0 (± 81.6) s; P = 0.093], but the initial and final T1 height values were significantly lower in the tetanic stimulation group (C: 98.0 vs. T: 82.7%; P http://ift.tt/2jWzVDp
Moderate hyperoxia induces inflammation, apoptosis and necrosis in human umbilical vein endothelial cells: An in-vitro study
BACKGROUND: Perioperative oxygen (O2) therapy can cause hyperoxia. Extreme hyperoxia can injure the cardiovascular system and remote organs. OBJECTIVE: Our primary objective was to test the hypothesis that exposure to moderate hyperoxia will induce injury to human umbilical vein endothelial cells (HUVECs), a model for studying the vascular endothelium under controlled conditions. DESIGN: In-vitro cell culture study. SETTING: Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Austria. Study period from the beginning of October 2013 to the end of July 2014. CELLS: HUVECs were isolated from fresh umbilical cords. INTERVENTIONS: HUVECs were exposed to constant hyperoxia (40% O2), cyclic hyperoxia/anoxia (40%/0% O2, average 20% O2), constant normoxia (21% O2) and constant anoxia (0% O2) using a cell culture bioreactor. MAIN OUTCOME MEASURES: Cell growth, viability and release of IL-6, IL-8 and macrophage migration inhibitory factor were assessed at baseline and after 6, 12, 24 and 48 h of treatment. A phosphokinase array was performed after 60 min of treatment to identify activated cellular signalling pathways. RESULTS: Constant hyperoxia and cyclic hyperoxia/anoxia impeded cell growth, reduced viability, triggered a proinflammatory response, proven by IL-6, IL-8 and migration inhibitory factor release, and induced apoptosis and necrosis. The inflammatory and cytotoxicity responses were highest in the constant hyperoxia group. Phosphokinase arrays revealed that different O2 concentrations activated distinct sets of cytoprotective and cell death–associated kinases, including mitogen-activated protein kinases, Src kinases, p53, Akt, mitogen-activated and stress-activated kinase, Lyn, Lck, p70S6, signal transducers and activators of transcription 5b and 6, glycogen synthase kinase 3a/b and 5′ AMP-activated protein kinases 1/2. CONCLUSION: Continuous moderate hyperoxia and cyclic moderate hyperoxia/anoxia-induced endothelial inflammation, apoptosis and necrosis. Given the large surface area of the vascular endothelium, moderately elevated O2 levels may contribute to cardiovascular inflammation and injury. TRIAL REGISTRATION: This in-vitro study was not registered in a database.http://ift.tt/2jWzPM3
Anaesthesia and orphan disease: Rapid sequence induction in systemic mastocytosis
No abstract availablehttp://ift.tt/2jWtJeh
Determination of a cut-off value of antral area measured in the supine position for the fast diagnosis of an empty stomach in the parturient: A prospective cohort study
BACKGROUND: Ultrasound measurement of the antral cross-sectional area of the stomach, performed in the supine position, has been described for preoperative assessment of gastric content in the adult, but, to date, no study has determined the cut-off value of the antral area for the diagnosis of an empty stomach in the parturient. Nevertheless, previous studies in parturients have reported that the use of a simple qualitative grading scale (0 to 2) was reliable for the estimation of the gastric fluid volume. However, this qualitative grading score requires turning the parturient into the right lateral decubitus position for the ultrasound examination, something which may not be easily feasible, particularly in the case of an obstetric emergency. OBJECTIVE: To calculate the cut-off value of the antral area, measured in the supine position during established labour, for the diagnosis of 'empty' stomach. DESIGN: A prospective cohort study. SETTING: Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Lyon, France. PATIENTS: Seventy-three women in established labour. INTERVENTIONS: For each parturient, ultrasound assessment of gastric contents was performed in the supine and right lateral decubitus position and scored 0 to 3 on a qualitative grading scale. This assessment was followed by ultrasound measurement of the antral cross-sectional area in both the supine and right lateral positions. MAIN OUTCOME MEASURES: To assess the performance of the antral area measured in the supine position for the diagnosis of an 'empty' stomach (gastric antrum grade 0), a receiver operating characteristic curve was plotted, and the area under the receiver operating characteristic curve was calculated. RESULTS: Data from 73 women were analysed. For the diagnosis of grade 0, the cut-off value for the antral area measured in the supine position was 381 mm2 (sensitivity, 81%; specificity, 76% and negative predictive value, 80%). CONCLUSION: With a parturient lying in the supine position, a single assessment of the antral cross-sectional area may be used for the fast diagnosis of an empty stomach. This tool could be useful in assessing the risk of aspiration for parturients who require emergency anaesthesia during labour.http://ift.tt/2jWzYiv
Anaesthesia and orphan diseases: Airway management in Proteus disease
No abstract availablehttp://ift.tt/2jWzuc0
A survey of the dose of inhalational agents used to maintain anaesthesia in infants
BACKGROUND: Various animal studies suggest that currently used anaesthetics are toxic to the developing brain. Many reviews advise that the total anaesthetic drug exposure should be reduced but the dose usually used in clinical practice has not been clearly elucidated. OBJECTIVES: To provide an overview of the dose ranges currently used in clinical practice during the maintenance phase of anaesthesia in infants undergoing anaesthesia for noncardiac surgery and diagnostic procedures. DESIGN: A two-centre mixed prospective (London) and retrospective (Utrecht) observational cohort study. SETTING: Two independent tertiary paediatric referral centres in March and November 2013; Great Ormond Street Hospital (GOSH), London, United Kingdom and Wilhelmina Children's Hospital, University Medical Center Utrecht (UMCU), The Netherlands. PATIENTS: A total of 76 infants were included in the analysis, 38 infants from each hospital. METHODS: Patients from GOSH were matched by procedure, age and weight with patients from the UMCU. The end-tidal concentrations of the inhalational agents were investigated from anaesthetic charts during the maintenance phase and corrected for the age-specific minimal alveolar concentration (MAC), expressed as a percentage from the MAC (%MAC). RESULTS: Three different types of inhalational anaesthetics were used: sevoflurane, desflurane, isoflurane. The mean %MAC was 0.85. No significant differences in %MAC were found between GOSH and the UMCU (P = 0.329); the mean %MAC in GOSH was 0.87 and in the UMCU was 0.82. There was a significant increase in the %MAC in relation to age (slope = 0.036 MAC month−1, P http://ift.tt/2jWBBwF
Bordetella pertussis infection in children with severe pneumonia, Philippines, 2012–2015
Source:Vaccine, Volume 35, Issue 7
Author(s): Alexander Sadiasa, Mariko Saito-Obata, Clyde Dapat
A case-comparison study was conducted based on an observational study of severe pneumonia among hospitalized children in the Philippines. The children, from 8days to 13years old and hospitalized with clinical diagnosis of severe or very severe pneumonia from August 2012 to February 2015, were recruited. Nasopharyngeal swabs were collected from 1152 cases and B. pertussis were detected from 34 cases by PCR. Pertussis-positive cases were more likely to have no fever, more than one week of coughing and breathing difficulty, decreased breathing sounds, and central cyanosis than pertussis- negative cases. The percentage of underweight was significantly higher in pertussis-positive cases than pertussis-negative cases. Pertussis-positive cases showed remarkably higher fatality rate than pertussis-negative cases. All of the fatal cases among pertussis-positive cases were less than 6months old. More attention should be given to protect young infants from pertussis.
http://ift.tt/2kqxRnV
Impact of universal infant hepatitis B vaccination in the US-affiliated Pacific Islands, 1985–2015
Source:Vaccine, Volume 35, Issue 7
Author(s): W.E. Abara, M.G. Collier, E.H. Teshale
The US-affiliated Pacific Island countries (USAPI) is an endemic region for hepatitis B virus (HBV) infection. Universal infant hepatitis B vaccination was introduced in the USAPI in the mid-1980s to mitigate the HBV burden. We assessed the impact of universal infant vaccination on the HBV infection prevalence over time among children born in the 1980s, 1990s, and 2000s in the USAPI. Demographic and serologic data from serial sero-surveys conducted between 1985 and 2015 were obtained. Descriptive statistics and analysis of variance were performed. From data obtained from 4827 children (2–11years), HBV prevalence decreased markedly: 8.4% in the 1980s; 2.5% in the 1990s; and 0.2% in the 2000s (P<0.0001) as vaccination coverage increased: 76.4% in the 1980s; 87.3% in the 1990s; and 97.5% in the 2000s (P<0.0001). These findings underscore the protective effect of universal infant hepatitis B vaccination over time on the HBV burden in an HBV endemic region.
http://ift.tt/2jCnkSm
Consecutive inoculations of influenza virus vaccine and poly(I:C) protects mice against homologous and heterologous virus challenge
Publication date: 15 February 2017
Source:Vaccine, Volume 35, Issue 7
Author(s): Miyu Moriyama, Shota Chino, Takeshi Ichinohe
Mucosal immunity induced through natural infection by influenza virus has potent cross-protective activity, compared to subcutaneous vaccination-induced systemic immunity. Compared to natural infection with influenza virus, however, a single intranasal vaccination with an inactivated influenza virus vaccine and poly(I:C) is not sufficient to induce primary immune response in naïve animals. The reasons for this moderate effect are not fully understood. Here, we demonstrated that intranasal vaccination with formalin-inactivated influenza virus vaccine and poly(I:C) for five consecutive days elicits high levels of virus-specific nasal IgA and serum IgG responses, while vaccination without poly(I:C) induced little response. Mice immunized with influenza virus vaccine and poly(I:C) for five consecutive days sustained high levels of virus-specific IgA in nasal wash and IgG in serum until at least 6months after vaccination. Furthermore, intranasal vaccination with influenza virus vaccine and poly(I:C) protected mice against homologous and heterologous influenza virus challenge. These results suggest that consecutive inoculations of influenza virus vaccine and poly(I:C) is an alternative method to induce primary immune responses in naïve subjects.
http://ift.tt/2kqpTLJ
Potential risk of repeated nasal vaccination that induces allergic reaction with mucosal IgE and airway eosinophilic infiltration in cynomolgus macaques infected with H5N1 highly pathogenic avian influenza virus
Publication date: 15 February 2017
Source:Vaccine, Volume 35, Issue 7
Author(s): Misako Nakayama, Yasushi Itoh, Shintaro Shichinohe, Rumi Nakabayashi, Hirohito Ishigaki, Yoshihiro Sakoda, Quynh Mai Le, Yoshihiro Kawaoka, Hiroshi Kida, Kazumasa Ogasawara
The efficacy and detrimental effect of mucosal vaccination with an inactivated influenza vaccine were examined in a macaque model by intranasal administration with small amounts of inactivated whole virus particles and challenge by a human-derived H5N1 highly pathogenic avian influenza virus infection. Repeated nasal inoculation with the whole particle vaccine of an inactivated virus, A/duck/Hokkaido/Vac-3/2007 (H5N1) (Vac-3), induced antigen-specific IgA and IgG antibody production in nasal swabs and plasma. Vac-3-specific IgE production was also found in the nasal swabs. Nasal vaccination with Vac-3 induced broader cross-clade neutralization activity than did subcutaneous vaccination. After challenge infection, repeated nasal vaccination almost completely prevented the propagation of virus in the upper and lower airways and protected cynomolgus macaques from viral pneumonia by induction of IgA-producing B cells in the lungs. On the other hand, eosinophil clusters were observed in the lungs of vaccinated macaques. Although Vac-3-specific IgE antibody and IL-13 levels were decreased after infection compared to those before infection and no anaphylaxis in vaccinated macaques was detected after challenge infection, our results suggest that we have to pay attention to potential allergic responses at repeated nasal vaccination, especially in people who have an airway allergy.
http://ift.tt/2jCFBix
Editorial Board/Aims and Scope
Source:Vaccine, Volume 35, Issue 7
http://ift.tt/2kqh8Bf
Interpreting the transmissibility of measles in two different post periods of supplementary immunization activities in Hubei, China
Publication date: 15 February 2017
Source:Vaccine, Volume 35, Issue 7
Author(s): Ka Chun Chong, Chi Zhang, Benny Chung Ying Zee, Tongyong Luo, Lei Wang, Greta Chun Huen Tam, Katherine Min Jia, Riyang Sun, Maggie Haitian Wang, Xuhua Guan
Although evidence has shown that supplementary immunization activity (SIA) campaigns greatly reduce the incidence of measles, their effects on disease transmissibility have seldom been monitored. A great decrease in the number of cases may be a false signal of early success towards measles elimination to policy makers. By interpreting the transmissibility in two different post-SIA periods in Hubei, China, the current study showed sustained measles transmissions despite a reduced number of cases. Two population-based cross-sectional serological surveys of measles antibodies were conducted in Hubei province in mid-2010 and mid-2011 after the implementation of SIAs. Immunoglobulin G (IgG) antibodies against measles were measured by enzyme-linked immunosorbent assay (ELISA). Based on the estimated age-specific susceptibility levels, the effective reproduction number (R), a key indicator of disease transmissibility, was determined by the next generation matrix in transmission model. The results revealed an overall IgG seroprevalence of 88.0% (95% confidence interval [CI]: 85.6–90.4%) and 89.6% (95%CI: 88.0–91.2%), respectively, in the two different periods. Comparatively lower seroprevalence rates were observed among children less than 24months of age and young adults 15 to 19years of age in 2011. The Rs were 0.76 and 1.53 for the two study periods. In conclusion, even though the incidence was reduced to below 1/100,000 in both 2010 and 2011, the reproduction number in 2011 indicates a high risk for sustained measles transmission. This finding was potentially due to a lower seropositivity rate among young adults that had not been covered in the first SIA. Thus, implementation of SIA targeted to appropriate age groups is recommended. Regular monitoring of seroprevalence is also suggested to track disease transmissibility and to align SIA with the appropriate age groups.
http://ift.tt/2jCyPZM
Adjuvant-active aqueous extracts from Artemisia rupestris L. improve immune responses through TLR4 signaling pathway
Publication date: 15 February 2017
Source:Vaccine, Volume 35, Issue 7
Author(s): Ailian Zhang, Yu Yang, Yan Wang, Gan Zhao, Xiumei Yang, Danyang Wang, Bin Wang
Activating innate immunity by an adjuvant is required in vaccine development. The study aims to investigate adjuvant effects of aqueous extracts of Artemisia rupestris L. (AEAR) in vivo and in vitro. ICR mice were subcutaneously administered with antigen and AEAR at various doses to evaluate their immune responses of antibodies, dendritic cells (DCs), regulatory T cells (Treg), splenic lymphocyte, and cytokine. The evaluation results showed that AEAR could largely increase titers of antigen-specific antibodies (IgG, IgG1, and IgG2a) and T cell proliferation. AEAR also increased expression of IFN-γ in CD8+T cells as well as IL-4 and INF-γ expression in CD4+T cells. Expression levels of MHC-II, CD40, CD80, and CD86 on DCs were significantly elevated, whereas the Treg frequency was significantly decreased. AEAR (200μg) showed remarkable adjuvant activity. Furthermore, AEAR enhanced MHC-II, CD40, CD80, and CD86 expression as well as the yields of TNF-α and IL-12 on DCs through toll-like receptor4 (TLR4) in vitro. Those results indicated that AEAR could serve as an efficacious immune stimulator for vaccines because it significantly enhanced specific immune responses by promoting DCs maturation and reduced Treg through TLR4 signaling pathway.
http://ift.tt/2kqgHaf
Evaluation of reproductive protection against bovine viral diarrhea virus and bovine herpesvirus-1 afforded by annual revaccination with modified-live viral or combination modified-live/killed viral vaccines after primary vaccination with modified-live viral vaccine
Publication date: 15 February 2017
Source:Vaccine, Volume 35, Issue 7
Author(s): Paul H. Walz, M. Daniel Givens, Soren P. Rodning, Kay P. Riddell, Bruce W. Brodersen, Daniel Scruggs, Thomas Short, Dale Grotelueschen
The objective of this study was to compare reproductive protection in cattle against bovine viral diarrhea virus (BVDV) and bovine herpesvirus 1 (BoHV-1) provided by annual revaccination with multivalent modified-live viral (MLV) vaccine or multivalent combination viral (CV) vaccine containing temperature-sensitive modified-live BoHV-1 and killed BVDV when MLV vaccines were given pre-breeding to nulliparous heifers. Seventy-five beef heifers were allocated into treatment groups A (n=30; two MLV doses pre-breeding, annual revaccination with MLV vaccine), B (n=30; two MLV doses pre-breeding, annual revaccination with CV vaccine) and C (n=15; saline in lieu of vaccine). Heifers were administered treatments on days 0 (weaning), 183 (pre-breeding), 366 (first gestation), and 738 (second gestation). After first calving, primiparous cows were bred, with pregnancy assessment on day 715. At that time, 24 group A heifers (23 pregnancies), 23 group B heifers (22 pregnancies), and 15 group C heifers (15 pregnancies) were commingled with six persistently infected (PI) cattle for 16days. Ninety-nine days after PI removal, cows were intravenously inoculated with BoHV-1. All fetuses and live offspring were assessed for BVDV and BoHV-1. Abortions occurred in 3/23 group A cows, 1/22 group B cows, and 11/15 group C cows. Fetal infection with BVDV or BoHV-1 occurred in 4/23 group A offspring, 0/22 group B offspring, and 15/15 group C offspring. This research demonstrates efficacy of administering two pre-breeding doses of MLV vaccine with annual revaccination using CV vaccine to prevent fetal loss due to exposure to BVDV and BoHV-1.
http://ift.tt/2jCBPpe
Cost-effectiveness of 13-valent pneumococcal conjugate vaccination in Mongolia
Source:Vaccine, Volume 35, Issue 7
Author(s): Neisha Sundaram, Cynthia Chen, Joanne Yoong, Munkh-Erdene Luvsan, Kimberley Fox, Amarzaya Sarankhuu, Sophie La Vincente, Mark Jit
ObjectiveThe Ministry of Health (MOH), Mongolia, is considering introducing 13-valent pneumococcal conjugate vaccine (PCV13) in its national immunization programme to prevent the burden of disease caused by Streptococcus pneumoniae. This study evaluates the cost-effectiveness and budget impact of introducing PCV13 compared to no PCV vaccination in Mongolia.MethodsThe incremental cost-effectiveness ratio (ICER) of introducing PCV13 compared to no PCV vaccination was assessed using an age-stratified static multiple cohort model. The risk of various clinical presentations of pneumococcal disease (meningitis, pneumonia, non-meningitis non-pneumonia invasive pneumococcal disease and acute otitis media) at all ages for thirty birth cohorts was assessed. The analysis considered both health system and societal perspectives. A 3+0 vaccine schedule and price of US$3.30 per dose was assumed for the baseline scenario based on Gavi, the Vaccine Alliance's advance market commitment tail price.ResultsThe ICER of PCV13 introduction is estimated at US$52 per disability-adjusted life year (DALY) averted (health system perspective), and cost-saving (societal perspective). Although indirect effects of PCV have been well-documented, a conservative scenario that does not consider indirect effects estimated PCV13 introduction to cost US$79 per DALY averted (health system perspective), and US$19 per DALY averted (societal perspective). Vaccination with PCV13 is expected to cost around US$920,000 in 2016, and thereafter US$820,000 every year. The programme is likely to reduce direct disease-related costs to MOH by US$440,000 in the first year, increasing to US$510,000 by 2025.ConclusionIntroducing PCV13 as part of Mongolia's national programme appears to be highly cost-effective when compared to no vaccination and cost-saving from a societal perspective at vaccine purchase prices offered through Gavi. Notwithstanding uncertainties around some parameters, cost-effectiveness of PCV introduction for Mongolia remains robust over a range of conservative scenarios. Availability of high-quality national data would improve future economic analyses for vaccine introduction.
http://ift.tt/2kqmix4
The effect of gamma-irradiation conditions on the immunogenicity of whole-inactivated Influenza A virus vaccine
Source:Vaccine, Volume 35, Issue 7
Author(s): Shannon C. David, Josyane Lau, Eve V. Singleton, Rachelle Babb, Justin Davies, Timothy R. Hirst, Shaun R. McColl, James C. Paton, Mohammed Alsharifi
Gamma-irradiation, particularly an irradiation dose of 50kGy, has been utilised widely to sterilise highly pathogenic agents such as Ebola, Marburg Virus, and Avian Influenza H5N1. We have reported previously that intranasal vaccination with a gamma-irradiated Influenza A virus vaccine (γ-Flu) results in cross-protective immunity. Considering the possible inclusion of highly pathogenic Influenza strains in future clinical development of γ-Flu, an irradiation dose of 50kGy may be used to enhance vaccine safety beyond the internationally accepted Sterility Assurance Level (SAL). Thus, we investigated the effect of irradiation conditions, including high irradiation doses, on the immunogenicity of γ-Flu. Our data confirm that irradiation at low temperatures (using dry-ice) is associated with reduced damage to viral structure compared with irradiation at room temperature. In addition, a single intranasal vaccination with γ-Flu irradiated on dry-ice with either 25 or 50kGy induced seroconversion and provided complete protection against lethal Influenza A challenge. Considering that low temperature is expected to reduce the protein damage associated with exposure to high irradiation doses, we titrated the vaccine dose to verify the efficacy of 50kGy γ-Flu. Our data demonstrate that exposure to 50kGy on dry-ice is associated with limited effect on vaccine immunogenicity, apparent only when using very low vaccine doses. Overall, our data highlight the immunogenicity of influenza virus irradiated at 50kGy for induction of high titre antibody and cytotoxic T-cell responses. This suggests these conditions are suitable for development of γ-Flu vaccines based on highly pathogenic Influenza A viruses.
http://ift.tt/2jCN9l1
Personalized cancer vaccines: Targeting the cancer mutanome
Source:Vaccine, Volume 35, Issue 7
Author(s): Xiuli Zhang, Piyush K. Sharma, S. Peter Goedegebuure, William E. Gillanders
The development of next generation sequencing technologies has revolutionized our understanding of how specific genetic events contribute to cancer initiation and progression. Dramatic improvements in instrument design and efficiency, combined with significant cost reductions has permitted a systematic analysis of the mutational landscape in a variety of cancer types. At the same time, a detailed map of the cancer mutanome in individual cancers offers a unique opportunity to develop personalized cancer vaccine strategies targeting neoantigens. Recent studies in both preclinical models and human cancer patients demonstrate that neoantigens (1) are important targets following checkpoint inhibition therapy, (2) have been identified as the target of adoptive T cell therapies, and (3) can be successfully targeted with personalized vaccines. Taken together, these observations provide strong rationale for the clinical translation of personalized cancer vaccines.
http://ift.tt/2jUIuMh
Physiological basis behind ergogenic effects of anabolic androgens
Publication date: Available online 31 January 2017
Source:Molecular and Cellular Endocrinology
Author(s): Ada S. Cheung, Mathis Grossmann
Anabolic androgenic steroids (AAS) are widely abused by the sporting community. Demonstrating performance enhancing effects of AAS in rigorous scientific studies is fraught with difficulty. In controlled studies, AAS have consistently been reported to increase muscle mass and strength. The clinical evidence that these anabolic effects are independent of, and additive to exercise are supported by preclinical studies suggesting that AAS and exercise affect muscle by overlapping, yet distinct mechanisms. AAS may also improve performance by their actions on other organ systems, such as the vasculature, and the erythropoietic and central nervous system, although this evidence is less strong. While most of the actions of AAS are thought to be mediated via classical androgen receptor-mediated genomic signalling, AAS may also produce rapid effects via non-genomic mechanisms.
http://ift.tt/2kr3BZM
Radioactive artificial 137 Cs and natural 40 K activity in 21 edible mushrooms of the genus Boletus species from SW China
Abstract
This study, for the first time, presents the results of activity concentration determinations for 137Cs and 40K in a high number (21 species, 87 composite samples, and 807 fruiting bodies) of mushrooms of the genus Boletus from across Yunnan in 2011–2014 and Sichuan (Boletus tomentipes) using high-resolution high-purity germanium detector. Activity concentrations of 137Cs demonstrated some variability and range from <4.4 to 83 ± 3 Bq kg−1 dry biomass in caps and from <3.8 to 37 ± 3 Bq kg−1 dry biomass in stipes, and of 40K, respectively, from 420 ± 41 to 1300 ± 110 and from 520 ± 61 to 1300 ± 140 Bq kg−1 dry biomass. No significant variations were observed regarding 137Cs and 40K activity concentrations among the same Boletus species from different sampling sites. No activity concentrations from 134Cs were detected in any mushrooms. Internal dose rates estimated were from intake of 1 kg of mushrooms per annum for 137Cs range for species and regions from around <0.0031 to 0.047 ± 0.003 μSv, while those for 40K were from around 0.22 ± 0.04 to 1.2 ± 0.1 μSv. The overall intake of 137Cs was low since low contamination was found in Boletus species.
http://ift.tt/2kUDWG1
Airborne bacteria associated with corrosion of mild steel 1010 and aluminum alloy 1100
Abstract
A novel approach to measure the contribution of airborne bacteria on corrosion effects of mild steel (MS) and aluminum alloy (AA) as a function of their exposure period, and the atmospheric chemical composition was investigated at an urban industrial coastal site, Singapore. The 16S rRNA and phylogenetic analyses showed that Firmicutes are the predominant bacteria detected in AA and MS samples. The dominant bacterial groups identified were Bacillaceae, Staphylococcaceae, and Paenibacillaceae. The growth and proliferation of these bacteria could be due to the presence of humidity and chemical pollutants in the atmosphere, leading to corrosion. Weight loss showed stronger corrosion resistance of AA (1.37 mg/cm2) than MS (26.13 mg/cm2) over the exposure period of 150 days. The higher corrosion rate could be a result of simultaneous action of pollutants and bacterial exopolysaccharides on the metal surfaces. This study demonstrates the significant involvement of airborne bacteria on atmospheric corrosion of engineering materials.
http://ift.tt/2knZXQG
Assessment of Lemna minor (duckweed) and Corbicula fluminea (freshwater clam) as potential indicators of contaminated aquatic ecosystems: responses to presence of psychoactive drug mixtures
Abstract
The pharmaceutical products are emerging pollutants continuously released into the environment, because they cannot be effectively removed by the wastewater treatment plants. In recent years, questions have been raised concerning the environmental risks related to these pollutants. The goal of this research was to evaluate the responses in Lemna minor after 7 days and in Corbicula fluminea after differing durations (1, 3, 7, and 19 days) of exposure to the psychoactive drug mixture (valproic acid, citalopram, carbamazepine, cyamemazine, hydroxyzine, oxazepam, norfluoxetine, lorazepam, fluoxetine, and sertraline) in different concentrations (0, 0 + ethanol, drug concentration (DC) 1 = river water concentration, DC2 = effluent concentration, and DC3 = 10× effluent concentration). In this aim, growth parameters of L. minor, gluthathione S-transferase (GSTs), catalase (CAT), ethoxyresorufin-O-deethylase (EROD) and/or gene expressions (pi-gst, cat, cytochrome P450 4 (cyp4), multidrug resistant 1 (mdr1), and superoxide dismutase (sod)) were measured. GST activities increased significantly in L. minor exposed to DC3, but no changes were found in CAT activity. In C. fluminea, EROD activity was induced significantly in both gill and digestive gland tissues after 3 days' exposure to DC3, while a GST increase was observed only in digestive gland tissues, suggesting that these pharmaceuticals induced an oxidative effect. Gene expression analysis revealed transient transcriptomic responses of cyp4, sod, and mdr1 under drug concentrations 2 or 3 and no change of expression for the other genes (cat and pi-gst) or condition (environmental drug concentration) tested. Finally, the data reported in this study represent important ecotoxicological information, confirming that this enzyme family (cyp4, sod, and mdr1) may be considered as a sensible and early indicator of exposure to drugs and emphasizing the involvement of selected genes in detoxification pathways.
http://ift.tt/2jA7RSQ
Phytoremediation of urban soils contaminated with trace metals using Noccaea caerulescens : comparing non-metallicolous populations to the metallicolous ‘Ganges’ in field trials
Abstract
Urban soil contamination with trace metals is a major obstacle to the development of urban agriculture as crops grown in urban gardens are prone to accumulate trace metals up to toxic levels for human consumption. Phytoextraction is considered as a potentially cost-effective alternative to conventional methods such as excavation. Field trials of phytoextraction with Noccaea caerulescens were conducted on urban soils contaminated with Cd, Cu, Pb, and Zn (respectively around 2, 150–200, 400–500, and 400–700 μg g−1 of dry soil). Metallicolous (Ganges population) and non-metallicolous (NMET) populations were compared for biomass production and trace metal uptake. Moreover, we tested the effect of compost and fertilizer addition. Maximal biomass of 5 t ha−1 was obtained with NMET populations on some plots. Compared to Ganges— the high Cd-accumulating ecotype from South of France often used in phytoextraction trials— NMET populations have an advantage for biomass production and for Zn accumulation, with an average Zn uptake of 2.5 times higher. The addition of compost seems detrimental due to metal immobilization in the soil with little or no effect on plant growth. In addition to differences between populations, variations of growth and metal accumulation were mostly explained by soil Cd and Zn concentrations and texture. Our field trials confirm the potential of using N. caerulescens for both Cd and Zn remediation of moderately contaminated soils—with uptake values of up to 200 g Cd ha−1 and 47 kg Zn ha−1—and show the interest of selecting the adequate population according to the targeted metal.
http://ift.tt/2kriSKe
Evaluation of forest structure, biomass and carbon sequestration in subtropical pristine forests of SW China
Abstract
Very old natural forests comprising the species of Fagaceae (Lithocarpus xylocarpus, Castanopsis wattii, Lithocarpus hancei) have been prevailing since years in the Ailaoshan Mountain Nature Reserve (AMNR) SW China. Within these forest trees, density is quite variable. We studied the forest structure, stand dynamics and carbon density at two different sites to know the main factors which drives carbon sequestration process in old forests by considering the following questions: How much is the carbon density in these forest trees of different DBH (diameter at breast height)? How much carbon potential possessed by dominant species of these forests? How vegetation carbon is distributed in these forests? Which species shows high carbon sequestration? What are the physiochemical properties of soil in these forests? Five-year (2005–2010) tree growth data from permanently established plots in the AMNR was analysed for species composition, density, stem diameter (DBH), height and carbon (C) density both in aboveground and belowground vegetation biomass. Our study indicated that among two comparative sites, overall 54 species of 16 different families were present. The stem density, height, C density and soil properties varied significantly with time among the sites showing uneven distribution across the forests. Among the dominant species, L. xylocarpus represents 30% of the total carbon on site 1 while C. wattii represents 50% of the total carbon on site 2. The average C density ranged from 176.35 to 243.97 t C ha−1. The study emphasized that there is generous degree to expand the carbon stocking in this AMNR through scientific management gearing towards conservation of old trees and planting of potentially high carbon sequestering species on good site quality areas.
http://ift.tt/2jAf8Cb
Removal of gadolinium-based contrast agents: adsorption on activated carbon
Abstract
Three carbon samples were employed in this work, including commercial (1690 m2 g−1), activated carbon prepared from guava seeds (637 m2 g−1), and activated carbon prepared from avocado kernel (1068 m2 g−1), to study the adsorption of the following gadolinium-based contrast agents (GBCAs): gadoterate meglumine Dotarem®, gadopentetate dimeglumine Magnevist®, and gadoxetate disodium Primovist®. The activation conditions with H3PO4 were optimized using a Taguchi methodology to obtain mesoporous materials. The best removal efficiency by square meter in a batch system in aqueous solution and model urine was achieved by avocado kernel carbon, in which mesoporosity prevails over microporosity. The kinetic adsorption curves were described by a pseudo-second-order equation, and the adsorption isotherms in the concentration range 0.5–6 mM fit the Freundlich equation. The chemical characterization of the surfaces shows that materials with a greater amount of phenolic functional groups adsorb the GBCA better. Adsorption strongly depends on the pH due to the combination of the following factors: contrast agent protonated forms and carbon surface charge. The tested carbon samples were able to adsorb 70–90% of GBCA in aqueous solution and less in model urine. This research proposes a method for the elimination of GBCA from patient urine before its discharge into wastewater.
http://ift.tt/2kUDVlr
Root-foraging behavior ensures the integrated growth of Vallisneria natans in heterogeneous sediments
Abstract
The present study was carried out to determine the efficacy of root foraging and the physiological response of Vallisnaria natans grown in heterogeneous sediments. V. natans was cultivated in two homogeneous and two heterogeneous sediments. The results suggested that V. natans grown in heterogeneous sediments presented a significantly higher root proportion in its total biomass, exhibited root foraging, and grew well, as indicated by a total biomass, ramet number, and plant height very close to those of plants grown in nutrient-rich clay sediment. Moreover, the more sensitive physiological response of the roots than the stems or the leaves to sediment nutrients suggested that root foraging occurred, and the approached values between the two heterogeneous sediments and the homogeneous clay sediment indicated that V. natans could satisfy its nutrient requirements via root foraging. The results may be useful in the recovery of macrophytes that remodel part (rather than all) of the substrate and can potentially improve habitats that are unsuitable for plant growth.
http://ift.tt/2knZWw6
Characteristics of ammonia gas and fine particulate ammonium from two distinct urban areas: Osaka, Japan, and Ho Chi Minh City, Vietnam
Abstract
Continuous and simultaneous measurements of ammonia gas (NH3) and fine particulate ammonium (PM2.5NH4+) were performed in two distinct urban areas: Osaka, Japan, and Ho Chi Minh City (HCMC), Vietnam. Measurements were performed using a new online instrument. Two measurement periods were conducted during February 11–March 12, 2015 (cold period), and July 1–September 14, 2015 (warm period), at the urban site in Osaka, while 17 days of measurements, from May 21 to June 8, 2015, were conducted at the urban site in HCMC. The average NH3 concentration at the HCMC site was much higher than that at the Osaka site. The differences in the NH3 levels between the two cities are a result of their different emission sources. Traffic emission is a significant contributor to the NH3 levels within the urban area in Osaka. Conversely, the contribution of traffic emission to the NH3 levels in the HCMC urban area is negligible. With a population of around 8.5 million people living in the urban area of HCMC, the high NH3 level is due to human sources and poor waste management systems, especially because of the high temperature (30 °C) and dense population of the city (density up to 42,000 inhabitants per km2). In contrast to the NH3 levels, the highest PM2.5NH4+ level occurred during the cold period at the Osaka site, and the average level at this site was higher than that at the HCMC site. The availability of atmospheric acids, low temperature, and high humidity facilitates the formation of ammonium. Our results indicate that NH3 plays a key role in secondary inorganic aerosol formation; therefore, it contributes to a significant amount of PM2.5 at the Osaka site. In contrast, the high levels of PM2.5 observed at the HCMC site are likely from road traffic emission, mainly motorcycles, rather than secondary inorganic aerosol formation.
http://ift.tt/2jA90tt
Drugs targeting intermediate filaments can improve neurosupportive properties of astrocytes
Publication date: Available online 31 January 2017
Source:Brain Research Bulletin
Author(s): Yolanda de Pablo, Meng Chen, Elin Möllerström, Marcela Pekna, Milos Pekny
In response to central nervous system (CNS) injury, astrocytes upregulate intermediate filament (nanofilament) proteins GFAP and vimentin. Whereas the intermediate filament upregulation in astrocytes is important for neuroprotection in the acute phase of injury, it might inhibit the regenerative processes later on. Thus, timely modulation of the astrocyte intermediate filaments was proposed as a strategy to promote brain repair. We used clomipramine, epoxomicin and withaferin A, drugs reported to decrease the expression of GFAP, and assessed their effect on neurosupportive properties and resilience of astrocytes to oxygen and glucose deprivation (OGD). Clomipramine decreased protein levels of GFAP, as well as vimentin and nestin, and did not affect astrocyte resilience to oxidative stress. Withaferin A sensitized astrocytes to OGD. Both clomipramine and epoxomicin promoted the attachment and survival of neurons co-cultured with astrocytes under standard culture conditions. Moreover, epoxomicin increased neurosupportive properties of astrocytes after OGD. Our data point to clomipramine and epoxomicin as potential candidates for astrocyte modulation to improve outcome after CNS injury.
http://ift.tt/2kgamve
Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania
Publication date: 23 February 2017
Source:Journal of Proteomics, Volume 155
Author(s): Snezhana Akpunarlieva, Stefan Weidt, Dhilia Lamasudin, Christina Naula, David Henderson, Michael Barrett, Karl Burgess, Richard Burchmore
Leishmania parasites multiply and develop in the gut of a sand fly vector in order to be transmitted to a vertebrate host. During this process they encounter and exploit various nutrients, including sugars, and amino and fatty acids. We have previously generated a mutant Leishmania line that is deficient in glucose transport and which displays some biologically important phenotypic changes such as reduced growth in axenic culture, reduced biosynthesis of hexose-containing virulence factors, increased sensitivity to oxidative stress, and dramatically reduced parasite burden in both insect vector and macrophage host cells. Here we report the generation and integration of proteomic and metabolomic approaches to identify molecular changes that may explain these phenotypes. Our data suggest changes in pathways of glycoconjugate production and redox homeostasis, which likely represent adaptations to the loss of sugar uptake capacity and explain the reduced virulence of this mutant in sand flies and mammals. Our data contribute to understanding the mechanisms of metabolic adaptation in Leishmania and illustrate the power of integrated proteomic and metabolomic approaches to relate biochemistry to phenotype.Biological significanceThis paper reports the application of comparative proteomic and metabolomic approaches to reveal the molecular basis for important phenotypic changes Leishmania parasites that are deficient in glucose uptake. Leishmania cause a very significant disease burden across the world and there are few effective drugs available for control. This work shows that proteomics and metabolomics can produce complementary data that advance understanding of parasite metabolism and highlight potential new targets for chemotherapy.
Graphical abstract
http://ift.tt/2juKCyk
Venomics of Naja sputatrix, the Javan spitting cobra: A short neurotoxin-driven venom needing improved antivenom neutralization
Publication date: Available online 31 January 2017
Source:Journal of Proteomics
Author(s): Nget Hong Tan, Kin Ying Wong, Choo Hock Tan
The venom proteome of Naja sputatrix (Javan spitting cobra) was elucidated through reverse-phase HPLC, nano-ESI-LCMS/MS and data mining. A total of 97 distinct protein forms belonging to 14 families were identified. The most abundant proteins are the three-finger toxins (3FTXs, 64.22%) and phospholipase A2 (PLA2, 31.24%), followed by nerve growth factors (1.82%), snake venom metalloproteinase (1.33%) and several proteins of lower abundance (<1%) including a variety of venom enzymes. At subproteome, the 3FTx is dominated by cytotoxins (48.08%), while short neurotoxins (7.89%) predominate over the long neurotoxins (0.48%) among other neurotoxins of lesser toxicity (muscarinic toxin-like proteins, 5.51% and weak neurotoxins, 2.26%). The major SNTX, CTX and PLA2 toxins were isolated with intravenous median lethal doses determined as 0.13, 1.06 and 0.50μg/g in mice, respectively. SABU, the Indonesia manufactured homologous tri-specific antivenom could neutralize the CTX and PLA2 fraction with moderate potency (potency=0.14–0.16mg toxin per ml antivenom). The SNTX, however, was very poorly neutralized with a potency level of 0.034mg/ml, indicating SNTX as the main limiting factor in antivenom neutralization. The finding helps elucidate the inferior efficacy of SABU reported in neutralizing N. sputatrix venom, and supports the call for antivenom improvement.Biological significanceThe Javan spitting cobra, Naja sputatrix is by itself a unique species and should not be confused as the equatorial and the Indochinese spitting cobras. The distinction among the spitting cobras was however unclear prior to the revision of cobra systematics in the mid-90's, and results of some earlier studies are now questionable as to which species was implicated back then. The current study successfully profiled the venom proteome of authenticated N. sputatrix, and showed that the venom is made up of approximately 64% three-finger toxins (including neurotoxins and cytotoxins) and 31% phospholipases A2 by total venom proteins. The findings verified that the paralyzing components in the venom i.e. neurotoxins are predominantly the short-chain subtype (SNTX) far exceeding the long-chain subtype (LNTX) which is more abundant in the venoms of monocled cobra and Indian common cobra. The neurotoxicity of N. sputatrix venom is hence almost exclusively SNTX-driven, and effective neutralization of the SNTX is the key to early reversal of paralysis. Unfortunately, as shown through a toxin-specific assay, the immunological neutralization of the SNTX using the Indonesian antivenom (SABU) was extremely weak, implying that SABU has limited therapeutic efficacy in treating N. sputatrix envenomation clinically. From the practical standpoint, actions need to be taken at all levels from laboratory to production and policy making to ensure that the shortcoming is overcome.
Graphical abstract
http://ift.tt/2kgiyfj
In-depth comparative analysis of the chicken eggshell membrane proteome
Publication date: 23 February 2017
Source:Journal of Proteomics, Volume 155
Author(s): Tamer A.E. Ahmed, Henri-Pierre Suso, Maxwell T. Hincke
The avian eggshell membrane (ESM) is stabilized by extensive cross-linkages, making the identification of its protein constituents technically challenging. Herein, we applied various extraction/solubilization conditions followed by proteomic analysis to characterize the protein constituents of ESM derived from the unfertilized chicken eggs. The egg white and eggshell proteomes (including previous published work) were determined and compared to ESM to identify proteins that are relatively or highly specific to ESM. Merging the results from different extraction/solubilization conditions with various proteomes allowed the identification of 472, 225, and 488 proteins in the ESM, egg white, and eggshell proteomes, respectively. Of these, 163 and 124 proteins were relatively or highly specific to ESM, respectively. GO term analysis of the common proteins and ESM unique proteins generated 8 and 9 significantly enriched functional groups, respectively. Different families of proteins that were identified as ESM-specific included collagens, CREMPs, histones, AvBDs, lysyl oxidase-like 2 (LOXL2), and ovocalyxin-36 (OCX36). These proteins serve as a foundation for the mechanically stable ESM that rests upon the egg white compartment and is a physical barrier against pathogen invasion. Overall, our results highlight the structural nature of the ESM constituents that are relevant to various biomedical applications, such as wound healing.Biological significanceThe eggshell membranes (ESM) are a highly resilient double-layered fibrous meshwork that is secreted while the forming egg transits a specialized oviduct segment, the white isthmus. The ESM protects against pathogen invasion and provides a platform for nucleation of the calcitic eggshell (ES). ESM is greatly stabilized by the extensive desmosine, isodesmosine and disulfide cross-linkages which make the identification of its protein constituents by standard proteomic approaches technically challenging. Comparative proteomic analyses of ESM, egg white, and ES proteins showed proteins groups that are relatively or highly specific to ESM. These groups of proteins serve as a foundation for the mechanically stable ESM that rests upon the egg white compartment and is a physical barrier against pathogen invasion. These features are essential for eggshell quality and for the prevention of pathogen invasion which reinforce food safety of the table egg.
http://ift.tt/2jUnN3n
Protein acetylation involved in streptomycin biosynthesis in Streptomyces griseus
Publication date: 23 February 2017
Source:Journal of Proteomics, Volume 155
Author(s): Yuji Ishigaki, Genki Akanuma, Minoru Yoshida, Sueharu Horinouchi, Saori Kosono, Yasuo Ohnishi
Protein acetylation, the reversible addition of an acetyl group to lysine residues, is a protein post-translational modification ubiquitous in living cells. Although the involvement of protein acetylation in the regulation of primary metabolism has been revealed, the function of protein acetylation is largely unknown in secondary metabolism. Here, we characterized protein acetylation in Streptomyces griseus, a streptomycin producer. Protein acetylation was induced in the stationary and sporulation phases in liquid and solid cultures, respectively, in S. griseus. By comprehensive acetylome analysis, we identified 134 acetylated proteins with 162 specific acetylated sites. Acetylation was found in proteins related to primary metabolism and translation, as in other bacteria. However, StrM, a deoxysugar epimerase involved in streptomycin biosynthesis, was identified as a highly acetylated protein by 2-DE-based proteomic analysis. The Lys70 residue, which is critical for the enzymatic activity of StrM, was the major acetylation site. Thus, acetylation of Lys70 was presumed to abolish enzymatic activity of StrM. In accordance with this notion, an S. griseus mutant producing the acetylation-mimic K70Q StrM hardly produced streptomycin, though the K70Q mutation apparently decreased the stability of StrM. A putative lysine acetyltransferase (KAT) SGR1683 in S. griseus, as well as the Escherichia coli KAT YfiQ, acetylated Lys70 of StrM in vitro. Furthermore, absolute quantification analysis estimated that 13% of StrM molecules were acetylated in mycelium grown in solid culture for 3days. These results indicate that StrM acetylation is of biological significance. We propose that StrM acetylation functions as a limiter of streptomycin biosynthesis in S. griseus.Biological significanceProtein acetylation has been extensively studied not only in eukaryotes, but also in prokaryotes. The acetylome has been analyzed in more than 14 bacterial species. Here, by comprehensive acetylome analysis, we showed that acetylation was found in proteins related to primary metabolism and translation in Streptomyces griseus, similarly to other bacteria. However, five proteins involved in secondary metabolism were also identified as acetylated proteins; these proteins are enzymes in the biosynthesis of streptomycin (StrB1 and StrS), grixazone (GriF), a nonribosomal peptide (NRPS1–2), and a siderophore (AlcC). Additionally, StrM in streptomycin biosynthesis was identified as a highly acetylated protein by 2-DE-based proteomic analysis; approximately 13% of StrM molecules were acetylated. The acetylation occurs at Lys70 to abolish the enzymatic activity of StrM, suggesting that StrM acetylation functions as a limiter of streptomycin biosynthesis in S. griseus. This is the first detailed analysis of protein acetylation of an enzyme involved in secondary metabolism.
Graphical abstract
http://ift.tt/2juTYtU
From genome to proteome: Looking beyond DNA and RNA in chronic lymphocytic leukemia
Publication date: 23 February 2017
Source:Journal of Proteomics, Volume 155
Author(s): Lauren A Thurgood, Tim K Chataway, Karen M Lower, Bryone J Kuss
Chronic lymphocytic leukemia (CLL) remains the most common leukemia in the Western world. Whilst its disease course is extremely heterogeneous (ranging from indolent to aggressive), current methods are unable to accurately predict the clinical journey of each patient. There is clearly a pressing need for both improved prognostication and treatment options for patients with this disease. Whilst molecular studies have analyzed both genetic mutations and gene expression profiles of these malignant B-cells, and as a result have shed light on the pathogenesis of CLL, proteomic studies have been largely overlooked to date. This review summarizes our current knowledge of the proteomics of CLL, and discusses some of the issues in CLL proteomic research, such as reproducibility and data interpretation. In addition, we look ahead to how proteomics may significantly help in the development of a successful treatment for this currently incurable disease.
Graphical abstract
http://ift.tt/2juIWoz
Proteomics towards the understanding of elicitor induced resistance of grapevine against downy mildew
Publication date: Available online 31 January 2017
Source:Journal of Proteomics
Author(s): Christelle Lemaître-Guillier, Agnès Hovasse, Christine Schaeffer-Reiss, Ghislaine Recorbet, Benoît Poinssot, Sophie Trouvelot, Xavier Daire, Marielle Adrian, Marie-Claire Héloir
Elicitors are known to trigger plant defenses in response to biotic stress, but do not systematically lead to effective resistance to pathogens. The reasons explaining such differences remain misunderstood. Therefore, elicitation and induced resistance (IR) were investigated through the comparison of two modified β-1,3 glucans applied on grapevine (Vitis vinifera) leaves before and after inoculation with Plasmopara viticola, the causal agent of downy mildew. The sulfated (PS3) and the shortened (H13) forms of laminarin are both known to elicit defense responses whereas only PS3 induces resistance against downy mildew. The analysis of the 2-DE gel electrophoresis revealed that PS3 and H13 induced distinct proteomic profiles after treatment and pathogen inoculation. Our results point out that the PS3-induced resistance is associated with the activation of the primary metabolism especially on amino acids and carbohydrates pathways. In addition, few proteins, such as the 12-oxophytodienoate reductase (OPR-like) related to the OPDA pathway, and an Arsenite-resistance protein (Serrate-like protein) could be considered as useful markers of induced resistance.SignificanceOne strategy to reduce the application of fungicides is the use of elicitors which induce plant defense responses. Nonetheless, the elicitors do not systematically lead to resistance against pathogens. The lack of correlation between plant defense activation and induced resistance (IR) requires the investigation of what makes the specificity of elicitor-IR.In this study, the two β-glucans elicitors, sulfated (PS3) and short (H13) laminarins, were used in the grapevine/Plasmopara viticola interaction since only the first one leads to resistance against downy mildew. To disclose IR specificity, proteomic approach has been employed to compare the two treatments before and after P. viticola inoculation. The analysis of the 2-DE revealed that PS3 and H13 induced distinct proteomic profiles after treatment and pathogen inoculation. Significant increase of the number of proteins regulated by PS3, relative to both H13 and time-points, is correlated with the resistance process establishment. Our results point that the PS3-induced resistance requires the activation of the primary metabolism especially on amino acids and carbohydrates pathways. In addition, few proteins, such as the 12-oxophytodienoate reductase (OPR-like) related to the OPDA pathway, and an Arsenite-resistance protein (Serrate-like protein) could constitute useful markers of PS3 induced resistance.
Graphical abstract
http://ift.tt/2kgccwg
Assessment of emissions of greenhouse gases and air pollutants in Indonesia and impacts of national policy for elimination of kerosene use in cooking
Source:Atmospheric Environment, Volume 154
Author(s): Didin Agustian Permadi, Asep Sofyan, Nguyen Thi Kim Oanh
This study presents an emission inventory (EI) for major anthropogenic sources of Indonesia in 2007 and 2010. The EI was developed using a combination of top-down and bottom-up approaches with comprehensive activity data collected at the provincial/district level to produce spatially and temporally distributed emission of toxic pollutants and greenhouse gases (GHGs). The sources were categorized into: 1) fuel combustion in power plant, 2) industry, 3) transportation, 4) residential and commercial combustion, 5) biomass open burning, and 6) non-combustion agricultural activity and waste disposal. The best estimates of the 2010 national emissions, in Gg, of toxic pollutants were: 1014 SO2; 3323 NOx; 24,849 CO; 4077 NMVOC; 1276 NH3; 2154 PM10; 1728 PM2.5; 246 BC; 718 OC; and GHGs: 540,275 CO2; 3979 CH4 and 180 N2O. During the period from 2007 to 2010, the national emissions increased by 0.7–8.8% (0.23–2.8% per year), varied with species, with the most significant changes obtained for the biomass open burning emissions. For 2010 results, the low and high emission estimates for different species were ranging from −58% to +122% of the corresponding best estimates. The largest range (high uncertainty) was for BC due to the wide range of the limitedly available emission factors. Spatially, higher emission intensity was seen in large urban areas of Java and Sumatra Islands. Temporally, dry months of August–October had higher emissions. During the first 3 years (2007–2010) of implementation, the national policy of elimination of kerosene use in cooking had successfully replaced 4.9 Tg kerosene with 2.6 Tg LPG in 30 designated provinces. The net emission reductions of different species ranged from 48 Mg (SO2) to 7.6 Tg for CO2. The global warming potential weighted emissions from the residential cooking alone, collectively for GHGs and short-lived climate pollutants in 20-yr CO2 eq., would reduce by 2%. More significant reductions in the residential combustion emissions are expected if the solid cooking fuel could be targeted in future fuel conversion programs. The benefits to human health resulted from the emission reduction of toxic pollutants from residential cooking could be substantial and should be assessed in future studies.
http://ift.tt/2kUmcua
Uncertainty and dynamics of natural wetland CH4 release in China: Research status and priorities
Source:Atmospheric Environment, Volume 154
Author(s): Da Wei, Xiaodan Wang
Natural wetlands represent the largest single source of methane (CH4), a potent greenhouse gas. China is home to the world's fourth largest wetland area, and it is facing intense climate- and human-related impacts. The scientific community in China has invested considerable effort into investigating wetland CH4 release and its dynamics. Static chamber and eddy covariance observations have verified the temperature, water regime and air pressure as factors that regulate the diurnal and seasonal variation of CH4 release. Non-growing seasons, especially freezing–thawing cycles, play a role in CH4 release. However, a knowledge gap still exists with respect to the inter-annual variability of CH4 release. Observations also suggest that water and temperature regimes control the micro- and macro-scale spatial pattern of CH4 release, respectively. Recent bookkeeping surveys, biogeochemical model simulations, and chemical transport model inversions, have narrowed the uncertainty range of national CH4 release to 2.46–3.20, 2.77–4.95 and 2.38–4.91 Tg CH4 yr−1, respectively. Wetland loss (especially cropland conversion in Northeast China), despite climate changes, decreased CH4 release by 45.2%–52.2% from the 1950s–2000s, and by 13.2%–15.4% from the 1980s–2000s. However, future warmer temperatures and rising CO2 are predicted to strengthen national CH4 release by 32% (RCP2.6), 55% (RCP4.5) and 91% (RCP8.5) by the 2080s, albeit without the variation in wetland extent having been considered. Furthermore, future research should emphasize the mechanisms involved in CH4 release during freezing–thawing cycles and interannual variability. Model–data fusion of eddy covariance and manipulative experiments, especially warming and CO2 enrichment, would benefit estimations and projections of CH4 release.
http://ift.tt/2jVUK1u
-
Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
-
Abstract Noise pollution is a major factor of environmental complaints in many cities, which has significant impacts on human health. As a...
