Journal of negative results in biomedicine最新文献

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Blink rate is associated with drug-induced parkinsonism in patients with severe mental illness, but does not meet requirements to serve as a clinical test: the Curacao extrapyramidal syndromes study XIII. 眨眼频率与严重精神疾病患者的药物性帕金森病相关,但不符合作为临床试验的要求:库拉索锥体外系综合征研究XIII。
Journal of negative results in biomedicine Pub Date : 2017-08-25 DOI: 10.1186/s12952-017-0079-y
Charlotte L Mentzel, P Roberto Bakker, Jim van Os, Marjan Drukker, Glenn E Matroos, Marina A J Tijssen, Peter N van Harten
{"title":"Blink rate is associated with drug-induced parkinsonism in patients with severe mental illness, but does not meet requirements to serve as a clinical test: the Curacao extrapyramidal syndromes study XIII.","authors":"Charlotte L Mentzel,&nbsp;P Roberto Bakker,&nbsp;Jim van Os,&nbsp;Marjan Drukker,&nbsp;Glenn E Matroos,&nbsp;Marina A J Tijssen,&nbsp;Peter N van Harten","doi":"10.1186/s12952-017-0079-y","DOIUrl":"https://doi.org/10.1186/s12952-017-0079-y","url":null,"abstract":"<p><strong>Background: </strong>Drug-induced parkinsonism (DIP) has a high prevalence and is associated with poorer quality of life. To find a practical clinical tool to assess DIP in patients with severe mental illness (SMI), the association between blink rate and drug-induced parkinsonism (DIP) was assessed.</p><p><strong>Methods: </strong>In a cohort of 204 SMI patients receiving care from the only mental health service of the previous Dutch Antilles, blink rate per minute during conversation was assessed by an additional trained movement disorder specialist. DIP was rated on the Unified Parkinson's Disease Rating Scale (UPDRS) in 878 assessments over a period of 18 years. Diagnostic values of blink rate were calculated.</p><p><strong>Results: </strong>DIP prevalence was 36%, average blink rate was 14 (standard deviation (SD) 11) for patients with DIP, and 19 (SD 14) for patients without. There was a significant association between blink rate and DIP (p < 0.001). With a blink rate cut-off of 20 blinks per minute, sensitivity was 77% and specificity was 38%. A 10% percentile cut-off model resulted in an area under the ROC curve of 0.61. A logistic prediction model between dichotomous DIP and continuous blink rate per minute an area under the ROC curve of 0.70.</p><p><strong>Conclusions: </strong>There is a significant association between blink rate and DIP as diagnosed on the UPDRS. However, blink rate sensitivity and specificity with regard to DIP are too low to replace clinical rating scales in routine psychiatric practice.</p><p><strong>Trial registration: </strong>The study was started over 20 years ago in 1992, at the time registering a trial was not common practice, therefore the study was never registered.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12952-017-0079-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35346167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Work-focused cognitive behavioral intervention for psychological complaints in patients on sick leave due to work-related stress: Results from a randomized controlled trial. 以工作为中心的认知行为干预治疗因工作压力而请病假的患者的心理疾患:一项随机对照试验的结果。
Journal of negative results in biomedicine Pub Date : 2017-08-22 DOI: 10.1186/s12952-017-0078-z
Vita Ligaya Dalgaard, Lars Peter Sønderbo Andersen, Johan Hviid Andersen, Morten Vejs Willert, Ole Carstensen, David John Glasscock
{"title":"Work-focused cognitive behavioral intervention for psychological complaints in patients on sick leave due to work-related stress: Results from a randomized controlled trial.","authors":"Vita Ligaya Dalgaard,&nbsp;Lars Peter Sønderbo Andersen,&nbsp;Johan Hviid Andersen,&nbsp;Morten Vejs Willert,&nbsp;Ole Carstensen,&nbsp;David John Glasscock","doi":"10.1186/s12952-017-0078-z","DOIUrl":"https://doi.org/10.1186/s12952-017-0078-z","url":null,"abstract":"<p><strong>Background: </strong>Work-related stress is a global problem with negative implications for individuals and society. The purpose of the current study was to evaluate a stress management intervention for patients on sick leave due to work-related stress complaints using a three-armed randomized controlled design.</p><p><strong>Methods: </strong>Participants were patients referred from three municipalities to the regional Department of Occupational Medicine. Inclusion criteria were: 1) sick leave due to work-related stress complaints, 2) a diagnosis of adjustment disorder or reactions to severe stress (ICD 10 code: F43,2 - F 43,9 not PTSD) or mild depressive episode (F 32.0). Through a double randomization procedure patients (n = 163) were randomized to either an intervention group (n = 58), a 'control group A' receiving a clinical examination (n = 56), or 'control group B' (n = 49) receiving no offers at the department. The intervention comprised six sessions of individual cognitive behavioral therapy and the offer of a small workplace intervention. Questionnaire data were analyzed with multivariate repeated measurements analysis. Primary outcomes assessed were perceived stress and general mental health. Secondary outcomes were sleep quality and cognitive failures. Follow-up was at four and 10 months after baseline.</p><p><strong>Results: </strong>Complaints were significantly reduced in all groups over time. No group effects were observed between the intervention group and control group A that was clinically assessed. Significant group effects were found for perceived stress and memory when comparing the intervention group to group B, but most likely not due to an intervention effect.</p><p><strong>Conclusion: </strong>Psychological complaints improved substantially over time in all groups, but there was no significant treatment effect on any outcomes when the intervention group was compared to control group A that received a clinical assessment.</p><p><strong>Trial registration: </strong>ISRCTN ISRCTN91404229. Registered 03 August 2012 (retrospectively registered).</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12952-017-0078-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35337924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
In vitro aggregating β-lactamase-polyQ chimeras do not induce toxic effects in an in vivo Caenorhabditis elegans model. 体外聚合的β-内酰胺酶-多Q嵌合体在体内草履虫模型中不会产生毒性作用。
Journal of negative results in biomedicine Pub Date : 2017-08-22 DOI: 10.1186/s12952-017-0080-5
Roel Van Assche, Charline Borghgraef, Jonathan Vaneyck, Mireille Dumoulin, Liliane Schoofs, Liesbet Temmerman
{"title":"In vitro aggregating β-lactamase-polyQ chimeras do not induce toxic effects in an in vivo Caenorhabditis elegans model.","authors":"Roel Van Assche, Charline Borghgraef, Jonathan Vaneyck, Mireille Dumoulin, Liliane Schoofs, Liesbet Temmerman","doi":"10.1186/s12952-017-0080-5","DOIUrl":"10.1186/s12952-017-0080-5","url":null,"abstract":"<p><strong>Background: </strong>A series of human diseases are caused by the misfolding and aggregation of specific proteins or peptides into amyloid fibrils; nine of these diseases, referred to as polyglutamine diseases, are associated with proteins carrying an expanded polyglutamine (polyQ) region. While the presence of this latter is thought to be the determinant factor for the development of polyQ diseases, the non-polyQ regions of the host proteins are thought to play a significant modulating role.</p><p><strong>Method: </strong>In order to better understand the role of non-polyQ regions, the toxic effects of model proteins bearing different polyQ regions (containing up to 79 residues) embedded at two distinct locations within the β-lactamase (BlaP) host enzyme were evaluated in Caenorhabditis elegans. This small organism can be advantageous for the validation of in vitro findings, as it provides a multicellular context yet avoids the typical complexity of common studies relying on vertebrate models. Several phenotypic assays were performed in order to screen for potential toxic effects of the different BlaP-polyQ proteins.</p><p><strong>Results: </strong>Despite the significant in vitro aggregation of BlaP-polyQ proteins with long polyQ regions, none of the BlaP-polyQ chimeras aggregated in the generated transgenic in vivo models.</p><p><strong>Conclusion: </strong>The absence of a toxic effect of the expression of BlaP-polyQ chimeras may find its cause in biochemical mechanisms present in vivo to cope with protein aggregation (e.g. presence of chaperones) or in C. elegans' limitations such as its short lifespan. It is plausible that the aggregation propensities of the different BlaP chimeras containing embedded polyQ sequences are too low in this in vivo environment to permit their aggregation. These experiments emphasize the need for several comparative and in vivo verification studies of biologically relevant in vitro findings, which reveal both the strengths and limitations of widely used model systems.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35337928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Polymorphism rs547984 on human chromosome 1q43 is not associated with primary open angle glaucoma in a Saudi cohort. 在沙特队列中,人类染色体1q43多态性rs547984与原发性开角型青光眼无关。
Journal of negative results in biomedicine Pub Date : 2017-06-26 DOI: 10.1186/s12952-017-0077-0
Taif A Azad, Nikhil B Edward, Altaf A Kondkar, Hatem Kalantan, Saleh Altuwaijri, Tahira Sultan, Faisal A Al-Mobarak, Saleh A Al-Obeidan, Khaled K Abu-Amero
{"title":"Polymorphism rs547984 on human chromosome 1q43 is not associated with primary open angle glaucoma in a Saudi cohort.","authors":"Taif A Azad,&nbsp;Nikhil B Edward,&nbsp;Altaf A Kondkar,&nbsp;Hatem Kalantan,&nbsp;Saleh Altuwaijri,&nbsp;Tahira Sultan,&nbsp;Faisal A Al-Mobarak,&nbsp;Saleh A Al-Obeidan,&nbsp;Khaled K Abu-Amero","doi":"10.1186/s12952-017-0077-0","DOIUrl":"https://doi.org/10.1186/s12952-017-0077-0","url":null,"abstract":"<p><strong>Background: </strong>To investigate the association between polymorphism rs547984, located in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene on human chromosome 1q43 and primary open angle glaucoma (POAG).</p><p><strong>Method: </strong>Polymorphism rs547984 was genotyped using Taq-Man® assay in 185 subjects comprising of 90 unrelated POAG cases and 95 controls of Saudi origin.</p><p><strong>Results: </strong>Association analysis between cases and controls revealed no significant genotype distribution under additive (p = 0.356), dominant (p = 0.517) and recessive (p = 0.309) models. Besides, the allele frequency distribution was also found to be non-significant (p = 0.70). The minor \"A\" allele frequency was found to be 0.49 and 0.50 among POAG cases and controls, respectively. In addition, specific clinical indices used to assess severity of glaucoma such as intraocular pressure (IOP), cup/disc ratio and number of anti-glaucoma medication also did not show any significant genotype distribution in POAG cases.</p><p><strong>Conclusion: </strong>Polymorphism rs547984 is neither associated with any clinical indices important for POAG such as IOP and cup/disc ratio nor is a risk factor for POAG in the Saudi cohort.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12952-017-0077-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35117406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Behavioral and neural adaptations in response to five weeks of balance training in older adults: a randomized controlled trial. 老年人对五周平衡训练的行为和神经适应反应:一项随机对照试验。
Journal of negative results in biomedicine Pub Date : 2017-06-13 DOI: 10.1186/s12952-017-0076-1
Jan Ruffieux, Audrey Mouthon, Martin Keller, Michael Wälchli, Wolfgang Taube
{"title":"Behavioral and neural adaptations in response to five weeks of balance training in older adults: a randomized controlled trial.","authors":"Jan Ruffieux,&nbsp;Audrey Mouthon,&nbsp;Martin Keller,&nbsp;Michael Wälchli,&nbsp;Wolfgang Taube","doi":"10.1186/s12952-017-0076-1","DOIUrl":"https://doi.org/10.1186/s12952-017-0076-1","url":null,"abstract":"<p><strong>Background: </strong>While the positive effect of balance training on age-related impairments in postural stability is well-documented, the neural correlates of such training adaptations in older adults remain poorly understood. This study therefore aimed to shed more light on neural adaptations in response to balance training in older adults.</p><p><strong>Methods: </strong>Postural stability as well as spinal reflex and cortical excitability was measured in older adults (65-80 years) before and after 5 weeks of balance training (n = 15) or habitual activity (n = 13). Postural stability was assessed during one- and two-legged quiet standing on a force plate (static task) and a free-swinging platform (dynamic task). The total sway path was calculated for all tasks. Additionally, the number of errors was counted for the one-legged tasks. To investigate changes in spinal reflex excitability, the H-reflex was assessed in the soleus muscle during quiet upright stance. Cortical excitability was assessed during an antero-posterior perturbation by conditioning the H-reflex with single-pulse transcranial magnetic stimulation.</p><p><strong>Results: </strong>A significant training effect in favor of the training group was found for the number of errors conducted during one-legged standing (p = .050 for the static and p = .042 for the dynamic task) but not for the sway parameters in any task. In contrast, no significant effect was found for cortical excitability (p = 0.703). For spinal excitability, an effect of session (p < .001) as well as an interaction of session and group (p = .009) was found; however, these effects were mainly due to a reduced excitability in the control group.</p><p><strong>Conclusions: </strong>In line with previous results, older adults' postural stability was improved after balance training. However, these improvements were not accompanied by significant neural adaptations. Since almost identical studies in young adults found significant behavioral and neural adaptations after four weeks of training, we assume that age has an influence on the time course of such adaptations to balance training and/or the ability to transfer them from a trained to an untrained task.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12952-017-0076-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35086224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
Does the placebo effect modulate drug bioavailability? Randomized cross-over studies of three drugs. 安慰剂效应是否调节药物的生物利用度?三种药物的随机交叉研究。
Journal of negative results in biomedicine Pub Date : 2017-05-23 DOI: 10.1186/s12952-017-0075-2
Muhammad M Hammami, Ahmed Yusuf, Faduma S Shire, Rajaa Hussein, Reem Al-Swayeh
{"title":"Does the placebo effect modulate drug bioavailability? Randomized cross-over studies of three drugs.","authors":"Muhammad M Hammami,&nbsp;Ahmed Yusuf,&nbsp;Faduma S Shire,&nbsp;Rajaa Hussein,&nbsp;Reem Al-Swayeh","doi":"10.1186/s12952-017-0075-2","DOIUrl":"https://doi.org/10.1186/s12952-017-0075-2","url":null,"abstract":"<p><strong>Background: </strong>Medication effect is the sum of its drug, placebo, and drug*placebo interaction effects. It is conceivable that the interaction effect involves modulating drug bioavailability; it was previously observed that being aware of caffeine ingestion may prolong caffeine plasma half-life. This study was set to evaluate such concept using different drugs.</p><p><strong>Methods: </strong>Balanced single-dose, two-period, two-group, cross-over design was used to compare the pharmacokinetics of oral cephalexin, ibuprofen, and paracetamol, each described by its name (overt) or as placebo (covert). Volunteers and study coordinators were deceived as to study aim. Drug concentrations were determined blindly by in-house, high performance liquid chromatography assays. Terminal-elimination half-life (t<sub>½</sub>) (primary outcome), maximum concentration (C<sub>max</sub>), C<sub>max</sub> first time (T<sub>max</sub>), terminal-elimination-rate constant (λ), area-under-the-concentration-time-curve, to last measured concentration (AUC<sub>T</sub>), extrapolated to infinity (AUC<sub>I</sub>), or to T<sub>max</sub> of overt drug (AUC<sub>Overttmax</sub>), and C<sub>max</sub>/AUC<sub>I</sub> were calculated blindly using standard non-compartmental method. Covert-vs-overt effect on drug pharmacokinetics was evaluated by analysis-of-variance (ANOVA, primary analysis), 90% confidence interval (CI) using the 80.00-125.00% bioequivalence range, and percentage of individual pharmacokinetic covert/overt ratios that are outside the +25% range.</p><p><strong>Results: </strong>Fifty, 30, and 50 healthy volunteers (18%, 10%, and 6% females, mean (SD) age 30.8 (6.2), 31.4 (6.6), and 31.2 (5.4) years) participated in 3 studies on cephalexin, ibuprofen, and paracetamol, respectively. Withdrawal rate was 4%, 0%, and 4%, respectively. Eighteen blood samples were obtained over 6, 10, and 14 h in each study period of the three drugs, respectively. ANOVA showed no significant difference in any pharmacokinetic parameter for any of the drugs. The 90% CIs for AUC<sub>T</sub>, AUC<sub>I</sub>, C<sub>max</sub>, AUC<sub>Overttmax</sub>, and C<sub>max</sub>/AUC<sub>I</sub> were within the bioequivalence range, except for ibuprofen C<sub>max</sub> (76.66-98.99), ibuprofen C<sub>max</sub>/AUC<sub>I</sub> (77.19-98.39), and ibuprofen (45.32-91.62) and paracetamol (51.45-98.96) AUC<sub>Overttmax</sub>. Out of the 126 individual covert/overt ratios, 2.0-16.7% were outside the +25% range for AUC<sub>T</sub>, 2.0-4.2% for AUC<sub>I</sub>, 25.0-44.9% for C<sub>max</sub>, 67.3-76.7% for AUC<sub>Overttmax</sub>, and 45.8-71.4% for T<sub>max</sub>.</p><p><strong>Conclusions: </strong>This study couldn't confirm that awareness of drug ingestion modulates its bioavailability. However, it demonstrates the trivial effect of blinding in bioequivalence studies and the extent of bio-variability that would be expected when comparing a drug product to itself.</p><p><strong>Trial reg","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12952-017-0075-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35020900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Absence of the dermatan sulfate chain of decorin does not affect mouse development. 皮肤素硫酸盐链的缺失不影响小鼠的发育。
Journal of negative results in biomedicine Pub Date : 2017-04-17 DOI: 10.1186/s12952-017-0074-3
Pierre Moffatt, Yeqing Geng, Lisa Lamplugh, Antonio Nanci, Peter J Roughley
{"title":"Absence of the dermatan sulfate chain of decorin does not affect mouse development.","authors":"Pierre Moffatt,&nbsp;Yeqing Geng,&nbsp;Lisa Lamplugh,&nbsp;Antonio Nanci,&nbsp;Peter J Roughley","doi":"10.1186/s12952-017-0074-3","DOIUrl":"https://doi.org/10.1186/s12952-017-0074-3","url":null,"abstract":"<p><strong>Background: </strong>In vitro studies suggest that the multiple functions of decorin are related to both its core protein and its dermatan sulfate chain. To determine the contribution of the dermatan sulfate chain to the functional properties of decorin in vivo, a mutant mouse whose decorin lacked a dermatan sulfate chain was generated.</p><p><strong>Results: </strong>Homozygous mice expressing only the decorin core protein developed and grew in a similar manner to wild type mice. In both embryonic and postnatal mice, all connective tissues studied, including cartilage, skin and cornea, appeared to be normal upon histological examination, and their collagen fibrils were of normal diameter and organization. In addition, abdominal skin wounds healed in an identical manner in the mutant and wild type mice.</p><p><strong>Conclusions: </strong>The absence of a dermatan sulfate chain on decorin does not appear to overtly influence its functional properties in vivo.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12952-017-0074-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34915847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 6
The effects of phosphanegold(I) thiolates on the biological properties of Acanthamoeba castellanii belonging to the T4 genotype. 硫代磷金对T4基因型卡斯特棘阿米巴生物学特性的影响
Journal of negative results in biomedicine Pub Date : 2017-04-03 DOI: 10.1186/s12952-017-0070-7
Ruqaiyyah Siddiqui, Farhat Abjani, Chien Ing Yeo, Edward R T Tiekink, Naveed Ahmed Khan
{"title":"The effects of phosphanegold(I) thiolates on the biological properties of Acanthamoeba castellanii belonging to the T4 genotype.","authors":"Ruqaiyyah Siddiqui,&nbsp;Farhat Abjani,&nbsp;Chien Ing Yeo,&nbsp;Edward R T Tiekink,&nbsp;Naveed Ahmed Khan","doi":"10.1186/s12952-017-0070-7","DOIUrl":"https://doi.org/10.1186/s12952-017-0070-7","url":null,"abstract":"<p><strong>Background: </strong>Gold compounds have shown promise in the treatment of non-communicable diseases such as rheumatoid arthritis and cancer, and are considered of value as anti-microbial agents against Gram-negative and Gram-positive bacteria, and have anti-parasitic properties against Schistosoma mansoni, Trypanosoma brucei, Plasmodium falciparum, Leishmania infantinum, Giardia lamblia, and Entamoeba histolytica. They are known to affect enzymatic activities that are required for the cellular respiration processes.</p><p><strong>Methods: </strong>Anti-amoebic effects of phosphanegold(I) thiolates were tested against clinical isolate of A. castellanii belonging to the T4 genotype by employing viability assays, growth inhibition assays, encystation assays, excystation assays, and zymographic assays.</p><p><strong>Results: </strong>The treatment of A. castellanii with the phosphanegold(I) thiolates tested (i) had no effect on the viability of A. castellanii as determined by Trypan blue exclusion test, (ii) did not affect amoebae growth using PYG growth medium, (iii) did not inhibit cellular differentiation, and (iv) had no effect on the extracellular proteolytic activities of A. castellanii.</p><p><strong>Conclusion: </strong>Being free-living amoeba, A. castellanii is a versatile respirator and possesses respiratory mechanisms that adapt to various aerobic and anaerobic environments to avoid toxic threats and adverse conditions. For the first time, our findings showed that A. castellanii exhibits resistance to the toxic effects of gold compounds and could prove to be an attractive model to study mechanisms of metal resistance in eukaryotic cells.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12952-017-0070-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34876325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 10
Facial cutaneo-mucosal venous malformations can develop independently of mutation of TEK gene but may be associated with excessive expression of Src and p-Src. 面部皮肤-粘膜静脉畸形可以独立于TEK基因突变而发生but可能与Src和p-Src的过度表达有关。
Journal of negative results in biomedicine Pub Date : 2017-03-20 DOI: 10.1186/s12952-017-0072-5
Nabila Brahami, Selvakumar Subramaniam, Moudjahed Saleh Al-Ddafari, Cecile Elkaim, Pierre-Olivier Harmand, Badr-Eddine Sari, Gérard Lefranc, Mourad Aribi
{"title":"Facial cutaneo-mucosal venous malformations can develop independently of mutation of TEK gene but may be associated with excessive expression of Src and p-Src.","authors":"Nabila Brahami,&nbsp;Selvakumar Subramaniam,&nbsp;Moudjahed Saleh Al-Ddafari,&nbsp;Cecile Elkaim,&nbsp;Pierre-Olivier Harmand,&nbsp;Badr-Eddine Sari,&nbsp;Gérard Lefranc,&nbsp;Mourad Aribi","doi":"10.1186/s12952-017-0072-5","DOIUrl":"https://doi.org/10.1186/s12952-017-0072-5","url":null,"abstract":"<p><p>We aimed to search for mutations in the germline and somatic DNA of the TEK gene and to analyze the expression level of Src and phospho-Src (p-Src) in tumor and healthy tissues from patients with facial cutaneo-mucosal venous malformations (VMCM). Eligible patients from twelve families and thirty healthy controls were recruited respectively at the Departments of Stomatology and Oral Surgery, and Transfusion Medicine of Tlemcen University Medical Centre. Immunoblot analyses of Src and p-Src were performed after direct DNA sequencing. No somatic or germline mutations were found in all the 23 exons and their 5' and 3' intronic flanking regions, except for one case in which a c.3025+20-3025+22 del mutation was highlighted at the intron 15, both in the germline and somatic DNA. Additionally, elevated expression levels of Src and p-Src were observed only in the patient with such mutation. However, when normalized to β-actin, the overall relative expression levels of both Src and p-Src were significantly increased in VMCM tissues when compared to healthy tissues (for both comparisons, p <0.001). In conclusion, we confirm the outcomes of our previous work suggesting that VMCM can develop independently of mutation of the TEK gene. Additionally, the results for Src activity are of particular interest in the context of specific targeted therapies and biological diagnosis. Nevertheless, such a conclusion should be confirmed through a mechanistic study and/or in a satisfactory number of patients.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12952-017-0072-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34832615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Experimental silicosis does not aggravate collagen-induced arthritis in mice. 实验性矽肺不会加重小鼠胶原诱导的关节炎。
Journal of negative results in biomedicine Pub Date : 2017-03-13 DOI: 10.1186/s12952-017-0071-6
Robby Engelmann, Brigitte Müller-Hilke
{"title":"Experimental silicosis does not aggravate collagen-induced arthritis in mice.","authors":"Robby Engelmann,&nbsp;Brigitte Müller-Hilke","doi":"10.1186/s12952-017-0071-6","DOIUrl":"https://doi.org/10.1186/s12952-017-0071-6","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effect of chronic lung inflammation on the incidence and severity of collagen-induced arthritis in mice.</p><p><strong>Methods: </strong>Chronic lung inflammation in the form of silicosis was induced via intranasal application of silica particles. Immunization with collagen Type II commenced one week later and mice were sacrificed six weeks after booster immunization. Thereafter, silicosis was confirmed via flow cytometry and arthritis was evaluated performing knee and paw histology.</p><p><strong>Results: </strong>Pronounced lung inflammation in the silica-treated compared to PBS-treated control mice was demonstrated by significantly elevated broncho-alveolar lavage (BAL) cell count, attributable to increased numbers of macrophages and granulocytes. Inflammation in the lungs was not associated with elevated PAD2 and PAD4 expression, yet silica treated animals had significantly higher aCCP serum titers. However, lung inflammation did not lead to an increase in the incidence of arthritis, nor did it exacerbate the macroscopic or histologic joint scores.</p><p><strong>Conclusions: </strong>Chronic lung inflammation resulting from silicosis does not aggravate collagen-induced arthritis in mice.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12952-017-0071-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34804884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
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