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1.
Juliana Frohnert Hansen Claus Henrik Nielsen Marianne M?ller Brorson Hanne Frederiksen Marie-Louise Hartoft-Nielsen ?se Krogh Rasmussen Klaus Bendtzen Ulla Feldt-Rasmussen 《PloS one》2015,10(6)
Phthalates are a group of endocrine disrupting chemicals, suspected to influence the immune system. The aim of this study was to investigate the influence of phthalates on cytokine secretion from human peripheral blood mononuclear cells. Escherichia coli lipopolysaccharide and phytohemagglutinin-P were used for stimulation of monocytes/macrophages and T cells, respectively. Cells were exposed for 20 to 22 hours to either di-ethyl, di-n-butyl or mono-n-butyl phthalate at two different concentrations. Both diesters were metabolised to their respective monoester and influenced cytokine secretion from both monocytes/macrophages and T cells in a similar pattern: the secretion of interleukin (IL)-6, IL-10 and the chemokine CXCL8 by monocytes/macrophages was enhanced, while tumour necrosis factor (TNF)-α secretion by monocytes/macrophages was impaired, as was the secretion of IL-2 and IL-4, TNF-α and interferon-γ by T cells. The investigated phthalate monoester also influenced cytokine secretion from monocytes/macrophages similar to that of the diesters. In T cells, however, the effect of the monoester was different compared to the diesters. The influence of the phthalates on the cytokine secretion did not seem to be a result of cell death. Thus, results indicate that both human innate and adaptive immunity is influenced in vitro by phthalates, and that phthalates therefore may affect cell differentiation and regenerative and inflammatory processes in vivo. 相似文献
2.
Bing-Lin Chen Jia-Bao Guo Ming-Shuo Liu Xin Li Jun Zou Xi Chen Ling-Li Zhang Yu-Shan Yue Xue-Qiang Wang 《PloS one》2015,10(8)
Objective
A systematic review is conducted to determine the effect of traditional Chinese exercise for patients with stroke.Methods
Studies are obtained from PubMed, Embase, Cochrane Library, EBSCO, Web of Science, and CNKI. Only randomized controlled trials were left to evaluate the effects of traditional Chinese exercise for patients with stroke, and with no limits on study data or language. The primary outcome was the Berg balance score (BBS), Functional walking scale. And a random-effects model was used to calculate the pooled mean difference (MD) with 95% confidence interval (CI).Results
A total of 9 studies on 820 participants conform to the inclusion criteria, whereas eight studies on 704 participants are used as data sources for the meta-analysis, all trials were published between 2004 and 2013. The BBS indicates that the efficacy of traditional Chinese exercise on balance of patients with stroke is better than that of other training or no training in short term [MD (95%CI) = 11.85 [5.41, 18.30], P < 0.00001]. And the short physical performance battery, Functional walking scale, limit of stability were observed significant differences on balance (p<0.05) and gait (p<0.05) between traditional Chinese exercise and other exercises or no exercise. In addition, there is an article showed that some other form (physiotherapy exercises focused on balance) significantly improved balance ability for stroke patients compared to tai chi chuan practice (Berg test = 0.01, Romberg, and standing on one leg).Conclusion
In our meta analysis, the positive findings of this study suggest traditional Chinese exercise has beneficial effects on the balance ability in short term. However, we drew the conclusion according to the extreme heterogeneity, and evidence of better quality and from a larger sample size is required. Because of the inconsistent outcomes, there are short of enough good evidence for patients with stroke to prove the effects of traditional Chinese exercise on gait.Systematic Review Registration
http://www.crd.york.ac.uk/PROSPERO PROSPERO registration number: CRD42013006474. 相似文献3.
Denise M. D. ?zdemir-van Brunschot Giel G. Koning Kees C. J. H. M. van Laarhoven Mehmet Ergün Sharon B. C. E. van Horne Maroeska M. Rovers Michiel C. Warlé 《PloS one》2015,10(3)
Objective
To compare the effectiveness of different technique modifications in laparoscopic donor nephrectomy.Design
Systematic review and meta-analyses.Data Sources
Searches of PubMed, EMBASE, Web of Science and Central from January 1st 1997 until April 1st 2014.Study Design
All cohort studies and randomized clinical trials comparing fully laparoscopic donor nephrectomy with modifications of the standard technique including hand-assisted, retroperitoneoscopic and single port techniques, were included.Data-Extraction and Analysis
The primary outcome measure was the number of complications. Secondary outcome measures included: conversion to open surgery, first warm ischemia time, estimated blood loss, graft function, operation time and length of hospital stay. Each technique modification was compared with standard laparoscopic donor nephrectomy. Data was pooled with a random effects meta-analysis using odds ratios, weighted mean differences and their corresponding 95% confidence intervals. To assess heterogeneity, the I2 statistic was used. First, randomized clinical trials and cohort studies were analyzed separately, when data was comparable, pooled analysis were performed.Results
31 studies comparing laparoscopic donor nephrectomy with other technique modifications were identified, including 5 randomized clinical trials and 26 cohort studies. Since data of randomized clinical trials and cohort studies were comparable, these data were pooled. There were significantly less complications in the retroperitoneoscopic group as compared to transperitoneal group (OR 0.52, 95%CI 0.33–0.83, I2 = 0%). Hand-assisted techniques showed shorter first warm ischemia and operation times.Conclusions
Hand-assistance reduces the operation and first warm ischemia times and may improve safety for surgeons with less experience in laparoscopic donor nephrectomy. The retroperitoneoscopic approach was significantly associated with less complications. However, given the, in general, poor to intermediate quality and considerable heterogeneity in the included studies, further high-quality studies are required.Trial Registration
The review protocol was registered in the PROSPERO database before the start of the review process (CRD number 42013006565). 相似文献4.
Jennifer Hanratty Nuala Livingstone Shannon Robalino Caroline B. Terwee Magdalena Glod Inalegwu P. Oono Jacqui Rodgers Geraldine Macdonald Helen McConachie 《PloS one》2015,10(12)
Background
Behaviour problems are common in young children with autism spectrum disorder (ASD). There are many different tools used to measure behavior problems but little is known about their validity for the population.Objectives
To evaluate the measurement properties of behaviour problems tools used in evaluation of intervention or observational research studies with children with ASD up to the age of six years.Methods
Behaviour measurement tools were identified as part of a larger, two stage, systematic review. First, sixteen major electronic databases, as well as grey literature and research registers were searched, and tools used listed and categorized. Second, using methodological filters, we searched for articles examining the measurement properties of the tools in use with young children with ASD in ERIC, MEDLINE, EMBASE, CINAHL, and PsycINFO. The quality of these papers was then evaluated using the COSMIN checklist.Results
We identified twelve tools which had been used to measure behaviour problems in young children with ASD, and fifteen studies which investigated the measurement properties of six of these tools. There was no evidence available for the remaining six tools. Two questionnaires were found to be the most robust in their measurement properties, the Child Behavior Checklist and the Home Situations Questionnaire—Pervasive Developmental Disorders version.Conclusions
We found patchy evidence on reliability and validity, for only a few of the tools used to measure behaviour problems in young children with ASD. More systematic research is required on measurement properties of tools for use in this population, in particular to establish responsiveness to change which is essential in measurement of outcomes of intervention.PROSPERO Registration Number
CRD42012002223 相似文献5.
Maria Glória Teixeira Jo?o Bosco Siqueira Jr Germano L. C. Ferreira Lucia Bricks Graham Joint 《PLoS neglected tropical diseases》2013,7(12)
A literature survey and analysis was conducted to describe the epidemiology of dengue disease in Brazil reported between 2000 and 2010. The protocol was registered on PROSPERO (CRD42011001826: http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42011001826). Between 31 July and 4 August 2011, the published literature was searched for epidemiological studies of dengue disease, using specific search strategies for each electronic database. A total of 714 relevant citations were identified, 51 of which fulfilled the inclusion criteria. The epidemiology of dengue disease in Brazil, in this period, was characterized by increases in the geographical spread and incidence of reported cases. The overall increase in dengue disease was accompanied by a rise in the proportion of severe cases. The epidemiological pattern of dengue disease in Brazil is complex and the changes observed during this review period are likely to have been influenced by multiple factors. Several gaps in epidemiological knowledge regarding dengue disease in Brazil were identified that provide avenues for future research, in particular, studies of regional differences, genotype evolution, and age-stratified seroprevalence.
Systematic Review Registration
PROSPERO registration number: CRD42011001826. 相似文献6.
Gimena Hernández Mónica Avila àngels Pont Olatz Garin Jordi Alonso Laurent Laforest Christopher J Cates Montserrat Ferrer 《Respiratory research》2014,15(1):83
Background
Although several systematic reviews investigated the safety of long-acting beta–agonists (LABAs) in asthma, they mainly addressed randomized clinical trials while evidence from non-randomized studies has been mostly neglected. We aim to assess the risk of serious adverse events in adults and children with asthma treated with LABAs and Inhaled Corticosteroids (ICs), compared to patients treated only with ICs, from published non-randomized studies.Methods
The protocol registration number was CRD42012003387 (http://www.crd.york.ac.uk/Prospero). Literature search for articles published since 1990 was performed in MEDLINE and EMBASE. Two authors selected studies independently for inclusion and extracted the data. A third reviewer resolved discrepancies. To assess the risk of serious adverse events, meta-analyses were performed calculating odds ratio summary estimators using random effect models when heterogeneity was found, and fixed effect models otherwise.Results
Of 4,415 candidate articles, 1,759 abstracts were reviewed and 220 articles were fully read. Finally, 19 studies met the inclusion criteria. Most of them were retrospective observational cohorts. Sample sizes varied from 50 to 514,216. The meta-analyses performed (69,939-624,303 participants according to the outcome considered) showed that odds ratio of the LABAs and ICs combined treatment when compared with ICs alone was: 0.88 (95% CI 0.69-1.12) for asthma-related hospitalization; 0.75 (95% CI 0.66-0.84) for asthma-related emergency visits; 1.02 (95% CI 0.94-1.10) for systemic corticosteroids; and 0.95 (95% CI 0.9-1.0) for the combined outcome.Conclusions
Evidence from observational studies shows that the combined treatment of LABAs and ICs is not associated with a higher risk of serious adverse events, compared to ICs alone. Major gaps identified were prospective design, paediatric population and inclusion of mortality as a primary outcome. 相似文献7.
Fu-Chen Kuo Sheng-Wen Su Chia-Fang Wu Meng-Chuan Huang Jentaie Shiea Bai-Hsiu Chen Yi-Ling Chen Ming-Tsang Wu 《PloS one》2015,10(6)
Background
The purpose of this study was to examine the relationship of phthalates exposure with thyroid function in pregnant women and their newborns.Methods
One hundred and forty-eight Taiwanese maternal and infant pairs were recruited from E-Da hospital in southern Taiwan between 2009 and 2010 for analysis. One-spot urine samples and blood samples in the third trimester of pregnant women and their cord blood samples at delivery were collected. Nine phthalate metabolites in urine were determined by triple quadrupole liquid chromatography tandem mass spectrometry, whereas serum from pregnant women and their cord blood were used to measure thyroid profiles (thyroid-stimulating hormone [TSH], thyroxine, free thyroxine, and triiodothyronine) by radioimmunoassay.Results
Median levels of urinary mono-n-butyl phthalate, mono-ethyl phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate (μg/g creatinine) were the three highest phthalate metabolites, which were 37.81, 34.51, and 21.73, respectively. Using Bonferroni correction at a significance of < 0.006, we found that urinary mono-benzyl phthalate (MBzP) levels were significantly and negatively associated with serum TSH in cord blood (β = -2.644, p = 0.003).Conclusions
Maternal urinary MBzP, of which the parental compound is butylbenzyl phthalate, may affect TSH activity in newborns. The alteration of thyroid homeostasis by certain phthalates in the early life, a critical period for neurodevelopment, is an urgent concern. 相似文献8.
Ma?na L'Azou Anne-Frieda Taurel Claude Flamand Philippe Quénel 《PLoS neglected tropical diseases》2014,8(11)
Dengue is a public health concern across the globe, and an escalating problem in the Americas. As part of a wider programme (covering Latin America and South East Asia) to characterize the epidemiology of dengue in dengue endemic areas, we undertook a systematic literature review to assess epidemiological trends (incidence, timing and duration of outbreaks/epidemics, age and sex distribution, serotype distribution, seroprevalence and disease severity) for dengue across the French Territories of the Americas (FTA), in French Guiana, Guadeloupe, Martinique, Saint Martin and Saint Barthélemy between 2000 and 2012 (CRD42012002341: http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42012002341). Of 413 relevant data sources identified, 45 were eligible for inclusion. A large proportion of the available data were from national surveillance reports, and 12 publications were from peer-reviewed journals. During the review period, 3–5 epidemics were identified in each of the island territories and French Guiana, and epidemics were often associated with a shift in the predominant circulating dengue virus serotype. Substantial gaps in epidemiological knowledge were identified. In particular, information regarding dengue virus genotype distribution, seroprevalence and age distribution of dengue were lacking. Additionally, much of the available data were from epidemic years; data from inter-epidemic periods were sparse. Nevertheless, the available epidemiological data showed that dengue is endemic across the FTA and suggest an evolution towards hyperendemicity, highlighting the need to continue the efforts with the existing surveillance programmes to assist in planning an effective vaccination programme once a dengue vaccine is deployed.
Protocol registration
PROSPERO CRD42012002341 相似文献9.
10.
Backgrounds
Drug-eluting stents (DES) with biodegradable polymers have been developed to address the risk of thrombosis associated with first-generation DES. We aimed to determine the efficacy and safety of biodegradable polymer biolimus-eluting stents (BES) versus durable polymer DES.Methods
Systematic database searches of MEDLINE (1950 to June 2013), EMBASE (1966 to June 2013), the Cochrane Central Register of Controlled Trials (Issue 6 of 12, June 2013), and a review of related literature were conducted. All randomized controlled trials comparing biodegradable polymer BES versus durable polymer DES were included.Results
Eight randomized controlled trials investigating 11,015 patients undergoing percutaneous coronary interventions were included in the meta-analysis. The risk of major adverse cardiac events did not differ significantly between the patients treated with the biodegradable polymer BES and the durable polymer DES (Relative risk [RR], 0.970; 95% CI, 0.848–1.111; p = 0.662). However, biodegradable polymer BES was associated with reduced risk of very late ST compared with the durable polymer DES, while the risk of early or late ST was similar (RR for early or late ST, 1.167; 95% CI 0.755–1.802; p = 0.487; RR 0.273; 95% CI 0.115–0.652; p = 0.003; p for interaction = 0.003).Conclusions
In this meta-analysis of randomized controlled trials, treatments with biodegradable polymer BES did not significantly reduce the risk of major adverse cardiac events, but demonstrated a significantly lower risk of very late ST when compared to durable polymer DES. This conclusion requires confirmation by further studies with long-term follow-up.PROSPERO register number
http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013004364#.UnM2lfmsj6J 相似文献11.
A literature survey and analysis was conducted to describe the epidemiology of dengue disease in Thailand reported between 2000 and 2011. The literature search identified 610 relevant sources, 40 of which fulfilled the inclusion criteria defined in the review protocol. Peaks in the number of cases occurred during the review period in 2001, 2002, 2008 and 2010. A shift in age group predominance towards older ages continued through the review period. Disease incidence and deaths remained highest in children aged ≤15 years and case fatality rates were highest in young children. Heterogeneous geographical patterns were observed with higher incidence rates reported in the Southern region and serotype distribution varied in time and place. Gaps identified in epidemiological knowledge regarding dengue disease in Thailand provide several avenues for future research, in particular studies of seroprevalence.
Protocol registration
PROSPERO CRD42012002170 相似文献12.
Xue-Qiang Wang Jie-Jiao Zheng Zhuo-Wei Yu Xia Bi Shu-Jie Lou Jing Liu Bin Cai Ying-Hui Hua Mark Wu Mao-Ling Wei Hai-Min Shen Yi Chen Yu-Jian Pan Guo-Hui Xu Pei-Jie Chen 《PloS one》2012,7(12)
Objective
To review the effects of core stability exercise or general exercise for patients with chronic low back pain (LBP).Summary of Background Data
Exercise therapy appears to be effective at decreasing pain and improving function for patients with chronic LBP in practice guidelines. Core stability exercise is becoming increasingly popular for LBP. However, it is currently unknown whether core stability exercise produces more beneficial effects than general exercise in patients with chronic LBP.Methods
Published articles from 1970 to October 2011 were identified using electronic searches. For this meta-analysis, two reviewers independently selected relevant randomized controlled trials (RCTs) investigating core stability exercise versus general exercise for the treatment of patients with chronic LBP. Data were extracted independently by the same two individuals who selected the studies.Results
From the 28 potentially relevant trials, a total of 5 trials involving 414 participants were included in the current analysis. The pooling revealed that core stability exercise was better than general exercise for reducing pain [mean difference (−1.29); 95% confidence interval (−2.47, −0.11); P = 0.003] and disability [mean difference (−7.14); 95% confidence interval (−11.64, −2.65); P = 0.002] at the time of the short-term follow-up. However, no significant differences were observed between core stability exercise and general exercise in reducing pain at 6 months [mean difference (−0.50); 95% confidence interval (−1.36, 0.36); P = 0.26] and 12 months [mean difference (−0.32); 95% confidence interval (−0.87, 0.23); P = 0.25].Conclusions
Compared to general exercise, core stability exercise is more effective in decreasing pain and may improve physical function in patients with chronic LBP in the short term. However, no significant long-term differences in pain severity were observed between patients who engaged in core stability exercise versus those who engaged in general exercise.Systematic Review Registration
http://www.crd.york.ac.uk/PROSPERO PROSPERO registration number: CRD42011001717. 相似文献13.
Joao C. Aguiar Jessica Bolton Joyce Wanga John B. Sacci Hideyuki Iriko Julie K. Mazeika Eun-Taek Han Keith Limbach Noelle B. Patterson Martha Sedegah Ann-Marie Cruz Takafumi Tsuboi Stephen L. Hoffman Daniel Carucci Michael R. Hollingdale Eileen D. Villasante Thomas L. Richie 《PloS one》2015,10(8)
Background
Nearly 100% protection against malaria infection can be achieved in humans by immunization with P. falciparum radiation-attenuated sporozoites (RAS). Although it is thought that protection is mediated by T cell and antibody responses, only a few of the many pre-erythrocytic (sporozoite and liver stage) antigens that are targeted by these responses have been identified.Methodology
Twenty seven P. falciparum pre-erythrocytic antigens were selected using bioinformatics analysis and expression databases and were expressed in a wheat germ cell-free protein expression system. Recombinant proteins were recognized by plasma from RAS-immunized subjects, and 21 induced detectable antibody responses in mice and rabbit and sera from these immunized animals were used to characterize these antigens. All 21 proteins localized to the sporozoite: five localized to the surface, seven localized to the micronemes, cytoplasm, endoplasmic reticulum or nucleus, two localized to the surface and cytoplasm, and seven remain undetermined. PBMC from RAS-immunized volunteers elicited positive ex vivo or cultured ELISpot responses against peptides from 20 of the 21 antigens.Conclusions
These T cell and antibody responses support our approach of using reagents from RAS-immunized subjects to screen potential vaccine antigens, and have led to the identification of a panel of novel P. falciparum antigens. These results provide evidence to further evaluate these antigens as vaccine candidates.Trial Registration
ClinicalTrials.gov NCT00870987 ClinicalTrials.gov NCT00392015 相似文献14.
Joe W. E. Moss Thomas S. Davies Iveta Garaiova Sue F. Plummer Daryn R. Michael Dipak P. Ramji 《PloS one》2016,11(3)
Introduction
Atherosclerosis is the underlying cause of cardiovascular disease that leads to more global mortalities each year than any other ailment. Consumption of active food ingredients such as phytosterols, omega-3 polyunsaturated fatty acids and flavanols are known to impart beneficial effects on cardiovascular disease although the combined actions of such agents in atherosclerosis is poorly understood. The aim of this study was to screen a nutritional supplement containing each of these active components for its anti-atherosclerotic effect on macrophages in vitro.Results
The supplement attenuated the expression of intercellular adhesion molecule-1 and macrophage chemoattractant protein-1 in human and murine macrophages at physiologically relevant doses. The migratory capacity of human monocytes was also hindered, possibly mediated by eicosapentaenoic acid and catechin, while the ability of foam cells to efflux cholesterol was improved. The polarisation of murine macrophages towards a pro-inflammatory phenotype was also attenuated by the supplement.Conclusion
The formulation was able to hinder multiple key steps of atherosclerosis development in vitro by inhibiting monocyte recruitment, foam cell formation and macrophage polarisation towards an inflammatory phenotype. This is the first time a combination these ingredients has been shown to elicit such effects and supports its further study in preclinical in vivo models. 相似文献15.
Kristian H. Mikkelsen Morten Frost Martin I. Bahl Tine R. Licht Ulrich S. Jensen Jacob Rosenberg Oluf Pedersen Torben Hansen Jens F. Rehfeld Jens J. Holst Tina Vilsb?ll Filip K. Knop 《PloS one》2015,10(11)
Objective
The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans.Methods
Meal tests with measurements of postprandial glucose tolerance and postprandial release of insulin and gut hormones were performed before, immediately after and 6 weeks after a 4-day, broad-spectrum, per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in a group of 12 lean and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gut microbiota composition.Results
Acute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in postprandial glucose tolerance, insulin secretion or plasma lipid concentrations were found. Apart from an acute and reversible increase in peptide YY secretion, no changes were observed in postprandial gut hormone release.Conclusion
As evaluated by selective cultivation of gut bacteria, a broad-spectrum 4-day antibiotics course with vancomycin, gentamycin and meropenem induced shifts in gut microbiota composition that had no clinically relevant short or long-term effects on metabolic variables in healthy glucose-tolerant males.Trial Registration
clinicaltrials.gov NCT01633762 相似文献16.
Brian Reichow Chiara Servili M. Taghi Yasamy Corrado Barbui Shekhar Saxena 《PLoS medicine》2013,10(12)
Background
The development of effective treatments for use by non-specialists is listed among the top research priorities for improving the lives of people with mental illness worldwide. The purpose of this review is to appraise which interventions for children with intellectual disabilities or lower-functioning autism spectrum disorders delivered by non-specialist care providers in community settings produce benefits when compared to either a no-treatment control group or treatment-as-usual comparator.Methods and Findings
We systematically searched electronic databases through 24 June 2013 to locate prospective controlled studies of psychosocial interventions delivered by non-specialist providers to children with intellectual disabilities or lower-functioning autism spectrum disorders. We screened 234 full papers, of which 34 articles describing 29 studies involving 1,305 participants were included. A majority of the studies included children exclusively with a diagnosis of lower-functioning autism spectrum disorders (15 of 29, 52%). Fifteen of twenty-nine studies (52%) were randomized controlled trials and just under half of all effect sizes (29 of 59, 49%) were greater than 0.50, of which 18 (62%) were statistically significant. For behavior analytic interventions, the best outcomes were shown for development and daily skills; cognitive rehabilitation, training, and support interventions were found to be most effective for improving developmental outcomes, and parent training interventions to be most effective for improving developmental, behavioral, and family outcomes. We also conducted additional subgroup analyses using harvest plots. Limitations include the studies'' potential for performance bias and that few were conducted in lower- and middle-income countries.Conclusions
The findings of this review support the delivery of psychosocial interventions by non-specialist providers to children who have intellectual disabilities or lower-functioning autism spectrum disorders. Given the scarcity of specialists in many low-resource settings, including many lower- and middle-income countries, these findings may provide guidance for scale-up efforts for improving outcomes for children with developmental disorders or lower-functioning autism spectrum disorders.Protocol Registration
PROSPERO CRD42012002641 Please see later in the article for the Editors'' Summary 相似文献17.
Akhirunnesa Mily Rokeya Sultana Rekha S. M. Mostafa Kamal Abu Saleh Mohammad Arifuzzaman Zeaur Rahim Lamia Khan Md. Ahsanul Haq Khaliqu Zaman Peter Bergman Susanna Brighenti Gudmundur H. Gudmundsson Birgitta Agerberth Rubhana Raqib 《PloS one》2015,10(9)
Background
Development of new tuberculosis (TB) drugs and alternative treatment strategies are urgently required to control the global spread of TB. Previous results have shown that vitamin D3 (vitD3) and 4-phenyl butyrate (PBA) are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects.Objective
To examine if oral adjunctive therapy with 5,000IU vitD3 or 2x500 mg PBA or PBA+vitD3 to standard chemotherapy would lead to enhanced recovery in sputum smear-positive pulmonary TB patients.Methods
Adult TB patients (n = 288) were enrolled in a randomized, double-blind, placebo-controlled trial conducted in Bangladesh. Primary endpoints included proportions of patients with a negative sputum culture at week 4 and reduction in clinical symptoms at week 8. Clinical assessments and sputum smear microscopy were performed weekly up to week 4, fortnightly up to week 12 and at week 24; TB culture was performed at week 0, 4 and 8; concentrations of LL-37 in cells, 25-hydroxyvitamin D3 (25(OH)D3) in plasma and ex vivo bactericidal function of monocyte-derived macrophages (MDM) were determined at week 0, 4, 8, 12 and additionally at week 24 for plasma 25(OH)D3.Results
At week 4, 71% (46/65) of the patients in the PBA+vitD3-group (p = 0.001) and 61.3% (38/62) in the vitD3-group (p = 0.032) were culture negative compared to 42.2% (27/64) in the placebo-group. The odds of sputum culture being negative at week 4 was 3.42 times higher in the PBA+vitD3-group (p = 0.001) and 2.2 times higher in vitD3-group (p = 0.032) compared to placebo. The concentration of LL-37 in MDM was significantly higher in the PBA-group compared to placebo at week 12 (p = 0.034). Decline in intracellular Mtb growth in MDM was earlier in the PBA-group compared to placebo (log rank 11.38, p = 0.01).Conclusion
Adjunct therapy with PBA+vitD3 or vitD3 or PBA to standard short-course therapy demonstrated beneficial effects towards clinical recovery and holds potential for host-directed-therapy in the treatment of TB.Trial Registration
clinicaltrials.gov NCT01580007 相似文献18.
Peter Y. Bai Gary A. Wittert Anne W. Taylor Sean A. Martin Robert W. Milne Zumin Shi 《PloS one》2015,10(4)
Objective
To investigate the associations between socio-demographic status, lifestyle factors, dietary patterns and urinary total phthalate concentration in a cohort of South Australian men.Method
We randomly selected 1527 males aged 39 to 84 from wave two of the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study. Total phthalate concentration was examined in fasting morning urine samples. Socio-demographic and lifestyle factors were assessed by questionnaire. Food intake was assessed by food frequency questionnaire (FFQ). Dietary patterns were constructed using factor analysis.Results
Total phthalates were detected in 99.6% of the urine samples. The overall geometric mean (95% CI) of total phthalate concentration was 112.4 (107.5–117.5) ng/mL. The least square geometric means (LSGMs) of total phthalate concentration were significantly higher among people who were obese (127.8 ng/mL), consuming less than two serves fruit per day (125.7 ng/mL) and drinking more than one can (375mL) of carbonated soft drink per day (131.9 ng/mL). Two dietary patterns were identified: a prudent dietary pattern and a western dietary pattern. Both the western dietary pattern (p = 0.002) and multiple lifestyle risk factors including smoking, obesity, insufficient physical activity and the highest quartile of the western dietary pattern (p<0.001), were positively associated with total phthalate levels. There was no significant relationship between total phthalate concentration and socio-demographic status.Conclusion
Phthalate exposure is ubiquitous and positively associated with lifestyle risk factors in urban dwelling Australian men. 相似文献19.
Laura Gonzalez-Fajardo Olga Lucía Fernández Diane McMahon-Pratt Nancy Gore Saravia 《PLoS neglected tropical diseases》2015,9(5)
Background
Therapeutic response in infectious disease involves host as well as microbial determinants. Because the immune and inflammatory response to Leishmania (Viannia) species defines the outcome of infection and efficacy of treatment, immunomodulation is considered a promising therapeutic strategy. However, since Leishmania infection and antileishmanial drugs can themselves modulate drug transport, metabolism and/or immune responses, immunotherapeutic approaches require integrated assessment of host and parasite responses.Methodology
To achieve an integrated assessment of current and innovative therapeutic strategies, we determined host and parasite responses to miltefosine and meglumine antimoniate alone and in combination with pentoxifylline or CpG 2006 in peripheral blood mononuclear cells (PBMCs) of cutaneous leishmaniasis patients. Parasite survival and secretion of TNF-α, IFN-γ, IL-10 and IL-13 were evaluated concomitantly in PBMCs infected with Luc-L. (V.) panamensis exposed to meglumine antimoniate (4, 8, 16, 32 and 64 μg SbV/mL) or miltefosine (2, 4, 8, 16 and 32 μM HePC). Concentrations of 4 μM of miltefosine and 8 μg SbV/mL were selected for evaluation in combination with immunomodulators based on the high but partial reduction of parasite burden by these antileishmanial concentrations without affecting cytokine secretion of infected PBMCs. Intracellular parasite survival was determined by luminometry and cytokine secretion measured by ELISA and multiplex assays.Principal Findings
Anti- and pro-inflammatory cytokines characteristic of L. (V.) panamensis infection were evaluable concomitantly with viability of Leishmania within monocyte-derived macrophages present in PBMC cultures. Both antileishmanial drugs reduced the parasite load of macrophages; miltefosine also suppressed IL-10 and IL-13 secretion in a dose dependent manner. Pentoxifylline did not affect parasite survival or alter antileishmanial effects of miltefosine or meglumine antimoniate. However, pentoxifylline diminished secretion of TNF-α, IFN-γ and IL-13, cytokines associated with the outcome of infection by species of the Viannia subgenus. Exposure to CpG diminished the leishmanicidal effect of meglumine antimoniate, but not miltefosine, and significantly reduced secretion of IL -10, alone and in combination with either antileishmanial drug. IL-13 increased in response to CpG plus miltefosine.Conclusions and Significance
Human PBMCs allow integrated ex vivo assessment of antileishmanial treatments, providing information on host and parasite determinants of therapeutic response that may be used to tailor therapeutic strategies to optimize clinical resolution. 相似文献20.
Claudia Spies Alawi Luetz Gunnar Lachmann Markus Renius Clarissa von Haefen Klaus-Dieter Wernecke Marcus Bahra Alexander Schiemann Marco Paupers Christian Meisel 《PloS one》2015,10(12)