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1.
Andreas Martens Sebastian V. Rojas Hassina Baraki Christian Rathert Natalie Schecker Sara Rojas Hernandez Kristin Schwanke Robert Zweigerdt Ulrich Martin Shunsuke Saito Axel Haverich Ingo Kutschka 《PloS one》2014,9(8)
Background
The limited effectiveness of cardiac cell therapy has generated concern regarding its clinical relevance. Experimental studies show that cell retention and engraftment are low after injection into ischemic myocardium, which may restrict therapy effectiveness significantly. Surgical aspects and mechanical loss are suspected to be the main culprits behind this phenomenon. As current techniques of monitoring intramyocardial injections are complex and time-consuming, the aim of the study was to develop a fast and simple model to study cardiac retention and distribution following intramyocardial injections. For this purpose, our main hypothesis was that macroscopic fluorescence imaging could adequately serve as a detection method for intramyocardial injections.Methods and Results
A total of 20 mice underwent ligation of the left anterior descending artery (LAD) for myocardial infarction. Fluorescent microspheres with cellular dimensions were used as cell surrogates. Particles (5×105) were injected into the infarcted area of explanted resting hearts (Ex vivo myocardial injetions EVMI, n = 10) and in vivo into beating hearts (In vivo myocardial injections IVMI, n = 10). Microsphere quantification was performed by fluorescence imaging of explanted organs. Measurements were repeated after a reduction to homogenate dilutions. Cardiac microsphere retention was 2.78×105±0.31×105 in the EVMI group. In the IVMI group, cardiac retention of microspheres was significantly lower (0.74×105±0.18×105; p<0.05). Direct fluorescence imaging revealed venous drainage through the coronary sinus, resulting in a microsphere accumulation in the left (0.90×105±0.20×105) and the right (1.07×105±0.17×105) lung. Processing to homogenates involved further particle loss (p<0.05) in both groups.Conclusions
We developed a fast and simple direct fluorescence imaging method for biodistribution analysis which enabled the quantification of fluorescent microspheres after intramyocardial delivery using macroscopic fluorescence imaging. This new technique showed massive early particle loss and venous drainage into the right atrium leading to substantial accumulation of graft particles in both lungs. 相似文献2.
Miriam Bolz Nicolas Ruggli Marie-Thérèse Ruf Meret E. Ricklin Gert Zimmer Gerd Pluschke 《PLoS neglected tropical diseases》2014,8(7)
Background
Buruli ulcer (BU) is a slowly progressing, necrotising disease of the skin caused by infection with Mycobacterium ulcerans. Non-ulcerative manifestations are nodules, plaques and oedema, which may progress to ulceration of large parts of the skin. Histopathologically, BU is characterized by coagulative necrosis, fat cell ghosts, epidermal hyperplasia, clusters of extracellular acid fast bacilli (AFB) in the subcutaneous tissue and lack of major inflammatory infiltration. The mode of transmission of BU is not clear and there is only limited information on the early pathogenesis of the disease available.Methodology/Principal Findings
For evaluating the potential of the pig as experimental infection model for BU, we infected pigs subcutaneously with different doses of M. ulcerans. The infected skin sites were excised 2.5 or 6.5 weeks after infection and processed for histopathological analysis. With doses of 2×107 and 2×106 colony forming units (CFU) we observed the development of nodular lesions that subsequently progressed to ulcerative or plaque-like lesions. At lower inoculation doses signs of infection found after 2.5 weeks had spontaneously resolved at 6.5 weeks. The observed macroscopic and histopathological changes closely resembled those found in M. ulcerans disease in humans.Conclusion/Significance
Our results demonstrate that the pig can be infected with M. ulcerans. Productive infection leads to the development of lesions that closely resemble human BU lesions. The pig infection model therefore has great potential for studying the early pathogenesis of BU and for the development of new therapeutic and prophylactic interventions. 相似文献3.
Laura Selva Rachid Benmessaoud Miguel Lanaspa Imane Jroundi Cinta Moraleda Sozinho Acacio Melania I?igo Alien Bastiani Manuel Monsonis Roman Pallares Quique Bassat Carmen Mu?oz-Almagro 《PloS one》2013,8(10)
Background
Dried blood spot (DBS) is a reliable blood collection method for storing samples at room temperature and easily transporting them. We have previously validated a Real-Time PCR for detection of Streptococcus pneumoniae in DBS. The objective of this study was to apply this methodology for the diagnosis of S. pneumoniae and Haemophilus influenzae b (Hib) in DBS samples of children with pneumonia admitted to two hospitals in Mozambique and Morocco.Methods
Ply and wzg genes of S. pneumoniae and bexA gene of Hib, were used as targets of Real-Time PCR. 329 DBS samples of children hospitalized with clinical diagnosis of pneumonia were tested.Results
Real-Time PCR in DBS allowed for a significant increase in microbiological diagnosis of S. pneumoniae and Hib. When performing blood bacterial culture, only ten isolates of S. pneumoniae and none of Hib were detected (3·0% positivity rate, IC95% 1·4-5·5%). Real-Time PCR from DBS samples increased the detection yield by 4x fold, as 30 S. pneumoniae and 11 Hib cases were detected (12·4% positivity rate, IC95% 9·0-16·5%; P<0·001).Conclusion
Real-Time PCR applied in DBS may be a valuable tool for improving diagnosis and surveillance of pneumonia caused by S. pneumoniae or Hib in developing countries. 相似文献4.
Aims
The goals of this paper were to evaluate the differentiation of bone marrow mesenchymal stem cells (BMSCs) into hepatocyte-like cells in vitro, and to determine whether stem cells can migrate and plant into the liver with portal hypertension accompanied by the end-stage of liver disease.Methods
BMSCs were isolated from rats and amplified with hepatocyte growth factor (HGF) and fibroblast growth factor-4 (FGF-4). The expression of alpha-fetoprotein (AFP), cytokeratin 18 (CK-18), and albumin (ALB) was detected by immunofluorescence in induced cells. Rats were randomly divided into experimental (with common bile duct ligation) and control groups. After injection of fluorescence labeled cells, cell distribution was observed under a fluorescence microscope. The integrated optical density (IOD) and cell distribution scores were evaluated using Image-Pro Plus 6.0 software. The portal pressure was measured before the rats were killed.Results
After being induced with HGF and FGF-4, the Golgi apparatus, endoplasmic reticulum, ribosomes, and mitochondria all significantly increased in the fifth generation cells. Immunofluorescent analysis showed that the induced cells expressed AFP, CK-18, and ALB. BMSCs were stained by CM-Dil, and the labeling rate was as high as 95.5%. The portal pressure in experimental group was much higher than that of the control group (18.04±2.35 vs. 9.75±1.40cm H2O p<0.01). The IOD of transplanted cells in the experimental group was also significantly higher than that of the control group (11.30±2.09×105 vs. 2.93±0.88×105, p<0.01). In addition, the cell distribution score in the experimental group was lower than that of the control group (1.99±0.36 vs. 2.36±0.27, P<0.05).Conclusions
The combination of HGF and FGF-4 induces the differentiation of BMSCs into hepatocyte-like cells, which express AFP, CK-18, and ALB. In addition, the recruitment of BMSCs (after transplantation in the spleen) was improved in rats with portal hypertension. 相似文献5.
Background
It is difficult to experimentally infect volunteers with RV strains to which the subject demonstrates serological immunity. However, in RV challenges, viral clearance begins before de novo adaptive immune responses would develop. We speculated that adaptive immunity to RV reflects heterologous immunity by effector memory cells.Methods
DCs were generated from monocytes using GM-CSF and IL-4 and RV39 loading accomplished with a dose of ∼350 TCID50/105 cells. RV-induced maturation was established as modulation of MHC class II, CD80, CD83, and CD86. Circulating RV targeting CD4 and CD8 T cells were investigated as induction of RV-specific proliferation (CFSE-dilution).Results
Maturation of DC by RV was confirmed as upregulation of MHC Class II (83.3±5.0% to 87.8±4.1%), CD80 (39.4±7.2% to 47.6±7.7%) and CD86 (78.4±4.7% to 84.1±3.4%). Both CD4 and CD8 memory T cells were recognized in the circulation of healthy subjects.Conclusions
RV drives DC maturation and results in their ability to present RV antigens to both T helper and cytotoxic lymphocytes. Both CD4 and CD8 cells capable of recognizing RV-associated antigens are present in the circulation of healthy subjects where they are presumably involved in immune surveillance and explain the rapid recruitment of an adaptive immune response during RV infection. 相似文献6.
Zhongyi Yang Yifei Sun Jing Xue Zhifeng Yao Junyan Xu Jingyi Cheng Wei Shi Beiling Zhu Yongping Zhang Yingjian Zhang 《PloS one》2013,8(10)
Objective
To assess the clinical value of dual tracers Positron emission tomography/computed tomography (PET/CT) 18F-fluoroestradiol (18F-FES) and 18F-fluorodeoxyglucose (18F-FDG) in predicting neoadjuvant chemotherapy response (NAC) of breast cancer.Methods
Eighteen consecutive patients with newly diagnosed, non-inflammatory, stage II and III breast cancer undergoing NAC were included. Before chemotherapy, they underwent both 18F-FES and 18F-FDG PET/CT scans. Surgery was performed after three to six cycles of chemotherapy. Tumor response was graded and divided into two groups: the responders and non-responders. We used the maximum standardized uptake value (SUVmax) to qualify each primary lesion.Results
Pathologic analysis revealed 10 patients were responders while the other 8 patients were non-responders. There was no statistical difference of SUVmax-FDG and tumor size between these two groups (P>0.05). On the contrary, SUVmax-FES was lower in responders (1.75±0.66 versus 4.42±1.14; U=5, P=0.002); and SUVmax-FES/FDG also showed great value in predicting outcome (0.16±0.06 versus 0.54±0.22; U=5, P=0.002).Conclusions
Our study showed 18F-FES PET/CT might be feasible to predict response of NAC. However, whether the use of dual tracers 18F-FES and 18F-FDG has complementary value should be further studied. 相似文献7.
Patricia L. Hibberd Lauren Kleimola Anne-Maria Fiorino Christine Botelho Miriam Haverkamp Irina Andreyeva Debra Poutsiaka Claire Fraser Gloria Solano-Aguilar David R. Snydman 《PloS one》2014,9(12)
Background
Although Lactobacillus rhamnosus GG ATCC 53103 (LGG) has been consumed by 2 to 5 million people daily since the mid 1990s, there are few clinical trials describing potential harms of LGG, particularly in the elderly.Objectives
The primary objective of this open label clinical trial is to assess the safety and tolerability of 1×1010 colony forming units (CFU) of LGG administered orally twice daily to elderly volunteers for 28 days. The secondary objectives were to evaluate the effects of LGG on the gastrointestinal microbiome, host immune response and plasma cytokines.Methods
Fifteen elderly volunteers, aged 66–80 years received LGG capsules containing 1×1010 CFU, twice daily for 28 days and were followed through day 56. Volunteers completed a daily diary, a telephone call on study days 3, 7 and 14 and study visits in the Clinical Research Center at baseline, day 28 and day 56 to determine whether adverse events had occurred. Assessments included prompted and open-ended questions.Results
There were no serious adverse events. The 15 volunteers had a total of 47 events (range 1–7 per volunteer), 39 (83%) of which were rated as mild and 40% of which were considered related to consuming LGG. Thirty-one (70%) of the events were expected, prompted symptoms while 16 were unexpected events. The most common adverse events were gastrointestinal (bloating, gas, and nausea), 27 rated as mild and 3 rated as moderate. In the exploratory analysis, the pro-inflammatory cytokine interleukin 8 decreased during LGG consumption, returning towards baseline one month after discontinuing LGG (p = 0.038) while there was no difference in other pro- or anti-inflammatory plasma cytokines.Conclusions
Lactobacillus rhamnosus GG ATCC 53103 is safe and well tolerated in healthy adults aged 65 years and older.Trial Registration
ClinicalTrials.gov NCT 01274598 相似文献8.
Christian-Heinz Anderwald Andrea Tura Alois Gessl Anton Luger Giovanni Pacini Michael Krebs 《PloS one》2013,8(10)
Background
Insulin-resistance is commonly found in adrenal incidentaloma (AI) patients. However, little is known about beta-cell secretion in AI, because comparisons are difficult, since beta–cell-function varies with altered insulin-sensitivity.Objectives
To retrospectively analyze beta–cell function in non-diabetic AI, compared to healthy controls (CON).Methods
AI (n=217, 34%males, 57±1years, body-mass-index:27.7±0.3kg/m2) and CON [n=25, 32%males, 56±1years, 26.7±0.8kg/m2] with comparable anthropometry (p≥0.31) underwent oral-glucose-tolerance-tests (OGTTs) with glucose, insulin, and C–peptide measurements. 1mg-dexamethasone-suppression-tests were performed in AI. AI were divided according to post–dexamethasone-suppression–test cortisol-thresholds of 1.8 and 5µg/dL into 3subgroups: pDexa<1.8µg/dL, pDexa1.8-5µg/dL and pDexa>5µg/dL. Using mathematical modeling, whole-body insulin-sensitivity [Clamp-like-Index (CLIX)], insulinogenic Index, Disposition Index, Adaptation Index, and hepatic insulin extraction were calculated.Results
CLIX was lower in AI combined (4.9±0.2mg·kg-1·min-1), pDexa<1.8µg/dL (4.9±0.3) and pDexa1.8-5µg/dL (4.7±0.3, p<0.04 vs.CON:6.7±0.4). Insulinogenic and Disposition Indexes were 35%–97% higher in AI and each subgroup (p<0.008 vs.CON), whereas C–peptide–derived Adaptation Index, compensating for insulin-resistance, was comparable between AI, subgroups, and CON. Mathematical estimation of insulin–derived (insulinogenic and Disposition) Indexes from associations to insulin-sensitivity in CON revealed that AI-subgroups had ~19%-32% higher insulin-secretion than expectable. These insulin-secretion-index differences negatively (r=-0.45, p<0.001) correlated with hepatic insulin extraction, which was 13-16% lower in AI and subgroups (p<0.003 vs.CON).Conclusions
AI-patients show insulin-resistance, but adequately adapted insulin secretion with higher insulin concentrations during an OGTT, because of decreased hepatic insulin extraction; this finding affects all AI-patients, regardless of dexamethasone-suppression-test outcome. 相似文献9.
Background and Objective
Reflux esophagitis (RE) is characterized by inflammation of the squamous epithelium (SQ) of the esophagus and may progress to Barrett’s esophagus (BE) characterized by intestinal metaplasia. The role of inflammation in this transition has been postulated but lacks experimental evidence. Here, the inflammatory responses in the esophagus of these patients were investigated.Patients and Methods
Fifty-one esophageal biopsies from with patients BE (n = 19), RE (n = 8) and controls (n = 23) were analyzed. T-cells were analyzed before and after ex vivo expansion (14 days) by multicolor flow cytometric analysis. The following markers were studied: CD3, CD4, CD8 (T-cell markers), Granzyme B (marker of cytotoxicity), CD103 (αE/epithelial integrin) and NKg2a (inhibitory receptor on T-cells and NK-cells).Results
Analysis of ex vivo cultures from normal looking SQ from controls, RE patients, and BE patients revealed no significant differences in the number and phenotypes of T-cells. In contrast, tissue from RE was different to normal SQ in four aspects: 1) higher percentages of CD3+CD4+-cells (72±7% vs 48±6%, p = 0.01) and 2) CD8+GranzymeB+ -cells (53±11% vs 26±4%, p<0.05), while 3) lower percentages of CD4+CD103+-cells (45±19% vs 80±3%, p = 0.02) and 4) CD8+NKg2a+- cells (31±12% vs 44±5%).Conclusion
Despite the fact that both tissues are exposed to the same reflux associated inflammatory triggers, the immune response observed in RE is clearly distinct from that in SQ of BE. The differences in immune responses in BE tissue might contribute to its susceptibility for transformation into intestinal metaplasia. 相似文献10.
Nicole H. T. M. Dukers-Muijrers Arjen G. C. L. Speksnijder Servaas A. Morré Petra F. G. Wolffs Marianne A. B. van der Sande Antoinette A. T. P. Brink Ingrid V. F. van den Broek Marita I. L. S. Werner Christian J. P. A. Hoebe 《PloS one》2013,8(11)
Background
Determination of Chlamydia trachomatis (Ct) treatment success is hampered by current assessment methods, which involve a single post-treatment measurement only. Therefore, we evaluated Ct detection by applying multiple laboratory measures on time-sequential post-treatment samples.Methods
A prospective cohort study was established with azithromycin-treated (1000 mg) Ct patients (44 cervicovaginal and 15 anorectal cases). Each patient provided 18 self-taken samples pre-treatment and for 8 weeks post-treatment (response: 96%; 1,016 samples). Samples were tested for 16S rRNA (TMA), bacterial load (quantitative PCR; Chlamydia plasmid DNA) and type (serovar and multilocus sequence typing). Covariates (including behavior, pre-treatment load, anatomic site, symptoms, age, and menstruation) were tested for their potential association with positivity and load at 3–8 weeks using regression analyses controlling for repeated measures.Findings
By day 9, Ct positivity decreased to 20% and the median load to 0.3 inclusion-forming units (IFU) per ml (pre-treatment: 170 IFU/ml). Of the 35 cases who reported no sex, sex with a treated partner or safe sex with a new partner, 40% had detection, i.e. one or more positive samples from 3–8 weeks (same Ct type over time), indicating possible antimicrobial treatment failure. Cases showed intermittent positive detection and the number of positive samples was higher in anorectal cases than in cervicovaginal cases. The highest observed bacterial load between 3–8 weeks post-treatment was 313 IFU/ml, yet the majority (65%) of positive samples showed a load of ≤2 IFU/ml. Pre-treatment load was found to be associated with later load in anorectal cases.Conclusions
A single test at 3–8 weeks post-treatment frequently misses Ct. Detection reveals intermittent low loads, with an unknown risk of later complications or transmission. These findings warrant critical re-evaluation of the clinical management of single dose azithromycin-treated Ct patients and fuel the debate on defining treatment failure. Clinicaltrials.gov Identifier: NCT01448876. 相似文献11.
Cristina Menni Toma Keser Massimo Mangino Jordana T. Bell Idil Erte Irena Akma?i? Frano Vu?kovi? Maja Pu?i? Bakovi? Olga Gornik Mark I. McCarthy Vlatka Zoldo? Tim D. Spector Gordan Lauc Ana M. Valdes 《PloS one》2013,8(12)
Objective
To determine the extent to which genetic and epigenetic factors contribute to variations in glycosylation of immunoglobulin G (IgG) in humans.Methods
76 N-glycan traits in circulating IgG were analyzed by UPLC in 220 monozygotic and 310 dizygotic twin pairs from TwinsUK. A classical twin study design was used to derive the additive genetic, common and unique environmental components defining the variance in these traits. Epigenome-wide association analysis was performed using the Illumina 27k chip.Results
51 of the 76 glycan traits studied have an additive genetic component (heritability, h 2)≥ 0.5. In contrast, 12 glycan traits had a low genetic contribution (h2<0.35). We then tested for association between methylation levels and glycan levels (P<2 x10-6). Among glycan traits with low heritability probe cg08392591 maps to a CpG island 5’ from the ANKRD11 gene, a p53 activator on chromosome 16. Probe cg26991199 maps to the SRSF10 gene involved in regulation of RNA splicing and particularly in regulation of splicing of mRNA precursors upon heat shock. Among those with high heritability we found cg13782134 (mapping to the NRN1L gene) and cg16029957 mapping near the QPCT gene to be array-wide significant. The proportion of array-wide epigenetic associations was significantly larger (P<0.005) among glycans with low heritability (42%) than in those with high heritability (6.2%).Conclusions
Glycome analyses might provide a useful integration of genetic and non-genetic factors to further our understanding of the role of glycosylation in both normal physiology and disease. 相似文献12.
Pablo E. Campos Anne L. Buffardi César P. Cárcamo Patricia J. García Clara Buendia Marina Chiappe Geoff P. Garnett Ana Maria Xet-Mull King K. Holmes 《PloS one》2013,8(11)
Background
As part of a community-randomized trial of a multicomponent intervention to prevent sexually transmitted infections, we created Mobile Teams (MTs) in ten intervention cities across Peru to improve outreach to female sex workers (FSW) for strengthened STI prevention services.Methods
Throughout 20 two-month cycles, MTs provided counseling; condoms; screening and specific treatment for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), and vaginal Trichomonas vaginalis (TV) infections; and periodic presumptive metronidazole treatment for vaginal infections.Results
MTs had 48,207 separate encounters with 24,814 FSW; numbers of sex work venues and of FSW reached increased steadily over several cycles. Approximately 50% of FSW reached per cycle were new. Reported condom use with last client increased from 73% to 93%. Presumptive metronidazole treatment was accepted 83% of times offered. Over 38 months, CT prevalence declined from 15·4% to 8·2%, and TV prevalence from 7·3% to 2·6%. Among participants in ≥9 cycles, CT prevalence decreased from 12·9% to 6·0% (p <0·001); TV from 4·6% to 1·5% (p <0·001); and NG from 0·8% to 0·4% (p =0·07).Conclusions
Mobile outreach to FSW reached many FSW not utilizing government clinics. Self-reported condom use substantially increased; CT and TV prevalences declined significantly. The community-randomized trial, reported separately, demonstrated significantly greater reductions in composite prevalence of CT, NG, TV, or high-titer syphilis serology in FSW in these ten intervention cities than in ten matched control cities. 相似文献13.
Andrea Nemethova Klaus Michel Pedro J. Gomez-Pinilla Guy E. Boeckxstaens Michael Schemann 《PloS one》2013,8(11)
Background
The cholinergic anti-inflammatory pathway is an endogenous mechanism by which the autonomic nervous system attenuates macrophage activation via nicotinic acetylcholine receptors (nAChR). This concept has however not been demonstrated at a cellular level in intact tissue. To this end, we have studied the effect of nicotine on the activation of resident macrophages in a mouse stomach preparation by means of calcium imaging.Methods
Calcium transients ([Ca2+]i) in resident macrophages were recorded in a mouse stomach preparation containing myenteric plexus and muscle layers by Fluo-4. Activation of macrophages was achieved by focal puff administration of ATP. The effects of nicotine on activation of macrophages were evaluated and the nAChR involved was pharmacologically characterized. The proximity of cholinergic nerves to macrophages was quantified by confocal microscopy. Expression of β2 and α7 nAChR was evaluated by β2 immunohistochemistry and fluorophore-tagged α-bungarotoxin.Results
In 83% of macrophages cholinergic varicose nerve fibers were detected at distances <900nm. The ATP induced [Ca2+]i increase was significantly inhibited in 65% or 55% of macrophages by 100µM or 10µM nicotine, respectively. This inhibitory effect was reversed by the β2 nAChR preferring antagonist dihydro-β-eryhtroidine but not by hexamethonium (non-selective nAChR-antagonist), mecamylamine (α3β4 nAChR-preferring antagonist), α-bungarotoxin or methyllycaconitine (both α7 nAChR-preferring antagonist). Macrophages in the stomach express β2 but not α7 nAChR at protein level, while those in the intestine express both receptor subunits.Conclusion
This study is the first in situ demonstration of an inhibition of macrophage activation by nicotine suggesting functional signaling between cholinergic neurons and macrophages in the stomach. The data suggest that the β2 subunit of the nAChR is critically involved in the nicotine-induced inhibition of these resident macrophages. 相似文献14.
Anne Louise Bischoff Nilofar Vahman F?lsgaard Charlotte Giwercman Carson Jakob Stokholm Louise Pedersen Maria Holmberg Amalie Bisgaard Sune Birch Theodore F. Tsai Hans Bisgaard 《PloS one》2013,8(4)
Background
Pregnant women were suspected to be at particular risk when H1N1pnd09 influenza became pandemic in 2009. Our primary objective was to compare the immune responses conferred by MF59®-adjuvanted vaccine (Focetria®) in H1N1pnd09-naïve pregnant and non-pregnant women. The secondary aims were to compare influences of dose and adjuvant on the immune response.Methods
The study was nested in the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2010) pregnancy cohort in 2009-2010 and conducted as a single-blinded block-randomised [1∶1∶1] controlled clinical trial in pregnant women after gestational week 20: (1) 7.5 µg H1N1pnd09 antigen with MF59-adjuvant (Pa7.5 µg); (2) 3.75 µg antigen half MF59-adjuvanted (Pa3.75 µg); (3) 15 µg antigen unadjuvanted (P15 µg); and in non-pregnant women receiving (4) 7.5 µg antigen full adjuvanted (NPa7.5 µg). Blood samples were collected at baseline, 3 weeks, 3 and 10 months after vaccination, adverse events were recorded prospectively.Results
58 pregnant women were allocated to Pa7.5 µg and 149 non-pregnant women were recruited to NPa7.5 µg. The sero-conversion rate was significantly increased in non-pregnant (NPa7.5 µg) compared with pregnant (Pa7.5 µg) women (OR = 2.48 [1.03–5.95], p = 0.04) and geometric mean titers trended towards being higher, but this difference was not statistically significant (ratio 1.27 [0.85–1.93], p = 0.23). The significant titer increase rate showed no difference between pregnant (Pa7.5 µg) and non-pregnant (NPa7.5 µg) groups (OR = 0.49 [0.13–1.85], p = 0.29).Conclusion
Our study suggests the immune response to the 7.5 µg MF59-adjuvanted Focetria® H1N1pnd09 vaccine in pregnant women may be diminished compared with non-pregnant women.Trial Registration
ClinicalTrials.gov . NCT01012557相似文献15.
Jakub Toczek Alexis Broisat Pascale Perret Marie-Dominique Desruet Daniel Fagret Laurent M. Riou Catherine Ghezzi 《PloS one》2014,9(7)
Background
[18F]-fluorodeoxyglucose (FDG) has been suggested for the clinical and experimental imaging of inflammatory atherosclerotic lesions. Significant FDG uptake in brown adipose tissue (BAT) has been observed both in humans and mice. The objective of the present study was to investigate the influence of periaortic BAT on apolipoprotein E-deficient (apoE−/−) mouse atherosclerotic lesion imaging with FDG.Methods
ApoE−/− mice (36±2 weeks-old) were injected with FDG (12±2 MBq). Control animals (Group A, n = 7) were injected conscious and kept awake at room temperature (24°C) throughout the accumulation period. In order to minimize tracer activity in periaortic BAT, Group B (n = 7) and C (n = 6) animals were injected under anaesthesia at 37°C and Group C animals were additionally pre-treated with propranolol. PET/CT acquisitions were performed prior to animal euthanasia and ex vivo analysis of FDG biodistribution.Results
Autoradiographic imaging indicated higher FDG uptake in atherosclerotic lesions than in the normal aortic wall (all groups, P<0.05) and the blood (all groups, P<0.01) which correlated with macrophage infiltration (R = 0.47; P<0.001). However, periaortic BAT uptake was either significantly higher (Group A, P<0.05) or similar (Group B and C, P = NS) to that observed in atherosclerotic lesions and was shown to correlate with in vivo quantified aortic FDG activity.Conclusion
Periaortic BAT FDG uptake was identified as a confounding factor while using FDG for the non-invasive imaging of mouse atherosclerotic lesions. 相似文献16.
Urvashi Bhan Amy B. Podsiad Melissa A. Kovach Megan N. Ballinger Venkateshwar Keshamouni Theodore J. Standiford 《PloS one》2015,10(1)
Introduction
Post influenza pneumonia is a leading cause of mortality and morbidity, with mortality rates approaching 60% when bacterial infections are secondary to multi-drug resistant (MDR) pathogens. Staphylococcus aureus, in particular community acquired MRSA (cMRSA), has emerged as a leading cause of post influenza pneumonia.Hypothesis
Linezolid (LZD) prevents acute lung injury in murine model of post influenza bacterial pneumoniaMethods
Mice were infected with HINI strain of influenza and then challenged with cMRSA at day 7, treated with antibiotics (LZD or Vanco) or vehicle 6 hours post bacterial challenge and lungs and bronchoalveolar lavage fluid (BAL) harvested at 24 hours for bacterial clearance, inflammatory cell influx, cytokine/chemokine analysis and assessment of lung injury.Results
Mice treated with LZD or Vanco had lower bacterial burden in the lung and no systemic dissemination, as compared to the control (no antibiotic) group at 24 hours post bacterial challenge. As compared to animals receiving Vanco, LZD group had significantly lower numbers of neutrophils in the BAL (9×103 vs. 2.3×104, p < 0.01), which was associated with reduced levels of chemotactic chemokines and inflammatory cytokines KC, MIP-2, IFN-γ, TNF-α and IL-1β in the BAL. Interestingly, LZD treatment also protected mice from lung injury, as assessed by albumin concentration in the BAL post treatment with H1N1 and cMRSA when compared to vanco treatment. Moreover, treatment with LZD was associated with significantly lower levels of PVL toxin in lungs.Conclusion
Linezolid has unique immunomodulatory effects on host inflammatory response and lung injury in a murine model of post-viral cMRSA pneumonia. 相似文献17.
Lo?c Louvet Dominique Bazin Janine Büchel Sonja Steppan Jutta Passlick-Deetjen Ziad A. Massy 《PloS one》2015,10(1)
Background
Cardiovascular disease including vascular calcification (VC) remains the leading cause of death in patients suffering from chronic kidney disease (CKD). The process of VC seems likely to be a tightly regulated process where vascular smooth muscle cells are playing a key role rather than just a mere passive precipitation of calcium phosphate. Characterisation of the chemical and crystalline structure of VC was mainly led in patients or animal models with CKD. Likewise, Mg2+ was found to be protective in living cells although a potential role for Mg2+ could not be excluded on crystal formation and precipitation. In this study, the crystal formation and the role of Mg2+ were investigated in an in vitro model of primary human aortic vascular smooth muscle cells (HAVSMC) with physical techniques.Methodology/Principal Findings
In HAVSMC incubated with increased Ca x Pi medium, only calcium phosphate apatite crystals (CPA) were detected by Micro-Fourier Transform InfraRed spectroscopy (µFTIR) and Field Effect Scanning Electron Microscope (FE — SEM) and Energy Dispersive X-ray spectrometry (EDX) at the cell layer level. Supplementation with Mg2+ did not alter the crystal composition or structure. The crystal deposition was preferentially positioned near or directly on cells as pictured by FE — SEM observations and EDX measurements. Large µFTIR maps revealed spots of CPA crystals that were associated to the cellular layout. This qualitative analysis suggests a potential beneficial effect of Mg2+ at 5 mM in noticeably reducing the number and intensities of CPA µFTIR spots.Conclusions/Significance
For the first time in a model of HAVSMC, induced calcification led to the formation of the sole CPA crystals. Our data seems to exclude a physicochemical role of Mg2+ in altering the CPA crystal growth, composition or structure. Furthermore, Mg2+ beneficial role in attenuating VC should be linked to an active cellular role. 相似文献18.
Kaori Yoshida Daisuke Nishizawa Takashi Ichinomiya Tatsuya Ichinohe Masakazu Hayashida Ken-ichi Fukuda Kazutaka Ikeda 《PloS one》2015,10(1)
Background
The analgesic efficacy of opioids is well known to vary widely among individuals, and various factors related to individual differences in opioid sensitivity have been identified. However, a prediction model to calculate appropriate opioid analgesic requirements has not yet been established. The present study sought to construct prediction formulas for individual opioid analgesic requirements based on genetic polymorphisms and clinical data from patients who underwent cosmetic orthognathic surgery and validate the utility of the prediction formulas in patients who underwent major open abdominal surgery.Methods
To construct the prediction formulas, we performed multiple linear regression analyses using data from subjects who underwent cosmetic orthognathic surgery. The dependent variable was 24-h postoperative or perioperative fentanyl use, and the independent variables were age, gender, height, weight, pain perception latencies (PPL), and genotype data of five single-nucleotide polymorphisms (SNPs). To examine the utility of the prediction formulas, we performed simple linear regression analyses using subjects who underwent major open abdominal surgery. Actual 24-h postoperative or perioperative analgesic use and the predicted values that were calculated using the multiple regression equations were incorporated as dependent and independent variables, respectively.Results
Multiple linear regression analyses showed that the four SNPs, PPL, and weight were retained as independent predictors of 24-h postoperative fentanyl use (R2 = 0.145, P = 5.66 × 10-10) and the two SNPs and weight were retained as independent predictors of perioperative fentanyl use (R2 = 0.185, P = 1.99 × 10-15). Simple linear regression analyses showed that the predicted values were retained as an independent predictor of actual 24-h postoperative analgesic use (R2 = 0.033, P = 0.030) and perioperative analgesic use (R2 = 0.100, P = 1.09 × 10-4), respectively.Conclusions
We constructed prediction formulas, and the possible utility of these prediction formulas was found in another type of surgery. 相似文献19.
Crystal L. Coolbaugh Ivan B. Anderson Machelle D. Wilson David A. Hawkins Ezra A. Amsterdam 《PloS one》2014,9(5)