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1.
Bradley Clark Vitor P. Costa Brendan J. O'Brien Luiz G. Guglielmo Carl D. Paton 《PloS one》2014,9(12)
Objectives
Competitive endurance athletes commonly undertake periods of overload training in the weeks prior to major competitions. This investigation examined the effects of two seven-day high-intensity overload training regimes (HIT) on performance and physiological characteristics of competitive cyclists.Design
The study was a matched groups, controlled trial.Methods
Twenty-eight male cyclists (mean ± SD, Age: 33±10 years, Mass 74±7 kg, VO2 peak 4.7±0.5 L·min−1) were assigned to a control group or one of two training groups for seven consecutive days of HIT. Before and after training cyclists completed an ergometer based incremental exercise test and a 20-km time-trial. The HIT sessions were ∼120 minutes in duration and consisted of matched volumes of 5, 10 and 20 second (short) or 15, 30 and 45 second (long) maximal intensity efforts.Results
Both the short and long HIT regimes led to significant (p<0.05) gains in time trial performance compared to the control group. Relative to the control group, the mean changes (±90% confidence limits) in time-trial power were 8.2%±3.8% and 10.4%±4.3% for the short and long HIT regimes respectively; corresponding increases in peak power in the incremental test were 5.5%±2.7% and 9.5%±2.5%. Both HIT (short vs long) interventions led to non-significant (p>0.05) increases (mean ± SD) in VO2 peak (2.3%±4.7% vs 3.5%±6.2%), lactate threshold power (3.6%±3.5% vs 2.9%±5.3%) and gross efficiency (3.2%±2.4% vs 5.1%±3.9%) with only small differences between HIT regimes.Conclusions
Seven days of overload HIT induces substantial enhancements in time-trial performance despite non-significant increases in physiological measures with competitive cyclists. 相似文献2.
Zuzanna Rowinska Simone Gorressen Marc W. Merx Thomas A. Koeppel Elisa A. Liehn Alma Zernecke 《PloS one》2014,9(7)
Introduction
The aim of our study was to develop a reproducible murine model of elastase-induced aneurysm formation combined with aortic transplantation.Methods
Adult male mice (n = 6–9 per group) underwent infrarenal, orthotopic transplantation of the aorta treated with elastase or left untreated. Subsequently, both groups of mice were monitored by ultrasound until 7 weeks after grafting.Results
Mice receiving an elastase-pretreated aorta developed aneurysms and exhibited a significantly increased diastolic vessel diameter compared to control grafted mice at 7 week after surgery (1.11±0.10 mm vs. 0.75±0.03 mm; p≤0,001). Histopathological examination revealed disruption of medial elastin, an increase in collagen content and smooth muscle cells, and neointima formation in aneurysm grafts.Conclusions
We developed a reproducible murine model of elastase-induced aneurysm combined with aortic transplantation. This model may be suitable to investigate aneurysm-specific inflammatory processes and for use in gene-targeted animals. 相似文献3.
Siwen Wang Jinsong Wang Peiliang Lin Zhibin Li Chen Yao Guangqi Chang Xiaoxi Li Shenming Wang 《PloS one》2013,8(8)
Introduction
We analyzed the short-term efficacy of endovascular treatment for aortic diseases by summarizing all available published data on endovascular stent-graft treatment for abdominal aortic aneurysm (AAA), thoracic aortic aneurysm (TAA), type A aortic dissection (type A AD) and type B aortic dissection (type B AD) in China.Methods
We performed a systematic analysis of 935 published series on retrograde endovascular treatment for aortic diseases in China from January 1996 to November 2010. Based on the inclusion criteria, 159 studies, involving a total of 5531 patients, were included.Results
There were no significant differences in procedural success among the studies (P>0.05). The rates of overall neurologic complications and stroke were significantly different in all two-group comparisons (P<0.01). The type A AD patients had the highest rates of neurologic complications (both 6.67±0.00%), and the AAA patients had the lowest rates (0.31±0.04% and 0.11±0.02%). Significant differences were noted in the rates of cardiac, renal, pulmonary and visceral complications, which were all higher in the type A AD patients than in the other three groups (P<0.01). The endoleak rate was highest in the TAA patients (19.27±5.74%) and was similar in the type A AD patients (P>0.05). A significant difference was noted between the 30-day mortality rate of the type A AD patients and the AAA or type B AD patients (P<0.05).Conclusion
Endovascular stent-graft is a feasible and safe treatment for aortic diseases, with high procedural success and low incidences of post-procedural complications and short-term mortality. Endovascular treatment for AAA and type B AD is more efficient than for type A AD and TAA. 相似文献4.
Introduction
Idiopathic Pulmonary Fibrosis (IPF) is a progressive, incurable fibrotic interstitial lung disease with a prognosis worse than many cancers. Its pathogenesis is poorly understood. Activated platelets can release pro-fibrotic mediators that have the potential to contribute to lung fibrosis. We determine platelet reactivity in subjects with IPF compared to age-matched controls.Methods
Whole blood flow cytometry was used to measure platelet-monocyte aggregate formation, platelet P-selectin expression and platelet fibrinogen binding at basal levels and following stimulation with platelet agonists. A plasma swap approach was used to assess the effect of IPF plasma on control platelets.Results
Subjects with IPF showed greater platelet reactivity than controls. Platelet P-selectin expression was significantly greater in IPF patients than controls following stimulation with 0.1 µM ADP (1.9% positive ±0.5 (mean ± SEM) versus 0.7%±0.1; p = 0.03), 1 µM ADP (9.8%±1.3 versus 3.3%±0.8; p<0.01) and 10 µM ADP (41.3%±4.2 versus 22.5%±2.6; p<0.01). Platelet fibrinogen binding was also increased, and platelet activation resulted in increased platelet-monocyte aggregate formation in IPF patients. Re-suspension of control platelets in plasma taken from subjects with IPF resulted in increased platelet activation compared to control plasma.Conclusions
IPF patients exhibit increased platelet reactivity compared with controls. This hyperactivity may result from the plasma environment since control platelets exhibit increased activation when exposed to IPF plasma. 相似文献5.
V. Lai Nguyen M. Eline Kooi Walter H. Backes Raf H. M. van Hoof Anne E. C. M. Saris Mirthe C. J. Wishaupt Femke A. M. V. I. Hellenthal Rob J. van der Geest Alfons G. H. Kessels Geert Willem H. Schurink Tim Leiner 《PloS one》2013,8(10)
Purpose
Increased microvascularization of the abdominal aortic aneurysm (AAA) vessel wall has been related to AAA progression and rupture. The aim of this study was to compare the suitability of three pharmacokinetic models to describe AAA vessel wall enhancement using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).Materials and Methods
Patients with AAA underwent DCE-MRI at 1.5 Tesla. The volume transfer constant (Ktrans), which reflects microvascular flow, permeability and surface area, was calculated by fitting the blood and aneurysm vessel wall gadolinium concentration curves. The relative fit errors, parameter uncertainties and parameter reproducibilities for the Patlak, Tofts and Extended Tofts model were compared to find the most suitable model. Scan-rescan reproducibility was assessed using the interclass correlation coefficient and coefficient of variation (CV). Further, the relationship between Ktrans and AAA size was investigated.Results
DCE-MRI examinations from thirty-nine patients (mean age±SD: 72±6 years; M/F: 35/4) with an mean AAA maximal diameter of 49±6 mm could be included for pharmacokinetic analysis. Relative fit uncertainties for Ktrans based on the Patlak model (17%) were significantly lower compared to the Tofts (37%) and Extended Tofts model (42%) (p<0.001). Ktrans scan-rescan reproducibility for the Patlak model (ICC = 0.61 and CV = 22%) was comparable with the Tofts (ICC = 0.61, CV = 23%) and Extended Tofts model (ICC = 0.76, CV = 22%). Ktrans was positively correlated with maximal AAA diameter (Spearman’s ρ = 0.38, p = 0.02) using the Patlak model.Conclusion
Using the presented imaging protocol, the Patlak model is most suited to describe DCE-MRI data of the AAA vessel wall with good Ktrans scan-rescan reproducibility. 相似文献6.
Allison G. Hays Matthias Stuber Glenn A. Hirsch Jing Yu Michael Sch?r Robert G. Weiss Gary Gerstenblith Sebastian Kelle 《PloS one》2013,8(3)
Objectives
Our objective is to test the hypothesis that coronary endothelial function (CorEndoFx) does not change with repeated isometric handgrip (IHG) stress in CAD patients or healthy subjects.Background
Coronary responses to endothelial-dependent stressors are important measures of vascular risk that can change in response to environmental stimuli or pharmacologic interventions. The evaluation of the effect of an acute intervention on endothelial response is only valid if the measurement does not change significantly in the short term under normal conditions. Using 3.0 Tesla (T) MRI, we non-invasively compared two coronary artery endothelial function measurements separated by a ten minute interval in healthy subjects and patients with coronary artery disease (CAD).Methods
Twenty healthy adult subjects and 12 CAD patients were studied on a commercial 3.0 T whole-body MR imaging system. Coronary cross-sectional area (CSA), peak diastolic coronary flow velocity (PDFV) and blood-flow were quantified before and during continuous IHG stress, an endothelial-dependent stressor. The IHG exercise with imaging was repeated after a 10 minute recovery period.Results
In healthy adults, coronary artery CSA changes and blood-flow increases did not differ between the first and second stresses (mean % change ±SEM, first vs. second stress CSA: 14.8%±3.3% vs. 17.8%±3.6%, p = 0.24; PDFV: 27.5%±4.9% vs. 24.2%±4.5%, p = 0.54; blood-flow: 44.3%±8.3 vs. 44.8%±8.1, p = 0.84). The coronary vasoreactive responses in the CAD patients also did not differ between the first and second stresses (mean % change ±SEM, first stress vs. second stress: CSA: −6.4%±2.0% vs. −5.0%±2.4%, p = 0.22; PDFV: −4.0%±4.6% vs. −4.2%±5.3%, p = 0.83; blood-flow: −9.7%±5.1% vs. −8.7%±6.3%, p = 0.38).Conclusion
MRI measures of CorEndoFx are unchanged during repeated isometric handgrip exercise tests in CAD patients and healthy adults. These findings demonstrate the repeatability of noninvasive 3T MRI assessment of CorEndoFx and support its use in future studies designed to determine the effects of acute interventions on coronary vasoreactivity. 相似文献7.
Daria Gotti Elena Raffetti Laura Albini Laura Sighinolfi Franco Maggiolo Elisa Di Filippo Nicoletta Ladisa Gioacchino Angarano Giuseppe Lapadula Angelo Pan Anna Degli Esposti Massimiliano Fabbiani Emanuele Focà Alfredo Scalzini Francesco Donato Eugenia Quiros-Roldan the Master Cohort Group 《PloS one》2014,9(4)
Objectives
We studied survival and associated risk factors in an Italian nationwide cohort of HIV-infected individuals after an AIDS-defining cancer (ADC) or non-AIDS-defining cancer (NADC) diagnosis in the modern cART era.Methods
Multi-center, retrospective, observational study of HIV patients included in the MASTER Italian Cohort with a cancer diagnosis from January 1998 to September 2012. Malignancies were divided into ADC or NADC on the basis of the Centre for Disease Control-1993 classification. Recurrence of cancer and metastases were excluded. Survivals were estimated according to the Kaplan-Meier method and compared according to the log-rank test. Statistically significant variables at univariate analysis were entered in a multivariate Cox regression model.Results
Eight hundred and sixty-six cancer diagnoses were recorded among 13,388 subjects in the MASTER Database after 1998: 435 (51%) were ADCs and 431 (49%) were NADCs. Survival was more favorable after an ADC diagnosis than a NADC diagnosis (10-year survival: 62.7%±2.9% vs. 46%±4.2%; p = 0.017). Non-Hodgkin lymphoma had lower survival rates than patients with Kaposi sarcoma or cervical cancer (10-year survival: 48.2%±4.3% vs. 72.8%±4.0% vs. 78.5%±9.9%; p<0.001). Regarding NADCs, breast cancer showed better survival (10-year survival: 65.1%±14%) than lung cancer (1-year survival: 28%±8.7%), liver cancer (5-year survival: 31.9%±6.4%) or Hodgkin lymphoma (10-year survival: 24.8%±11.2%). Lower CD4+ count and intravenous drug use were significantly associated with decreased survival after ADCs or NADCs diagnosis. Exposure to cART was found to be associated with prolonged survival only in the case of ADCs.Conclusions
cART has improved survival in patients with an ADC diagnosis, whereas the prognosis after a diagnosis of NADCs is poor. Low CD4+ counts and intravenous drug use are risk factors for survival following a diagnosis of ADCs and Hodgkin lymphoma in the NADC group. 相似文献8.
Antonio Rivero-Juárez Luis F. Lopez-Cortes Angela Camacho Almudena Torres-Cornejo Juan A. Pineda Manuel Marquez-Solero Antonio Caruz Rosa Ruiz-Valderas Julian Torre-Cisneros Alicia Gutierrez-Valencia Antonio Rivero 《PloS one》2012,7(11)
Background
The aim of the study was to analyze the different impact of standard and low-dose Peg-IFN-α2a/RBV therapies on HCV viral decline in HIV/HCV genotype 3 co-infected patients during the first weeks of treatment.Methods
Plasma HCV viral decline was analyzed between baseline and weeks 1, 2 and 4 in two groups of treatment-naïve HCV genotype 3 patients with HIV co-infection. The Standard Dose Group (SDG) included patients who received Peg-IFN at 180 µg/per week with a weight-adjusted dose of ribavirin; Low-Dose Group (LDG) patients received Peg-IFN at 135 µg/per week with 800 mg/day ribavirin. The effect of IL28B genotype on HCV viral decline was evaluated in both groups. HCV viral decline was analyzed using a multivariate linear regression model.Results
One hundred and six patients were included: 48 patients in the SDG and 58 in the LDG. HCV viral decline for patients in the LDG was less than for those in the SDG (week 1∶1.72±0.74 log10 IU/mL versus 1.78±0.67 log10 IU/mL, p = 0.827; week 2∶2.3±0.89 log10 IU/mL versus 3.01±1.02 log10 IU/mL, p = 0.013; week 4∶3.52±1.2 log10 IU/mL versus 4.09±1.1 log10 IU/mL, p = 0.005). The linear regression model identified the Peg-IFN/RBV dose as an independent factor for HCV viral decline at week 4.Conclusions
Our results showed that HCV viral decline was less for patients in the low-dose group compared to those receiving the standard dose. Until a randomized clinical trial is conducted, clinicians should be cautious about using lower doses of Peg-IFN/RBV in HIV/HCV genotype 3 co-infected patients. 相似文献9.
Andrzej F. Frydrychowski Pawel J. Winklewski Arkadiusz Szarmach Grzegorz Halena Tomasz Bandurski 《PloS one》2013,8(4)
Purpose
The purpose of the study was to assess the responses of pial artery pulsation (cc-TQ) and subarachnoid width (sas-TQ) to acetazolamide challenge in patients with chronic carotid artery stenosis and relate these responses to changes in peak systolic velocity (PSV), cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time to peak response (TTP).Methods
Fifteen patients with carotid artery stenosis ≥90% on the ipsilateral side and <50% on the contralateral side were enrolled into the study. PSV was assessed using colour-coded duplex sonography, CBF, CBV, MTT and TTP with perfusion computed tomography, cc-TQ and sas-TQ with near-infrared transillumination/backscattering sounding (NIR-T/BSS).Results
Based on the ipsilateral/contralateral cc-TQ ratio after acetazolamide challenge two groups of patients were distinguished: the first group with a ratio ≥1 and the second with a ratio <1. In the second group increases in CBF and CBV after the acetazolamide test were significantly higher in both hemispheres (ipsilateral: +33.0%±8.1% vs. +15.3%±4.4% and +26.3%±6.6% vs. +14.3%±5.1%; contralateral: +26.8%±7.0% vs. +17.6%±5.6% and +20.0%±7.3% vs. +10.0%±3.7%, respectively), cc-TQ was significantly higher only on the ipsilateral side (+37.3%±9.3% vs. +26.6%±8.6%) and the decrease in sas-TQ was less pronounced on the ipsilateral side (−0.7%±1.5% vs. −10.2%±1.5%), in comparison with the first group. The changes in sas-TQ following the acetazolamide test were consistent with the changes in TTP.Conclusions
The ipsilateral/contralateral cc-TQ ratio following acetazolamide challenge may be used to distinguish patient groups characterized by different haemodynamic parameters. Further research on a larger group of patients is warranted. 相似文献10.
Hao Xiang Kristen J. Mertz Vincent C. Arena Luann L. Brink Xiaohui Xu Yongyi Bi Evelyn O. Talbott 《PloS one》2013,8(4)
Background and Objective
High concentrations of air pollutants have been linked to increased incidence of stroke in North America and Europe but not yet assessed in mainland China. The aim of this study is to evaluate the association between stroke hospitalization and short-term elevation of air pollutants in Wuhan, China.Methods
Daily mean NO2, SO2 and PM10 levels, temperature and humidity were obtained from 2006 through 2008. Data on stroke hospitalizations (ICD 10: I60–I69) at four hospitals in Wuhan were obtained for the same period. A time-stratified case-crossover design was performed by season (April-September and October-March) to assess effects of pollutants on stroke hospital admissions.Results
Pollution levels were higher in October-March with averages of 136.1 µg/m3 for PM10, 63.6 µg/m3 for NO2 and 71.0 µg/m3 for SO2 than in April-September when averages were 102.0 µg/m3, 41.7 µg/m3 and 41.7 µg/m3, respectively (p<.001). During the cold season, every 10 µg/m3 increase in NO2 was associated with a 2.9% (95%C.I. 1.2%–4.6%) increase in stroke admissions on the same day. Every 10 ug/m3 increase in PM10 daily concentration was significantly associated with an approximate 1% (95% C.I. 0.1%–1.4%) increase in stroke hospitalization. A two-pollutant model indicated that NO2 was associated with stroke admissions when controlling for PM10. During the warm season, no significant associations were noted for any of the pollutants.Conclusions
Exposure to NO2 is significantly associated with stroke hospitalizations during the cold season in Wuhan, China when pollution levels are 50% greater than in the warm season. Larger and multi-center studies in Chinese cities are warranted to validate our findings. 相似文献11.
Purpose
This study compares the effects of neutral temperature, cold and ice-slush beverages, with and without 0.5% menthol on cycling performance, core temperature (Tco) and stress responses in a tropical climate (hot and humid conditions).Methods
Twelve trained male cyclists/triathletes completed six 20-km exercise trials against the clock in 30.7°C±0.8°C and 78%±0.03% relative humidity. Before and after warm-up, and before exercise and every 5 km during exercise, athletes drank 190 mL of either aromatized (i.e., with 0.5 mL of menthol (5 gr/L)) or a non-aromatized beverage (neutral temperature: 23°C±0.1°C, cold: 3°C±0.1°C, or ice-slush: −1°C±0.7°C). During the trials, heart rate (HR) was continuously monitored, whereas core temperature (Tco), thermal comfort (TC), thermal sensation (TS) and rate of perceived exertion (RPE) were measured before and after warm-up, every 5 km of exercise, and at the end of exercise and after recovery.Results
Both the beverage aroma (P<0.02) and beverage temperature (P<0.02) had significant and positive effects on performance, which was considerably better with ice-slush than with a neutral temperature beverage, whatever the aroma (P<0.002), and with menthol vs non-menthol (P<0.02). The best performances were obtained with ice-slush/menthol and cold/menthol, as opposed to neutral/menthol. No differences were noted in HR and Tco between trials.Conclusion
Cold water or ice-slush with menthol aroma seems to be the most effective beverage for endurance exercise in a tropical climate. Further studies are needed to explore its effects in field competition. 相似文献12.
Background
Recent clinical studies have shown that recanalization rates are lower in stent-assisted coil embolization than in coiling alone in the treatment of cerebral aneurysms.Objective
This study aimed to assess and compare the hemodynamic effect of stent struts and straightening of vessels by stent placement on reducing flow velocity in sidewall aneurysms, with the goal of reducing recanalization rates.Methods
We evaluated 16 sidewall aneurysms treated with Enterprise stents. We performed computational fluid dynamics simulations using patient-specific geometries before and after treatment, with or without stent struts.Results
Stent placement straightened vessels by a mean (±standard deviation) of 12.9°±13.1° 6 months after treatment. Placement of stent struts in the initial vessel geometries reduced flow velocity in aneurysms by 23.1%±6.3%. Straightening of vessels without stent struts reduced flow velocity by 9.6%±12.6%. Stent struts had significantly stronger effects on reducing flow velocity than straightening (P = 0.004, Wilcoxon test). Deviation of the effects was larger by straightening than by stent struts (P = 0.01, F-test). The combination of stent struts and straightening reduced flow velocity by 32.6%±12.2%. There was a trend that larger inflow angles produced a larger reduction in flow velocity by straightening of vessels (P = 0.16).Conclusion
In sidewall aneurysms, stent struts have stronger effects (approximately 2 times) on reduction in flow velocity than straightening of vessels. Hemodynamic effects by straightening vary in each case and can be predicted by inflow angles of pre-operative vessel geometry. These results may be useful to design a treatment strategy for reducing recanalization rates. 相似文献13.
Peng-Yuan Zhuang Jun Shen Xiao-Dong Zhu Ju-Bo Zhang Zhao-You Tang Lun-Xiu Qin Hui-Chuan Sun 《PloS one》2013,8(3)
Background
Interferon (IFN)-α is effective in inhibiting tumor growth and metastasis of hepatocellular carcinoma (HCC). However, the biologic mechanisms of IFN-α treatment in lung metastasis are not yet clear.Methods
The effect of IFN-α treatment was studied by using an orthotopic xenograft model and measuring tumor size and lung metastasis. Pretreatment with IFN-α before implantation of tumor was done to explore the effect of IFN-α on lung tissues. Cytokines and macrophages were measured by immunohistochemistry and/or PCR assay, using human origin or mouse origin primers to differentiate the sources. Circulating tumor cells (CTCs) were also assayed by flow cytometry.Results
IFN-α treatment did not decrease the number of CTCs (0.075%±0.020% versus 0.063%±0.018%, P = 0.574, IFN-α–treated versus control groups), but did decrease the number and size of lung metastasis (number: 1.75±1.0 versus 28.0±6.3, P = 0.008; size [pixels]: 116.8±72.2 versus 5226.4±1355.7, P = 0.020), and inhibited macrophage infiltration (0.20%±0.04% versus 1.36%±0.21%, P = 0.0058) and alteration of matrix metalloproteinase (MMP)-9 expression (mean integrated optical density (IOD): 5.1±1.7 versus 21.9±0.4, P<0.000) in the lung, which was independent of the primary tumor.Conclusion
IFN-α inhibited lung metastasis by directly modulating the lung microenvironment. 相似文献14.
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15.
Radioimmunoimaging of Liver Metastases with PET Using a 64Cu-Labeled CEA Antibody in Transgenic Mice
Stefanie Nittka Marcel A. Krueger John E. Shively Hanne Boll Marc A. Brockmann Fabian Doyon Bernd J. Pichler Michael Neumaier 《PloS one》2014,9(9)
Purpose
Colorectal cancer is one of the most common forms of cancer, and the development of novel tools for detection and efficient treatment of metastases is needed. One promising approach is the use of radiolabeled antibodies for positron emission tomography (PET) imaging and radioimmunotherapy. Since carcinoembryonic antigen (CEA) is an important target in colorectal cancer, the CEA-specific M5A antibody has been extensively studied in subcutaneous xenograft models; however, the M5A antibody has not yet been tested in advanced models of liver metastases. The aim of this study was to investigate the 64Cu-DOTA-labeled M5A antibody using PET in mice bearing CEA-positive liver metastases.Procedures
Mice were injected intrasplenically with CEA-positive C15A.3 or CEA-negative MC38 cells and underwent micro-computed tomography (micro-CT) to monitor the development of liver metastases. After metastases were detected, PET/MRI scans were performed with 64Cu-DOTA-labeled M5A antibodies. H&E staining, immunohistology, and autoradiography were performed to confirm the micro-CT and PET/MRI findings.Results
PET/MRI showed that M5A uptake was highest in CEA-positive metastases. The %ID/cm3 (16.5%±6.3%) was significantly increased compared to healthy liver tissue (8.6%±0.9%) and to CEA-negative metastases (5.5%±0.6%). The tumor-to-liver ratio of C15A.3 metastases and healthy liver tissue was 1.9±0.7. Autoradiography and immunostaining confirmed the micro-CT and PET/MRI findings.Conclusion
We show here that the 64Cu-DOTA-labeled M5A antibody imaged by PET can detect CEA positive liver metastases and is therefore a potential tool for staging cancer, stratifying the patients or radioimmunotherapy. 相似文献16.
Veronica Alfieri Marina Aiello Roberta Pisi Panagiota Tzani Elisa Mariani Emilio Marangio Dario Olivieri Gabriele Nicolini Alfredo Chetta 《Respiratory research》2014,15(1)
Background
We investigated whether a relationship between small airways dysfunction and bronchial hyperresponsiveness (BHR), expressed both in terms of ease of airway narrowing and of excessive bronchoconstriction, could be demonstrated in asthma.Methods
63 (36 F; mean age 42 yr ± 14) stable, mild-to-moderate asthmatic patients (FEV1 92% pred ±14; FEV1/FVC 75% ± 8) underwent the methacholine challenge test (MCT). The degree of BHR was expressed as PD20 (in μg) and as ∆FVC%. Peripheral airway resistance was measured pre- and post-MCT by impulse oscillometry system (IOS) and expressed as R5-R20 (in kPa sL−1).Results
All patients showed BHR to methacholine (PD20 < 1600 μg) with a PD20 geometric (95% CI) mean value of 181(132–249) μg and a ∆FVC% mean value of 13.6% ± 5.1, ranging 2.5 to 29.5%. 30 out of 63 patients had R5-R20 > 0.03 kPa sL−1 (>upper normal limit) and showed ∆FVC%, but not PD20 values significantly different from the 33 patients who had R5-R20 ≤ 0.03 kPa sL−1 (15.8% ± 4.6 vs 11.5% ± 4.8, p < 0.01 and 156(96–254) μg vs 207 (134–322) μg, p = 0.382). In addition, ∆FVC% values were significantly related to the corresponding pre- (r = 0.451, p < 0.001) and post-MCT (r = 0.376, p < 0.01) R5-R20 values.Conclusions
Our results show that in asthmatic patients, small airway dysfunction, as assessed by IOS, is strictly associated to BHR, expressed as excessive bronchoconstriction, but not as ease of airway narrowing. 相似文献17.
18.
Eveline A. Martens Blandine Gatta-Cherifi Hanne K. Gonnissen Margriet S. Westerterp-Plantenga 《PloS one》2014,9(10)
Background
Protein supplementation has been shown to reduce the increases in intrahepatic triglyceride (IHTG) content induced by acute hypercaloric high-fat and high-fructose diets in humans.Objective
To assess the effect of a 12-wk iso-energetic high protein-low carbohydrate (HPLC) diet compared with an iso-energetic high carbohydrate-low protein (HCLP) diet on IHTG content in healthy non-obese subjects, at a constant body weight.Design
Seven men and nine women [mean ± SD age: 24±5 y; BMI: 22.9±2.1 kg/m2] were randomly allocated to a HPLC [30/35/35% of energy (En%) from protein/carbohydrate/fat] or a HCLP (5/60/35 En%) diet by stratification on sex, age and BMI. Dietary guidelines were prescribed based on individual daily energy requirements. IHTG content was measured by 1H-magnetic resonance spectroscopy before and after the dietary intervention.Results
IHTG content changed in different directions with the HPLC (CH2H2O: 0.23±0.17 to 0.20±0.10; IHTG%: 0.25±0.20% to 0.22±0.11%) compared with the HCLP diet (CH2H2O: 0.34±0.20 vs. 0.38±0.21; IHTG%: 0.38±0.22% vs. 0.43±0.24%), which resulted in a lower IHTG content in the HPLC compared with the HCLP diet group after 12 weeks, which almost reached statistical significance (P = 0.055).Conclusions
A HPLC vs. a HCLP diet has the potential to preserve vs. enlarge IHTG content in healthy non-obese subjects at a constant body weight.Trial Registration
Clinicaltrials.gov NCT01551238相似文献19.
Anne Guimier Sandrine Ferrand Ga?lle Pierron Jér?me Couturier Isabelle Janoueix-Lerosey Valérie Combaret Véronique Mosseri Estelle Thebaud Marion Gambart Dominique Plantaz Aurélien Marabelle Carole Coze Xavier Rialland Sylvie Fasola Eve Lapouble Paul Fréneaux Michel Peuchmaur Jean Michon Olivier Delattre Gudrun Schleiermacher 《PloS one》2014,9(7)
Background
Somatically acquired genomic alterations with MYCN amplification (MNA) are key features of neuroblastoma (NB), the most common extra-cranial malignant tumour of childhood. Little is known about the frequency, clinical characteristics and outcome of NBs harbouring genomic amplification(s) distinct from MYCN.Methods
Genomic profiles of 1100 NBs from French centres studied by array-CGH were re-examined specifically to identify regional amplifications. Patients were included if amplifications distinct from the MYCN locus were seen. A subset of NBs treated at Institut Curie and harbouring MNA as determined by array-CGH without other amplification was also studied. Clinical and histology data were retrospectively collected.Results
In total, 56 patients were included and categorised into 3 groups. Group 1 (n = 8) presented regional amplification(s) without MNA. Locus 12q13-14 was a recurrent amplified region (4/8 cases). This group was heterogeneous in terms of INSS stages, primary localisations and histology, with atypical clinical features. Group 2 (n = 26) had MNA as well as other regional amplifications. These patients shared clinical features of those of a group of NBs MYCN amplified (Group 3, n = 22). Overall survival for group 1 was better than that of groups 2 and 3 (5 year OS: 87.5%±11% vs 34.9%±7%, log-rank p<0.05).Conclusion
NBs harbouring regional amplification(s) without MNA are rare and seem to show atypical features in clinical presentation and genomic profile. Further high resolution genetic explorations are justified in this heterogeneous group, especially when considering these alterations as predictive markers for targeted therapy. 相似文献20.
Emil Zeynalov Niloofar Rezvani Chikao Miyazaki Xiaoguang Liu Marguerite T. Littleton-Kearney 《PloS one》2014,9(7)