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1.
Environ Res ; 212(Pt C): 113375, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35533714

RESUMO

INTRODUCTION: Knowledge on the health of greenspace workers is scarce, even though they are exposed to many occupational hazards. The aim of this study was to analyze mortality by cause, prevalence of some non-cancer diseases, and incidence of the main cancers among greenspace workers. METHODS: A sub-cohort of greenspace workers was formed within the AGRICAN cohort. Demographic information, health characteristics and self-reported diseases at enrollment were described separately in terms of frequencies (%), median and Interquartile Range (IQR) for greenspace workers, farmers, and other non-agricultural workers. Causes of death and cancer incidence were identified through linkage with cancer registries from enrollment (2005-2007) to 2015. Hazard ratio (HR) and 95% Confidence Intervals [95% CI] were estimated using Cox proportional hazard regression with age as the underlying timescale. RESULTS: The sub-cohort included 6247 greenspace workers who were higher proportion men, younger and more frequently smokers than farmers and non-agricultural workers. Male and female greenspace workers reported more history of allergic diseases; and males, more history of depression. Compared to other workers male greenspace workers showed a non-significant higher mortality from ischemic cardiological diseases (HR = 1.14 [0.81-1.60]). Incidence was higher in male greenspace workers than farmers for overall cancer (HR = 1.15 [1.04-1.27]), cancer of the prostate (HR = 1.21 [1.02-1.44]), thyroid (HR = 2.84 [1.26-6.41]), testis (HR = 3.98 [1.50-10.58]) and skin melanoma (HR = 2.15 [1.33-3.47]). Non-significant increased risks were also found for sarcomas, larynx and breast. In women, risk of breast cancer was higher in greenspace workers than in farmers (HR = 1.71 [1.17-2.50]). CONCLUSIONS: Whereas greenspace workers have often been included with other pesticide applicators in epidemiological studies, our analyses highlighted the differences between these two populations. They demonstrate the need to study them separately and to investigate more thoroughly the role of specific occupational exposures such as pesticides as well as the effect on women.


Assuntos
Neoplasias da Mama , Exposição Ocupacional , Praguicidas , Fazendeiros , Feminino , Humanos , Incidência , Masculino , Parques Recreativos
2.
Environ Res ; 203: 111822, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34352232

RESUMO

CONTEXT: The greenspace sector includes a broad range of occupations: gardeners, landscapers, municipal workers, maintenance operators of public facilities, golf-course employees and other sports facilities, horticulturists, plant and tree nursery workers etc. The health impact of occupational pesticide exposure has mainly been studied among farmers. Other professionals such as greenspace workers are also extremely exposed, presenting specific exposure features (practices, types of pesticide used). The aim of this review was to summarize epidemiological literature that examine the relationship between pesticide exposure and the risk of cancer and long-term health effects in greenspace workers. METHOD: Six main groups of greenspace workers were identified and examined through a systematic literature review based on PubMed and Scopus. The studies were then grouped according to their design, health outcomes and the type of population studied. RESULTS: Forty-four articles were selected among the 1679 identified. Fifteen studies were conducted exclusively among greenspace workers, while ten also studied these workers with other pesticide applicators. Six were cohorts from the general population in which greenspace workers were identified. Elevated risks were found in several studies for leukaemia, soft-tissue sarcoma, multiple myeloma, non-Hodgkin lymphoma and Parkinson's disease. DISCUSSION: The majority of studies used rough parameters for defining exposure such as job titles which could lead to the misclassification of exposure, with the risk of false or positive negative conclusions. Health outcomes were mainly collected through registries or death certificates, and information regarding potential confounders was often missing. CONCLUSION: The review identified only 15 studies conducted exclusively among greenspace workers. Elevated risk was found for several sites of cancer and Parkinson's diseases. Further epidemiological research is needed, conducted specifically on these workers, to better characterize this population, its exposure to pesticides and the related health effects.


Assuntos
Doenças dos Trabalhadores Agrícolas , Neoplasias , Doenças do Sistema Nervoso , Exposição Ocupacional , Praguicidas , Estudos Epidemiológicos , Humanos , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Exposição Ocupacional/análise , Parques Recreativos , Praguicidas/análise , Praguicidas/toxicidade
3.
Nature ; 484(7395): 485-8, 2012 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-22538610

RESUMO

Much of our knowledge of galaxies comes from analysing the radiation emitted by their stars, which depends on the present number of each type of star in the galaxy. The present number depends on the stellar initial mass function (IMF), which describes the distribution of stellar masses when the population formed, and knowledge of it is critical to almost every aspect of galaxy evolution. More than 50 years after the first IMF determination, no consensus has emerged on whether it is universal among different types of galaxies. Previous studies indicated that the IMF and the dark matter fraction in galaxy centres cannot both be universal, but they could not convincingly discriminate between the two possibilities. Only recently were indications found that massive elliptical galaxies may not have the same IMF as the Milky Way. Here we report a study of the two-dimensional stellar kinematics for the large representative ATLAS(3D) sample of nearby early-type galaxies spanning two orders of magnitude in stellar mass, using detailed dynamical models. We find a strong systematic variation in IMF in early-type galaxies as a function of their stellar mass-to-light ratios, producing differences of a factor of up to three in galactic stellar mass. This implies that a galaxy's IMF depends intimately on the galaxy's formation history.

4.
Ultrasound Obstet Gynecol ; 47(5): 548-53, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26481090

RESUMO

OBJECTIVE: To estimate the impact of adding low-molecular-weight heparin (LMWH) or unfractionated heparin to low-dose aspirin started ≤ 16 weeks' gestation on the prevalence of pre-eclampsia (PE) and the delivery of a small-for-gestational-age (SGA) neonate. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed by searching the medical databases PubMed, EMBASE, Web of Science and Cochrane Central. Pregnant women randomized to receive LMWH or unfractionated heparin in addition to low-dose aspirin were compared with those who received low-dose aspirin alone. Outcome measures were PE, severe PE, early-onset PE and SGA. Pooled relative risks (RRs) with 95% CI were calculated using a random-effects model. RESULTS: Eight RCTs met the inclusion criteria; the indication for recruitment was previous recurrent miscarriage in five studies (three included women with thrombophilia) and a history of severe or early-onset PE in three studies (including women with thrombophilia in one). LMWH was administered in seven studies and unfractionated heparin in one. In women with a history of PE, treatment with LMWH and aspirin, compared with aspirin alone, was associated with a significant reduction in development of PE (three trials (n = 379); RR, 0.54 (95% CI, 0.31-0.92); P = 0.03) and in delivery of SGA neonates (two trials (n = 363); RR, 0.54 (95% CI, 0.32-0.91); P = 0.02). These outcomes were not significantly reduced in women with recurrent miscarriage who received LMWH and aspirin, compared with aspirin alone. The small number of studies precluded sensitivity analyses and the evaluation of publication biases. Blinding to the allocation treatment was absent in all RCTs. CONCLUSIONS: Based on limited evidence, the addition of LMWH to low-dose aspirin could reduce the prevalence of PE and SGA in women with a history of PE. This observation should be the basis of a well-conducted future trial rather than a recommendation for immediate clinical application. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Aspirina/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Pré-Eclâmpsia/prevenção & controle , Aspirina/uso terapêutico , Quimioterapia Combinada/métodos , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
5.
Biochim Biophys Acta ; 1840(11): 3257-63, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24973564

RESUMO

BACKGROUND: When activated, NF-κB can promote the nuclear import and transcription of DNA possessing NF-κB consensus sequences. Here, we investigated whether NF-κB is involved in the plasmid electrotransfer process. METHODS: Mouse tibial cranial muscles were transfected with plasmids encoding luciferase bearing or not NF-κB consensus sequences. Luciferase transgene expression was evaluated noninvasively by luminescence imaging and the number of pDNA copies in the same muscles by qPCR. RT-PCR of heat shock protein HsP70 mRNA evidenced cell stress. Western blots of phosphorylated IkBα were studied as a marker of NF-κB activation. RESULTS: Intra-muscular injection of a plasmid bearing a weak TATA-like promoter results in a very low muscle transfection level. Electrotransfer significantly increased both the number of pDNA copy and the transgene expression of this plasmid per DNA copy. Insertion of NF-κB consensus sequences into pDNA significantly increased the level of gene expression both with and without electrotransfer. Electrotransfer-induced cellular stress was evidenced by increased HsP70 mRNA. Phosphorylated IκBα was slightly increased by simple pDNA injection and a little more by electrotransfer. We also observed a basal level of phosphorylated IκBα and thus of free NF-κB in the absence of any stimulation. GENERAL SIGNIFICANCE: pDNA electrotransfer can increase transgene expression independently of NF-κB. The insertion of NF-κB consensus sequences into pDNA bearing a weak TATA-like promoter leads to enhanced transgene expression in muscle with or without gene electrotransfer. Finally, our results suggest that the basal amount of free NF-κB in muscle might be sufficient to enhance the activity of pDNA bearing NF-κB consensus sequences.

6.
Sci Total Environ ; 919: 170816, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38346656

RESUMO

Since 2014, the Agricultural Operator Exposure Model (AOEM) has been the harmonised European model used for estimating non-dietary operator exposure to pesticide. It is based on studies conducted by the pesticide companies and it features 13 different crops including non-agricultural areas such as amenity grasslands. The objective of this study was to compare the dermal exposure measured during a field study conducted in a non-agricultural area with the corresponding values estimated by the model AOEM. The non-controlled field study was conducted in France in 2011 and included 24 private and public gardeners who apply glyphosate with knapsack sprayers. Dermal exposure was measured using the whole-body method and cotton gloves. Each measured value had an estimated value given by AOEM and we tested their correlation using linear regression. The model overestimated body exposure for all observations and there was no correlation between values. However, it underestimated hand exposure by 42 times and it systematically underestimated the exposure when the operators were wearing gloves, especially during the application. The model failed at being conservative regarding hand exposure and highly overestimated the protection afforded by the gloves. At a time of glyphosate renewed approval in Europe, non-controlled field studies conducted by academics are needed to improve AOEM model, especially in the non-agricultural sector. Indeed, among the 34 studies included in the model, none were conducted on a non-agricultural area and only four assessed the exposure when using a knapsack sprayer. Moreover, knapsack sprayers being the main equipment used worldwide in both agricultural and non-agricultural settings, it is also crucial to integrate new data specific to this equipment in the model. Operator exposure should be estimated with accuracy in the registration process of pesticides to ensure proper safety as well as in epidemiological studies to improve exposure assessment.


Assuntos
Exposição Ocupacional , Praguicidas , Praguicidas/análise , Parques Recreativos , Exposição Ocupacional/análise , Agricultura , Glifosato
7.
ESMO Open ; 8(5): 101626, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37713930

RESUMO

BACKGROUND: Patients with glioblastomas have a dismal prognosis, and there is no circulating predictive or prognostic biomarker. Circulating progastrin, hPG80, is a tumor-promoting peptide present in the blood of patients with various cancers that has been shown to have prognostic value. We evaluated the prognostic value of plasma hPG80 in patients with isocitrate dehydrogenase-wild type glioblastoma after surgery. PATIENTS AND METHODS: A multicentric retrospective study in glioblastoma patients treated with standard radio-chemotherapy was conducted. The hPG80 levels were measured in plasma EDTA samples collected after surgery with an ELISA DxPG80.lab kit (Biodena Care, Montpellier, France), which has a detection threshold of 1.2 pM. The relationship between post-operative hPG80 plasma levels, in combination with other known prognostic factors, and patients' progression-free survival (PFS) and overall survival (OS) was evaluated. RESULTS: Sixty-nine patients were assessable. Plasma samples were collected after tumor biopsy (B), partial resection (PR), and complete resection (CR) for 22, 25, and 22 patients, respectively. At a median concentration of 5.37 pM (interquartile range 0.00-13.90 pM), hPG80 was detected in 48 (70%) patients (hPG80+). CR was associated with significant lower values of hPG80 levels: the median value was 0.7 versus 9.1 pM for PR (P = 0.02) and 8.3 pM for B (P = 0.004). The hPG80 detection rate was also significantly lower: 50% (CR) versus 72% (PR) versus 86% (B) (P = 0.005). The median follow-up was 39 months [22.4 months-not reached]. hPG80 post-operative detection was associated with numerically shorter PFS (6.4 versus 9.4 months, P = 0.13) and OS (14.5 versus 20.9 months, P = 0.11). In multivariate analysis, hPG80 was a prognostic factor for OS (P = 0.034). CONCLUSIONS: Circulating hPG80 could serve as a new prognostic biomarker after surgery in patients with glioblastoma treated with radio-chemotherapy.


Assuntos
Glioblastoma , Humanos , Glioblastoma/cirurgia , Glioblastoma/tratamento farmacológico , Estudos Retrospectivos , Prognóstico , Biomarcadores
8.
J Nutr Health Aging ; 26(9): 896-903, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36156682

RESUMO

OBJECTIVES: Among patients over 75 years, little is known about functional decline due to COVID-19. The aim of this study was to explore this functional decline, compare to other infectious pneumonia. DESIGN AND SETTING: This case-control study included all COVID-19 patients hospitalized from March to December 2020 in Acute Geriatric Ward in Nantes University Hospital matched 1/1 with patients with pneumonia hospitalized in geriatric department between March 2017 and March 2019 (controls) on sex, age. Functional decline was assessed at 3 month follow up as it is routinely done after hospitalization in geriatric ward. We performed multivariable analyses to compare clinical outcomes between patients with COVID-19 vs controls. RESULTS: 132 pairs were matched on age (mean: 87 y-o), and sex (61% of women). In multivariable logistic regression analysis, there were no statistical significant association between COVID-19 infection and functional decline (OR=0.89 p=0.72). A statistical significant association was found between functional decline and Charlson comorbidity index (OR=1.17, p=0.039); prior fall (OR=2.08, p=0.012); malnutrition (OR=1.97, p=0.018); length of hospital stay (OR=1.05, p=0.002) and preadmission ADL(OR=1.25, p=0.049). CONCLUSION: COVID-19 does not seem to be responsible for a more frequent or severe functional decline than other infectious pneumonia in older and comorbid population after 3 month follow up. In this population, pneumonia is associated with functional decline in almost 1 in 2 cases. The individual preadmission frailty seems to be a more important predictor of functional decline, encouraging multidimensional care management for this population.


Assuntos
COVID-19 , Pneumonia , Idoso , COVID-19/epidemiologia , Estudos de Casos e Controles , Feminino , Avaliação Geriátrica/métodos , Hospitalização , Humanos , Pneumonia/complicações , Pneumonia/epidemiologia , Sobreviventes
9.
Ultrasound Obstet Gynecol ; 38(1): 116-8, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21713991

RESUMO

Allantoic cysts are a somewhat rare entity. They are identifiable on antenatal ultrasound examination but are not easily distinguishable from pseudocysts, which are often associated with a poor prognosis. Their etiology remains obscure and obstructive uropathies have been proposed to be one of the underlying mechanisms. We report on a case in which both allantoic cysts and a patent urachus were detected antenatally and turned out to be associated with posterior urethral valves (PUV). The cysts were first seen in the early second trimester, with a full fetal bladder and patent urachus. They disappeared by the 29(th) week. During the subsequent sonographic examinations, the bladder was emptying regularly. The kidneys remained normal throughout the pregnancy. It is hypothesized that the increased pressure within the urinary tract kept the urachus patent, led to the formation of allantoic cysts and, later, to their perforation; this allowed the fetus to empty his bladder and kept him from the usual complications of PUV. This case emphasizes the importance of detection and characterization of umbilical cord cysts on antenatal ultasound examination and suggests that obstructive uropathies should be included in the differential diagnosis of umbilical cord cyst communicating with the fetal bladder.


Assuntos
Cisto do Úraco/diagnóstico por imagem , Uretra/anormalidades , Doenças Uretrais/diagnóstico por imagem , Doenças da Bexiga Urinária/diagnóstico por imagem , Adulto , Alantoide/diagnóstico por imagem , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/embriologia , Masculino , Gravidez , Ultrassonografia Pré-Natal , Cisto do Úraco/embriologia , Uretra/diagnóstico por imagem , Doenças Uretrais/embriologia , Doenças da Bexiga Urinária/embriologia
10.
Proc Inst Mech Eng H ; 225(9): 907-19, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22070028

RESUMO

Total hip arthroplasty (THA) enjoys excellent rates of success in older patients, but younger patients are still at risk of aseptic loosening and bone resorption from stress shielding. One solution to the stress shielding problem is to use a hip stem with mechanical properties matching those of cortical bone. The objective of the present study was to investigate numerically the biomechanical performance of such a biomimetic hip stem based on a hydroxyapatite (HA)-coated carbon fibre composite. A finite element model (FEM) of the biomimetic stem was constructed. Contact elements were studied to model the bone-implant interface in a non-osseointegrated and osseointegrated state in the best way. Three static load cases representing slow walking, stair climbing, and gait in a healthy individual were considered. Stress shielding and bone-implant interface micromotions were evaluated and compared with the results of a similar FEM based on titanium alloy (Ti-6Al-4V). The composite stems allowed for reduced stress shielding when compared with a traditional Ti-6Al-4V stem. Micromotions were slightly higher with the composite stem, but remained below 40 microm on most of the HA-coated surface. It is concluded that a biomimetic composite stem might offer a better compromise between stress shielding and micromotions than the Ti-6Al-4V stem with the same external geometry.


Assuntos
Materiais Biocompatíveis/química , Materiais Biomiméticos , Carbono/química , Prótese de Quadril , Modelos Biológicos , Fenômenos Biomecânicos , Fibra de Carbono , Simulação por Computador , Cabeça do Fêmur/anatomia & histologia , Cabeça do Fêmur/fisiologia , Humanos , Osseointegração , Estresse Mecânico
11.
J Mater Sci Mater Med ; 20(11): 2223-33, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19554427

RESUMO

It is well known that interstitials affect the mechanical properties of titanium and titanium alloys. Their effects on the fatigue properties of titanium foams have not, however, been documented in the literature. This paper presents the effect of the oxygen content on the static and dynamic compression properties of titanium foams. Increasing the oxygen content from 0.24 to 0.51 wt% O in solution significantly increases the yield strength and reduces the ductility of the foams. However, the fatigue limit is not significantly affected by the oxygen content and falls within the 92 MPa +/- 12 MPa range for all specimens investigated in this study. During cyclic loading, deformation is initially coming from cumulative creep followed by the formation of microcracks. The coalescence of these microcracks is responsible for the rupture of the specimens. Fracture surfaces of the specimens having lower oxygen content show a more ductile aspect than the specimens having higher oxygen content.


Assuntos
Oxigênio/química , Titânio/química , Ligas/química , Força Compressiva , Teste de Materiais , Metais/química , Microscopia Eletrônica de Varredura/métodos , Equipamentos Ortopédicos , Porosidade , Pós , Pressão , Soluções , Propriedades de Superfície , Temperatura , Resistência à Tração
12.
BMC Biotechnol ; 6: 16, 2006 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-16524461

RESUMO

BACKGROUND: Optical imaging is an attractive non-invasive way to evaluate the expression of a transferred DNA, mainly thanks to its lower cost and ease of realization. In this study optical imaging was evaluated for monitoring and quantification of the mouse knee joint and tibial cranial muscle electrotransfer of a luciferase encoding plasmid. Optical imaging was applied to study the kinetics of luciferase expression in both tissues. RESULTS: The substrate of luciferase (luciferin) was injected either intraperitonealy (i.p.) or in situ into the muscle or the knee joint. Luminescence resulting from the luciferase-luciferin reaction was measured in vivo with a cooled CCD camera and/or in vitro on tissue lysate. Maximal luminescence of the knee joint and muscle after i.p. (2.5 mg) or local injection of luciferin (50 microg in the knee joint, 100 microg in the muscle) were highly correlated. With the local injection procedure adopted, in vivo and in vitro luminescences measured on the same muscles significantly correlated. Luminescence measurements were reproducible and the signal level was proportional to the amount of plasmid injected. In vivo luciferase activity in the electrotransfered knee joint was detected for two weeks. Intramuscular electrotransfer of 0.3 or 3 microg of plasmid led to stable luciferase expression for 62 days, whereas injecting 30 microg of plasmid resulted in a drop of luminescence three weeks after electrotransfer. These decreases were partially associated with the development of an immune response. CONCLUSION: A particular advantage of the i.p. injection of substrate is a widespread distribution at luciferase production sites. We have also highlighted advantages of local injection as a more sensitive detection method with reduced substrate consumption. Besides, this route of injection is relatively free of uncontrolled parameters, such as diffusion to the target organ, crossing of biological barriers and evidencing variations in local enzymatic kinetics, probably related to the reaction medium in the targeted organ. Optical imaging was shown to be a sensitive and relevant technique to quantify variations of luciferase activity in vivo. Further evaluation of the effective amount of luciferase in a given tissue by in vivo optical imaging relies on conditions of the enzymatic reaction and light absorption and presently requires in vitro calibration for each targeted organ.


Assuntos
Eletroporação , Articulação do Joelho/metabolismo , Luciferases de Vaga-Lume/análise , Substâncias Luminescentes/análise , Medições Luminescentes , Músculo Esquelético/metabolismo , Transfecção/métodos , Animais , Feminino , Luciferina de Vaga-Lumes/administração & dosagem , Expressão Gênica , Genes Reporter , Processamento de Imagem Assistida por Computador , Injeções , Injeções Intraperitoneais , Cinética , Luciferases de Vaga-Lume/genética , Camundongos , Camundongos Endogâmicos C57BL , Microscopia , Reprodutibilidade dos Testes
13.
Circ Res ; 87(6): 448-52, 2000 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-10988235

RESUMO

Ischemia induces both hypoxia and inflammation that trigger angiogenesis. The inflammatory reaction is modulated by production of anti-inflammatory cytokines. This study examined the potential role of a major anti-inflammatory cytokine, interleukin (IL)-10, on angiogenesis in a model of surgically induced hindlimb ischemia. Ischemia was produced by artery femoral occlusion in both C57BL/6J IL-10(+/+) and IL-10(-/-) mice. After 28 days, angiogenesis was quantified by microangiography, capillary, and arteriole density measurement and laser Doppler perfusion imaging. The protein levels of IL-10 and vascular endothelial growth factor (VEGF) were determined by Western blot analysis in hindlimbs. IL-10 was markedly expressed in the ischemic hindlimb of IL-10(+/+) mice. Angiogenesis in the ischemic hindlimb was significantly increased in IL-10(-/-) compared with IL-10(+/+) mice. Indeed, angiographic data showed that vessel density in the ischemic leg was 10.2+/-0.1% and 5.7+/-0.4% in IL-10(-/-) and IL-10(+/+) mice, respectively (P:<0.01). This corresponded to improved ischemic/nonischemic leg perfusion ratio by 1.4-fold in IL-10(-/-) mice compared with IL-10(+/+) mice (0.87+/-0. 05 versus 0.63+/-0.01, respectively; P:<0.01). Revascularization was associated with a 1.8-fold increase in tissue VEGF protein level in IL-10(-/-) mice compared with IL-10(+/+) mice (P:<0.01). In vivo electrotransfer of murine IL-10 cDNA in IL-10(-/-) mice significantly inhibited both the angiogenic process and the rise in VEGF protein level observed in IL-10(-/-) mice. No changes in vessel density or VEGF content were observed in the nonischemic hindlimb. These findings underscore the antiangiogenic effect of IL-10 associated with the downregulation of VEGF expression and suggest a role for the inflammatory balance in the modulation of ischemia-induced angiogenesis.


Assuntos
Membro Posterior/irrigação sanguínea , Interleucina-10/metabolismo , Isquemia/fisiopatologia , Neovascularização Fisiológica , Animais , Arteríolas/fisiologia , Capilares/fisiologia , DNA Complementar/genética , Fatores de Crescimento Endotelial/metabolismo , Técnicas de Transferência de Genes , Interleucina-10/genética , Isquemia/genética , Fluxometria por Laser-Doppler , Linfocinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
14.
Circ Res ; 85(8): e17-24, 1999 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-10521249

RESUMO

The potential role of anti-inflammatory cytokines in the modulation of the atherosclerotic process remains unknown. Interleukin (IL)-10 has potent deactivating properties in macrophages and T cells and modulates many cellular processes that may interfere with the development and stability of the atherosclerotic plaque. IL-10 is expressed in human atherosclerosis and is associated with decreased signs of inflammation. In the present study, we show that IL-10-deficient C57BL/6J mice fed an atherogenic diet and raised under specific pathogen-free conditions exhibit a significant 3-fold increase in lipid accumulation compared with wild-type mice. Interestingly, the susceptibility of IL-10-deficient mice to atherosclerosis was exceedingly high (30-fold increase) when the mice were housed under conventional conditions. Atherosclerotic lesions of IL-10-deficient mice showed increased T-cell infiltration, abundant interferon-gamma expression, and decreased collagen content. In vivo, transfer of murine IL-10 achieved 60% reduction in lesion size. These results underscore the critical roles of IL-10 in both atherosclerotic lesion formation and stability. Moreover, IL-10 appears to be crucial as a protective factor against the effect of environmental pathogens on atherosclerosis.


Assuntos
Arteriosclerose/imunologia , Interleucina-10/deficiência , Animais , Arteriosclerose/patologia , Arteriosclerose/terapia , Colesterol/sangue , Dieta Aterogênica , Feminino , Interleucina-10/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL
15.
Biochim Biophys Acta ; 1474(3): 353-9, 2000 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-10779687

RESUMO

Gene transfer using electrical pulses is a rapidly expanding field. Many studies have been performed in vitro to elucidate the mechanism of DNA electrotransfer. In vivo, the use of efficient procedures for DNA electrotransfer in tissues is recent, and the question of the implied mechanisms is largely open. We have evaluated the effects of various combinations of square wave electric pulses of variable field strength and duration, on cell permeabilization and on DNA transfection in the skeletal muscle in vivo. One high voltage pulse of 800 V/cm, 0.1 ms duration (short high pulse) or a series of four low voltage pulses of 80 V/cm, 83 ms duration (long low pulses) slightly amplified transfection efficacy, while no significant permeabilization was detected using the (51)Cr-EDTA uptake test. By contrast, the combination of one short high pulse followed by four long low pulses led to optimal gene transfer efficiency, while inducing muscle fibers permeabilization. These results are consistent with additive effects of electropermeabilization and DNA electrophoresis on electrotransfer efficiency. Finally, the described new combination, as compared to the previously reported use of repeated identical pulses of intermediate voltage, leads to similar gene transfer efficiency, while causing less permeabilization and thus being likely less deleterious. Thus, combination of pulses of various strengths and durations is a new procedure for skeletal muscle gene transfer that may represents a clear improvement in view of further clinical development.


Assuntos
Técnicas de Transferência de Genes , Músculo Esquelético , Animais , Permeabilidade da Membrana Celular , Eletroporação/métodos , Terapia Genética/métodos , Camundongos , Camundongos Endogâmicos C57BL , Fibras Musculares Esqueléticas , Transfecção/métodos
16.
Biochim Biophys Acta ; 1676(2): 138-48, 2004 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-14746908

RESUMO

We have studied radiolabelled plasmid DNA biodistribution and degradation in the muscle at different times after injection, with or without electrotransfer using previously defined conditions. Radiolabelled plasmid progressively left the muscle and was degraded as soon as 5 min after plasmid injection, with or without electrotransfer. Autoradiography showed that the major part of injected radioactivity was detected in the interfibrilar space of a large proportion of the muscle. Large zones of accumulation of radioactivity, which seems to be contained in some fibres (more than 20 microm), were identified as soon as 5 min after electrotransfer. Such structures were never observed on slices of non-electrotransferred muscles. However, these structures were not frequent and probably lesional. The surprising fact is that despite the amount of intact plasmid having been greatly reduced between 5 min and 3 h after injection, the level of transfection remains unchanged whether electric pulses were delivered 20 s or 3 h after injection. Such a behavior was similarly observed when injecting 0.3, 3 or 30 microg of plasmid DNA. Moreover, the transfection level was correlated to the amount of plasmid DNA injected. These results suggest that as soon as it is injected, plasmid DNA is proportionally partitioned between at least two compartments. While a major part of plasmid DNA is rapidly cleared and degraded, the electrotransferable pool of plasmid DNA represents a very small part of the amount injected and belongs to another compartment where it is protected from endogenous DNAses.


Assuntos
DNA/metabolismo , Músculo Esquelético/metabolismo , Plasmídeos/farmacologia , Animais , Autorradiografia , DNA/análise , DNA/isolamento & purificação , Desoxirribonuclease I/farmacologia , Eletroforese , Eletroporação , Feminino , Amplificação de Genes , Genes Reporter , Injeções Intramusculares , Camundongos , Camundongos Endogâmicos C57BL , Fibras Musculares Esqueléticas/química , Fibras Musculares Esqueléticas/metabolismo , Plasmídeos/administração & dosagem , Plasmídeos/análise , Fatores de Tempo , Transfecção/métodos , Trítio/análise
17.
J Biomed Mater Res A ; 73(4): 398-408, 2005 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-15892136

RESUMO

Hydroxyapatite [HA, Ca10(PO4)6(OH)2] coatings on polymer composite substrates were investigated for their bioactivity and their physicochemical and mechanical characteristics. HA holds key characteristics for use in orthopedic applications, such as for coating of the femoral stem in a hip replacement device. The plasma-spray technique was used to project HA onto a carbon fiber/polyamide 12 composite substrate. The resulting HA coatings exhibited mechanical adhesion as high as 23 MPa, depending on the surface treatment of the composite substrate. The purpose of this investigation was to evaluate the bioactivity of an HA-coated composite substrate. HA- coated samples have been immersed in simulated body fluid (SBF) and maintained within a shaker bath for periods of 1, 7, 14, 21, and 28 days at 37 degrees C. Scanning electron microscopy, energy dispersive X-ray spectroscopy, and X-ray diffraction techniques were performed on the samples before and after immersion into SBF. SBF was analyzed using inductively coupled plasma atomic emission spectrometry for element concentration and evaluation of the solution's purity. SBF conditioning led to the deposition of crystalline HA onto the surface of the coatings. The calcium-to-phosphorous ratios of initial HA coating and of newly deposited HA were respectively 1.72 and 1.65, close to the HA theoretical calcium/phosphorous value of 1.67. Results demonstrated that bioactive HA coatings were produced by plasma spraying, because SBF conditioning induced newly formed HA with high crystallinity. Mechanical adhesion of the HA coatings was not significantly affected upon SBF conditioning.


Assuntos
Artroplastia de Quadril/métodos , Materiais Biocompatíveis/química , Substitutos Ósseos/química , Materiais Revestidos Biocompatíveis , Durapatita/farmacologia , Quadril/patologia , Ortopedia/métodos , Polímeros/química , Materiais Biomiméticos/química , Líquidos Corporais/química , Cálcio/química , Carbono/química , Durapatita/química , Concentração de Íons de Hidrogênio , Teste de Materiais , Microscopia Eletrônica de Varredura , Fósforo/química , Próteses e Implantes , Espectrometria por Raios X , Espectrofotometria Atômica , Estresse Mecânico , Propriedades de Superfície , Fatores de Tempo , Difração de Raios X
18.
J Radiol ; 86(9 Pt 1): 1003-15, 2005 Sep.
Artigo em Francês | MEDLINE | ID: mdl-16224340

RESUMO

PURPOSE: To evaluate the use of US-guided vacuum biopsy for diagnosis and treatment of probably benign breast masses. MATERIALS AND METHOD: Retrospective review of 382 US guided vacuum biopsies over a 44 months period (september 2001 to may 2005) with the 11-g handheld mammotome. A total of 308 benign tumors, 59 borderline lesions and 15 carcinomas were diagnosed. The average number of specimens is 13.1 (3-37). Surgical resection has been systematic for carcinomas and selective for papillomas. Surgical correlation (n:35) or mammographic follow-up (n:347) are presented. RESULTS: Complete removal occurred in 371/382 (97.1%) immediately after biopsy and 337/382 (88.2%) after one month: 138/142 (93.7%) for fibroadenomas and 52/53 (98.1%) papillomas less than 15 mm. Open surgical biopsy was carried out for 35 patients on the basis of incomplete removal (3 cases) or histologic findings (8 invasive carcinomas, 7 ductal carcinoma in situ, 3 atypical ductal hyperplasia, 1 fibrocystic changes with atypia and 11 papillomas). No lesion was under-diagnosed and the rate of avoided surgery was 94.5%. Of the 347 lesions that were not surgically biopsied (42 borderline lesions and 305 benign lesions), 337 were monitored at 1-43 months (average: 20 months, > or =24 months: 57 patients). Ten underwent additional biopsy but no missed cancer was detected. Patients tolerance was good or very good in 83%, and the complication rate was 1.3%. CONCLUSION: US-guided vacuum biopsy is an accurate and well tolerated technique. It is an alternative to surgery for masses less than 15 mm including fibroadenomas and papillomas or in patients with imaging-histologic discordance at core biopsy.


Assuntos
Biópsia por Agulha/métodos , Neoplasias da Mama/patologia , Ultrassonografia de Intervenção , Adolescente , Adulto , Idoso , Biópsia por Agulha/instrumentação , Mama/patologia , Carcinoma/patologia , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/patologia , Feminino , Fibroadenoma/patologia , Seguimentos , Humanos , Pessoa de Meia-Idade , Papiloma/patologia , Estudos Retrospectivos , Vácuo
19.
J Mech Behav Biomed Mater ; 45: 90-100, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25688031

RESUMO

Finite element (FE) analysis is a widely used tool for extensive preclinical testing of orthopaedic implants such as hip resurfacing femoral components, including evaluation of different stem fixation scenarios (cementation vs osseointegration, etc.). Most FE models use surface-to-surface contact elements to model the load-bearing interfaces that connect bone, cement and implant and neglect the mechanical effects of phenomena such as residual stresses from bone cement curing. The objective of the current study is to evaluate and quantify the effect of different stem fixation scenarios and related phenomena such as residual stresses from bone cement curing. Four models of a previously clinically available implant (Durom) were used to model different stem fixation scenarios of a new biomimetic stem: a cemented stem, a frictional stem, a partially and completely bonded stem, with and without residual stresses from bone cement curing. For the frictional stem, stem-bone micromotions were increased from 0% to 61% of the available surface subjected to micromotions between 10 and 40µm with the inclusion of residual stresses from bone cement curing. Bonding the stem, even partially, increased stress in the implant at the stem-head junction. Complete bonding of the stem decreased bone strain at step tip, at the cost of increased strain shielding when compared with the frictional stem and partially bonded stem. The increase of micromotions and changes in bone strain highlighted the influence of interfacial conditions on load transfer, and the need for a better modeling method, one capable of assessing the effect of phenomena such as interdigitation and residual stresses from bone cement curing.


Assuntos
Artroplastia de Quadril , Biomimética/instrumentação , Retenção da Prótese/métodos , Cimentos Ósseos , Densidade Óssea , Remodelação Óssea , Fêmur/fisiologia , Fêmur/cirurgia , Análise de Elementos Finitos , Prótese de Quadril , Humanos , Estresse Mecânico , Suporte de Carga
20.
Neurology ; 43(6): 1078-83, 1993 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8170545

RESUMO

Five patients with partial epilepsy of diverse etiology insidiously developed action-activated jerks. The disorder was limited to one arm in two patients and to the legs in another, and was multifocal in the remaining two. Each jerk was related to an EMG silent period lasting 100 to 400 msec, causing a lapse followed by resumption of posture. Simultaneous EEG-EMG recording showed each postural lapse to be time-locked with a sharp or spike and slow-wave transient over the contralateral sensorimotor cortex, where almost continuous paroxysmal activity occurred. The three patients who were able to cooperate during neurologic evaluation also exhibited motor neglect in the most affected body segment and decreased awareness of the disorder. In three patients, the phenomenon was medically resistant, and in two of them it was continuous and could be defined as epilepsia partialis continua. In the other two, medical treatment induced remission of EEG, motor, and neuropsychological abnormalities. This disabling movement disorder can be classified as "epileptic negative myoclonus" and may result from focal-discharge-related transient disruption of cortical function in the sensorimotor cortex.


Assuntos
Epilepsias Parciais/fisiopatologia , Mioclonia/fisiopatologia , Adolescente , Adulto , Ataxia/etiologia , Criança , Pré-Escolar , Eletroencefalografia , Eletromiografia , Epilepsias Parciais/complicações , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/tratamento farmacológico , Seguimentos , Humanos , Masculino , Transtornos dos Movimentos/etiologia , Exame Neurológico , Resultado do Tratamento
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