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1.
FASEB J ; 37(8): e23037, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37392372

RESUMEN

The striatum is a brain structure involved in the control of voluntary movement. Striatum contains high amounts of retinoic acid, the active metabolite of vitamin A, as well as retinoid receptors, RARß and RXRγ. Previous studies revealed that disruption of retinoid signaling initiated during development is deleterious for striatal physiology and related motor functions. However, the alteration of retinoid signaling, and the importance of vitamin A supply during adulthood on striatal physiology and function has never been established. In the present study, we investigated the impact of vitamin A supply on striatal function. Adult Sprague-Dawley rats were fed with three specific diets, either sub-deficient, sufficient, or enriched in vitamin A (0.4, 5, and 20 international units [IU] of retinol per g of diet, respectively) for 6 months. We first validated that vitamin A sub-deficient diet in adult rats constitutes a physiological model of retinoid signaling reduction in the striatum. We then revealed subtle alterations of fine motor skills in sub-deficient rats using a new behavioral apparatus specifically designed to test forepaw reach-and-grasp skills relying on striatal function. Finally, we showed using qPCR analysis and immunofluorescence that the striatal dopaminergic system per se was not affected by vitamin A sub-deficiency at adult age. Rather, cholinergic synthesis in the striatum and µ-opioid receptor expression in striosomes sub-territories were the most affected by vitamin A sub-deficiency starting at adulthood. Taken together these results revealed that retinoid signaling alteration at adulthood is associated with motor learning deficits together with discrete neurobiological alterations in the striatum.


Asunto(s)
Cuerpo Estriado , Vitamina A , Ratas , Animales , Ratas Sprague-Dawley , Retinoides , Dieta
2.
BMC Cancer ; 23(1): 742, 2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37563551

RESUMEN

Bone sarcomas are rare tumors representing 0.2% of all cancers. While osteosarcoma and Ewing sarcoma mainly affect children and young adults, chondrosarcoma and chordoma have a preferential incidence in people over the age of 40. Despite this range in populations affected, all bone sarcoma patients require complex transdisciplinary management and share some similarities. The cornerstone of all bone sarcoma treatment is monobloc resection of the tumor with adequate margins in healthy surrounding tissues. Adjuvant chemo- and/or radiotherapy are often included depending on the location of the tumor, quality of resection or presence of metastases. High dose radiotherapy is largely applied to allow better local control in case of incomplete primary tumor resection or for unresectable tumors. With the development of advanced techniques such as proton, carbon ion therapy, radiotherapy is gaining popularity for the treatment of bone sarcomas, enabling the delivery of higher doses of radiation, while sparing surrounding healthy tissues. Nevertheless, bone sarcomas are radioresistant tumors, and some mechanisms involved in this radioresistance have been reported. Hypoxia for instance, can potentially be targeted to improve tumor response to radiotherapy and decrease radiation-induced cellular toxicity. In this review, the benefits and drawbacks of radiotherapy in bone sarcoma will be addressed. Finally, new strategies combining a radiosensitizing agent and radiotherapy and their applicability in bone sarcoma will be presented.


Asunto(s)
Neoplasias Óseas , Condrosarcoma , Osteosarcoma , Sarcoma de Ewing , Sarcoma , Niño , Adulto Joven , Humanos , Sarcoma/radioterapia , Sarcoma/cirugía , Osteosarcoma/patología , Neoplasias Óseas/radioterapia , Neoplasias Óseas/patología , Sarcoma de Ewing/patología , Condrosarcoma/radioterapia , Condrosarcoma/cirugía
3.
Haemophilia ; 29(5): 1202-1218, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37572328

RESUMEN

INTRODUCTION: It is necessary to gain insights into adherence to healthcare in people with severe haemophilia (PwSH), especially during the transition from paediatric to adult care, which is an important phase in lives of young people with childhood chronic disease. This adherence can be considered as a marker of successful transition. OBJECTIVES: The main objective of the quantitative phase of the TRANSHEMO project was to compare the adherence to healthcare between adolescents and young adults (YAs) with severe haemophilia. The secondary objective was to identify the determinants (facilitators and barriers) of this adherence and associations between these determinants. METHODS: A multicentre, observational, cross-sectional study was conducted in 2017-2019 on PwSH aged between 14 and 17 years (adolescents) or between 20 and 29 years (YAs), included in the FranceCoag registry and having completed the questionnaires. The adherence to healthcare (treatment regimens and clinical follow-up) was compared between adolescents and YAs using the chi-squared test. The determinants of this adherence were analysed by structural equation modelling. RESULTS: There were 277 participants, 107 adolescents, and 170 YAs. The rate of adolescents adhering to healthcare was 82.2%, while the rate of YAs was 61.2% (p < .001). The barriers to the adherence to healthcare were being YA, having repeated at least one school grade and presenting mental health concerns. CONCLUSION: Adolescents had better adherence to healthcare than YAs. According to the determinants enlightened in this project, targeted supportive strategies and adapted therapeutic education programs can be developed for young PwSH to facilitate their adherence to healthcare.


Asunto(s)
Hemofilia A , Transición a la Atención de Adultos , Adolescente , Adulto , Humanos , Adulto Joven , Enfermedad Crónica , Estudios Transversales , Hemofilia A/terapia , Hemofilia A/tratamiento farmacológico , Encuestas y Cuestionarios
4.
Nutr Neurosci ; 25(4): 779-790, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32924835

RESUMEN

Vitamin A (retinol) and related retinoids are micronutrients provided by food. Retinol derivatives are growth factors important for development, cell differentiation and tissue homeostasis, especially in the brain.Objective: The hippocampus is a pivotal brain structure for learning and memory and hippocampal-dependent memory is highly sensitive to retinoids action. However, the underlying mechanisms are still unclear. In this study, we characterized the impact of vitamin A deficiency on memory and neuronal plasticity, focusing on the CA1 region of the hippocampus in rats.Methods: Weaned male Wistar rats were fed a control (5 UI/g) or deficient vitamin A diet (0 UI/g) for 10 weeks. The effect of vitamin A supplementation (20 UI/g) for 3 weeks was also tested. Memory performances were assessed in the Y-maze (n = 24-30/group), retinoic acid levels were measured (LC-MS/MS) in the serum and in the hippocampus (n = 5/group), CA1 neuronal architecture was analyzed with Golgi staining (n = 17-20 neurons/group) and electrophysiological patch-clamp recordings were performed on hippocampal brain slices (n = 6-11/group).Results: Vitamin A deficiency from weaning significantly lowered hippocampal levels of retinoic acid, reduced dendritic length and branching of CA1 pyramidal neurons and decreased spontaneous glutamatergic synaptic events and synaptic plasticity. When replenishment with moderate dose of dietary vitamin A for 3 weeks was done, most of the synaptic and morphological alterations were absent.Conclusion: This study provides new mechanistic insight to understand the critical role of retinoic acid in hippocampal function.


Asunto(s)
Espectrometría de Masas en Tándem , Vitamina A , Animales , Cromatografía Liquida , Hipocampo/metabolismo , Masculino , Plasticidad Neuronal , Neuronas , Ratas , Ratas Wistar
5.
BMC Nephrol ; 22(1): 278, 2021 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-34376184

RESUMEN

BACKGROUND: The recent COVID-19 pandemic has raised concerns about patient diagnosis and follow-up of chronically ill patients. Patients suffering from chronic illnesses, concomitantly infected by SARS-CoV-2, globally tend to have a worse prognosis and poor outcomes. Renal tropism and acute kidney injury following SARS-CoV-2 infection has recently been described in the literature, with elevated mortality rates. Furthermore, patients with pre-existing chronic kidney disease, infected by SARS-CoV-2, should be monitored carefully. Here, we report the case of a 69-year-old patient with splenic marginal zone lymphoma, suffering from longstanding chronic kidney disease following SARS-CoV-2 infection. CASE PRESENTATION: A 69-year-old male patient previously diagnosed with pulmonary embolism and splenic marginal zone lymphoma (Splenomegaly, Matutes 2/5, CD5 negative and CD23 positive), was admitted to the hospital with shortness of breath, fever and asthenia. A nasopharyngeal swab test was performed in addition to a CT-scan, which confirmed SARS-CoV-2 infection. Blood creatinine increased following SARS-CoV-2 infection at 130 µmol/l, with usual values at 95 µmol/l. The patient was discharged at home with rest and symptomatic medical treatment (paracetamol and hydration), then readmitted to the hospital in August 2020. A kidney biopsy was therefore conducted as blood creatinine levels were abnormally elevated. Immunodetection performed in a renal biopsy specimen confirmed co-localization of SARS-CoV2 nucleocapsid and protease 3C proteins with ACE2, Lewis x and sialyl-Lewis x antigens in proximal convoluted tubules and podocytes. Co-localization of structural and non-structural viral proteins clearly demonstrated viral replication in proximal convoluted tubules in this chronically ill patient. Additionally, we observed the co-localization of sialyl-Lewis x and ACE2 receptors in the same proximal convoluted tubules. Reverse Transcriptase-Polymerase Chain Reaction test performed on the kidney biopsy was negative, with very low Ct levels (above 40). The patient was finally readmitted to the haematology department for initiation of chemotherapy, including CHOP protocol and Rituximab. CONCLUSIONS: Our case emphasizes on the importance of monitoring kidney function in immunosuppressed patients and patients suffering from cancer following SARS-CoV-2 infection, through histological screening. Further studies will be required to decipher the mechanisms underlying chronic kidney disease and the putative role of sialyl-Lewis x and HBGA during SARS-CoV-2 infection.


Asunto(s)
COVID-19/complicaciones , Túbulos Renales/virología , Insuficiencia Renal Crónica/virología , SARS-CoV-2/fisiología , Replicación Viral , Anciano , Enzima Convertidora de Angiotensina 2/análisis , Biopsia , COVID-19/sangre , COVID-19/diagnóstico , Proteínas de la Nucleocápside de Coronavirus/análisis , Creatinina/sangre , Humanos , Riñón/química , Riñón/patología , Riñón/virología , Túbulos Renales/química , Túbulos Renales/patología , Antígeno Lewis X/análisis , Linfoma de Células B de la Zona Marginal/complicaciones , Masculino , Insuficiencia Renal Crónica/patología , Antígeno Sialil Lewis X/análisis , Neoplasias del Bazo/complicaciones
6.
Traffic ; 17(5): 487-99, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26847957

RESUMEN

Phagocytosis is a mechanism used by macrophages to internalize and eliminate microorganisms or cellular debris. It relies on profound rearrangements of the actin cytoskeleton that is the driving force allowing plasma membrane extension around the particle. The closure step of phagocytosis, however, remains poorly defined. We used a dedicated experimental setup with Total Internal Reflection Fluorescence Microscopy (TIRFM) to monitor phagosome formation and closure in three dimensions in living cells. We show that dynamin-2, which mediates the scission of endocytic vesicles, was recruited early and concomitantly with actin during phagosome formation. Dynamin-2 accumulated at the site of phagosome closure in living macrophages. Inhibition of its activity with dominant negative mutants or drugs demonstrated that dynamin-2 is implicated in actin dynamics and pseudopod extension. Depolymerization of actin led to impaired dynamin-2 recruitment or activity. Finally, we show that dynamin-2 plays a critical role in the effective scission of the phagosome from the plasma membrane. Thus, we establish that a cross talk between actin and dynamin takes place for phagosome formation and closure before dynamin functions for scission.


Asunto(s)
Actinas/metabolismo , Dinaminas/metabolismo , Fagosomas/metabolismo , Fagocitosis
7.
Cancer Discov ; 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38564707

RESUMEN

Activating point mutations in the MET tyrosine kinase domain (TKD) are oncogenic in a subset of papillary renal cell carcinomas (PRCC). Here, using comprehensive genomic profiling among >600,000 patients, we identify activating MET TKD point mutations as putative oncogenic driver across diverse cancers, with a frequency of ~0.5%. The most common mutations in the MET TKD defined as oncogenic or likely oncogenic according to OncoKB resulted in amino acid substitutions at positions H1094, L1195, F1200, D1228, Y1230, M1250, and others. Preclinical modeling of these alterations confirmed their oncogenic potential, and also demonstrated differential patterns of sensitivity to type I and type II MET inhibitors. Two patients with metastatic lung adenocarcinoma harboring MET TKD mutations (H1094Y, F1200I) and no other known oncogenic drivers achieved confirmed partial responses to a type I MET inhibitor. Activating MET TKD mutations occur in multiple malignancies and may confer clinical sensitivity to currently available MET inhibitors.

8.
Front Nutr ; 9: 811843, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35178422

RESUMEN

BACKGROUND: The mechanisms leading to a loss of dopaminergic (DA) neurons from the substantia nigra pars compacta (SNc) in Parkinson's disease (PD) have multifactorial origins. In this context, nutrition is currently investigated as a modifiable environmental factor for the prevention of PD. In particular, initial studies revealed the deleterious consequences of vitamin A signaling failure on dopamine-related motor behaviors. However, the potential of vitamin A supplementation itself to prevent neurodegeneration has not been established yet. OBJECTIVE: The hypothesis tested in this study is that preventive vitamin A supplementation can protect DA neurons in a rat model of PD. METHODS: The impact of a 5-week preventive supplementation with vitamin A (20 IU/g of diet) was measured on motor and neurobiological alterations induced by 6-hydroxydopamine (6-OHDA) unilateral injections in the striatum of rats. Rotarod, step test and cylinder tests were performed up to 3 weeks after the lesion. Post-mortem analyses (retinol and monoamines dosages, western blots, immunofluorescence) were performed to investigate neurobiological processes. RESULTS: Vitamin A supplementation improved voluntary movements in the cylinder test. In 6-OHDA lesioned rats, a marked decrease of dopamine levels in striatum homogenates was measured. Tyrosine hydroxylase labeling in the SNc and in the striatum was significantly decreased by 6-OHDA injection, without effect of vitamin A. By contrast, vitamin A supplementation increased striatal expression of D2 and RXR receptors in the striatum of 6-OHDA lesioned rats. CONCLUSIONS: Vitamin A supplementation partially alleviates motor alterations and improved striatal function, revealing a possible beneficial preventive approach for PD.

9.
Toxins (Basel) ; 14(6)2022 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-35737062

RESUMEN

Pinnatoxins (PnTX) and Portimines (Prtn), two toxins produced by the benthic dinoflagellate Vulcanodinium rugosum, are known to be lethal to mice after intraperitoneal or oral administration. They are also known to accumulate in shellfish such as mussels and clams, but their effect on fish and the upper food chain remains unknown. In this work, juveniles of the fish Liza ramada (Mullet) were exposed to a strain of V. rugosum producing PnTX G and Prtn A. The fishes' viability and contamination were recorded at times interval. Results showed that L. ramada juveniles were able to feed on V. rugosum and that their tissues could be contaminated by PnTX G and Prtn A without impact on fish viability. Furthermore, the microalgae temporary cysts survived and germinated after fish gut passage. This study showed the potential of L. ramada to transfer PnTX and Prtn toxins to the upper food chain and to disseminate V. rugosum in environment.


Asunto(s)
Bivalvos , Dinoflagelados , Microalgas , Smegmamorpha , Animales , Peces , Ratones , Supervivencia Tisular
10.
Med Care Res Rev ; 79(2): 175-197, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34157906

RESUMEN

Consumer cost-sharing has been shown to diminish utilization of preventive services. Recent efforts, including provisions within the Affordable Care Act, have sought to increase use of preventive care through elimination of cost-sharing for clinically indicated services. We conducted a rapid review of the literature to determine the impact of cost-share elimination on utilization of preventive services. Searches were conducted in PubMed, Scopus, and CINAHL Complete databases as well as in grey literature. A total of 35 articles were included in qualitative synthesis and findings were summarized for three clinical service categories: cancer screenings, contraceptives, and additional services. Impacts of cost-sharing elimination varied depending on clinical service, with a majority of findings showing increases in use. Studies that included socioeconomic status reported that those who were financially vulnerable incurred substantial increases in utilization. Future investigations on additional clinical services are warranted as is research to better elucidate populations who most benefit from cost-sharing elimination.


Asunto(s)
Seguro de Costos Compartidos , Patient Protection and Affordable Care Act , Bases de Datos Factuales , Detección Precoz del Cáncer , Humanos , Servicios Preventivos de Salud , Estados Unidos
11.
Pain ; 163(11): 2224-2231, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-35239543

RESUMEN

ABSTRACT: In pediatric patients, pain remains the most common complaint after surgery. This French multicenter epidemiological study (AlgoDARPEF) aimed to evaluate the use of a smartphone application (App) to assess the duration and severity of pain experienced by children undergoing outpatient surgery. Children younger than 18 years scheduled for an elective outpatient procedure in one of the participating centers were eligible. Parents were invited to provide daily information for 10 days regarding their child's pain and comfort through a smartphone App using the Parents' Postoperative Pain Measure-Short-Form (PPPM-SF). Children older than 6 years could also provide self-assessments of pain using a numerical rating scale (NRS)-11. Data regarding pain medication, preoperative anxiety, postoperative nausea and vomiting, and parent satisfaction were also analyzed. Repeated-measures analyses of variances (ANOVAs) were used to compare the self-assessments and hetero-assessments of pain. Eleven centers participated in the study, and 1573 patients were recruited. Forty-nine percentage of parents (n = 772) actually used the App at least once. In all surgeries, the average pain rating on the PPPM-SF scale did not exceed 3/10 throughout the follow-up period, as well as for 4 main surgical specialties. Age, visceral surgery, and preoperative anxiety ≥ 4/10 were identified as independent risk factors for experiencing at least 1 episode of pain ≥4/10 during the first 48 postoperative hours. Although these findings indicated that postoperative pain management seems to be satisfactory in the families who used the App, some improvements in anxiety management are suggested. This study shows that inviting parents to use a smartphone App to assess and report the quality of postoperative management in pediatric patients provides useful information. A continuous report regarding pain and adverse events over a 10-day postoperative period by a self-reporting or parent's contribution is possible. Future studies should investigate the ability of live data collection using an App to ensure fast, efficient interactions between patients and physicians.


Asunto(s)
Procedimientos Quirúrgicos Ambulatorios , Teléfono Inteligente , Procedimientos Quirúrgicos Ambulatorios/efectos adversos , Niño , Estudios de Seguimiento , Humanos , Dolor Postoperatorio/tratamiento farmacológico , Estudios Prospectivos
12.
J Parkinsons Dis ; 11(3): 949-970, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34120916

RESUMEN

Evidence shows that altered retinoic acid signaling may contribute to the pathogenesis and pathophysiology of Parkinson's disease (PD). Retinoic acid is the bioactive derivative of the lipophilic vitamin A. Vitamin A is involved in several important homeostatic processes, such as cell differentiation, antioxidant activity, inflammation and neuronal plasticity. The role of vitamin A and its derivatives in the pathogenesis and pathophysiology of neurodegenerative diseases, and their potential as therapeutics, has drawn attention for more than 10 years. However, the literature sits in disparate fields. Vitamin A could act at the crossroad of multiple environmental and genetic factors of PD. The purpose of this review is to outline what is known about the role of vitamin A metabolism in the pathogenesis and pathophysiology of PD. We examine key biological systems and mechanisms that are under the control of vitamin A and its derivatives, which are (or could be) exploited for therapeutic potential in PD: the survival of dopaminergic neurons, oxidative stress, neuroinflammation, circadian rhythms, homeostasis of the enteric nervous system, and hormonal systems. We focus on the pivotal role of ALDH1A1, an enzyme expressed by dopaminergic neurons for the detoxification of these neurons, which is under the control of retinoic acid. By providing an integrated summary, this review will guide future studies on the potential role of vitamin A in the management of symptoms, health and wellbeing for PD patients.


Asunto(s)
Enfermedad de Parkinson , Vitamina A , Neuronas Dopaminérgicas , Humanos , Enfermedades Neuroinflamatorias , Enfermedad de Parkinson/tratamiento farmacológico , Tretinoina
13.
Sci Rep ; 11(1): 10609, 2021 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-34011952

RESUMEN

In cancer cells only, TLR3 acquires death receptor properties by efficiently triggering the extrinsic pathway of apoptosis with Caspase-8 as apical protease. Here, we demonstrate that in the absence of Caspase-8, activation of TLR3 can trigger a form of programmed cell death, which is distinct from classical apoptosis. When TLR3 was activated in the Caspase-8 negative neuroblastoma cell line SH-SY5Y, cell death was accompanied by lysosomal permeabilization. Despite caspases being activated, lysosomal permeabilization as well as cell death were not affected by blocking caspase-activity, positioning lysosomal membrane permeabilization (LMP) upstream of caspase activation. Taken together, our data suggest that LMP with its deadly consequences represents a "default" death mechanism in cancer cells, when Caspase-8 is absent and apoptosis cannot be induced.


Asunto(s)
Apoptosis , Caspasa 8/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/patología , Receptor Toll-Like 3/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Activación Enzimática/efectos de los fármacos , Humanos , Interferón Tipo I/farmacología , Membranas Intracelulares/efectos de los fármacos , Membranas Intracelulares/metabolismo , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Necroptosis/efectos de los fármacos , Permeabilidad/efectos de los fármacos , Poli I-C/farmacología
14.
Cells ; 10(2)2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33672032

RESUMEN

Chordomas are rare, slow-growing tumors of the axial skeleton. These tumors are locally aggressive and refractory to conventional therapies. Radical surgery and radiation remain the first-line treatments. Despite these aggressive treatments, chordomas often recur and second-line treatment options are limited. The mechanisms underlying chordoma radioresistance remain unknown, although several radioresistant cancer cells have been shown to respond favorably to aldehyde dehydrogenase (ALDH) inhibition. The study of chordoma has been delayed by small patient cohorts and few available models due to the scarcity of these tumors. We thus created cellular 3D models of chordoma by using low-adherence culture systems. Then, we evaluated their radiosensitivity using colony-forming and spheroid size assays. Finally, we determined whether pharmacologically inhibiting ALDH increased their radiosensitivity. We found that 3D cellular models of chordoma (derived from primary, relapse, and metastatic tumors) reproduce the histological and gene expression features of the disease. The metastatic, relapse, and primary spheroids displayed high, medium, and low radioresistance, respectively. Moreover, inhibiting ALDH decreased the radioresistance in all three models.


Asunto(s)
Aldehído Deshidrogenasa/efectos de los fármacos , Cordoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Aldehído Deshidrogenasa/metabolismo , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Cordoma/patología , Cordoma/cirugía , Humanos , Tolerancia a Radiación/fisiología
15.
Neurobiol Aging ; 85: 1-10, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31689598

RESUMEN

Dietary micronutrients constitute a major environmental factor influencing aging processes. Vitamin A (vit. A) is the precursor of retinoic acid, a bioactive molecule that controls the expression of several genes involved in brain function. Evidence suggests a reduction of vit. A bioavailability with aging, but its impact on neuronal network is poorly understood. We investigated the mechanisms linking memory impairments with specific alterations of retinoic acid metabolism in the hippocampus. We compared young (10 weeks) and aged (16 months) rats, supplemented or not with dietary vit. A (20 IU retinol/g) for 4 weeks. Our study reveals that aging induced dysregulation of gene expression involved in vit. A and retinoic acid metabolism in the liver. Furthermore, vit. A supplementation restored the integrity of the hippocampal neuronal morphology altered by aging. Importantly, we found a high correlation between hippocampal levels of retinoic acid and memory performance. The present work establishes the link between collapse of retinoid metabolism and age-related cognitive decline, highlighting the role of vit. A in maintaining memory through aging.


Asunto(s)
Envejecimiento , Hipocampo/metabolismo , Trastornos de la Memoria/etiología , Memoria , Tretinoina/metabolismo , Animales , Expresión Génica/efectos de los fármacos , Ratas Wistar , Tretinoina/farmacología , Tretinoina/fisiología
16.
Methods Mol Biol ; 1784: 165-175, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29761398

RESUMEN

Complementary methods to observe frustrated phagocytosis and phagosome closure using total internal reflection fluorescence microscopy (TIRFM) are described here. Frustrated phagocytosis occurs when phagocytic cells are exposed to an opsonized surface and spread as if trying to engulf it, allowing for the observation of phagocytic spreading and the biochemical events that directly precede it. Phagosome formation and closure is an inherently three-dimensional process though, and cannot be studied in the "frustrated" situation. Here we describe a method to visualize with unprecedented high-resolution phagosome formation and closure in three dimensions. It allows for observation of the base of the phagocytic cup, the extending pseudopods, as well as the precise site of phagosome scission.


Asunto(s)
Técnicas de Cultivo de Célula/métodos , Macrófagos/citología , Microscopía Fluorescente/métodos , Fagocitosis/genética , Animales , Electroporación , Ratones , Fagosomas/genética , Fagosomas/metabolismo , Células RAW 264.7
17.
J Vis Exp ; (114)2016 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-27683961

RESUMEN

Phagocytosis is a mechanism used by specialized cells to internalize and eliminate microorganisms or cellular debris. It relies on profound rearrangements of the actin cytoskeleton that is the driving force for plasma membrane extension around the particle. In addition, efficient engulfment of large material relies on focal exocytosis of intracellular compartments. This process is highly dynamic and numerous molecular players have been described to have a role during phagocytic cup formation. The precise regulation in time and space of all of these molecules, however, remains elusive. In addition, the last step of phagosome closure has been very difficult to observe because inhibition by RNA interference or dominant negative mutants often results in stalled phagocytic cup formation. We have set up a dedicated experimental approach using total internal reflection fluorescence microscopy (TIRFM) combined with epifluorescence to monitor step by step the extension of pseudopods and their tips in a phagosome growing around a particle loosely bound to a coverslip. This method allows us to observe, with high resolution the very tips of the pseudopods and their fusion during closure of the phagosome in living cells for two different fluorescently tagged proteins at the same time.

18.
Ann Intensive Care ; 6(1): 76, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27502195

RESUMEN

BACKGROUND: The ultrasound (US)-guided technique has been recommended for central venous catheter (CVC) placement in critical care. However, several surveys have shown that the majority of physicians continue to perform landmark procedures. In our region, we have implemented special courses to promote the use of US with formal training and simulators. Ultrasound machines have also been installed in almost every ICU in our area. We designed a survey to investigate whether the training program established for years and the widespread of ultrasound devices in the ICU of our region will be associated with a high rate of physicians performing US procedures. METHODS: A survey comprising 14 questions was designed to elicit information on training in US techniques, the use of US for CVC placement, reasons for nonuse of US and their opinion concerning the need to teach the landmark technique to residents. This survey was electronically sent to every physician of the BoReal study group (32 ICUs located in the North West of France). RESULTS: We received 190 responses (response rate 66 %) including 34 % of residents. Only 11 % of respondents reported the absence of training in the US technique, and 3 % reported they did not have access to an ultrasound machine. A total of 68 % declared "always" (18 %) or "almost always" (50 %) using US to guide CVC placement. Our results are better than those of previous surveys. The main reasons why physicians did not use the US technique were that they thought that US guidance was unnecessary (36 %) or because the ultrasound machine was not immediately available (33 %). Ninety-one percentages think that the landmark technique should still be taught to the residents. A higher proportion of residents compared to seniors declared that they always or almost always used the US technique. CONCLUSION: Training in ultrasound techniques and the widespread availability of ultrasound machines in ICUs seem to improve the rate of US procedures. However, despite strong scientific evidence a proportion of physicians continue to consider the landmark technique as an alternative to US. Training and education are potentially still the best ways to overcome such barriers or conviction.

19.
Anaesth Crit Care Pain Med ; 34(4): 191-7, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26141685

RESUMEN

UNLABELLED: Anaesthesia has evolved in France since the last epidemiologic survey in 1996. The national database program for medical information systems (the PMSI) can be used to track specific knowledge concerning anaesthesia for a selected period of time. The goal of this study was to perform a contemporary epidemiological description of anaesthesia in France for the year 2010. METHODS: The data concerning private or public hospital stays were collected from the national PMSI database. All surgical/medical institutions performing anaesthesia in France and French Overseas Departments and Territories were queried concerning the number of anaesthesias, patient age, sex ratios, institution characteristics, hospitalization types, the duration of hospital stays, and the surgical procedures performed. RESULTS: In 2010, the number of anaesthesia procedures performed was 11,323,630 during 8,568,630 hospital stays. We found that 9,544,326 (84.3%) anaesthetic procedures were performed in adults (> 18 years of age; excluding childbirth), 845,568 (7.5%) were related to childbirth and 933,736 (8.2%) were acts in children (up to 18 years of age). The mean duration of hospital stay was 5.7±8.2 days. 56.5% of adults and 39.5% of children were managed as inpatient hospital stays. The male/female sex ratio and mean age were 42/58 and 54±19 years, respectively. In adults, anaesthesia was predominantly performed for abdominal surgery (24.5%), orthopaedics (16.7%), gynaecology (10.3%), ophthalmology (9.7%) and vascular surgeries (7.1%). For paediatric populations, the main surgical activities were Ear-Nose-Throat surgery (43.1%), orthopaedic surgery (15.1%) and urological surgeries (12.8%). DISCUSSION: The number of anaesthesias performed in France has dramatically increased (42.7%) since the last major epidemiological survey. Anaesthesia in the 21th century has been adapted to associated demographic changes: an older population with more comorbidities and fewer in-hospital procedures.


Asunto(s)
Anestesiología/tendencias , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos Ambulatorios/estadística & datos numéricos , Anestesia/estadística & datos numéricos , Anestesia Obstétrica/estadística & datos numéricos , Anestesiología/estadística & datos numéricos , Niño , Preescolar , Bases de Datos Factuales , Femenino , Francia , Encuestas de Atención de la Salud , Hospitalización/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Pacientes Internos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Factores Sexuales , Factores Socioeconómicos , Procedimientos Quirúrgicos Operativos/estadística & datos numéricos , Adulto Joven
20.
Anaesth Crit Care Pain Med ; 34(4): 199-204, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26233282

RESUMEN

INTRODUCTION: Epidemiological data on French ambulatory anaesthesias are restricted. The aim of this study was to perform an epidemiological analysis of this activity for the year 2010. METHODS: Using the national database program for medical information systems (the PMSI), we have listed all institutions in France and her overseas territories performing ambulatory anaesthesia. We have assessed the number and nature of anaesthetic procedures, in terms of type of institution, age and surgeries. These results were correlated with French general demographics. RESULTS: Ambulatory anaesthetic procedures represented 44.4% of all anaesthesias, excluding childbirth, (n=4644,791 ambulatory acts), among which 88% were performed on adults and 12% on minors. The "65-74 years" age group had the highest annual relative rate of ambulatory anaesthesia. Rate of ambulatory anaesthesia was higher in children compared to adults (60% versus 42.8%, respectively). Outpatient surgery was mainly developed in Private Clinics as compared to public institutions. CONCLUSION: Ambulatory anaesthesia has dramatically increased over fourteen years. It represents almost half of all anaesthetic acts, and its development is promising, especially in University Hospitals and adult populations.


Asunto(s)
Atención Ambulatoria/estadística & datos numéricos , Procedimientos Quirúrgicos Ambulatorios/estadística & datos numéricos , Anestesia , Anestesiología/tendencias , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Anestesiología/estadística & datos numéricos , Niño , Preescolar , Bases de Datos Factuales , Femenino , Francia , Encuestas de Atención de la Salud , Hospitales Privados/estadística & datos numéricos , Hospitales Públicos/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Pediatría/estadística & datos numéricos , Factores Socioeconómicos , Adulto Joven
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