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1.
Artigo em Francês | MEDLINE | ID: mdl-33570039

RESUMO

Soon after the pandemic, numerous publications described cases of neurological disorders associated with the SARS-CoV-2 infection. The range of neurological symptoms is becoming increasingly more extensive as the pandemic progresses. However, it is not yet well established whether the manifestations are due to direct viral damage to the nervous system or indirect consequences of the infection. This review presents an inventory of the biochemical markers studied in the context of neurological disorders related to SARS-CoV-2. By reflecting various physiopathological mechanisms, these biomarkers allow both a better understanding of the pathophysiology of Covid-19 and a contribution to the diagnosis of neurologic troubles; they could participate in the prognostic evaluation of patients.

3.
Neurochirurgie ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33582206

RESUMO

BACKGROUND: Sports concussion is a major problem that affects thousands of people every year. Concussion-related neurometabolic changes are thought to underlie neurophysiological alterations and post-concussion symptoms such as headaches and sensitivity to light and noise, disabilities of concentration and tiredness. The injury triggers a complex neurometabolic cascade involving multiple mechanisms. There are pharmaceutical treatments that target one mechanism, but specific nutrients have been found to impact several pathways, thus offering a broader approach. This has prompted intensive research into the use of nutrient supplements as a concussion prevention and treatment strategy. METHOD: We realized a bibliographic state of art providing a contemporary clinical and preclinical studies dealing with nutritional factors in sport-related concussion. RESULTS: Numerous supplements, including n-3 polyunsaturated fatty acids, sulfur amino acids, antioxidants and minerals, have shown promising results as aids to concussion recovery or prevention in animal studies, most of which use a fluid percussion technique to cause brain injury, and in a few human studies of severe or moderate traumatic brain injury. Current ongoing human trials can hopefully provide us with more information, in particular on new options, i.e. probiotics, lactate or amino acids, for the use of nutritional supplements for concussed athletes. CONCLUSION: Nutritional supplementation has emerged as a potential strategy to prevent and/or reduce the deleterious effects of sports-related concussion and subconcussive impacts.

4.
PLoS Biol ; 18(12): e3000948, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33284790

RESUMO

Chronic inflammation is now a well-known precursor for cancer development. Infectious prostatitis are the most common causes of prostate inflammation, but emerging evidence points the role of metabolic disorders as a potential source of cancer-related inflammation. Although the widely used treatment for prostate cancer based on androgen deprivation therapy (ADT) effectively decreases tumor size, it also causes profound alterations in immune tumor microenvironment within the prostate. Here, we demonstrate that prostates of a mouse model invalidated for nuclear receptors liver X receptors (LXRs), crucial lipid metabolism and inflammation integrators, respond in an unexpected way to androgen deprivation. Indeed, we observed profound alterations in immune cells composition, which was associated with chronic inflammation of the prostate. This was explained by the recruitment of phagocytosis-deficient macrophages leading to aberrant hyporesponse to castration. This phenotypic alteration was sufficient to allow prostatic neoplasia. Altogether, these data suggest that ADT and inflammation resulting from metabolic alterations interact to promote aberrant proliferation of epithelial prostate cells and development of neoplasia. This raises the question of the benefit of ADT for patients with metabolic disorders.

5.
Acta Ophthalmol ; 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33354927

RESUMO

PURPOSE: To conduct a systematic review and meta-analysis on the levels of oxidative stress markers and antioxidants in keratoconus compared to healthy subject. METHOD: The PubMed, Cochrane Library, Embase, Science Direct and Google Scholar databases were searched on 1st June 2020 for studies reporting oxidative and antioxidative stress markers in keratoconus and healthy controls. Main meta-analysis was stratified by type of biomarkers, type of samples (tears, cornea, aqueous humour and blood) and type of corneal samples (stromal cells, epithelium and endothelium). RESULTS: We included 36 articles, for a total of 1328 keratoconus patients and 1208 healthy controls. There is an overall increase in oxidative stress markers in keratoconus compared with healthy controls (standard mean deviation (SMD) = 0.94, 95% confidence interval (95% CI) 0.55-1.33), with a significant increase in reactive oxygen and nitrogen species (1.09, 0.41-1.78) and malondialdehyde (1.78, 0.83-2.73). There is an overall decrease in antioxidants in keratoconus compared with healthy controls (-0.63, -0.89 to -0.36), with a significant decrease in total antioxidant capacity/status (-1.65, -2.88 to -0.43), aldehyde/NADPH dehydrogenase (-0.77, -1.38 to -0.17), lactoferrin/transferrin/albumin (-1.92, -2.96 to -0.89) and selenium/zinc (-1.42, -2.23 to -0.61). Oxidative stress markers were higher in tears and in cornea of keratoconus than in aqueous humour, and antioxidants were decreased in tears, aqueous humour and blood without difference between sample type. Oxidative stress markers increased in stromal cells and antioxidants decreased in endothelium. CONCLUSION: Oxidative stress markers and antioxidants were dysregulated in keratoconus, involving an imbalance of redox homeostasis in tears, cornea, aqueous humour and blood.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33147613

RESUMO

OBJECTIVES: Patients with RA have a higher prevalence of infertility than the general population. This study sought to examine the impact of RA disease activity and treatments on ovarian reserve measured by serum anti-Müllerian hormone (AMH) levels in the ESPOIR cohort. We sought to better define the indications for fertility preservation. METHODS: Patients and serum analysis data were derived from the French national cohort ESPOIR. Enrolled patients (n = 102; 18-37-year-olds) fulfilled ACR/EULAR 2010 criteria for RA. Serum AMH levels were measured at T0, T6, T12, T24 and T36 months post-diagnosis. The impacts of RA activity (DAS28 and CRP level) and treatments (MTX only or with other medications) were evaluated at each study visit. RESULTS: A gradual decrease in patients' serum AMH levels was observed over time, in line with the descending curve described for healthy women. Serum AMH levels of RA patients in comparison with the values considered normal for age did not reveal any significant differences (P > 0.05). We did not observe any impact of RA treatments. We demonstrated an inverse correlation between AMH variation and disease activity (DAS28: r = -0.27, P = 0.003; CRP: r = -0.16, P = 0.06). CONCLUSION: This is the first study to determine serum AMH levels of a large cohort of RA patients over 36 months. Rapid disease activity control appears to be required to limit changes in the ovarian reserve. Fertility preservation is not likely to be necessary if inflammation is promptly controlled. ClinicalTrials.gov Identifier: NCT03666091.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33237026

RESUMO

In order to propose a course of action to be taken in the face of any hyperhomocysteinemia, we have reported for the first time in a French journal the recommendations made within the framework of the European E-HOD project for the diagnosis and treatment of remethylation disorders. The remethylation route ensures homocysteine-methionine conversion. It is linked to the folate cycle and the intracellular metabolism of cobalamins. Remethylation disorders can be classified into three groups: 1) isolated disorders (cblD-HC, cblE, cblG) corresponding to an isolated deficit in the production of methylcobalamin, cofactor of methionine synthase; 2) combined disorders (cblC, cblD-MMA/HC, cblF, cblJ) corresponding to an alteration of the transport and intracellular metabolism of cobalamins, which causes a defect in the synthesis of the two functional forms of cobalamin: methylcobalamin and adenosylcobalamin, a cofactor for methyl malonylCoA mutase; 3) MTHFR deficit, an abnormality of the folate cycle. The biological anomalies observed are hyperhomocysteinemia and hypomethioninaemia associated in the case of disorders combined with increased urinary excretion of methylmalonic acid. The clinical presentation is however heterogeneous according to the remethylation disorder but also for the same pathology according to the age. Given the large number of pathologies grouped together in remethylation disorders, this point is illustrated by only two clinical cases concerning the same deficit (deficit in MTHFR) but with different discovery circumstances: a neonatal form and a late form.

8.
Ann Biol Clin (Paris) ; 78(5): 499-518, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026346

RESUMO

The French society of clinical biology "Biochemical markers of COVID-19" has set up a working group with the primary aim of reviewing, analyzing and monitoring the evolution of biological prescriptions according to the patient's care path and to look for markers of progression and severity of the disease. This study covers all public and private sectors of medical biology located in metropolitan and overseas France and also extends to the French-speaking world. This article presents the testimonies and data obtained for the "Overseas and French-speaking countries" sub-working group made up of 45 volunteer correspondents, located in 20 regions of the world. In view of the delayed spread of the SARS-CoV-2 virus, the overseas regions and the French-speaking regions have benefited from feedback from the first territories confronted with COVID-19. Thus, the entry of the virus or its spread in epidemic form could be avoided, thanks to the rapid closure of borders. The overseas territories depend very strongly on air and/or sea links with the metropolis or with the neighboring continent. The isolation of these countries is responsible for reagent supply difficulties and has necessitated emergency orders and the establishment of stocks lasting several months, in order to avoid shortages and maintain adequate patient care. In addition, in countries located in tropical or intertropical zones, the diagnosis of COVID-19 is complicated by the presence of various zoonoses (dengue, Zika, malaria, leptospirosis, etc.).


Assuntos
Serviços de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Saúde Global/estatística & dados numéricos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Medicina de Viagem/organização & administração , Adulto , África/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , Betacoronavirus/fisiologia , Biomarcadores/análise , Biomarcadores/sangue , Camboja/epidemiologia , Criança , Serviços de Laboratório Clínico/organização & administração , Serviços de Laboratório Clínico/estatística & dados numéricos , Busca de Comunicante/métodos , Busca de Comunicante/estatística & dados numéricos , Infecções por Coronavirus/transmissão , Diagnóstico Diferencial , Feminino , França/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Recém-Nascido , Ilhas/epidemiologia , Idioma , Laos/epidemiologia , Louisiana/epidemiologia , Masculino , Pessoal de Laboratório Médico/organização & administração , Pessoal de Laboratório Médico/estatística & dados numéricos , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/transmissão , Estudos Retrospectivos , Inquéritos e Questionários , Análise de Sobrevida , Medicina de Viagem/métodos , Medicina de Viagem/estatística & dados numéricos , Doença Relacionada a Viagens , Clima Tropical , Medicina Tropical/métodos , Medicina Tropical/organização & administração , Medicina Tropical/estatística & dados numéricos , Vietnã/epidemiologia
9.
J Vis Exp ; (163)2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-33044446

RESUMO

Acute respiratory distress syndrome (ARDS) is a common cause of hypoxemic respiratory failure and death in critically ill patients, and there is an urgent need to find effective therapies. Preclinical studies have shown that inhaled halogenated agents may have beneficial effects in animal models of ARDS. The development of new devices to administer halogenated agents using modern intensive care unit (ICU) ventilators has significantly simplified the dispensing of halogenated agents to ICU patients. Because previous experimental and clinical research suggested potential benefits of halogenated volatiles, such as sevoflurane or isoflurane, for lung alveolar epithelial injury and inflammation, two pathophysiologic landmarks of diffuse alveolar damage during ARDS, we designed an animal model to understand the mechanisms of the effects of halogenated agents on lung injury and repair. After general anesthesia, tracheal intubation, and the initiation of mechanical ventilation, ARDS was induced in piglets via the intratracheal instillation of hydrochloric acid. Then, the piglets were sedated with inhaled sevoflurane or isoflurane using an ICU-type device, and the animals were ventilated with lung-protective mechanical ventilation during a 4 h period. During the study period, blood and alveolar samples were collected to evaluate arterial oxygenation, the permeability of the alveolar-capillary membrane, alveolar fluid clearance, and lung inflammation. Mechanical ventilation parameters were also collected throughout the experiment. Although this model induced a marked decrease in arterial oxygenation with altered alveolar-capillary permeability, it is reproducible and is characterized by a rapid onset, good stability over time, and no fatal complications. We have developed a piglet model of acid aspiration that reproduces most of the physiological, biological, and pathological features of clinical ARDS, and it will be helpful to further our understanding of the potential lung-protective effects of halogenated agents delivered through devices used for inhaled ICU sedation.

10.
Front Neurol ; 11: 856, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922357

RESUMO

Background: Mild traumatic brain injury (mTBI) management in emergency departments is a complex process involving clinical evaluation, laboratory testing, and computerized tomography (CT) scanning. Protein S100B has proven to be a useful blood biomarker for early evaluation of mTBI, as it reduces the required CT scans by one-third. However, to date, the ability of S100B to identify positive abnormal findings in the CT scans of patients suffering from mTBI caused by ski practice has not been investigated. Thus, the primary aim of this study was to investigate the diagnostic performance of S100B as an mTBI management biomarker in patients with ski-related mTBI. Materials and Methods: One hundred and thirty adult mTBI patients presenting to the emergency department of Hôpital du Valais in Sion, Switzerland, with a Glasgow Coma Scale (GCS) score of 13-15 and clinical indication for a CT scan were included in the study. Blood samples for S100B measurement were collected from each patient and frozen in 3-hour post-injury intervals. CT scans were performed for all patients. Later, serum S100B levels were compared to CT scan findings in order to evaluate the biomarker's performance. Results: Of the 130 included cases of mTBI, 87 (70%) were related to ski practice. At the internationally established threshold of 0.1 µg/L, the receiver operating characteristic curve of S100B serum levels for prediction of abnormal CT scans showed 97% sensitivity, 11% specificity, and a 92% negative predictive value. Median S100B concentrations did not differ according to sex, age, or GCS score. Additionally, there was no significant difference between skiers and non-skiers. However, a statistically significant difference was found when comparing the median S100B concentrations of patients who suffered fractures or had polytrauma and those who did not suffer fractures. Conclusion: The performance of S100B in post-mTBI brain lesion screenings seems to be affected by peripheral lesions and/or ski practice. The lack of neurospecificity of the biomarker in this context does not allow unnecessary CT scans to be reduced by one-third as expected.

11.
Front Immunol ; 11: 1645, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849565

RESUMO

Context and Objectives: Inflammation is the leading mechanism involved in both physiological and pathological rupture of fetal membranes. Our aim was to obtain a better characterization of the inflammasome-dependent inflammation processes in these tissues, with a particular focus on the nucleotide-binding oligomerization domain (NOD)-like receptor, pyrin domain containing protein 7 (NLRP7) inflammasome. Methods: The presence of NLRP7 inflammasome actors [NLRP7, apoptosis-associated speck-like protein containing a CARD domain (ASC), and caspase-1] was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) in human amnion and choriodecidua at the three trimesters and at term. The protein concentrations were then determined by enzyme-linked immunosorbent assay in term tissues, with or without labor. The presence of Mycoplasma salivarium and Mycoplasma fermentans in human fetal membranes was investigated using a PCR approach. Human amnion epithelial cells (AECs) were treated for 4 or 20 h with fibroblast-stimulating lipopeptide-1 (FSL-1), a M. salivarium-derived ligand. Transcripts and proteins quantity was then measured by RT-quantitative PCR and Western blotting, respectively. NLRP7 and ASC colocalization was confirmed by immunofluorescence. Western blots allowed analysis of pro-caspase-1 and gasdermin D cleavage. Results: NLRP7, ASC, and caspase-1 transcripts were expressed in both sheets of human fetal membranes during all pregnancy stages, but only ASC protein expression was increased with labor. In addition, M. salivarium and M. fermentans were detected for the first time in human fetal membranes. NLRP7 and caspase-1 transcripts, as well as NLRP7, ASC, and pro-caspase-1 protein levels, were increased in FSL-1-treated AECs. The NLRP7 inflammasome assembled around the nucleus, and pro-caspase-1 and gasdermin D were cleaved into their mature forms after FSL-1 stimulation. Conclusion: Two new mycoplasmas, M. salivarium and M. fermentans, were identified in human fetal membranes, and a lipopeptide derived from M. salivarium was found to induce NLRP7 inflammasome formation in AECs.

12.
Clin Biochem ; 85: 5-11, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32781055

RESUMO

Mild traumatic brain injury (mTBI) is one of the common causes of emergency department visits around the world. Up to 90% of injuries are classified as mTBI. Cranial computed tomography (CCT) is a standard diagnostic tool for adults with mTBI. Alternatively, children can be admitted for inpatient observation with CCT scans performed only on those with clinical deterioration. The use of blood biomarkers is a supplementary tool for identifying patients at risk of intracerebral lesions who may need imaging. This review provides a contemporary clinical and laboratory framework for blood biomarker testing in mTBI management. The S100B protein is used routinely in the management of mTBI in Europe together with clinical guidelines. Due to its excellent negative predictive value, S100B protein is an alternative choice to CCT scanning for mTBI management under considered, consensual and pragmatic use. In this review, we propose points to help clinicians and clinical pathologists use serum S100B protein in the clinical routine. A review of the literature on the different biomarkers (GFAP, UCH-L1, NF [H or L], tau, H-FABP, SNTF, NSE, miRNAs, MBP, ß trace protein) is also conducted. Some of these other blood biomarkers, used alone (GFAP, UCH-L1) or in combination (GFAP + H-FABP ± S100B ± IL10) can improve the specificity of S100B.

13.
Front Physiol ; 11: 609, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655405

RESUMO

Preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 37 weeks of gestation, complicates approximately 2-4% of pregnancies and is responsible for 40% of all spontaneous preterm births. PPROM arises from complex pathophysiological pathways with a key actor: inflammation. Sterile inflammation is a feature of senescence-associated fetal membrane maturity. During specific steps of sterile inflammation, cells also release highly inflammatory damage-associated molecular pattern markers (DAMPs), such as high-mobility group box 1 (HMGB1) or S100A8/A9, known to link and activate the receptor for advanced glycation end products (RAGE). The objective of this study was to measure longitudinally during pregnancy concentrations of the soluble form of RAGE (sRAGE) and its main ligands (AGE, HMGB1, S100A8/A9) in blood specimens. We studied 246 pregnant women (82 with PPROM and 164 matched control pregnant women without complications) from a cohort of 7,866 pregnant women recruited in the first trimester and followed during pregnancy until delivery. sRAGE, AGE, HMGB1, and S100A8/A9 concentrations were measured in plasma and in serum-extracted extracellular vesicles from first trimester (T1), second trimester (T2), and delivery (D). In plasma, we observed, in both PPROM and control groups, (i) a significant increase of HMGB1 concentrations between T1 vs. T2, T1 vs. D, but not between T2 vs. D; (ii) a significant decrease of sRAGE concentrations between T1 and T2 and a significant increase between T2 and D; (iii) a significant decrease of AGE from T1 to D; (iv) no significant variation of S100A8/A9 between trimesters. In intergroup comparisons (PPROM vs. control group), there were no significant differences in time variation taking into account the matching effects. There was a correlation between plasma and serum-extracted extracellular vesicle concentrations of sRAGE, AGE, HMGB1, and S100A8/A9. Our results suggest that the rupture of fetal membranes (physiological or premature) is accompanied by a variation in plasma concentrations of sRAGE, HMGB1, and AGE. The study of RAGE and its main ligands in extracellular vesicles did not give additional insight into the pathophysiological process conducting to PPROM.

14.
Front Physiol ; 11: 581, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670078

RESUMO

Context: Sterile inflammation has been shown to play a key role in the rupture of the fetal membranes (FMs). Moreover, an early and exacerbated runaway inflammation can evolve into a preterm premature rupture of membranes and lead to potential preterm birth. In this context, we investigated the receptor for advanced glycation end products (RAGE), an axis implied in physiological sterile inflammation, in conjunction with two major ligands: AGEs and High-Mobility Group Box 1 (HMGB1). Our first objective was to determine the spatiotemporal expression profiles of the different actors of the RAGE-signaling axis in human FMs, including its intracellular adaptors Diaphanous-1 and Myd88. Our second goal was to evaluate the functionality of RAGE signaling in terms of FMs inflammation. Methods: The presence of the actors (RAGE, HMGB1, Myd88, and Diaphanous-1) at the mRNA level was investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in the human amnion and choriodecidua at the three trimesters and at term. Measurements were conducted at two distinct zones: the zone of intact morphology (ZIM) and the zone of altered morphology (ZAM). Then, proteins were quantified using Western blot analysis, and their localization was evaluated by immunofluorescence in term tissues. In addition, pro-inflammatory cytokine secretion was quantified using a Multiplex assay after the treatment of amnion and choriodecidua explants with two RAGE ligands (AGEs and HMGB1) in the absence or presence of a RAGE inhibitor (SAGEs). Results: The FMs expressed the RAGE-signaling actors throughout pregnancy. At term, RNA and protein overexpression of the RAGE, HMGB1, and Diaphanous-1 were found in the amnion when compared to the choriodecidua, and the RAGE was overexpressed in the ZAM when compared to the ZIM. The two RAGE ligands (AGEs and HMGB1) induced differential cytokine production (IL1ß and TNFα) in the amnion and choriodecidua. Conclusion: Considered together, these results indicate that RAGE signaling is present and functional in human FMs. Our work opens the way to a better understanding of FMs weakening dependent on a RAGE-based sterile inflammation.

15.
Ann Biol Clin (Paris) ; 78(4): 438-440, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32576545

RESUMO

Hyperprolactinemia is common and accounts for 20 to 25% of secondary amenorrhea causes. Here, we report a case of moderate hyperprolactinemia observed in a 40-year-old patient consulting for spaniomenorrhea and inguinal pain during a bartholinitis episode. After eliminating all known causes of hyperprolactinemia, alprazolam intake is finally assumed. This hyperprolactinemia is found in a few bibliographic studies and is also noted in the summary of product characteristics. However, benzodiazepines are not known as hyperprolactinemia-inducing drugs by the endocrinologists and do not appear in the list of drugs established by a consensus of experts from the French Society of Endocrinology. This article aims to increase awareness of prescribing physicians and biologists of the possible occurrence of hyperprolactinemia in patients treated by benzodiazepines, especially since the intake of this molecule is particularly common in France, whether it is a medical prescription or self-medication.


Assuntos
Alprazolam/efeitos adversos , Benzodiazepinas/efeitos adversos , Hiperprolactinemia/induzido quimicamente , Adulto , Amenorreia/induzido quimicamente , Amenorreia/complicações , Feminino , Humanos , Hiperprolactinemia/complicações
16.
Ann Biol Clin (Paris) ; 78(3): 269-277, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32540814

RESUMO

The SARS-CoV-2 virus is responsible for an epidemic disease called COVID-19, which was initially evidenced in Wuhan, China, and spread very rapidly in China and around the world. In France, the first isolated case seems now to be reported in December 2019, stage 3 of the COVID-19 epidemic was triggered on March 14th, the start of the planned containment exit from May 11th. Healthcare services have faced a large influx of patients who may be beyond their capacity to receive and care, particularly in the Large-East and Ile-de-France regions. Some patients show an evolution of the disease never observed before with other coronaviruses and develop in a few days a very important inflammatory reaction, which can lead to death of patients. A working group of the French Society of Clinical Biology (SFBC) was set up with the objective of providing updated information on the current status of the biological prescriptions (focusing on biochemistry ones) and their evolution during the epidemic, and of analyzing the biological parameters associated with comorbidities and patient evolution in order to link biological results with medical events. The expanded working group covers all sectors of medical biology in France and extends to the French-speaking world: hospital sectors (CHU and CH, Army Training Hospitals) and the private sector opening a field of view on the biological situation in establishments for dependent elderly, social establishments and clinical medical institutions. The purpose of this article is the presentation of this working group and its immediate and future actions.


Assuntos
Betacoronavirus , Bioquímica/organização & administração , Biomarcadores/análise , Serviços de Laboratório Clínico/organização & administração , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Sociedades Científicas/organização & administração , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Bioquímica/normas , Biomarcadores/sangue , Serviços de Laboratório Clínico/normas , Redes Comunitárias/organização & administração , Redes Comunitárias/normas , Redes Comunitárias/tendências , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , França/epidemiologia , História do Século XXI , Humanos , Colaboração Intersetorial , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Prática Profissional/organização & administração , Prática Profissional/normas , Prática Profissional/tendências , Sociedades Científicas/normas , Comunicação por Videoconferência/organização & administração , Comunicação por Videoconferência/normas
17.
Antioxidants (Basel) ; 9(5)2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32365668

RESUMO

It has been proven that dietary eicosapentaenoic acid (C20:5 n-3 or EPA) protects the heart against the deleterious effects of sepsis in female rats. We do not know if this is the case for male rodents. In this case, the efficiency of other n-3 polyunsaturated fatty acids (PUFAs) remains to be determined in both female and male rats. This study aimed at (i) determining whether dietary EPA is cardioprotective in septic male rats; (ii) evaluating the influence of dietary α-linolenic (C18:3 n-3 or ALA) on cardiac function during this pathology; and (iii) finding out the physiological and molecular mechanisms responsible for the observed effects. Sixty male rats were divided into three dietary groups. The animals were fed a diet deficient in n-3 PUFAs (DEF group), a diet enriched with ALA (ALA group) or a diet fortified with EPA (EPA group) for 6 weeks. Thereafter, each group was subdivided into 2 subgroups, one being subjected to cecal ligation and puncture (CLP) and the other undergoing a fictive surgery. Cardiac function was determined in vivo and ex vivo. Several parameters related to the inflammation process and oxidative stress were determined. Finally, the fatty acid compositions of circulating lipids and cardiac phospholipids were evaluated. The results of the ex vivo situation indicated that sepsis triggered cardiac damage in the DEF group. Conversely, the ex vivo data indicated that dietary ALA and EPA were cardioprotective by resolving the inflammation process and decreasing the oxidative stress. However, the measurements of the cardiac function in the in vivo situation modulated these conclusions. Indeed, in the in vivo situation, sepsis deteriorated cardiac mechanical activity in the ALA group. This was suspected to be due to a restricted coronary flow which was related to a lack of cyclooxygenase substrates in membrane phospholipids. Finally, only EPA proved to be beneficial in sepsis. Its action necessitates both resolution of inflammation and increased coronary perfusion. In that sense, dietary ALA, which does not allow the accumulation of vasodilator precursors in membrane lipids, cannot be protective during the pathology.

18.
Exp Cell Res ; 391(2): 112030, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32330509

RESUMO

Re-epithelialization of the alveolar surface is a key process of lung alveolar epithelial barrier repair after acute lung injury. The receptor for advanced glycation end-products (RAGE) pathway plays key roles in lung homeostasis, and its involvement in wound repair has been already reported in human bronchial epithelial cells. However, its effects on lung alveolar epithelial repair after injury remain unknown. We investigated whether RAGE stimulation with its ligands high-mobility group box 1 protein (HMGB1) or advanced glycation end-products (AGEs), alone or associated with RAGE inhibition using RAGE antagonist peptide, affects in vitro wound healing in human alveolar epithelial A549 cells. We further asked whether these effects could be associated with changes in cell proliferation and migration. We found that treatment of A549 cells with HMGB1 or AGEs promotes RAGE-dependent wound healing after a scratch assay. In addition, both RAGE ligands increased cell proliferation in a RAGE-dependent manner. Treatment with HMGB1 increased migration of alveolar epithelial cells at 12 h, independently of RAGE, whereas AGEs stimulated migration as measured 48 h after injury in a RAGE-dependent manner. Taken together, these results suggest that RAGE pathway is involved in lung alveolar epithelial wound repair, possibly through enhanced cell migration and proliferation.

19.
Free Radic Biol Med ; 153: 71-79, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32330586

RESUMO

Evaluating the activity of cardiac mitochondria is probably the best way to estimate early cellular damage in chronic pathology. Early diagnosis allows rapid therapeutic intervention thus increasing patient survival rate in a number of diseases. However, data on human cardiac mitochondria are scarce in the international literature. Here, we describe a method to extract and study functional mitochondria from the small-sized right atrial aliquots (minimum of 400 mg) obtained during extracorporeal circulation and usually considered as surgical waste products. The mitochondria were purified through several mechanical processes (fine myocardial cutting, tissue grinding and potter Elvehjem homogenising), an enzymatic proteolytic action (subtilisin) and differential centrifugations. In chronic pathologies, including obesity, early disturbances of mitochondrial function can occur. The effects of obesity on the rate of mitochondrial oxygen consumption and H2O2 release were thus determined with three different substrates (glutamate/malate, succinate/rotenone and palmitoylcarnitine/malate). The human atrial mitochondria were of high quality from a functional viewpoint, compared to rat ventricle organelles, but the extraction yield of the human mitochondria was twice lower than that of rat mitochondria. Tests showed that glutamate/malate-related ADP-stimulated respiration was strongly increased in obese subjects, although the oxidation of the other two substrates was unaffected. Reactive oxygen species (ROS) production by the isolated mitochondria was low in comparison with that of the lean subjects. These results confirm those found in one of our previous studies in the ventricles of rats fed a high-fat diet. In conclusion, the described method is simple, reliable and sensitive. It allows for the description of the impact of obesity on the function of atrial mitochondria while using only a small patient sampling (n = 5 in both the lean and the obese groups).

20.
Respir Res ; 21(1): 81, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32264897

RESUMO

BACKGROUND: Subphenotypes were recently reported within clinical acute respiratory distress syndrome (ARDS), with distinct outcomes and therapeutic responses. Experimental models have long been used to mimic features of ARDS pathophysiology, but the presence of distinct subphenotypes among preclinical ARDS remains unknown. This review will investigate whether: 1) subphenotypes can be identified among preclinical ARDS models; 2) such subphenotypes can identify some responsive traits. METHODS: We will include comparative preclinical (in vivo and ex vivo) ARDS studies published between 2009 and 2019 in which pre-specified therapies were assessed (interleukin (IL)-10, IL-2, stem cells, beta-agonists, corticosteroids, fibroblast growth factors, modulators of the receptor for advanced glycation end-products pathway, anticoagulants, and halogenated agents) and outcomes compared to a control condition. The primary outcome will be a composite of the four key features of preclinical ARDS as per the American Thoracic Society consensus conference (histologic evidence of lung injury, altered alveolar-capillary barrier, lung inflammatory response, and physiological dysfunction). Secondary outcomes will include the single components of the primary composite outcome, net alveolar fluid clearance, and death. MEDLINE, Embase, and Cochrane databases will be searched electronically and data from eligible studies will be extracted, pooled, and analyzed using random-effects models. Individual study reporting will be assessed according to the Animal Research: Reporting of In Vivo Experiments guidelines. Meta-regressions will be performed to identify subphenotypes prior to comparing outcomes across subphenotypes and treatment effects. DISCUSSION: This study will inform on the presence and underlying pathophysiological features of subphenotypes among preclinical models of ARDS and should help to determine whether sufficient evidence exists to perform preclinical trials of subphenotype-targeted therapies, prior to potential clinical translation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (ID: CRD42019157236).

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