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1.
Rev Med Liege ; 74(5-6): 281-286, 2019 05.
Artigo em Francês | MEDLINE | ID: mdl-31206267

RESUMO

Alcohol addiction is a complex and multifactorial disease influenced by social, psychological and biological aspects. The current pharmacological drugs used in the management of alcohol dependence have shown only a modest efficacy and the relapse rate remains high in this disease. Recently, the gut microbiota, a huge and dynamic ecosystem made up of billions of microorganisms living in our intestine, has been shown to regulate many important functions for human health. Indeed, the gut microbiota is known to influence our metabolism, our immune system as well as our nervous system with consequences for brain functions, mood and behaviour. We have shown that heavy and chronic alcohol consumption induced important changes in the composition of the gut microbiota. Furthermore, the microbial changes are associated with the severity of depression, anxiety and alcohol craving that are important factors predicting the risk of relapse. This suggests the existence of a gut-brain axis in alcohol dependence and supports the development of new therapeutic alternatives, targeting the gut microbiota, in the management of alcohol dependence.


L'addiction à l'alcool est une maladie complexe, impliquant à la fois des facteurs sociaux, psychologiques et biologiques. La prise en charge des patients alcoolo-dépendants est difficile car les médicaments actuels ont une efficacité limitée dans le maintien de l'abstinence, et le taux de rechute reste très élevé. Récemment, le microbiote intestinal, un écosystème constitué de milliards de micro-organismes vivant dans notre intestin, est devenu un acteur clé de la santé humaine. Il est connu pour réguler notre métabolisme, notre système immunitaire, mais également notre système nerveux, et donc notre comportement et notre humeur. Nos études récentes ont montré que la consommation abusive d'alcool entraîne des modifications importantes de la composition du microbiote intestinal. Nous avons également montré que ces altérations microbiennes étaient associées à la sévérité des symptômes de dépression, d'anxiété et d'appétence à l'alcool, suggérant ainsi l'existence d'un dialogue entre l'intestin et le cerveau. Ces résultats encouragent la recherche de nouvelles pistes thérapeutiques, ciblant le microbiote intestinal, dans le traitement de la dépendance à l'alcool.


Assuntos
Alcoolismo , Microbioma Gastrointestinal , Alcoolismo/microbiologia , Ansiedade , Encéfalo , Depressão , Humanos
3.
Eur Respir J ; 38(5): 1105-16, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21540307

RESUMO

Malignant pleural mesothelioma (MPM) is an aggressive tumour with a limited response to conventional therapy. The aim of this study was to evaluate the anticancer effect of a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-azaCdR), and two histone deacetylase inhibitors, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA). Human mesothelioma cells were treated with each epigenetic drug, either alone or in combinations. The cytotoxic effects on treated cells and the expression of specific tumour antigens were evaluated. The recognition of treated cells by a specific CD8+ T-cell clone was also measured. Additionally, the effect of combined treatments was tested in a murine model of mesothelioma. We showed that VPA and SAHA synergised with 5-azaCdR to kill MPM cells and induce tumour antigen expression in the remaining living tumour cells. As a consequence, tumour cells expressing these antigens were recognised and lysed by specific CD8+ cytotoxic T-cells. In vivo, treatment with 5-azaCdR/VPA inhibited tumour growth, and promoted lymphocyte infiltration and an immune response against tumour cells. Appropriate epigenetic drug combinations, in addition to inducing mesothelioma cell death, also affect the immunogenic status of these cells. This property could be exploited in clinical investigations to develop MPM treatments combining chemotherapeutic and immunotherapeutic approaches.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/análogos & derivados , Metilases de Modificação do DNA/administração & dosagem , Inibidores de Histona Desacetilases/administração & dosagem , Mesotelioma/tratamento farmacológico , Neoplasias Pleurais/tratamento farmacológico , Linfócitos T Citotóxicos/imunologia , Ácido Valproico/administração & dosagem , Animais , Antígenos de Neoplasias/imunologia , Azacitidina/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Decitabina , Sinergismo Farmacológico , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Proteínas de Membrana/imunologia , Mesotelioma/imunologia , Mesotelioma/patologia , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Neoplasias Pleurais/imunologia , Neoplasias Pleurais/patologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Vorinostat
4.
Artigo em Inglês | MEDLINE | ID: mdl-32971216

RESUMO

There is a growing amount of evidence showing a reciprocal relation between the gut microbiota and the brain. Substance use disorders (SUD), which are a major cause of preventable morbidity and mortality worldwide, have an influence on the gut microbiota and on the gut-brain axis. The communication between the microbiota and the brain exists through different pathways: (1) the immune response elicited by bacterial products, coupled with alterations of the intestinal barrier allowing these products to enter the bloodstream, (2) the direct and indirect effects of bacterial metabolites such as short chain fatty acids (SCFAs) or tryptophan on the brain, (3) and the hypothalamic-pituitary-adrenal (HPA) axis, whose peripheral afferents can be influenced by the microbiota, and can in turn activate microglia. Among substances of abuse, alcohol has been the subject of the greatest number of studies in this field. In some but not all patients suffering from alcohol-use-disorder (AUD), alcohol alters the composition of the gut microbiota and the permeability of the intestinal barrier, directly and through dysbiosis. It has also been well demonstrated that alcohol induces a peripheral inflammation; it is still unclear whether it induces a central inflammation, as there are contradictory results in human studies. In animal studies, it has been shown that neuroinflammation increases during alcohol withdrawal. Literature on opioids and stimulants is less numerous. Chronic morphine intake induces dysbiosis, increased intestinal permeability and a probable neuroinflammation, which could explain symptoms such as tolerance, hyperalgesia and deficit in reward behavior. Cocaine induces a dysbiosis and conversely the microbiome can modulate the behavioral response to stimulant drugs. Tobacco cessation is associated with an increase in microbiota diversity. Taken together, the findings of our narrative literature review suggest a bidirectional influence in the pathogenesis of substance use disorders.


Assuntos
Eixo Encéfalo-Intestino/fisiologia , Microbioma Gastrointestinal/fisiologia , Sistema Hipotálamo-Hipofisário/metabolismo , Drogas Ilícitas , Sistema Hipófise-Suprarrenal/metabolismo , Animais
5.
Acta Gastroenterol Belg ; 83(4): 616-621, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33321019

RESUMO

The human intestine is colonized by a variety of microbes that influence the metabolic responses, the immune system and the nervous system. Dietary patterns are important factors that shape the composition of the gut microbiota. Many animal models of alcohol exposure have highlighted the key role of the alcohol-induced gut microbiota alterations, leaky gut and translocation of microbial products in the development of alcoholic liver disease (ALD). However, in humans, there is no clear picture defining an "alcoholic microbiome", and the link between intestinal dysbiosis and ALD development is far from being understood. Although we do not comprehend all the mechanistic insights, clinical studies aiming at modulating the gut microbiota of alcoholic patients have shown some beneficial effects. Here we review the potential therapeutic effects of probiotics in ALD and give some clinical perspectives on the role of prebiotics and the use of fecal microbiota transplantation.


Assuntos
Alcoolismo , Microbioma Gastrointestinal , Hepatopatias Alcoólicas , Probióticos , Animais , Disbiose , Transplante de Microbiota Fecal , Humanos , Hepatopatias Alcoólicas/terapia , Probióticos/uso terapêutico
6.
Scand J Rheumatol ; 38(2): 104-11, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19274517

RESUMO

OBJECTIVE: The aim of this study was to determine the effects of pharmacologically relevant concentrations of rhein (1,8-dihydroxy-3-carboxyanthraquinone) on the cell proliferation rate of human chondrocytes and synoviocytes. METHODS: Cultures of human osteoarthritic synoviocytes and chondrocytes were incubated with 10(-6), 10(-5), and 10(-4) M rhein. [3H]thymidine incorporation was used to determine rhein proliferative effects after incubation periods of 24 h, 48 h, and 1 week. The cytotoxicity of the drug was assayed with a nonradioactive assay kit. Nuclear extracts were used to detect variations in cell-cycle proteins (p21, p27, and cyclin D1) by Western blotting. The effect of rhein on apoptosis was investigated by measurement of caspase-3/7 activity and DNA fragmentation. RESULTS: Rhein was found to downregulate the proliferation rate of both chondrocytes and synoviocytes, two-fold for 10(-5) M rhein and five- to six-fold for 10(-4) M rhein. No cytotoxicity of the drug was observed. Rhein (10(-4) M) decreased caspase-3/7 activity and did not induce DNA fragmentation. Western blots showed that 10(-4) M rhein increased the expression of p21 and/or p27, but not that of cyclin D1. CONCLUSIONS: Rhein has previously been shown to reduce the interleukin (IL)-1beta deleterious effects on osteoarthritis (OA) cartilage through inhibition of the expression of degrading enzymes. Here, rhein was also found to inhibit proliferation of both synoviocytes and chondrocytes, suggesting that the drug may decrease the development of the inflammatory synovial tissue that accompanies joint pathologies. Both its anti-catabolic and anti-proliferative effects may explain its beneficial effect in the treatment of joint diseases.


Assuntos
Antraquinonas/farmacologia , Apoptose/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Membrana Sinovial/efeitos dos fármacos , Antraquinonas/metabolismo , Anti-Inflamatórios/metabolismo , Cartilagem Articular/citologia , Proteínas de Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/patologia , DNA/biossíntese , Fragmentação do DNA , Relação Dose-Resposta a Droga , Humanos , Osteoartrite/patologia , Osteoartrite/fisiopatologia , Membrana Sinovial/patologia
7.
Ann Rheum Dis ; 67(5): 644-50, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17728334

RESUMO

AIM: Up to 50% of patients with systemic sclerosis (SSc) have complaints of dyspnoea. We evaluated the independent contributions of dyspnoea to function and health related quality of life (HRQoL) in SSc and also assessed the contributions of pulmonary hypertension, measured by the pulmonary artery systolic pressure (PASP), and interstitial lung disease, measured by the forced vital capacity (FVC), to dyspnoea. METHODS: We assessed dyspnoea, PASP, FVC, function and HRQoL in a cohort of unselected patients with SSc. Multiple linear regression was used to assess the independent contributions of dyspnoea, PASP and FVC to function and HRQoL, after controlling for possible confounding variables. RESULTS: A total of 194 patients with mean disease duration of 11.6 years were studied. Dyspnoea was a significant independent predictor of function and HRQoL. A model including age, gender, disease duration, disease severity and dyspnoea explained 33.3%, 10.6%, 39.2% and 29.4% of the variance of the Stanford Health Assessment Questionnaire, the Short-Form 36 (SF-36) mental component summary score, the SF-36 physical component summary score and the World Health Organization Disability Assessment Schedule II. PASP and FVC were significant independent predictors of dyspnoea but only 21.9% of the variance in dyspnoea was explained by age, gender, disease duration, FVC and PASP. The FVC was a significant independent predictor of function and HRQoL. CONCLUSION: In an unselected population of SSc patients, dyspnoea is a very important contributor to function and HRQoL. Interstitial lung disease, as measured by the FVC, contributes significantly to the sense of dyspnoea, function and HRQoL in SSc. Pulmonary hypertension, assessed echocardiographically by the PASP, predicts the degree of dyspnoea but not function and HRQoL in SSc.


Assuntos
Dispneia/etiologia , Qualidade de Vida , Escleroderma Sistêmico/complicações , Adulto , Idoso , Avaliação da Deficiência , Dispneia/fisiopatologia , Dispneia/psicologia , Feminino , Nível de Saúde , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/psicologia , Modelos Lineares , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/psicologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/psicologia , Inquéritos e Questionários , Capacidade Vital
9.
Clin Rheumatol ; 27(1): 77-83, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17570008

RESUMO

The objective was to investigate the frequency of anti-cyclic citrullinated peptides (CCP) antibodies in systemic sclerosis (SSc) and primary biliary cirrhosis (PBC), utilizing a new "third generation" anti-CCP ELISA (anti-CCP3) kit and a conventional anti-CCP2 assay. Patients with PBC, SSc, RA, and normal controls were included in the study. Serum samples were screened for autoantibodies by indirect immunofluorescence (IIF), antibodies to CCP by a second- and third-generation ELISA, antibodies to "scleroderma" antigens (CENP B, Scl-70, PM/Scl and fibrillarin-Scl-34) by a line immunoassay (LIA), and IgM RF by ELISA. The frequency of anti-CCP2 antibodies in SSc and PBC samples was 14.8% (11/74) and 6.2% (5/80), respectively, and the frequency of anti-CCP3 antibodies in SSc was 13.5% (10/74) and in PBC was 3.7% (3/80). By comparison, in the RA group the frequency of anti-CCP3 and anti-CCP2 antibodies was 79.1% (38/48) and 77% (37/48), respectively. Anti-CCP3 ELISA had a sensitivity, specificity, and positive and negative likelihood ratios (LR) of 79% (95% confidence interval [CI] = 64-89%), 93% (95% CI = 88-96%), 11.8 (95% CI = 6.8-20.3), and 0.22 (95% CI = 0.12-0.38), respectively. By comparison, the anti-CCP2 assay had a sensitivity, specificity, and positive and negative LRs of 77% (95% CI = 62-87), 90% (95% CI = 85-94), 8.3 (95% CI = 5.2-13.2), and 0.25 (95% CI = 0.15-0.42), respectively. In patients with SSc, there was an association of anti-CCP2 antibodies with the presence of arthritis, but there was no association of anti-CCP2 or anti-CCP3 with anti-CENP B, anti-Scl 70, or RF. This study confirmed the high specificity and sensitivity of both anti-CCP assays for the diagnosis of RA. The presence of anti-CCP antibodies in SSc was only correlated with the presence of arthritis.


Assuntos
Artrite Reumatoide/imunologia , Autoanticorpos/análise , Cirrose Hepática Biliar/imunologia , Peptídeos Cíclicos/imunologia , Escleroderma Sistêmico/imunologia , Artrite Reumatoide/diagnóstico , Autoanticorpos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Cirrose Hepática Biliar/diagnóstico , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/diagnóstico
10.
Rev Chir Orthop Reparatrice Appar Mot ; 94(1): 37-42, 2008 Feb.
Artigo em Francês | MEDLINE | ID: mdl-18342028

RESUMO

PURPOSE OF THE STUDY: Dislocation is a well-known complication of total hip arthroplasty. The risk can be reduced to one or two cases per thousand using a double mobility cup. The survival rate achieved with the Bousquet implant is 95% at 10 years. The complications with this implant are early mobilization and inguinal pain. An overly large cup and insufficient primary and secondary fixation can be implicated. The design of the original implant was later modified to limit these early complications. The purpose of this work was to check the validity of the changes made. PATIENTS AND METHODS: The chromium-cobalt moulded cup was used. The outer surface of this cup presents large geometric striations and is coated with hydroxyapatite. The cup has the shape of a half sphere of 180 degrees and a posterior wall prolongation measuring 6.5mm. Three mechanisms were used for the primary fixation: an asymmetrical growth ring, four anchorage stems, and a superior screw. Two hundred cups were implanted in 194 patients. The femoral piece was a Charnley stainless steel implant (n=139), a titanium SEM implant (n=59) or another implant (n=12). Cement was used for 193 implantations. The series included 97 women and 103 men with osteoarthritis (n=180), necrosis (n=16), surgery for fracture and primary arthroplasty (n=9). The Harris and Postel-Merle-d'Aubigné scores were noted. Eight radiographic criteria were analyzed to assess the position of the cup and the radiological course of the interface. RESULTS: Mean time to surgery was six years. Mean age at surgery was 70 years (range: 32-91) and varied depending on the operators from 67 to 73 years. At last follow-up: 17 patients had died, eight were lost to follow-up and five were bedridden. Three patients underwent revision surgery. Thus, this analysis included 170 prostheses followed for more than five years (mean: six years, range: 5-7 years). The Harris score improved from 48 to 92 and the Postel-Merle-d'Aubigné score from 2/5/4 to 5.8/5.9/5.5 (range: 4-6/5-6/1-6). None of the patients complained of anterior pain during hip flexion against resistance. Cup inclination was 46 degrees on average (range: 62-22 degrees ). Medialization, lateralization or ascension greater than 10mm of the centre of rotation was not observed on the postoperative films. At last follow-up, no measurable mobilization or migration could be identified on plain X-rays. Lucent lines, condensations and bony defects around the cup, when visible postoperatively, were not found on the last follow-up X-rays. There were two cemented femoral pieces, which developed a lucent line in the nonspecific metaphyseal area. There were no cases of granuloma and no cam effect. Three patients underwent revision for femoral loosening, fracture of the femur below the prosthesis, and hematogenous infection. There were no cases of dislocation. DISCUSSION: Changing the design of the implant to modify its volume, material and primary fixation has eliminated the early mobilizations and inguinal pain described for the original Bousquet cup. These options have not had any deleterious effect on prosthesis stability. The question of long-term wear remains an important problem and requires optimization: a neck as thin as possible, optimized surfacing, elimination of laser marks, extraction leads, head skirts.


Assuntos
Luxação do Quadril/prevenção & controle , Prótese de Quadril , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Fatores de Tempo
11.
Orthop Traumatol Surg Res ; 104(2): 161-164, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29292123

RESUMO

BACKGROUND: Previous surgical procedures raise technical challenges in performing total knee arthroplasty (TKA) and may affect TKA outcomes. Survival rates of TKA done after trauma or surgery to the knee have not been accurately determined in large populations. The objectives of this retrospective study in 263 patients with TKA after knee trauma or surgery and a follow-up of 10 years were to assess survival, functional outcomes, and the nature and frequency of complications. HYPOTHESIS: Knee trauma or surgery before TKA increases the risk of complications and decreases implant survival. MATERIAL AND METHODS: Two hundred and sixty-three patients (122 [47%] females and 141 [53%] males) underwent TKA between 2005 and 2009 at nine centres in France. Mean age at surgery was 61 years. The patients had knee osteoarthritis secondary to a fracture (n=66), osteotomy (n=131), or ligament injury (n=66). Mean time from trauma or surgery to TKA was 145 months (range, 72-219 months). RESULTS: Major complications were infection (n=12, 4.5%), skin problems (n=8, 3%), and stiffness (n=8, 3%). Ten-year survival to implant exchange for any reason was 89%±2.8%. Flexion range increased by 2.5°±17° (p=0.02) to a mean of 110° (range, 30° to 140°); extension range increased by 4°±7° (p<0.001) to a mean of -1.19 (range, -20° to 0°). Of the 263 patients, 157 (60%) reported little or no pain at last follow-up. Mean postoperative hip-knee-ankle angle was 179°±3.2° (range, 171°-188°). CONCLUSION: TKA performed after knee injury or surgery carries a risk of specific complications (infection, skin problems, and stiffness) and may have a lower survival rate compared to primary TKA. LEVEL OF EVIDENCE: IV, retrospective cohort study.


Assuntos
Artroplastia do Joelho/efeitos adversos , Traumatismos do Joelho/complicações , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Complicações Pós-Operatórias/etiologia , Falha de Prótese , Idoso , Idoso de 80 Anos ou mais , Feminino , França , Humanos , Articulação do Joelho/fisiopatologia , Prótese do Joelho , Ligamentos Articulares/lesões , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/etiologia , Osteotomia/efeitos adversos , Amplitude de Movimento Articular , Estudos Retrospectivos
12.
Biochimie ; 89(11): 1312-21, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17686565

RESUMO

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease caused by mutations in the ABCD1 gene, which encodes a peroxisomal ABC transporter, ALDP, supposed to participate in the transport of very long chain fatty acids (VLCFA). The adrenoleukodystrophy-related protein (ALDRP), which is encoded by the ABCD2 gene, is the closest homolog of ALDP and is considered as a potential therapeutic target since functional redundancy has been demonstrated between the two proteins. Pharmacological induction of Abcd2 by fibrates through the activation of PPARalpha has been demonstrated in rodent liver. DHEA, the most abundant steroid in human, is described as a PPARalpha activator and also as a prohormone able to mediate induction of several genes. Here, we explored the in vitro and in vivo effects of DHEA on the expression of peroxisomal ABC transporters. We show that Abcd2 and Abcd3 but not Abcd4 are induced in primary culture of rat hepatocytes by DHEA-S. We also demonstrate that Abcd2 and Abcd3 but not Abcd4 are inducible by an 11-day treatment with DHEA in the liver of male rodents but not in brain, testes and adrenals. Finally and contrary to Abcd3, we show that the mechanism of induction of Abcd2 is independent of PPARalpha.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Desidroepiandrosterona/farmacologia , PPAR alfa/metabolismo , Regulação para Cima/efeitos dos fármacos , Subfamília D de Transportador de Cassetes de Ligação de ATP , Acil-CoA Oxidase/genética , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Androstenodiol/farmacologia , Animais , Peso Corporal , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Células Cultivadas , Feminino , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão , PPAR alfa/deficiência , PPAR alfa/genética , Ratos , Ratos Wistar , Caracteres Sexuais , Testículo/efeitos dos fármacos , Testículo/metabolismo
13.
Clin Exp Rheumatol ; 25(4): 546-55, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17888210

RESUMO

OBJECTIVE: To determine the effects of rhein on the expression of matrix metalloproteinases (MMP-1, -3, 13) and ADAMTs 4, 5 (a disintegrin and metalloproteinase with thrombospondin type-I repeat)/aggrecanases-1, -2 in interleukin-1-stimulated bovine articular chondrocytes, and to investigate the signalling pathways involved in the effects of the drug on gene expression and cell proliferation. METHODS: Bovine chondrocytes were treated with 10(-4) M rhein for 18 h, followed by 10 ng/ml IL-1Beta for 30 min (cytoplasmic extracts) or 24 h (RNA extraction and EMSA). mRNA was assessed by RT-PCR for the expression of MMPs and aggrecanases, and the phosphorylation of MAP kinases was studied by Western blotting. NF-kappaB and AP-1 DNA binding were determined by gel retardation assay. The effects of inhibitors of these signalling pathways were compared to those of rhein. The proliferation of human chondrocytes and synoviocytes treated with the drug was also investigated. RESULTS: IL-1Beta-induced stimulation of the MMPs and aggrecanase-1 was markedly inhibited by rhein. The drug reduced IL-1Beta-induced NF-kappaB and AP-1 DNA binding, as well as the phosphorylation of ERK and JNK. Similar effects were produced by the specific inhibitors of these signalling pathways. In addition, rhein reduced the proliferation of both human chondrocytes and synoviocytes. CONCLUSION: Our data indicate that rhein may reduce the deleterious effects of IL-1Beta on osteoarthritic cartilage through its effects on the ERK- and JNK-dependent pathways. Both its anti-catabolic and anti-proliferative properties may explain its value in the treatment of joint diseases.


Assuntos
Proteínas ADAM/antagonistas & inibidores , Antraquinonas/farmacologia , Proliferação de Células/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , MAP Quinase Quinase 4/fisiologia , Metaloproteases/antagonistas & inibidores , Pró-Colágeno N-Endopeptidase/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Proteína ADAMTS4 , Proteína ADAMTS5 , Animais , Cartilagem Articular/citologia , Bovinos , Células Cultivadas , Condrócitos/citologia , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Interleucina-1/farmacologia , Inibidores de Metaloproteinases de Matriz , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia
14.
Rev Sci Instrum ; 78(3): 035104, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17411214

RESUMO

The use of a multiplexing readout for an array of bolometers simplifies the electronics and wiring, so making the readout of large arrays of bolometers (>100) feasible. Here we describe a time domain multiplexing technique and its performance based on the use of quantum-point-contact high-electron-mobility-transistors as low temperature (to approximately 100 mK) switches for measuring high impedance (5...70 MOmega) resistances and sensors. The presented system is well matched to ground based millimetric astronomy demands.

15.
Transl Psychiatry ; 7(2): e1048, 2017 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-28244981

RESUMO

In recent years, some new processes have been proposed to explain how alcohol may influence behavior, psychological symptoms and alcohol seeking in alcohol-dependent subjects. In addition to its important effect on brain and neurotransmitters equilibrium, alcohol abuse also affects peripheral organs including the gut. By yet incompletely understood mechanisms, chronic alcohol abuse increases intestinal permeability and alters the composition of the gut microbiota, allowing bacterial components from the gut lumen to reach the systemic circulation. These gut-derived bacterial products are recognized by immune cells circulating in the blood or residing in target organs, which consequently synthesize and release pro-inflammatory cytokines. Circulating cytokines are considered important mediators of the gut-brain communication, as they can reach the central nervous system and induce neuroinflammation that is associated with change in mood, cognition and drinking behavior. These observations support the possibility that targeting the gut microbiota, by the use of probiotics or prebiotics, could restore the gut barrier function, reduce systemic inflammation and may have beneficial effect in treating alcohol dependence and in reducing alcohol relapse.


Assuntos
Alcoolismo/imunologia , Encéfalo/imunologia , Citocinas/imunologia , Microbioma Gastrointestinal/imunologia , Inflamação/imunologia , Mucosa Intestinal/metabolismo , Afeto , Alcoolismo/metabolismo , Alcoolismo/terapia , Animais , Encéfalo/metabolismo , Cognição , Humanos , Permeabilidade , Prebióticos , Probióticos/uso terapêutico
16.
Orthop Traumatol Surg Res ; 103(5): 663-668, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28629944

RESUMO

INTRODUCTION: Dislocation after total hip arthroplasty (THA) is a leading reason for surgical revision. The risk factors for dislocation are controversial, particularly those related to the patient and to the surgical procedure itself. The differences in opinion on the impact of these factors stem from the fact they are often evaluated using retrospective studies or in limited patient populations. This led us to carry out a prospective case-control study on a large population to determine: 1) the risk factors for dislocation after THA, 2) the features of these dislocations, and 3) the contribution of patient-related factors and surgery-related factors. HYPOTHESIS: Risk factors for dislocation related to the patient and procedure can be identified using a large case-control study. PATIENTS AND METHODS: A multicenter, prospective case-control study was performed between January 1 and December 31, 2013. Four patients with stable THAs were matched to each patient with a dislocated THA. This led to 566 primary THA cases being included: 128 unstable, 438 stable. The primary matching factors were sex, age, initial diagnosis, surgical approach, implantation date and type of implants (bearing size, standard or dual-mobility cup). RESULTS: The patients with unstable THAs were 67±12 [37-73]years old on average; there were 61 women (48%) and 67 men (52%). Hip osteoarthritis (OA) was the main reason for the THA procedure in 71% (91/128) of the unstable group. The dislocation was posterior in 84 cases and anterior in 44 cases. The dislocation occurred within 3 months of the primary surgery in 48 cases (38%), 3 to 12 months after in 23 cases (18%), 1 to 5years after in 20 cases (16%), 5 to 10years after in 17 cases (13%) and more than 10years later in 20 cases. The dislocation recurred within 6 months of the initial dislocation in 23 of the 128 cases (18%). The risk factors for instability were a high ASA score with an odds ratio (OR) of 1.93 (95% CI: 1.4-2.6), neurological disability (cognitive, motor or psychiatric disorders) with an OR of 3.9 (95% CI: 2.15-7.1), history of spinal disease (lumbar stenosis, spinal fusion, discectomy, scoliosis and injury sequelae) with an OR of 1.89 (95% CI: 1.0-3.6), unrepaired joint capsule (all approaches) with an OR of 4.1 (95% CI: 2.3-7.37), unrepaired joint capsule (posterior approach) with an OR of 6.0 (95% CI: 2.2-15.9), and cup inclination outside Lewinnek's safe zone (30°-50°) with OR of 2.4 (95% CI: 1.4-4.0). DISCUSSION: This large comparative study isolated important patient-related factors for dislocation that surgeons must be aware of. We also found evidence that implanting the cup in 30° to 50° inclination has a major impact on preventing dislocation. LEVEL OF EVIDENCE: Level III; case-control study.


Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Luxação do Quadril/epidemiologia , Instabilidade Articular/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Nível de Saúde , Luxação do Quadril/etiologia , Prótese de Quadril/efeitos adversos , Humanos , Cápsula Articular/cirurgia , Instabilidade Articular/etiologia , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/epidemiologia , Osteoartrite do Quadril/cirurgia , Estudos Prospectivos , Fatores de Risco , Doenças da Coluna Vertebral/epidemiologia , Fatores de Tempo
17.
Clin Exp Rheumatol ; 11(6): 603-8, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8299251

RESUMO

Intervertebral bony bridging and enthesopathy can occur in both diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS) and we have seen difficulties in the radiological differentiation between them. We describe 6 patients selected because the bridges resembled syndesmophytes and this initially suggested a diagnosis of AS, although other considerations showed them to be part of the radiologic picture of DISH. The previously reported suggestions of the coexistence of DISH and AS are reviewed.


Assuntos
Hiperostose Esquelética Difusa Idiopática/diagnóstico por imagem , Espondilite Anquilosante/diagnóstico por imagem , Idoso , Diagnóstico Diferencial , Humanos , Hiperostose Esquelética Difusa Idiopática/complicações , Hiperostose Esquelética Difusa Idiopática/patologia , Masculino , Pessoa de Meia-Idade , Radiografia , Espondilite Anquilosante/complicações , Espondilite Anquilosante/patologia
18.
Ergonomics ; 38(2): 197-208, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28084934

RESUMO

According to tribology science, the friction force produced at the sliding interface between a rubber piece and an inflexible surface presents three main components: the first is due to molecular adhesion between the two bodies, it occurs at the regions of real contact; the second is a hysteresis component resulting from the periodic excitation of the bulk of the rubber by surface roughness; the third is due to effects of product shape. The shape of the elastomer product and the conditions in which the friction occurs (lubricant, roughness of the inflexible surface, etc.) determine the appearance of each one of these components and its importance. Experimentations made by the French national research and safety Institute (INRS) revealed adhesion and hysteresis components in the lubricated friction of an elastomer over a representative sample of industrial floor surfaces. Measurements have been made by means of a portable friction tester (PFT) assessing sliding resistance of floor coverings. The sliding movement takes place between a braked test wheel and the floor covering. The effect of product shape is insignificant as the wheel is covered with smooth elastomer. The friction force produced at the sliding interface between the elastomer and the floor covering has been evaluated on smooth and rough floors, and under different lubrication conditions (flooded with water, large, medium and small quantities of mineral oil). Several test wheels, with different and sometimes used rubber coverings, have been employed. The friction force is altered when the elastomer composition or the state of the elastomer that is covering the test wheel changes. The differences pointed out depend also on floor covering roughness and lubrication. The importance of either the adhesion or hysteresis components of the friction force in accordance with the composition and the state of the elastomer that is covering the test wheel, the lubricant amount, and the floor covering roughness enable the interpretation of these differences. Some experimental results are explained from the squeeze lubricant film process. This experimental study permits a better understanding of phenomena produced at the sliding interface between a rubber sole and a floor covering when a pedestrian slips. It also plays a great part in bringing the portable friction tester into operation in order to carry out a measurement campaign of slipping resistance of industrial floors.

19.
Ergonomics ; 38(2): 209-219, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28084935

RESUMO

The slipping resistance of footwear or floor surfaces is a characteristic which it is vital to be able to quantify. Work is being carried out at the International Standard Organization (ISO) and at the European Committee for Standardization (CEN) into the slip resistance of both work shoes and protective footwear, involving analysis of the latest developments in both the validity of measuring methods and the extent of the influence of certain experimental parameters on the slip resistance. Two industrial factors, independent of the measuring process but essential to the determination of the coefficient of friction of the models have been experimentally studied, namely the effect of the manufacture of the footwear or floor surfaces on the scattering of the specific coefficient of friction of a referenced model and the effect on the coefficient of friction of mechanical wear and tear on the soles as a result of their use respectively. Work into slipping on industrial floor surfaces is less advanced. Yet, problems raised call for the same approach than for problems linked to slipping resistance of footwear, and applications will be also at first related to standardized measurement conditions.

20.
Appl Ergon ; 33(1): 95-100, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11827142

RESUMO

The present study falls within the scope of work on the prevention of slips occurring on industrial workplace floor surfaces. Floor microgeometry is a determining factor in anti-slip flooring. Industrial environment-based quantification of floor microgeometrical properties is more restricting than laboratory quantification. The aim of the present study was to develop a duplication technique allowing reproduction of in situ floor microgeometry so as to be able to quantify this microgeometry in the laboratory. Duplicates were produced from a sample of five industrial floors. Surface microgeometry was characterized for both industrial floors and associated duplicates in order to study their microgeometrical changes following the duplicating operation. The purpose of this process was to reach a conclusion on the "reliability" of the duplication technique, on which the use of such duplicates depends. Parameters established from digitalized surfaces reveal differences of less than 5% between duplicates and original floor and this enables us to conclude that these duplicates offer a high degree of reliability with respect to results dispersion.


Assuntos
Acidentes por Quedas/prevenção & controle , Pisos e Cobertura de Pisos , Segurança , Humanos , Indústrias , Reprodutibilidade dos Testes
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