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3.
Eur J Cancer ; 49(13): 2910-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23668917

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological side-effect of cancer treatment and may lead to declines in patients' daily functioning and quality of life. To date, there are no modern clinimetrically well-evaluated outcome measures available to assess disability in CIPN patients. The objective of the study was to develop an interval-weighted scale to capture activity limitations and participation restrictions in CIPN patients using the Rasch methodology and to determine its validity and reliability properties. A preliminary Rasch-built Overall Disability Scale (pre-R-ODS) comprising 146 items was assessed twice (interval: 2-3 weeks; test-retest reliability) in 281 CIPN patients with a stable clinical condition. The obtained data were subjected to Rasch analyses to determine whether model expectations would be met, and if necessarily, adaptations were made to obtain proper model fit (internal validity). External validity was obtained by correlating the CIPN-R-ODS with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) neuropathy scales and the Pain-Intensity Numeric-Rating-Scale (PI-NRS). The preliminary R-ODS did not meet Rasch model's expectations. Items displaying misfit statistics, disordered thresholds, item bias or local dependency were systematically removed. The final CIPN-R-ODS consisting of 28 items fulfilled all the model's expectations with proper validity and reliability, and was unidimensional. The final CIPN-R-ODS is a Rasch-built disease-specific, interval measure suitable to detect disability in CIPN patients and bypasses the shortcomings of classical test theory ordinal-based measures. Its use is recommended in future clinical trials in CIPN.


Assuntos
Antineoplásicos/efeitos adversos , Avaliação da Deficiência , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Inquéritos e Questionários , Atividades Cotidianas , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Consenso , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Doenças do Sistema Nervoso Periférico/fisiopatologia , Doenças do Sistema Nervoso Periférico/psicologia , Valor Preditivo dos Testes , Qualidade de Vida , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
4.
Ann Oncol ; 24(2): 454-462, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22910842

RESUMO

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. PATIENTS AND METHODS: After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. RESULTS: Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. CONCLUSION: Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estudos Transversais , Nível de Saúde , Humanos , Avaliação de Resultados em Cuidados de Saúde , Qualidade de Vida , Resultado do Tratamento
5.
Curr Med Chem ; 19(32): 5474-80, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22876925

RESUMO

Adiponectin is the most abundant adipokine circulating in the organism. Different molecular forms of adiponectin exist: low, middle and high molecular isoforms, as well as globular adiponectin, all of which have different biological properties. Adiponectin is considered a key adipokine in metabolic diseases such as type 2 diabetes, metabolic syndrome and related complications, especially cardiovascular diseases. In these metabolic conditions, circulating adiponectin is reduced. It is now well known that adiponectin has beneficial effects on endothelial cells and endothelial function and is also cardioprotective. Unlike metabolic diseases, systemic autoimmune and chronic inflammatory joint diseases are characterized by increased production of adiponectin. There is evidence to suggest that adiponectin may be related to disease activity and/or severity in different conditions such as rheumatoid arthritis, systemic lupus erythematosus and osteoarthritis. Since adiponectin has been found to display both pro and anti-inflammatory activities, controversial findings have been observed on the role of total adiponectin in systemic autoimmune and inflammatory joint diseases. Thus, the relative contribution of each adiponectin isoform to the inflammatory response and joint and/or tissue damage requires further study.


Assuntos
Adiponectina/metabolismo , Doenças Autoimunes/metabolismo , Adiponectina/química , Animais , Humanos , Osteoartrite/metabolismo , Espondilartrite/metabolismo
6.
Chir Main ; 29(5): 315-20, 2010 Oct.
Artigo em Francês | MEDLINE | ID: mdl-20462781

RESUMO

OBJECTIVES: To evaluate the fingertip reconstruction with occlusive dressing and explore the mechanisms and the mediators of this "fingertip regeneration". PATIENT AND METHODS: Nineteen patients who sustained a fingertip injury were treated with occlusive dressing. Two prospective studies: a clinical analysis of the aesthetics and the functional results, a biologic analysis of the dressings in order to search microorganisms, cytokines, and growth factors. RESULTS: Among 15 patients reviewed, the healing was acquired in 2.7 weeks (2.5). The thickness of the fingertip was excellent in 30% and good in 70%. The Weber test was 3.8mm for the fingertip reconstruction against 3mm for the opposite side. The analysis of the dressing exudates brings to light a pullulement of saprophyte bacterium of the skin but also pathologic species, and presence of angiogenic factors (PDGF, VEGF, EGF). CONCLUSIONS: The occlusive dressings remain a reliable and reproducible alternative for treatment of fingertip injuries in zone 1 and 2. This reconstruction seems to depend on bacterium pullulement and cellular growth factors liberation.


Assuntos
Traumatismos dos Dedos/terapia , Curativos Oclusivos , Cicatrização , Adolescente , Adulto , Idoso , Exsudatos e Transudatos/química , Exsudatos e Transudatos/microbiologia , Traumatismos dos Dedos/patologia , Traumatismos dos Dedos/cirurgia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Procedimentos de Cirurgia Plástica , Reprodutibilidade dos Testes , Pele/lesões , Pele/patologia , Resultado do Tratamento
7.
Toxicol In Vitro ; 17(1): 59-67, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12537963

RESUMO

The present work describes an isozyme-related effect of collagenase perfusion on hepatocyte microsomal cytochrome (CYP)-dependent monooxygenase activities: CYP 1A1/2-, 2B1/2-, 3A1/2- and 2E1-dependent activities in microsomes from rat hepatocytes after isolation were about 60% of that of liver microsomes, and CYP 4A1-dependent activity was equivalent to liver microsomes. In contrast, the microsomal protein content of the various CYP isoforms was not affected by hepatocyte isolation. This is in accordance with the hypothesis of CYP inactivation during the process of hepatocyte isolation by collagenase digestion. L-NAME (1 mM) was found unable to protect from the decline of CYP-dependent monooxygenase activities following hepatocyte isolation. It is possible that the decrease in glutathione peroxidase activity observed in the presence of L-NAME, namely depression of defense against peroxynitrite, could counteract the beneficial effect of L-NAME on nitric oxide synthesis inhibition. The present work also shows that L-NAME could not avoid the progressive, isoform-specific, most probably turnover-related, decline of CYP proteins and related monooxygenase activities in cultured hepatocytes. Dysregulations in the mechanisms of CYP expression in rat hepatocyte cultures, presently unknown but nitric oxide independent, thus appear to occur in cultured rat hepatocytes.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Inibidores Enzimáticos/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Animais , Técnicas de Cultura de Células , Colagenases/farmacologia , Hepatócitos , Cinética , Microssomos Hepáticos , Óxido Nítrico , Ratos , Ratos Wistar
8.
Toxicol In Vitro ; 16(1): 89-99, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11812644

RESUMO

We evaluated the antioxidant status, namely cellular lipid peroxidation, by measuring thiobarbituric acid reactive substances (TBARS), cellular reduced glutathione (GSH) content, glutathione reductase (GSSG-R), glutathione transferase (GST), glutathione peroxidase (GSH-Px) and catalase activities in rat liver, hepatocytes immediately after isolation and in two-dimensional (2D) culture (on non-coated or collagen-coated dishes, as collagen-collagen or collagen-Matrigel sandwich cultures) or three-dimensional (3D) culture on Matrigel-coated dishes. Microsomal cytochrome P450 (CYP)- and UDP-glucuronosyl transferase (UGT)- dependent activities were also assessed in rat livers and hepatocyte cultures. The overall antioxidant status of rat hepatocytes immediately after isolation was not significantly different from that of rat livers. During culture, GSH was increased in 2D but not in 3D cultures in accordance with morphological observations; that is that matrix-cell interactions involving GSH, important in 2D, are minimal in 3D cultures. While UGT- and GST-dependent activities were equivalent in cultured hepatocytes and in rat livers, both catalase and GSH-Px activities decreased with time in all culture configurations. Constitutive CYP-dependent activities were drastically decreased in hepatocytes after isolation and attachment and did not recover in any culture configuration tested. Our results highlight that, although 2D sandwich cultures and 3D cultures on Matrigel allow longevity of rat hepatocyte cultures and optimal induction of CYPs, an imbalance in phase I/phase II detoxication processes in cultured rat hepatocytes occurs, whatever the culture configuration.


Assuntos
Antioxidantes/metabolismo , Técnicas de Cultura de Células/métodos , Hepatócitos/citologia , Hepatócitos/enzimologia , Animais , Células Cultivadas , Enzimas/análise , Enzimas/metabolismo , Glutationa/metabolismo , Peroxidação de Lipídeos/fisiologia , Masculino , Microssomos Hepáticos/enzimologia , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
9.
Mol Cell Biochem ; 218(1-2): 139-46, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11330829

RESUMO

We assessed the hepatic antioxidant status of spontaneously (SHR) and desoxicorticosterone acetate (DOCA)-induced hypertensive rats and that of respective normotensive Wistar Kyoto (WKY) and Sprague-Dawley (SPRD) rats. For this we evaluated, ex vivo in liver cytosols, reduced glutathione (GSH) content, glutathione-related enzyme (peroxidase, reductase and transferase) activities as well as the rate of lipid peroxidation in 9-11 week-old rats. The antioxidant status and the cytotoxicity of acetaminophen, a radical- and hydrogen peroxide-mediated hepatotoxic compound, were also assessed in vitro in cultured hepatocytes isolated from hypertensive (SHR, DOCA) and normotensive control (WKY, SPRD) rats. Our results suggest that a difference exists in the hepatic antioxidant status between rat strains, with GSH levels being lower (-15%) and lipid peroxidation rate higher (+30%) in WKY compared to SPRD rats. In hepatocyte cultures from WKY rats, both GSH content and catalase activity were lower (-30 and -70% respectively) compared to hepatocyte cultures from SPRD rats. This was associated with a 35% higher cytotoxicity of acetaminophen in cultured hepatocytes from WKY rats compared to that in hepatocytes from SPRD rats. Hypertension in DOCA rats (mmHg: 221+/-9 vs. 138+/-5 in control SPRD rats) was associated with decreases (about 30%) in both glutathione peroxidase (GSH-Px) and catalase activities, ex vivo in livers and in vitro in hepatocyte cultures. Hypertension in SHR (mmHg: 189+/-7 vs. 130+/-5 in control WKY rats) was also associated with decreases (about 50%) in GSH-Px activity, ex vivo in livers and in vitro in hepatocyte cultures but catalase activity was not modified. The IC50 of acetaminophen was also lower in hepatocytes from hypertensive rats compared to respective controls, which could be related to the weakened antioxidant status in hepatocytes from hypertensive rats. Our data thus suggest that hepatocyte cultures are appropriated tools in which to assess hepatotoxicity and hepatoprotection in hypertension.


Assuntos
Antioxidantes/metabolismo , Desoxicorticosterona/farmacologia , Glutationa/metabolismo , Hepatócitos/metabolismo , Hipertensão Maligna/enzimologia , Hipertensão Maligna/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Acetaminofen/farmacologia , Analgésicos não Narcóticos/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Catalase/efeitos dos fármacos , Catalase/metabolismo , Células Cultivadas , Citosol/efeitos dos fármacos , Citosol/enzimologia , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Hipertensão Maligna/induzido quimicamente , Fígado/enzimologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Especificidade da Espécie , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
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