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1.
Contemp Clin Trials ; 110: 106561, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34487920

RESUMO

BACKGROUND: Current evidence shows that low-level laser therapy (LLLT) is an effective non-invasive and non-pharmacological strategy to treat diabetic foot ulcers (DFU). However, knowledge of parameterization efficacy remains unclear. METHODS: This randomized, double-blind, controlled trial will be conducted at the Physical Therapy University Clinic. Eighty volunteers will be randomized into four groups. The control group will receive placebo LLLT + conventional treatment. The three active groups will receive 10 (G10), 8 (G8), or 4 J/cm2 (G4) of GaAs 904 nm LLLT plus conventional treatment twice a week for 20 sessions. Conventional treatment involves cleaning and dressing the ulcers. The main outcome will be the area of ulcers and Wagner classification score. Assessments will take place before treatment, after 5 and 10 weeks of treatment, and in the third month after treatment, by a blinded evaluator. IMPLICATIONS: This trial can potentially provide important information and assist in clinical decision-making regarding DFU treatment with LLLT. TRIAL REGISTRATION: NCT04246814, registered 29th January 2020.

2.
Sci Rep ; 11(1): 16430, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385527

RESUMO

Until there is an effective implementation of COVID-19 vaccination program, a robust testing strategy, along with prevention measures, will continue to be the most viable way to control disease spread. Such a strategy should rely on disparate diagnostic tests to prevent a slowdown in testing due to lack of materials and reagents imposed by supply chain problems, which happened at the beginning of the pandemic. In this study, we have established a single-tube test based on RT-LAMP that enables the visual detection of less than 100 viral genome copies of SARS-CoV-2 within 30 min. We benchmarked the assay against the gold standard test for COVID-19 diagnosis, RT-PCR, using 177 nasopharyngeal RNA samples. For viral loads above 100 copies, the RT-LAMP assay had a sensitivity of 100% and a specificity of 96.1%. Additionally, we set up a RNA extraction-free RT-LAMP test capable of detecting SARS-CoV-2 directly from saliva samples, albeit with lower sensitivity. The saliva was self-collected and the collection tube remained closed until inactivation, thereby ensuring the protection of the testing personnel. As expected, RNA extraction from saliva samples increased the sensitivity of the test. To lower the costs associated with RNA extraction, we performed this step using an alternative protocol that uses plasmid DNA extraction columns. We also produced the enzymes needed for the assay and established an in-house-made RT-LAMP test independent of specific distribution channels. Finally, we developed a new colorimetric method that allowed the detection of LAMP products by the visualization of an evident color shift, regardless of the reaction pH.


Assuntos
Teste para COVID-19/métodos , COVID-19/virologia , Colorimetria/métodos , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , SARS-CoV-2/isolamento & purificação , COVID-19/diagnóstico , Humanos , Pandemias , Portugal/epidemiologia , RNA Viral/genética , SARS-CoV-2/genética , Saliva/química , Saliva/virologia , Sensibilidade e Especificidade
3.
Z Rheumatol ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34287668

RESUMO

BACKGROUND: Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands. It can be associated with other connective tissue diseases, including systemic lupus erythematosus (SLE). OBJECTIVE: This study aimed to determine the incidence of secondary SS (sSS) in patients diagnosed with SLE (SLE-SS) and compare the clinical and serological features of SLE-SS to SLE only. METHODS: A retrospective observational study including patients diagnosed with SLE (SLICC criteria) seen at the Rheumatology Department between 1990 and 2020 was performed. A total of 453 SLE patients were assessed for fulfilment of the criteria for SS using the European questionnaire and Schirmer test, fluorescein staining/non-stimulated whole-salivary flow, anti-Ro/La antibodies, and lip biopsy. Anti-Ro/SSA and anti-La/SSB antibodies and rheumatoid factor (RF) were measured at entry and at SS assessment. SLE-SS was defined according to the American-European Consensus Criteria (AECC). SLE-SS was defined as a case that initially only fulfilled SLE classification criteria but which exhibited disease progression during follow-up and then met classification criteria for sSS. RESULTS: SLE-SS occurred in 11% of the SLE patients. In comparison to SLE-only patients, the SLE-SS group was older at inclusion and onset, and had a longer disease course. Sicca syndrome, oral ulcers, pulmonary involvement, and peripheral neuropathy were more frequent. Anti-SSA, anti-SSB, RF, and total IgG were higher in the SLE-SS group. CONCLUSION: SLE-SS appears to be a subgroup of patients with distinct clinical and serologic features. The frequency of SLE-SS increases with age. Patients with SLE-SS have a higher frequency of oral ulcers, anti-Ro and anti-La antibodies, and a lower frequency of renal disease, anti-dsDNA antibodies, anti-SM, and lower C3 and C4 hypocomplementemia.

5.
Z Rheumatol ; 80(5): 481-486, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33709168

RESUMO

Anti-tumor necrosis factor­α (TNF-α)-induced lupus (ATIL) represents a diagnostic and treatment challenge. Most cases are caused by infliximab and in some cases by etanercept and adalimumab. Symptoms can range from cutaneous manifestations to more rare and serious conditions. Diagnosis requires a temporal relationship between symptoms and positive autoantibody determination. Arthritis and cutaneous symptoms are the most common manifestations accompanied by positive antinuclear antibody (ANA) and anti-double strand DNA (dsDNA) determinations. The etiology of ATILS remains to be definitively established. Several mechanisms have been proposed for anti-TNF-α-induced lupus, including apoptosis, immunosuppression and humoral autoimmunity. Treatment includes discontinuation of anti-TNF­α agents and in some cases corticosteroids and immunosuppressors. Questions to be answered: (1) Are soluble TNF receptor fusion proteins such as etanercept and anti-TNF chimeric antibodies equally likely to cause ATIL? (2) Can patients with ATIL switch from one anti-TNF­α antagonist to another? (3) Can the concurrent use of a conventional synthetic disease-modifying antirheumatic drug (csDMARD) like methotrexate or hydroxychloroquine reduce the probability of ATIL?


Assuntos
Antirreumáticos , Inibidores do Fator de Necrose Tumoral , Adalimumab , Anticorpos Monoclonais , Antirreumáticos/efeitos adversos , Etanercepte/efeitos adversos , Humanos , Fator de Necrose Tumoral alfa
6.
RMD Open ; 7(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33455920

RESUMO

BACKGROUND: The recent outbreak of COVID-19 has raised concerns in the rheumatology community about the management of immunosuppressed patients diagnosed with inflammatory rheumatic diseases. It is not clear whether the use of biological agents may suppose a risk or protection against SARS-CoV-2 infection; however, it has been suggested that severe respiratory forms of COVID-19 occur as a result of exacerbated inflammation status and cytokine production. This prompted the use of interleukin 6 (IL-6) (tocilizumab and sarilumab) and IL-1 inhibitors (anakinra) in severe COVID-19 disease and more recently JAK1/2 inhibitor (baricitinib). Therefore, patients with rheumatic diseases provide a great opportunity to learn about the use of biological agents as protective drugs against SARS-CoV-2. OBJECTIVES: To estimate COVID-19 infection rate in patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) for inflammatory rheumatic diseases (RMD), determine the influence of biological agents treatment as risk or protective factors and study the prognosis of patients with rheumatic diseases receiving biological agents compared to the general population in a third-level hospital setting in León, Spain. METHODS: We performed a retrospective observational study including patients seen at our rheumatology department who received bDMARDs for rheumatic diseases between December 1st 2019 and December 1st 2020, and analysed COVID-19 infection rate. All patients who attended our rheumatology outpatient clinic with diagnosis of inflammatory rheumatic disease receiving treatment with biological agents were included. Main variable was the hospital admission related to COVID-19. The covariates were age, sex, comorbidities, biological agent, duration of treatment, mean dose of glucocorticoids and need for intensive care unit . We performed an univariate and multivariate logistic regression models to assess risk factors of COVID-19 infection. RESULTS: There were a total of 4464 patients with COVID-19 requiring hospitalisation. 40 patients out of a total of 820 patients with rheumatic diseases (4.8%) receiving bDMARDs contracted COVID-19 and 4 required hospital care. Crude incidence rate of COVID-19 requiring hospital care among the general population was 3.6%, and it was 0.89% among the group with underlying rheumatic diseases. 90% of patients receiving bDMARDS with COVID-19 did not require hospitalisation. Out of the 4464 patients, 869 patients died, 2 of which received treatment with biological agents. Patients with rheumatic diseases who tested positive for COVID-19 were older (female: median age 60.8 IQR 46-74; male: median age 61.9 IQR 52-70.3) than those who were negative for COVID-19 (female: median age 58.3 IQR 48-69; male: median age 56.2 IQR 47-66), more likely to have hypertension (45% vs 26%, OR 2.25 (CI 1.18-4.27),p 0.02), cardiovascular disease (23 % vs 9.6%, OR 2.73 (1.25-5.95), p 0.02), be smokers (13% vs 4.6%, OR 2.95 (CI 1.09-7.98), p 0.04), receiving treatment with rituximab (20% vs 8%, 2.28 (CI 1.24-6.32), p 0.02) and a higher dose of glucocorticoids (OR 2.5 (1.3-10.33, p 0.02) and were less likely to be receiving treatment with IL-6 inhibitors (2.5% vs 14%, OR 0.16, (CI 0.10-0.97, p 0.03). When exploring the effect of the rest of the therapies between groups (affected patients vs unaffected), we found no significant differences in bDMARD proportions. IL-1 inhibitors, IL-6 inhibitors, JAK inhibitors and belimumab-treated patients showed the lowest incidence of COVID-19 among adult patients with rheumatic diseases. We found no differences in sex or rheumatological disease between patients who tested positive for COVID-19 and patients who tested negative. CONCLUSIONS: Overall, the use of biological disease-modifying antirheumatic drugs (bDMARDs) does not associate with severe manifestations of COVID-19. Patients with rheumatic disease diagnosed with COVID-19 were more likely to be receiving a higher dose of glucocorticoids and treatment with rituximab. IL-6 inhibitors may have a protective effect.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Fatores Biológicos/uso terapêutico , COVID-19/tratamento farmacológico , Surtos de Doenças , Glucocorticoides/uso terapêutico , Substâncias Protetoras/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Rituximab/uso terapêutico , SARS-CoV-2/isolamento & purificação , Idoso , Anticorpos Monoclonais Humanizados/farmacologia , COVID-19/epidemiologia , Feminino , Humanos , Interleucina-6/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Espanha/epidemiologia , Resultado do Tratamento
8.
Int J Low Extrem Wounds ; : 1534734620914439, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32394760

RESUMO

Diabetic foot ulcers (DFUs) are considered one of the most aggressive and expensive complications of diabetes. Low-level laser therapy (LLLT) has been highlighted as a potential modality of treatment to accelerate the healing of ulcers. This systematic review and meta-analysis aimed to investigate the efficacy of LLLT in the treatment of DFU and identify the LLLT application parameters recommended for the treatment of DFU over the past 10 years. A systematic search was conducted in PubMed, BVS, PEDro, Scopus, Web of Science, and CINAHL up to March 31, 2019. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines, randomized controlled trials (RCTs) that assessed the effect of LLLT on the treatment of DFU were included. Thirteen RCTs with a total of 361 participants were included in this review. Three RCTs reported a reduction in the percentage size of the ulcers and were included in the meta-analysis. The meta-analysis of the percentage size difference demonstrated a significant reduction in ulcer size in the LLLT group compared with controls (22.96 [95% confidence interval = 18.22-27.69; z = 9.51, P < .0001]). Treatment with 632.8 to 685 nm, 50 mW/cm2, 3 to 6 J/cm2, and irradiation for 30 to 80 seconds, 3 times weekly for a month is of benefit to patients with DFU. LLLT is effective and safe for the treatment of DFU. Additionally, well-designed, high-quality studies are needed to allow its ideal parameterization for clinical practice.

9.
Autophagy ; 15(5): 771-784, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30563404

RESUMO

The tumor suppressor TP53/p53 is a known regulator of apoptosis and macroautophagy/autophagy. However, the molecular mechanism by which TP53 regulates 2 apparently incompatible processes remains unknown. We found that Drosophila lacking p53 displayed impaired autophagic flux, higher caspase activation and mortality in response to oxidative stress compared with wild-type flies. Moreover, autophagy and apoptosis were differentially regulated by the p53 (p53B) and ΔNp53 (p53A) isoforms: while the former induced autophagy in differentiated neurons, which protected against cell death, the latter inhibited autophagy by activating the caspases Dronc, Drice, and Dcp-1. Our results demonstrate that the differential use of p53 isoforms combined with the antagonism between apoptosis and autophagy ensures the generation of an appropriate p53 biological response to stress.


Assuntos
Apoptose/genética , Autofagia/genética , Drosophila melanogaster/genética , Estresse Oxidativo/fisiologia , Proteína Supressora de Tumor p53/fisiologia , Animais , Animais Geneticamente Modificados , Células Cultivadas , Drosophila melanogaster/fisiologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiologia , Transdução de Sinais/genética , Proteína Supressora de Tumor p53/genética
10.
Molecules ; 23(2)2018 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-29382109

RESUMO

Many substances of forensic interest are chiral and available either as racemates or pure enantiomers. Application of chiral analysis in biological samples can be useful for the determination of legal or illicit drugs consumption or interpretation of unexpected toxicological effects. Chiral substances can also be found in environmental samples and revealed to be useful for determination of community drug usage (sewage epidemiology), identification of illicit drug manufacturing locations, illegal discharge of sewage and in environmental risk assessment. Thus, the purpose of this paper is to provide an overview of the application of chiral analysis in biological and environmental samples and their relevance in the forensic field. Most frequently analytical methods used to quantify the enantiomers are liquid and gas chromatography using both indirect, with enantiomerically pure derivatizing reagents, and direct methods recurring to chiral stationary phases.


Assuntos
Ciências Forenses/métodos , Preparações Farmacêuticas/análise , Cromatografia Gasosa/instrumentação , Cromatografia Gasosa/métodos , Cromatografia Líquida/instrumentação , Cromatografia Líquida/métodos , Ciências Forenses/instrumentação
11.
Rio de Janeiro; s.n; 2004. 99 p. ilus.
Tese em Português | LILACS | ID: lil-443872

RESUMO

Trata-se de uma pesquisa qualitativa tipo estudo de caso descritivo, com 13 profissionais de enfermagem do serviço de quimioterapia. Os objetivos orientam para: 1- Descrever a percepção dos profissionais de enfermagem de um serviço de quimioterapia sobre os riscos ocupacionais; 2- Identificar os riscos ocupacionais evidenciados no processo de trabalho; 3- Levantar a ocorrência de problemas de saúde em profissionais de enfermagem deste serviço; 4- Estabelecer uma relação entre os riscos percebidos pelos profissionais de enfermagem e os evidenciados na observação sobre o processo de trabalho em quimioterapia; 5- Descrever a relação entre as atitudes de proteção dos profissionais de enfermagem e os riscos ocupacionais percebidos e identificados naquele setor. Para responder estes objetivos, os profissionais responderam a um questionário e foi feita a observação sistemática direta das situações de trabalho durante o processo de aplicação da quimioterapia. A coleta dos dados foi realizada de setembro a outubro de 2004. Evidenciou-se que os profissionais de enfermagem são do sexo feminino, idade média de 33 anos, tempo de serviço de 5,3 anos e predomínio com formação de técnicas de enfermagem. Todas receberam treinamento para o serviço. As profissionais de enfermagem (13) reconhecem que os riscos ocupacionais podem afetar a saúde, mas não os conhecem ou reconhecem no processo de trabalho. A maioria das trabalhadoras percebe os riscos através da exposição aos citostáticos (12) e material pérfuro-cortante (8). Os problemas de saúde destacados foram: pulmonar (3), osteomuscular (3), hematológico (2) e dermatológico (1). As medidas de proteção individual e coletiva não são cumpridas adequadamente e são subestimados os riscos, o que é incoerente com a percepção expressada, pois referem que estes causam danos a saúde. Os acidentes de trabalho foram provocados por material pérfuro-cortante (1) e derramamento de quimioterápico (4). Quanto à segurança e satisfação, 8 e 12...


Assuntos
Humanos , Acidentes de Trabalho , Doenças Profissionais , Exposição Ocupacional , Enfermagem do Trabalho , Riscos Ocupacionais , Percepção , Tratamento Farmacológico/enfermagem , Brasil/epidemiologia , Epidemiologia Descritiva , Pesquisa Qualitativa
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