RESUMO
We present a case of adult-onset Still's disease, a rare disease that presented with a rare complication, myocarditis. After initial therapy with prednisolone 1 mg/kg/day, the patient experienced dyspnea due to severe pleural effusion and palpitations on account of new-onset supraventricular tachycardia. Therapy with three consecutive pulses of 1000 mg of methylprednisolone and anakinra 100 mg/day proved to be effective, with a progressive resolution of all symptoms. However, at three months follow-up, oligoarthritis recurred along with high serum ferritin. Secondary failure to anakinra was assumed, and a switch to tocilizumab 162 mg was made. Nevertheless, arthralgia of the wrists and knees as well as high serum ferritin still persisted after two months of therapy. Chronic disease was assumed, and the patient switched to canakinumab 4 mg/kg/dose q4week, and a complete resolution of symptoms occurred with normalization of inflammation markers. Follow-up cardiac magnetic resonance showed a complete resolution of heart involvement.
RESUMO
Platelet-rich plasma injections have been a therapeutic option with exponential growth in several pathologies in the last decades, particularly musculoskeletal for their effect on improving pain and functionality. Rheumatoid arthritis is a chronic joint disease, which involves inflammation of the synovial membrane with cartilage and juxta-articular bone destruction. Conventional and biological disease-modifying anti-rheumatoid drugs are the cornerstone of the treatment of this disease. However, the use of intra-articular glucocorticoids is often necessary and the role of platelet-rich plasma injections in these patients remains uncertain. A literature review was carried out through the PubMed database, Cochrane and Google Scholar for the search terms "rheumatoid arthritis" and "platelet-rich plasma". Eleven studies have been included in this review: two of these are in vitro studies, five are animal studies, one case report, two case series and one randomized controlled trial. Most of the studies demonstrated a decrease in pain and inflammatory mediators and improvement of functional outcomes, with no severe adverse effects reported. However, the quantity and quality of literature about the effects and safety of plasma-rich plasma injections in rheumatoid arthritis patients are still scarce. It is essential that well-designed randomized controlled trials are made on this topic to understand if platelet-rich plasma may be useful as a coadjuvant therapy in rheumatoid arthritis.
RESUMO
Fungal infections remain a major health concern with aromatic plants and their metabolites standing out as promising antifungal agents. The present study aims to assess, for the first time, the antifungal and anti-inflammatory potential of Bupleurum subsp. paniculatum (Brot.) H.Wolff essential oil from Portugal. The oil obtained by hydrodistillation and characterized by GC-MS, showed high amounts of monoterpene hydrocarbons, namely α-pinene (29.0-36.0%), ß-pinene (26.1-30.7%) and limonene (10.5-13.5%). The antifungal potential was assessed, according to CLSI guidelines, against several clinical and collection strains. The essential oil showed a broad fungicidal effect being more potent against Cryptococcus neoformans and dermatophytes. Moreover, a significant germ tube inhibition was observed in Candida albicans as well as a disruption of mature biofilms, thus pointing out an effect of the oil against relevant virulent factors. Furthermore, fungal ultrastructural modifications were detected through transmission electron microscopy, highlighting the nefarious effect of the oil. Of relevance, the oil also evidenced anti-inflammatory activity through nitric oxide inhibition in macrophages activated with lipopolysaccharide. In addition, the essential oil's bioactive concentrations did not present toxicity towards macrophages. Overall, the present study confirmed the bioactive potential of B. rigidum subsp. paniculatum essential oil, thus paving the way for the development of effective drugs presenting concomitantly antifungal and anti-inflammatory properties.
RESUMO
BACKGROUND: The use of TNF-inhibitors and/or the IL-6 receptor antagonist, tocilizumab, in rheumatoid arthritis (RA) have pleiotropic effects that also involve circulating B-cells. The main goal of this study was to assess the effect of TNF-inhibitors and tocilizumab on B-cell phenotype and gene expression in RA. METHODS: Blood samples were collected from untreated early RA (ERA) patients, established RA patients under methotrexate treatment, established RA patients before and after treatment with TNF-inhibitors and tocilizumab, and healthy donors. B-cell subpopulations were characterized by flow cytometry and B-cell gene expression was analyzed by real-time PCR on isolated B-cells. Serum levels of BAFF, CXCL13 and sCD23 were determined by ELISA. RESULTS: The frequency of total CD19+ B cells in circulation was similar between controls and all RA groups, irrespective of treatment, but double negative (DN) IgD-CD27- memory B cells were significantly increased in ERA and established RA when compared to controls. Treatment with TNF-inhibitors and tocilizumab restored the frequency of IgD-CD27- B-cells to normal levels, but did not affect other B cell subpopulations. TACI, CD95, CD5, HLA-DR and TLR9 expression on B-cells significantly increased after treatment with either TNF-inhibitors and/ or tocilizumab, but no significant changes were observed in BAFF-R, BCMA, CD69, CD86, CXCR5, CD23, CD38 and IgM expression on B-cells when comparing baseline with post-treatment follow-ups. Alterations in B-cell gene expression of BAFF-R, TACI, TLR9, FcγRIIB, BCL-2, BLIMP-1 and ß2M were found in ERA and established RA patients, but no significant differences were observed after TNF-inhibitors and tocilizumab treatment when comparing baseline and follow-ups. Serum levels of CXCL13, sCD23 and BAFF were not significantly affected by treatment with TNF-inhibitors and tocilizumab. CONCLUSIONS: In RA patients, the use of TNF-inhibitors and/ or tocilizumab treatment affects B-cell phenotype and IgD-CD27- memory B cells in circulation, but not B-cell gene expression levels.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Subpopulações de Linfócitos B/imunologia , Memória Imunológica , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/farmacologia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/metabolismo , Subpopulações de Linfócitos B/efeitos dos fármacos , Subpopulações de Linfócitos B/metabolismo , Biomarcadores , Quimiocina CXCL13/sangue , Seguimentos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Imunoglobulina D/metabolismo , Imunofenotipagem , Contagem de Linfócitos , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Fenótipo , Receptores CXCR5/metabolismo , Receptores de IgE/sangue , Resultado do Tratamento , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismoRESUMO
Fabry's disease (FD) is a lysosomal storage disorder associated with an alpha-galactosidase A deficiency. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients with established diagnosis is unknown, but as musculoskeletal pain may be an important complaint at presentation, misdiagnosed cases are anticipated. With this study, we aim to calculate the frequency of FD-associated mutations in a cohort of JIA patients. Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded in the Portuguese rheumatic diseases register (http://Reuma.pt). Molecular genetic testing to detect GLA gene mutations was performed. After the multiplex polymerase chain reactions technique for DNA amplification, direct sequencing of the complete sequence of GLA gene was completed. From a cohort of 292 patients with JIA (188 females, 104 males), mutations were identified in 5 patients (all female). Four patients had the mutation D313Y, a rare GLA variant, which is associated with low enzymatic levels in plasma, but normal lysosomal levels. One patient presented the missense mutation R118C, which was previously described in Mediterranean patients with FD. This is the first screening of FD mutations in a cohort of JIA patients. No "classic" pathogenic FD mutations were reported. The late-onset FD-associated mutation, R118C, was found in a frequency of 0.34% (1/292).
RESUMO
ABSTRACT Objective To identify factors associated with loss to follow-up in Tuberculosis (TB) treatment, including patients' level of knowledge regarding treatment of this disease. Methods 42 loss to follow-up cases and 84 control cases that were finishing the sixth month of their first treatment for tuberculosis were selected for this study. Primary data were gathered through interviews, while secondary data were obtained from the notification form of the disease, between December 2011 and April 2012. Factors associated with loss to follow-up were analyzed by means of a conditional logistic regression multivariate model for matched case-control groups. Results No significant differences were observed between loss to follow-up cases and controls regarding socioeconomic factors, lifestyle, clinical condition, treatment-related behaviors and the access of patients to sources of information on TB. In the regression multivariate analysis, significant associations with retreatment after loss to follow-up that were detected include: scarce knowledge on tuberculosis, lack of adherence to consultation during the current treatment, noncompliance with follow-up consultation deadline, smoking and HIV negative. Conclusion When compared to controls, cases undergoing TB retreatment after loss to follow-up have less knowledge on the disease, which is a sign for the professionals responsible for health education of the need to invest more time and efforts in activities that help the patient understand the disease and its treatment, as well as to have higher levels of adherence. In addition, noncompliance with the follow-up consultation deadline, failure to attend consultations during the current treatment and smoking are also factors that may be influenced by poor knowledge on the disease, which leads to the treatment loss to follow-up.(AU)
RESUMEN Objetivo Identificar los factores asociados con la pérdida del seguimiento en el tratamiento de la tuberculosis (TB), incluyendo el nivel de conocimiento de los pacientes sobre el tratamiento de esta enfermedad. Métodos Se seleccionaron 42 casos de pérdida de seguimiento y 84 controles que se encontraban terminando el sexto mes de su primer tratamiento contra la TB. Los datos primarios fueron recolectados mediante entrevistas, mientras que los secundarios, a partir del formulario de notificación de la enfermedad, entre diciembre de 2011 y abril de 2012. Se utilizó modelo multivariado de regresión logística condicional para analizar los factores asociados con la pérdida del seguimiento entre grupos de casos y controles emparejados. Resultados No hay diferencias significativas entre los casos y controles en cuanto a factores socioeconómicos, estilos de vida, condición clínica, comportamientos relacionados con el tratamiento de la enfermedad, así como el acceso a fuentes de información sobre tuberculosis. En el análisis de regresión se observaron las siguientes asociaciones significativas con el retratamiento después de la pérdida del seguimiento: bajo conocimiento sobre tuberculosis, falta de adherencia a la consulta en el tratamiento actual, incumplimiento de la fecha límite de la consulta de seguimiento, tabaquismo y VIH negativo. Conclusión En comparación con los controles, en los casos de retratamiento de la enfermedad después de la pérdida del seguimiento presentan menor conocimiento sobre tuberculosis, lo que es una señal, para los profesionales responsables de la educación sanitaria, de la necesidad de invertir más tiempo y esfuerzos en actividades que lleven al paciente a comprender la enfermedad y su tratamiento, así como para obtener mayores niveles de adherencia Además, incumplir la fecha límite de las consultas de seguimiento, no asistir a las consultas del actual tratamiento y el tabaquismo también son factores que pueden estar influenciados por el escaso conocimiento de estos pacientes acerca de su enfermedad, lo lleva a la pérdida del seguimiento del tratamiento.(AU)
Assuntos
Humanos , Pacientes Desistentes do Tratamento , Tuberculose/epidemiologia , Educação em Saúde , Adesão à Medicação , Fatores EpidemiológicosRESUMO
OBJECTIVE: To identify factors associated with loss to follow-up in Tuberculosis (TB) treatment, including patients' level of knowledge regarding treatment of this disease. METHODS: 42 loss to follow-up cases and 84 control cases that were finishing the sixth month of their first treatment for tuberculosis were selected for this study. Primary data were gathered through interviews, while secondary data were obtained from the notification form of the disease, between December 2011 and April 2012. Factors associated with loss to follow-up were analyzed by means of a conditional logistic regression multivariate model for matched case-control groups. RESULTS: No significant differences were observed between loss to follow-up cases and controls regarding socioeconomic factors, lifestyle, clinical condition, treatment-related behaviors and the access of patients to sources of information on TB. In the regression multivariate analysis, significant associations with retreatment after loss to follow-up that were detected include: scarce knowledge on tuberculosis, lack of adherence to consultation during the current treatment, noncompliance with follow-up consultation deadline, smoking and HIV negative. CONCLUSION: When compared to controls, cases undergoing TB retreatment after loss to follow-up have less knowledge on the disease, which is a sign for the professionals responsible for health education of the need to invest more time and efforts in activities that help the patient understand the disease and its treatment, as well as to have higher levels of adherence. In addition, noncompliance with the follow-up consultation deadline, failure to attend consultations during the current treatment and smoking are also factors that may be influenced by poor knowledge on the disease, which leads to the treatment loss to follow-up.
Assuntos
Antituberculosos/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Perda de Seguimento , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Idoso , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores Socioeconômicos , Tuberculose Pulmonar/epidemiologiaRESUMO
OBJECTIVE: The new Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria aimed to improve the performance of systemic lupus erythematosus (SLE) classification over the American College of Rheumatology (ACR) 1997 criteria. However, the SLICC 2012 criteria need further external validation. Our objective was to compare the sensitivity for SLE classification between the ACR 1997 and the SLICC 2012 criteria sets in a real-life, multicenter, international SLE population. METHODS: We conducted a cross-sectional observational study of patients with a clinical diagnosis of SLE followed at the participating rheumatology centers and registered in the Portuguese and Spanish national registries. The sensitivity of the 2 classification sets was compared using McNemar's test. The sensitivity of ACR 1997 and SLICC 2012 was further examined in 5 subgroups, defined according to disease duration. RESULTS: We included 2,055 SLE patients (female 91.4%, white 93.5%, mean ± SD age at disease onset 33.1 ± 14.4 years, mean ± SD age at SLE diagnosis 35.3 ± 14.7 years, and mean ± SD age at the time of the study 47.4 ± 14.6 years) from 17 centers. The sensitivity for SLE classification was higher with the SLICC 2012 than with the ACR 1997 (93.2% versus 85.6%; P < 0.0001). Of 296 patients not fulfilling the ACR 1997, 62.8% could be classified with the SLICC 2012. The subgroup of patients with ≤5 years since disease onset presented the largest difference in sensitivity between the SLICC 2012 and the ACR 1997 (89.3% versus 76.0%; P < 0.0001); this difference diminished with longer disease duration, and it was no longer significant for patients with >20 years of disease duration. CONCLUSION: The SLICC 2012 criteria were more sensitive than the ACR 1997 criteria in real-life clinical practice in SLE. The SLICC 2012 criteria may allow patients to be classified as having SLE earlier in the disease course.
Assuntos
Lúpus Eritematoso Sistêmico/classificação , Reumatologia/normas , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Estados UnidosRESUMO
Malaria infection continues to be a major problem in many parts of the world including the Americas, Asia, and Africa. Insecticide-treated bed-nets have shown to reduce malaria cases by 50%; however, improper handling and human behavior can diminish their effectiveness. We formulate and analyze a mathematical model that considers the transmission dynamics of malaria infection in mosquito and human populations and investigate the impact of bed-nets on its control. The effective reproduction number is derived and existence of backward bifurcation is presented. The backward bifurcation implies that the reduction of R below unity alone is not enough to eradicate malaria, except when the initial cases of infection in both populations are small. Our analysis demonstrate that bed-net usage has a positive impact in reducing the reproduction number R. The results show that if 75% of the population were to use bed-nets, malaria could be eliminated. We conclude that more data on the impact of human and mosquito behavior on malaria spread is needed to develop more realistic models and better predictions.
Assuntos
Culicidae , Malária/epidemiologia , Malária/transmissão , Modelos Biológicos , Mosquiteiros , Animais , Humanos , PrevalênciaRESUMO
Aerial parts of Apium nodiflorum collected in Portugal and Italy were submitted to hydrodistillation; also a supercritical fluid extract was obtained from Italian plants. The extracts were analyzed by GC and GC/MS. Both essential oils, obtained from Portuguese and Italian plants, posses high content of phenylpropanoids (51.6 vs. 70.8%); in the former, the percentage split in myristicin (29.1%) and dillapiol (22.5%), whereas in the latter, the total percentage is only of dillapiol (70.8%). The co-occurrence of myristicin and dillapiol is frequent because dillapiol results from enzymatic methoxylation of myristicin. Antimicrobial activity of phenylpropanoids has been patented, what suggest the potential of plants with high amounts of these compounds. Minimal inhibitory concentration (MIC) and minimal lethal concentration, determined according to NCCLS, were used to evaluate the antifungal activity of the essential oils against yeasts, Aspergillus species and dermatophytes. Essential oils exhibited higher antifungal activity than other Apiaceae against dermatophytes, with MIC ranging from 0.04 to 0.32 µl/ml. These results support the potential of A. nodiflorum oil in the treatment of dermatophytosis and candidosis.
Assuntos
Apiaceae/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Arthrodermataceae/efeitos dos fármacos , Aspergillus/efeitos dos fármacos , Dióxido de Carbono/metabolismo , Cromatografia com Fluido Supercrítico/métodos , Cromatografia Gasosa-Espectrometria de Massas , Itália , Testes de Sensibilidade Microbiana , Óleos Voláteis/isolamento & purificação , Extratos Vegetais/isolamento & purificação , PortugalRESUMO
Satureja thymbra L. is well known in Italy by the popular name of "Santoreggia sarda". It grows only in Sardinia and nowadays it is restricted to the slope of the Colle San Michele in Cagliari. The composition of the aromatic extracts obtained by supercritical CO2 and by hydrodistillation and their antifungal activity is reported. The collected extracts were analyzed by GC-FID and GC-MS methods. No significant differences were observed in the composition of the volatile extracts depending on the extraction method. The results showed the presence of thymol, gamma-terpinene, beta-caryophyllene, p-cymene, carvacrol and borneol as main components. The minimal inhibitory concentration (MIC) and the minimal lethal concentration (MLC) were used to evaluate the antifungal activity of the oils against Candida albicans, C. tropicalis, C. krusei, C. guillermondii, C. parapsilosis, Cryptococcus neoformans, Trichophyton rubrum, T. mentagrophytes, T. mentagrophytes var. interdigitale, Trichophyton rubrum, T. verrucosum, Microsporum canis, M. gypseum, Epidermophyton floccosum, Aspergillus niger, A. fumigatus and A. flavus. The volatile extracts revealed a wide-spectrum antifungal activity. They were fungicidal and similarly potent against yeasts, dermatophyte and Aspergillus stains, with MICs ranging from 0.16 to 0.32 pL x mL(-1).
Assuntos
Dióxido de Carbono/química , Cromatografia com Fluido Supercrítico/métodos , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Satureja/químicaRESUMO
In this study, flowering aerial parts of wild Achillea millefolium growing on the Mediterranean coast (Sardinia Island, Italy) and on the Atlantic coast (Portugal- Serra de Montemuro) were used as a matrix for supercritical extraction of volatile oil with CO2 (SFE). The collected extracts were analyzed by GC-FID and GC-MS methods and their composition were compared with that of the essential oil isolated by hydrodistillation. A strong chemical variability in essential oils depending on the origin of the samples was observed. The results showed the presence of two type oils. The Italian volatile extracts (SFE and essential oil) are predominantly composed by alpha-asarone (25.6-33.3%, in the SFE extract and in the HD oil, respectively), beta-bisabolene (27.3-16.6%) and alpha-pinene (10.0-17.0%); whereas the main components of the Portuguese extracts are trans-thujone (31.4-29.0%), trans-crhysanthenyl acetate (19.8-15.8%) and beta-pinene (1.2-11.1%). The minimal inhibitory concentration (MIC) and the minimal lethal concentration (MLC) were used to evaluate the antifungal activity of the oils against Candida albicans, C. tropicalis, C. krusei, C. guillermondii, C. parapsilosis, Cryptococcus neoformans, Trichophyton rubrum, T. mentagrophytes, T. mentagrophytes var. interdigitale, T. verrucosum, Microsporum canis, M. gypseum, Epidermophyton floccosum, Aspergillus niger, A. fumigatus and A. flavus. The oils showed the highest activity against dermatophyte strains, with MIC values ranging from 0.32-1.25 microL mL(-1).
Assuntos
Achillea/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
Isolation of volatile concentrates from leaves, flowers and fruits of Vitex agnus-castus L. have been obtained by supercritical extraction with carbon dioxide. The composition of the volatile concentrates has been analysed by GC/MS. In all plant organs, the extracts are composed chiefly of alpha-pinene, sabinene, 1,8-cineole, alpha-terpinyl acetate, (E)-caryophyllene, (E)-beta-farnesene, bicyclogermacrene, spathulenol and manool. The main difference observed was in the content of sclarene, which was not present in the samples from flowers or fruits. To complete the investigation, a comparison with the hydrodistilled oil has been carried out. The minimal inhibitory concentration (MIC) and the minimal lethal concentration were used to evaluate the antifungal activity of the oils against dermatophyte strains (Trichophyton mentagrophytes, Microsporum canis, T. rubrum, M. gypseum and Epidermophyton floccosum). Antifungal activity of the leaf essential oil was the highest, with MIC values of 0.64 microL mL(-1) for most of the strains.
Assuntos
Antifúngicos/análise , Arthrodermataceae/efeitos dos fármacos , Óleos Voláteis/química , Vitex/química , Antifúngicos/farmacologia , Flores/química , Frutas/química , Itália , Testes de Sensibilidade Microbiana , Óleos Voláteis/farmacologia , Folhas de Planta/químicaRESUMO
The chemical composition and antifungal activity of the essential oils of Lavandula pedunculata (Miller) Cav., harvested in North and Central Portugal, were investigated. The essential oils were isolated by hydrodistillation and analyzed by GC and GC/MS. The minimal-inhibitory concentration (MIC) and the minimal-lethal concentration (MLC) of the essential oils and of their major constituents were used to evaluate the antifungal activity against different strains of fungi involved in candidosis, dematophytosis, and aspergillosis. The oils were characterized by a high percentage of oxygenated monoterpenes, the main compounds being 1,8-cineole (2.4-55.5%), fenchone (1.3-59.7%), and camphor (3.6-48.0%). Statistical analysis differentiated the essential oils into two main types, one characterized by the predominance of fenchone and the other one by the predominance of 1,8-cineole. Within the 1,8-cineole chemotype, two subgroups were well-defined taking into account the percentages of camphor. A significant antifungal activity of the oils was found against dermatophyte strains. The essential oil with the highest content of camphor was the most active with MIC and MLC values ranging from 0.32-0.64 microl/ml.
Assuntos
Antifúngicos/farmacologia , Lavandula/química , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Antifúngicos/química , Arthrodermataceae/efeitos dos fármacos , Cromatografia Gasosa , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Óleos de Plantas/químicaRESUMO
The essential oils and supercritical CO(2) extracts of wild Daucus carota L. subsp. carota growing spontaneously in Sardinia and in Portugal were investigated. The main components in the Sardinian essential oil of flowering and mature umbels with seeds are beta-bisabolene (17.6-51.0%) and 11-alpha-(H)-himachal-4-en-1-beta-ol (9.0-21.6%); instead, the oils from Portuguese samples are predominantly composed of geranyl acetate (5.2-65.0%) and alpha-pinene (3.5-37.9%). Supercritical extracts contain lower amounts of monoterpenes and higher amounts of sesquiterpene hydrocarbons. Antifungal activities of the Sardinian oils were the highest, particularly for dermatophytes and Cryptococcus neoformans, with MIC values of 0.16-0.64 microL mL(-1).