IL-6 levels are associated with clinical status in patients with Myasthenia Gravis

Background: Myasthenia gravis (MG) is an autoimmune disease marked by fluctuating course of muscle weakness. Objectives: The current study was designed to evaluate plasma levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL17A) in patients with MG and controls and to investigate whether cytokines levels are associated with clinical parameters. This study was conducted at the Neuromuscular Diseases Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brazil. Methods: Peripheral blood was drawn, and plasma levels of cytokines were measured by cytometric bead array (CBA) in 80 treated patients with MG and 50 controls. The MG Composite (MGC) was used to evaluate muscle weakness and severity of typical motor symptoms of MG. Results: Patients with MG undergoing treatment exhibit lower levels of all evaluated cytokines compared to controls. There was a negative correlation between IL-6 levels and the MG Composite score, indicating that higher levels of IL-6 were associated with better control of the disease. Conclusion: This exploratory study suggests that IL-6 is associated with MG clinical status, as assessed by the MG

Urinary Levels of IL-1 β

Objectives. To evaluate the association between inflammatory biomarkers, neurotrophic factors, birth conditions, and the presence of motor development abnormalities in preterm neonates. Methods. Plasma and urinary levels of cytokines (IL-1β, IL-6, IL-10, TNF, and IL-12p70), chemokines (CXCL8/IL-8, CCL2/MCP-1, CCL5/RANTES, CXCL10/IP-10, and CXCL9/MIG), and neurotrophic factors (BDNF and GDNF) were evaluated in 40 preterm neonates born between 28 and 32 incomplete weeks of gestation, at four distinct time points: at birth (umbilical cord blood) (T0), at 48 (T1), at 72 hours (T2), and at 3 weeks after birth (T3). Biomarkers levels were compared between different time points and then associated with Test of Infant Motor Performance (TIMP) percentiles. Results. Maternal age, plasma, and urinary concentrations of inflammatory molecules and neurotrophic factors were significantly different between groups with normal versus lower than expected motor development. Higher levels of GDNF were found in the group with lower than expected motor development, while IL-1β and CXCL8/IL-8 values were higher in the group with typical motor development. Conclusion. Measurements of cytokines and neurotrophic factors in spot urine may be useful in the follow-up of motor development in preterm neonates

NEUROINFLAMAÇÃO NA ESCLEROSE LATERAL AMIOTRÓFICA

A esclerose lateral amiotrófica (ELA) esporádica é uma doença neurodegenerativaque acomete o neurônio motor. Sua etiologia ainda não foi totalmente esclarecida e é considerada multifatorial. O objetivo desse trabalho é fazer uma revisão narrativa sobre os mecanismos fisiopatológicos da ELA esporádica, com foco no papel da neuroinflamação, além de descrever estudos envolvendo a pesquisa de biomarcadores de diagnóstico e prognóstico. O processo de neuroinflamação na ELA é considerado secundário às alterações que levam à morte neuronal, podendo influenciar na taxa de progressão dadoença. Existem diversos estudos sobre o perfil dos fatores inflamatóriosna ELA, por vezes com resultados contraditórios, reforçando a dificuldade de análise desses fatores num organismo dinâmico. Ainda assim, no contexto da ELA, o estudo de possíveis biomarcadores diagnósticos e/ou prognósticos é válido e de grande interesse, pois permitiria um avanço nos ensaios clínicos que buscam novos tratamentos, bem como na condução e planejamento de cada caso

Effectiveness of sequential viscosupplementation in temporomandibular joint internal derangements and symptomatology : a case series

Viscosupplementation is a minimally invasive technique that replaces synovial fluid by intra-articular injection of hyaluronic acid (HA). Although effective in some joints, there is not conclusive evidence regarding temporomandibular disorders. +is case series described the efficacy of a viscosupplementation protocol in intra-articular temporomandibular disorders. Ten patients with a diagnosis of disc displacement and/or osteoarthritis by Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were submitted to four monthly injections of low or medium molecular weight HA. Pain, mandibular function, image analysis by tomography and magnetic resonance, and quality of life were assessed at baseline and follow-ups (1 and 6 months). Pain, jaw range-of-motion, mandibular function, and quality of life improved at follow-up evaluations. Osteoarthritis changes decreased, and 20% of patients improved mandibular head excursion after treatment. Resolution of effusion and improvement in disc morphology were observed for most patients. +is viscosupplementation protocol reduced pain and symptoms associated with internal derangement of temporomandibular joint, improved quality of life, and showed benefits from both low and medium molecular weight HA in alternate cycles

IL-17 Genetic and Immunophenotypic Evaluation in Chronic Graft-versus-Host Disease

Although interleukin-17 (IL-17) is a recently discovered cytokine associated with several autoimmune diseases, its role in the pathogenesis of chronic graft-versus-host disease (cGVHD) was not established yet. The objective of this study was to investigate the association of IL17A and IL17F genes polymorphisms and IL-17A and IL-17F levels with cGVHD. IL-17A expression was also investigated in CD4+ T cells of patients with systemic cGVHD. For Part I of the study, fifty-eight allo-HSCT recipients and donors were prospectively studied. Blood samples were obtained to determine IL17A and IL17F genes polymorphisms. Cytokines levels in blood and saliva were assessed by ELISA at days +35 and +100 after HSCT. In Part II, for the immunophenotypic evaluation, eight patients with systemic cGVHD were selected and the expression of IL-17A was evaluated. We found association between recipient AA genotype with systemic cGVHD. No association was observed between IL-17A levels and cGVHD. Lower IL-17A levels in the blood were associated with AA genotype. In flow cytometry analysis, decreased expression of IL-17A was observed in patients with cGVHD after stimulation. In conclusion, IL-17A may have an important role in the development of systemic cGVHD

Evaluation of New Potential Inflammatory Markers in Patients with Nonvalvular Atrial Fibrillation

Atrial fibrillation (AF), the most common arrhythmia in clinical practice, is associated with an increase in mortality and morbidity due to its high potential to cause stroke and systemic thromboembolism. Inflammatory mechanisms may play a role in the pathogenesis of AF and its maintenance. We aimed to evaluate a range of inflammatory markers as potentially involved in the pathophysiology of individuals with nonvalvular AF (NVAF). A total of 105 subjects were enrolled and divided into two groups: patients with NVAF (n = 55, mean age 72 ± 8 years) and a control group of individuals in sinus rhythm (n = 50, mean age 71 ± 8 years). Inflammatory-related mediators were quantified in plasma samples by using Cytometric Bead Array and Multiplex immunoassay. Subjects with NVAF presented significantly elevated values of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF), interferon-gamma, growth differentiation factor-15, myeloperoxidase, as well as IL-4, interferon-gamma-induced protein (IP-10), monokine induced by interferon-gamma, neutrophil gelatinase-associated lipocalin, and serum amyloid A in comparison with controls. However, after multivariate regression analysis adjusting for confounding factors, only IL-6, IL-10, TNF, and IP-10 remained significantly associated with AF. We provided a basis for the study of inflammatory markers whose association with AF has not been addressed before, such as IP-10, in addition to supporting evidence about molecules that had previously been associated with the disease. We expect to contribute to the discovery of markers that can be implemented in clinical practice hereafter

The phylum Bryozoa: From biology to biomedical potential

Less than one percent of marine natural products characterized since 1963 have been obtained from the phylum Bryozoa which, therefore, still represents a huge reservoir for the discovery of bioactive metabolites with its ~6000 described species. The current review is designed to highlight how bryozoans use sophisticated chemical defenses against their numerous predators and competitors, and which can be harbored for medicinal uses. This review collates all currently available chemoecological data about bryozoans and lists potential applications/benefits for human health. The core of the current review relates to the potential of bryozoan metabolites in human diseases with particular attention to viral, brain, and parasitic diseases. It additionally weighs the pros and cons of total syntheses of some bryozoan metabolites versus the synthesis of non-natural analogues, and explores the hopes put into the development of biotechnological approaches to provide sustainable amounts of bryozoan metabolites without harming the natural environment.SCOPUS: re.jinfo:eu-repo/semantics/publishe

IL-17 Genetic and Immunophenotypic Evaluation in Chronic Graft-versus-Host Disease

Although interleukin-17 (IL-17) is a recently discovered cytokine associated with several autoimmune diseases, its role in the pathogenesis of chronic graft-versus-host disease (cGVHD) was not established yet. The objective of this study was to investigate the association of IL17A and IL17F genes polymorphisms and IL-17A and IL-17F levels with cGVHD. IL-17A expression was also investigated in CD4+ T cells of patients with systemic cGVHD. For Part I of the study, fifty-eight allo-HSCT recipients and donors were prospectively studied. Blood samples were obtained to determine IL17A and IL17F genes polymorphisms. Cytokines levels in blood and saliva were assessed by ELISA at days +35 and +100 after HSCT. In Part II, for the immunophenotypic evaluation, eight patients with systemic cGVHD were selected and the expression of IL-17A was evaluated. We found association between recipient AA genotype with systemic cGVHD. No association was observed between IL-17A levels and cGVHD. Lower IL-17A levels in the blood were associated with AA genotype. In flow cytometry analysis, decreased expression of IL-17A was observed in patients with cGVHD after stimulation. In conclusion, IL-17A may have an important role in the development of systemic cGVHD

Cognitive Status Correlates with CXCL10/IP-10 Levels in Parkinson’s Disease

Cognitive impairment and depressive symptoms are of great interest in Parkinson’s disease (PD), since they are very common and lead to increased disability with poor quality of life. Inflammatory mechanisms have been implicated in PD and its nonmotor symptoms. In the current pilot study, we aimed to evaluate plasma levels of chemokines in PD patients and to analyze the putative association of chemokines with depressive symptoms and cognitive performance. We hypothesized that higher chemokines levels are associated with worse cognitive performance and increased depressive symptoms in PD. For this purpose, 40 PD patients and 25 age- and gender-matched controls were subjected to a clinical evaluation including cognitive and mood tests. Peripheral blood was drawn and plasma levels of CCL2/MCP-1, CCL11/eotaxin, CCL24/eotaxin-2, and CXCL10/IP-10 were measured by enzyme-linked immunosorbent assay. PD patients and control individuals presented comparable plasma concentrations of all the evaluated chemokines. In PD patients, CXCL10/IP-10 plasma levels correlated positively with Hoehn and Yahr staging scale. In addition, the higher CXCL10/IP-10 levels, the worse performance on cognitive tests. Although there was no significant difference between PD patients and control individuals regarding chemokines levels, our preliminary results showed that CXCL10/IP-10 may be associated with cognitive status in PD

Recombinant vaccines of a CD4+ T-cell epitope promote efficient control of Paracoccidioides brasiliensis burden by restraining primary organ infection.

Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+ T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay. The highly virulent Pb18 yeast strain was used to challenge our vaccine candidates. Fungal challenge evoked robust P10-specific memory CD4+ T cells secreting protective Th-1 cytokines in most groups of immunized mice. Furthermore, the highest level of fungal burden control was achieved when rAdPbT was inoculated in a homologous prime-boost regimen, with 10-fold less CFU recovering than in non-vaccinated mice. Systemic Pb18 spreading was only prevented when rAdPbT was previously inoculated. In summary, we present here VLP/P10 formulations as vaccine candidates against PCM, some of which have demonstrated for the first time their ability to prevent progression of this pernicious fungal disease, which represents a significant social burden in developing countries