RESUMO

BACKGROUND: Evidence describing the types and annual costs of biological treatments for psoriasis in Latin America is scarce. This study aimed to estimate the frequency of use and costs of biologic therapy for psoriasis in Colombia in 2019. METHODS: This secondary data analysis uses the International Classification of Diseases terms associated with psoriasis, excluding those related to psoriatic arthritis, based on data from the registry of the Colombian Ministry of Health. We estimated the prevalence of psoriasis per 100,000 inhabitants; then, we retrieved the frequency of use of biologic therapy in patients with psoriasis and estimated the cost per year of each and overall therapies in 2019 in US dollars (USD). RESULTS: There were 100,823 patients with psoriasis in Colombia in 2019, which amounts to a prevalence of 0.2% in the general population. Of those patients, 4.9% received biologic therapy, most frequently males (60%). The most commonly used biological therapies for psoriasis in Colombia in 2019 were ustekinumab (35.2%), with an annual cost per patient of $12,880 USD; adalimumab (26%), with a yearly cost per patient of $7130 USD; and secukinumab (19.8%), with an annual cost per patient of $6825 USD. CONCLUSION: This is the first study to describe the use and cost of biological therapy for psoriasis in Colombia. It provides valuable cost-awareness information for the Colombian health system.

Assuntos

Adalimumab , Terapia Biológica , Psoríase , Humanos , Psoríase/economia , Psoríase/tratamento farmacológico , Psoríase/terapia , Psoríase/epidemiologia , Colômbia/epidemiologia , Masculino , Feminino , Adalimumab/uso terapêutico , Adalimumab/economia , Adulto , Pessoa de Meia-Idade , Terapia Biológica/economia , Terapia Biológica/estatística & dados numéricos , Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Ustekinumab/uso terapêutico , Ustekinumab/economia , Prevalência , Adulto Jovem , Fármacos Dermatológicos/economia , Fármacos Dermatológicos/uso terapêutico , Idoso , Sistema de Registros/estatística & dados numéricos , Custos de Medicamentos/estatística & dados numéricos , Custos de Cuidados de Saúde/estatística & dados numéricos , Adolescente

RESUMO

BACKGROUND: Psoriasis significantly burdens patients' lives, but there is limited data on this in Brazil. METHODS: Between May 2022 and January 2023, we conducted a cross-sectional online survey of 563 Brazilian residents aged ≥18 years who had been diagnosed with psoriasis. Spearman's correlation (r) was used to test the correlation between self-assessed disease severity (Simplified Psoriasis Index [saSPI] extent score; range 0 [clear/minor] to 40 [widespread/severe]) and health-related quality of life (QoL, score of 1 means perfect health) and capability (ICECAP-A: score of 1 means full capability) measures. Multivariable linear regression was used to identify predictors of QoL and capability. A thematic analysis examined the free-text responses and identified common themes. RESULTS: The mean age of participants was 42.1 ± 12.4 years, and over half had at least one other long-term condition. The mean QoL score was 0.59 ± 0.25, and the mean capability score was 0.71 ± 0.21. At the time of survey completion, over 80% of respondents reported some level of pain and/or discomfort, and 86% reported feeling anxious and/or depressed. The mean self-assessed saSPI was 7.8 ± 8.6, which negatively correlated with health-related QoL (r = -0.49, P < 0.05) and capability (r = -0.44, P < 0.05). Significant predictors of poorer QoL and reduced capability included high saSPI, number of psoriasis flares and comorbidities, female gender, Black ethnicity, and employment status (unemployed, long-term sick). Frequently reported areas that impacted patients were social stigma/prejudice, powerlessness, lack of education and public awareness, and difficulty obtaining appropriate care/treatment. CONCLUSIONS: We found that the clinical manifestations, severity, and associated comorbidities of psoriasis negatively impacted health-related QoL and capability, along with feelings of stigmatization and barriers to specialist treatment. This highlights the need for better access to care and awareness of the disease to improve the lives of people living with psoriasis in Brazil.

RESUMO

Background: Uncaria tomentosa (Willd. ex Schult.) DC. (Rubiaceae) is traditionally used by Amazonian indigenous groups to treat inflammatory diseases. To date, there are no systematic reviews and meta-analyses on the use of U. tomentosa for inflammation control in animals supporting the traditional knowledge about this species. This study was conducted to evaluate the effect of U. tomentosa extracts in modulating inflammatory mediators and to determine which types of inflammatory diseases can be treated by this species. Methods: We conducted a systematic review and meta-analysis of preclinical studies published before 26 July 2023, identified in PubMed, Embase, and Scopus. Four independent reviewers extracted the data and assessed the risks of bias. The effects of U. tomentosa on inflammatory diseases and the inflammatory mediators involved were extracted from the studies. Standardized mean differences (SMD) and 95% confidence intervals (95%CI) of the outcomes were estimated. The meta-analyses were conducted using RevMan 5.4 (Cochrane Collaboration). This protocol was registered in PROSPERO (CRD42023450869). Results: Twenty-four of 523 studies were included. U. tomentosa extracts decreased the cytokines interleukin (IL)-6 (SMD: -0.72, 95%CI: -1.15, -0.29, p = 0.001) and transcription factor nuclear factor kappa-B (NF-κB) (SMD: -1.19, 95%CI: -1.89, -0.48, p = 0.001). However, the extracts did not significantly alter IL-1 (SMD: -0.16, 95%CI: -0.87, +0.56, p = 0.67), IL-10 (SMD: -0.05, 95%CI:-0.35, 0.45, p = 0.80), or tumor necrosis factor-alpha (TNF-α) levels (SMD: 0.18, 95%CI: -0.25, 0.62, p = 0.41). Conclusion: Many extracts of stem bark, roots, and leaves of U. tomentosa, mostly aqueous and hydroethanolic, exhibited anti-inflammatory and/or immunomodulatory activities and low toxicity. The extracts decreased NF-κB and IL-6. These findings suggest that this species has the potential to treat inflammatory diseases in which these markers are increased, according to the ethnopharmacological use. These activities are not related to a specific class of compounds.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=450869, Identifier CRD42023450869.

RESUMO

The notion that viruses played a crucial role in the evolution of life is not a new concept. However, more recent insights suggest that this perception might be even more expansive, highlighting the ongoing impact of viruses on host evolution. Endogenous retroviruses (ERVs) are considered genomic remnants of ancient viral infections acquired throughout vertebrate evolution. Their exogenous counterparts once infected the host's germline cells, eventually leading to the permanent endogenization of their respective proviruses. The success of ERV colonization is evident so that it constitutes 8% of the human genome. Emerging genomic studies indicate that endogenous retroviruses are not merely remnants of past infections but rather play a corollary role, despite not fully understood, in host genetic regulation. This review presents some evidence supporting the crucial role of endogenous retroviruses in regulating host genetics. We explore the involvement of human ERVs (HERVs) in key physiological processes, from their precise and orchestrated activities during cellular differentiation and pluripotency to their contributions to aging and cellular senescence. Additionally, we discuss the costs associated with hosting a substantial amount of preserved viral genetic material.

Assuntos

Retrovirus Endógenos , Retrovirus Endógenos/genética , Retrovirus Endógenos/fisiologia , Humanos , Animais , Diferenciação Celular , Interações Hospedeiro-Patógeno/genética , Interações entre Hospedeiro e Microrganismos/genética , Infecções por Retroviridae/virologia , Senescência Celular/genética , Provírus/genética , Provírus/fisiologia , Evolução Molecular

RESUMO

OBJECTIVE: To evaluate the effects of magnifying the damage caused by obesity induced by monosodium glutamate, using a model of maternal periodontitis, on the structure of the anterior tibialis muscle of the offspring. MATERIALS AND METHODS: Twenty-four female Wistar rats were divided into four experimental groups: control (n = 6), obese (n = 6), control with periodontitis (n = 6) and obese with periodontitis (n = 6). At 78 days of life, the rats were mated with males without any experimental intervention. The offspring of these rats (n = 1/L), at 120 days of life, were weighed and measured, then euthanized. Plasma was collected for analysis of cytokines IL-6, IL-10, IL-17 and TNF-α. Adipose tissues were collected and weighed, and the anterior tibial muscle was designated for histomorphological analyses (n = 6/group). RESULTS: Monosodium glutamate offspring showed significant muscle changes, such as a reduction in the size of fibres and neuromuscular junctions, and an increase in the nucleus and capillaries. However, all these changes were more expressed in monosodium glutamate-obese with periodontitis offspring. CONCLUSION: This leads us to suggest a magnifying effect promoted by periodontitis to the damage already well described by monosodium glutamate-obesity, determined by low-intensity inflammation, causing greater muscle damage.

Assuntos

Músculo Esquelético , Obesidade , Periodontite , Ratos Wistar , Glutamato de Sódio , Animais , Glutamato de Sódio/efeitos adversos , Feminino , Ratos , Músculo Esquelético/patologia , Gravidez , Obesidade/complicações , Obesidade/metabolismo , Periodontite/patologia , Periodontite/metabolismo , Periodontite/complicações , Masculino , Efeitos Tardios da Exposição Pré-Natal , Fator de Necrose Tumoral alfa/metabolismo , Citocinas/metabolismo

RESUMO

The heat shock response (HSR) is a crucial biochemical pathway that orchestrates the resolution of inflammation, primarily under proteotoxic stress conditions. This process hinges on the upregulation of heat shock proteins (HSPs) and other chaperones, notably the 70 kDa family of heat shock proteins, under the command of the heat shock transcription factor-1. However, in the context of chronic degenerative disorders characterized by persistent low-grade inflammation (such as insulin resistance, obesity, type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases) a gradual suppression of the HSR does occur. This work delves into the mechanisms behind this phenomenon. It explores how the Western diet and sedentary lifestyle, culminating in the endoplasmic reticulum stress within adipose tissue cells, trigger a cascade of events. This cascade includes the unfolded protein response and activation of the NOD-like receptor pyrin domain-containing protein-3 inflammasome, leading to the emergence of the senescence-associated secretory phenotype and the propagation of inflammation throughout the body. Notably, the activation of the NOD-like receptor pyrin domain-containing protein-3 inflammasome not only fuels inflammation but also sabotages the HSR by degrading human antigen R, a crucial mRNA-binding protein responsible for maintaining heat shock transcription factor-1 mRNA expression and stability on heat shock gene promoters. This paper underscores the imperative need to comprehend how chronic inflammation stifles the HSR and the clinical significance of evaluating the HSR using cost-effective and accessible tools. Such understanding is pivotal in the development of innovative strategies aimed at the prevention and treatment of these chronic inflammatory ailments, which continue to take a heavy toll on global health and well-being.

Assuntos

Diabetes Mellitus Tipo 2 , Humanos , Fatores de Transcrição de Choque Térmico , Inflamassomos/metabolismo , Inflamassomos/farmacologia , Resposta ao Choque Térmico , Proteínas de Choque Térmico/metabolismo , Inflamação , RNA Mensageiro , Proteínas NLR/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo

RESUMO

INTRODUCCIÓN: La seroprevalencia del SARS-CoV-2 en las enfermedades inflamatorias inmunomediadas (IMID) sigue siendo fuente de controversia. OBJETIVO: Comparar la seroprevalencia de anticuerpos (Ac) anti SARS-CoV-2 en pacientes con IMID en tratamientos con fármacos antirreumáticos modificadores de la enfermedad biológicos (FAMEb) o sintéticos dirigidos (FAMEsd) frente a un grupo de personas sin IMID. MÉTODOS: Estudio de pacientes con IMID y tratamientos con FAMEb y FAMEsd y de individuos sin IMID. Mediante la técnica de inmunoensayo por quimioluminiscencia indirecta, se determinaron las serologías IgG frente al SARS-CoV-2 entre octubre/2020 y mayo/2021. RESULTADOS: Se estudiaron 1.100 sujetos, 550 pacientes con IMID y 550 personas sin IMID. Se observó una seroprevalencia de 16% (88/550) en los pacientes frente a 19,3% (106/550) en el grupo de personas sin IMID, sin significación estadística (OR 0,790 [IC 95% 0,558-1,118]). Comparando los tratamientos con FAMEb o FAMEsd, se observó una tendencia a una menor seroprevalencia con rituximab, en relación con los individuos sin IMID (OR 0,296 [IC 95% 0,0871,007]). Asimismo, se encontró menor seroprevalencia en los pacientes que además de su FAMEb recibían tratamiento con metotrexato, en comparación con el grupo de personas sin IMID (OR 0,432 [IC 95% 0,223-0,835]). CONCLUSIONES: Las IMID en tratamiento con FAMEb o FAMEsd no influyen en la seroprevalencia frente al SARS-CoV-2 de los pacientes. El tratamiento concomitante con metotrexato disminuye de forma significativa la seroprevalencia en estos pacientes.

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BACKGROUND: The seroprevalence of SARS-CoV-2 in immunemediated inflammatory diseases (IMID) remains controversial. AIM: To compare the seroprevalence of antibodies (Ab) to SARS-CoV-2 in patients with IMID receiving treatment with biological diseasemodifying antirheumatic drugs (bDMARD) or targeted synthetic (tsDMARD) versus a group of people without IMID. METHODS: Study of patients with IMID and treatments with bDMARD and tsDMARD and individuals without IMID. IgG serology against SARS-CoV-2 was measured using the two-step sandwich immunoassay technique by indirect chemiluminescence between October 2020 and May 2021. RESULTS: A total of 1100 subjects were studied, 550 patients with IMID and 550 persons without IMID. A seroprevalence of 16% (88/550) was observed in patients versus 19.3% (106/550) in the group of people without IMID, without statistical significance (OR 0.790 [95% CI 0.558-1.118]). Comparing the treatments with bD- MARD or tsDMARD, there was a tendency to lower seroprevalence with rituximab, in relation to individuals without IMID (OR 0.296 [95% CI 0.087-1.007]). In addition, lower seroprevalence was found in patients who received methotrexate treatment in addition to their bDMARD, compared to the group of individuals without IMID (OR 0.432 [95% CI 0.223-0.835]). CONCLUSIONS: IMIDs in treatment with bDMARDs or tsDMARDs do not influence the seroprevalence against SARS-CoV-2 in patients. Concomitant treatment with methotrexate significantly decreased seroprevalence in these patients.

Assuntos

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , COVID-19/epidemiologia , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/tratamento farmacológico , Doenças do Sistema Imunitário/epidemiologia , Terapia Biológica , Imunoglobulina G/imunologia , Estudos Soroepidemiológicos , Prevalência , Estudos Transversais , Antirreumáticos/uso terapêutico , Medicamentos Biossimilares , COVID-19/imunologia

RESUMO

Inflammation is a protective response of the body potentially caused by microbial, viral, or fungal infections, tissue damage, or even autoimmune reactions. The cardinal signs of inflammation are consequences of immunological, biochemical, and physiological changes that trigger the release of pro-inflammatory chemical mediators at the local of the injured site thus, increasing blood flow, vascular permeability, and leukocyte recruitment. The aim of this study is to give an overview of the inflammatory process, focusing on chemical mediators. The literature review was based on a search of journals published between the years 2009 and 2023, regarding the role of major chemical mediators in the inflammatory process and current studies in pathogenesis, diagnosis, and therapy. Some of the recent contributions in the study of inflammatory pathologies and their mediators, including cytokines and chemokines, the kinin system, free radicals, nitric oxide, histamine, cell adhesion molecules, leukotrienes, prostaglandins and the complement system and their role in human health and chronic diseases.

Assuntos

Inflamação , Leucócitos , Humanos , Inflamação/patologia , Citocinas , Prostaglandinas , Histamina , Mediadores da Inflamação/metabolismo

RESUMO

BACKGROUND AND AIMS: Systemic inflammatory diseases could act as an unfavorable condition in which epicardial adipose tissue (EAT) becomes harmful to cardiovascular health. The objectives were: (a) to quantitatively compare the presence of EAT between patients with systemic inflammatory diseases and controls; (b) to analyze the association between EAT and subclinical atheromatosis in individuals with systemic inflammatory diseases. METHODS: Studies that have quantified EAT in a population with systemic inflammatory diseases compared to a control group, or that describe the association between EAT and the presence of subclinical atheromatosis in patients with systemic inflammatory diseases were included. A quantitative analysis was performed for the first objective. This systematic review was performed according to PRISMA guidelines. RESULTS: Twenty-one studies including 1448 patients with systemic inflammatory diseases, were considered eligible for this study. Patients with systemic inflammatory disease have a higher volume (MD: 10.4cm3 [1.8-19.1]; p<0.01), higher thickness (MD: 1.0mm [0.8-1.2]; p<0.01), and a statistically non-significant higher area (MD: 3.1cm2 [1.0-5.2]; p=0.46) of EAT compared to the control group. Most studies reported a significant association between EAT and subclinical atheromatosis in patients with different systemic inflammatory diseases. CONCLUSION: This study demonstrated that EAT is increased in patients with systemic inflammatory diseases compared with healthy controls, and that EAT measurement is closely correlated with subclinical atherosclerosis in these patients. The causality of this association should be tested in prospective studies.

Assuntos

Aterosclerose , Pericárdio , Humanos , Estudos Prospectivos , Pericárdio/diagnóstico por imagem , Aterosclerose/etiologia , Tecido Adiposo/diagnóstico por imagem

RESUMO

Objective: Assess the perceived protection afforded by a range of COVID-19 vaccines in immune-mediated inflammatory diseases patients previously vaccinated against SARS-CoV-2. Study design: Survey. Methods: On-line cross-sectional survey aimed at evaluating the perceived protection (and its determinants) afforded by a range of COVID-19 vaccines among immune-mediated inflammatory diseases previously vaccinated for COVID-19. Results: Out of 493 eligible respondents who lived in Brazil, 397 (80.5%) were confident that their primary vaccination series would protect them against severe COVID-19. In multivariate analysis, only overlapping immune-mediated inflammatory diseases remained (negatively) associated with the perception of protection. Conclusions: No influence was found between COVID-19 vaccine types and the perception of protection after initial vaccinations.

RESUMO

Leukotrienes (LTs) are derived from arachidonic acid metabolism by the 5-lipoxygenase (5-LO) enzyme. The production of LTs is stimulated in the pathogenesis of rheumatoid arthritis (RA), osteoarthritis, and periodontitis, with a relevant contribution to bone resorption. However, its role in bone turnover, particularly the suppression of bone formation by modulating the function of osteoclasts and osteoblasts, remains unclear. We investigated the effects of LTs on bone metabolism and their impact on osteogenic differentiation and osteoclastogenesis using a 5-LO knockout (KO) mouse model. Results from micro-computed tomography (µCT) analysis of femur from 8-week-old 5-LO-deficient mice showed increased cortical bone and medullary region in females and males and decreased trabecular bone in females. In the vertebra, we observed increased marrow area in both females and males 5-LO KO and decreased trabecular bone only in females 5-LO KO. Immunohistochemistry (IHC) analysis showed higher levels of osteogenic markers tissue-nonspecific alkaline phosphatase (TNAP) and osteopontin (OPN) and lower expression of osteoclastogenic marker tartrate-resistant acid phosphatase (TRAP) in the femurs of 5-LO KO mice versus wild-type (WT). Alkaline phosphatase activity and mineralization assay results showed that the 5-LO absence enhances osteoblasts differentiation and mineralization but decreases the proliferation. Alkaline phosphatase (ALP), Bglap, and Sp7 gene expression were higher in 5-LO KO osteoblasts compared to WT cells. Eicosanoids production was higher in 5-LO KO osteoblasts except for thromboxane 2, which was lower in 5-LO-deficient mice. Proteomic analysis identified the downregulation of proteins related to adenosine triphosphate (ATP) metabolism in 5-LO KO osteoblasts, and the upregulation of transcription factors such as the adaptor-related protein complex 1 (AP-1 complex) in long bones from 5-LO KO mice leading to an increased bone formation pattern in 5-LO-deficient mice. We observed enormous differences in the morphology and function of osteoclasts with reduced bone resorption markers and impaired osteoclasts in 5-LO KO compared to WT osteoclasts. Altogether, these results demonstrate that the absence of 5-LO is related to the greater osteogenic profile. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Assuntos

Reabsorção Óssea , Osteogênese , Masculino , Feminino , Camundongos , Animais , Fosfatase Alcalina/metabolismo , Microtomografia por Raio-X , Proteômica , Osteoclastos/metabolismo , Osteoblastos/metabolismo , Reabsorção Óssea/patologia , Diferenciação Celular , Camundongos Knockout , Leucotrienos/metabolismo , Leucotrienos/farmacologia

RESUMO

Inflammatory bowel diseases (IBD), including ulcerative colitis, are chronic and idiopathic inflammations of the gastrointestinal tract. A disruption of the epithelial barrier and an imbalance between Th1 and Th2 subsets are associated with the onset and progression of these diseases. Mesenchymal stromal cells (MSC) are a promising therapy for IBD. However, cell-tracking studies have shown that intravenously infused MSC localize to the lungs and present short-term survival. To reduce practical complexities arising from living cells, we generated membrane particles (MP) from MSC membranes, which possess some of the immunomodulatory properties of MSC. This study investigated the effect of MSC-derived MP and conditioned media (CM) as cell-free therapies in the dextran sulfate sodium (DSS)-induced colitis model. Acute colitis was induced in C57BL/6 mice by oral administration of 2% DSS in drinking water ad libitum from days 0 to 7. Mice were treated with MP, CM, or living MSC on days 2 and 5. Our findings revealed that MP, CM, and living MSC ameliorated DSS-induced colitis by reducing colonic inflammation, the loss of colonic goblet cells, and intestinal mucosa permeability, preventing apoptosis of damaged colonic cells and balancing Th1 and Th2 activity. Therefore, MSC-derived MP have high therapeutic potential for treating IBD, overcoming the deficiencies of living MSC therapy, and opening novel frontiers in inflammatory diseases medicine.

Assuntos

Colite , Doenças Inflamatórias Intestinais , Células-Tronco Mesenquimais , Animais , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Sulfato de Dextrana , Doenças Inflamatórias Intestinais/terapia , Colite/terapia , Colite/tratamento farmacológico , Colo , Inflamação , Meios de Cultivo Condicionados/farmacologia , Citocinas/uso terapêutico

RESUMO

Abstract Objective: To present an updated review of recommendations for the vaccination of children with immune-mediated diseases, with an emphasis on rheumatic and inflammatory diseases. Source of data: Studies published in the PubMed and Scielo databases between 2002 and 2022, Guidelines of Brazilian Scientific Societies, Manuals and Technical Notes of the Ministry of Health of Brazil, on current immunization schedules for special populations. Data synthesis: Immunosuppressive drugs and biological agents reduce the immunogenicity of vaccines and favor susceptibility to infections. The safety and efficacy of immunogens are important points for vaccination in children with immune-mediated diseases. The safety threshold of a vaccine applied to immunocompromised individuals can be reduced when compared to healthy individuals. Very often, the recommendations for the immunization of children with immunemediated diseases follow the recommendations for immunocompromised patients. Vaccination against COVID-19, on the other hand, should ideally occur when the disease is stabilized and in the absence of a low degree of immunosuppression. The patients should be informed about the possibility that the immunization may fail during treatment with immunosuppressants. Specific vaccination schedules should be considered to ensure better protection. Conclusions: Recent studies have allowed updating the recommendations on the safety and immunogenicity of vaccination in children with immune-mediated diseases, especially for live attenuated vaccines. There is a scarcity of data on the safety and efficacy of COVID-19 vaccines in patients, particularly pediatric patients, with rheumatic diseases. The completion of ongoing studies is expected to help guide recommendations on COVID-19 vaccines in this group of patients.

RESUMO

Asthma is the most common chronic lung disease, with increasing morbidity and mortality worldwide. Accumulation of peribronchial leukocytes is the hallmark of asthma, in particular, eosinophils, which have been reported as the primary cell associated with the induction of airway hyperresponsiveness. Continued exacerbation and accumulation of other leukocytes, such as neutrophils, Th1, and Th17 cells correlate with many of the long-term effects of asthma, such as airway remodeling. We have patented the TnP family of synthetic cyclic peptides, which is in the preclinical phase of developmental studies for chronic inflammatory diseases. The aim of this work was to investigate whether TnP could show anti-inflammatory activity in a murine model of asthma that includes a mixed phenotype of eosinophilic and neutrophilic inflammation. For this, Balb/c mice, sensitized with OVA and exposed to 1% challenge with OVA aerosol, were submitted to prophylactic treatment, receiving TnP at 0.3 mg/kg orally, 1 h before each challenge. We found that sensitized mice challenged with OVA and treated with TnP showed no airway hyperreactivity or lung remodeling. TnP acts systemically in secondary lymphoid organs and locally in the lung, inhibiting the production of Th2/Th17 cytokines. Furthermore, TnP prevented the infiltration of eosinophils and neutrophils in the BAL and lung tissue, inhibited the production of IgE/IgG1, prevented hyperplasia of mucus-producing cells, and decreased the thickening and deposition of sub-epithelial collagen. Our results showed TnP as a candidate molecule for the treatment of airway remodeling associated with inflammatory diseases, such as asthma.

Assuntos

Remodelação das Vias Aéreas , Asma , Animais , Camundongos , Líquido da Lavagem Broncoalveolar , Asma/tratamento farmacológico , Citocinas , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico

RESUMO

BACKGROUND: Gout is the most common inflammatory rheumatic disease and elevated levels of serum urate (SU) are the main cause for its development. Major histocompatibility complex class 1 (MHC-1) plays an important role in the development of multiple inflammatory diseases; however, there is little evidence of its involvement in gout. The present study focused on evaluating the association of the rs4349859 and rs116488202 single nucleotide polymorphisms (SNPs) close to the MHC-1 region in patients with gout. METHODS AND RESULTS: One hundred and seventy-six individuals of Mexican origin were included, of which 81 were patients with primary gout and 95 were healthy controls. The rs4349859 and rs116488202 SNPs were genotyped using TaqMan probes by allelic discrimination by real-time PCR. Serum concentrations of biochemical parameters were measured with enzymatic methods. Descriptive statistics were applied and P-values < 0.05 were considered significant. It was observed that the rs4349859 and rs116488202 SNPs showed significant association with the risk of gout (OR = 146, 95%CI = 44.8-480.2, P < 0.01; OR = 2885, 95%CI = 265-31398, P < 0.01, respectively). Our results also showed significantly higher serum SU levels in gout patients with respect to controls (P < 0.01) in the carriers of the GA genotype compared with the GG genotype of the rs4349859 variant, and in the carriers of the CT genotype compared with the CC genotype of the rs116488202 variant. CONCLUSION: The study revealed that rs4349859 and rs116488202 SNPs close to MHC-I region confers strong susceptibility to gout in Mexican population, and the heterozygous genotypes of both were associated with higher levels of SU.

Assuntos

Gota , Ácido Úrico , Humanos , Gota/genética , Genótipo , Polimorfismo de Nucleotídeo Único/genética , Heterozigoto , Predisposição Genética para Doença

RESUMO

Curcumin (CUR) is a polyphenol extracted from the rhizome of Curcuma longa that possesses potent anti-inflammatory and antioxidant potential. Despite CUR's numerous beneficial effects on human health, it has limitations, such as poor absorption. Nano-based drug delivery systems have recently been applied to improve CUR's solubility and bioavailability and potentialize its health effects. This review investigated the effects of different CUR-based nanomedicines on inflammatory and immunomodulated diseases. PUBMED, EMBASE, COCHRANE, and GOOGLE SCHOLAR databases were searched, and the Scale for Assessment of Narrative Review Articles (SANRA) was used for quality assessment and PRISMA guidelines. Overall, 66 studies were included comprising atherosclerosis, rheumatoid arthritis (RA), Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), inflammatory bowel diseases (IBD), psoriasis, liver fibrosis, epilepsy, and COVID-19. The available scientific studies show that there are many known nanoformulations with curcumin. They can be found in nanosuspensions, nanoparticles, nanoemulsions, solid lipid particles, nanocapsules, nanospheres, and liposomes. These formulations can improve CUR bioavailability and can effectively be used as adjuvants in several inflammatory and immune-mediated diseases such as atheroma plaque formation, RA, dementia, AD, PD, MS, IBD, psoriasis, epilepsy, COVID-19, and can be used as potent anti-fibrotic adjuvants in fibrotic liver disease.

RESUMO

OBJECTIVE: To present an updated review of recommendations for the vaccination of children with immune-mediated diseases, with an emphasis on rheumatic and inflammatory diseases. SOURCE OF DATA: Studies published in the PubMed and Scielo databases between 2002 and 2022, Guidelines of Brazilian Scientific Societies, Manuals and Technical Notes of the Ministry of Health of Brazil, on current immunization schedules for special populations. DATA SYNTHESIS: Immunosuppressive drugs and biological agents reduce the immunogenicity of vaccines and favor susceptibility to infections. The safety and efficacy of immunogens are important points for vaccination in children with immune-mediated diseases. The safety threshold of a vaccine applied to immunocompromised individuals can be reduced when compared to healthy individuals. Very often, the recommendations for the immunization of children with immune-mediated diseases follow the recommendations for immunocompromised patients. Vaccination against COVID-19, on the other hand, should ideally occur when the disease is stabilized and in the absence of a low degree of immunosuppression. The patients should be informed about the possibility that the immunization may fail during treatment with immunosuppressants. Specific vaccination schedules should be considered to ensure better protection. CONCLUSIONS: Recent studies have allowed updating the recommendations on the safety and immunogenicity of vaccination in children with immune-mediated diseases, especially for live attenuated vaccines. There is a scarcity of data on the safety and efficacy of COVID-19 vaccines in patients, particularly pediatric patients, with rheumatic diseases. The completion of ongoing studies is expected to help guide recommendations on COVID-19 vaccines in this group of patients.

Assuntos

Vacinas contra COVID-19 , COVID-19 , Criança , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Vacinação , Vacinas

RESUMO

Periodontitis is a chronic non-communicable disease caused by a dysbiotic microbiota. Pathogens can spread to the bloodstream, colonize other tissues or organs, and favor the onset of other pathologies, such as Alzheimer's disease (AD). Pathogens could permanently or transiently colonize the brain and induce an immune response. Thus, we analyzed the evidence combining oral bacteria's detection in the brain, both in animals and humans affected with AD. This systematic review was carried out following the PRISMA guideline. Studies that detected oral bacteria at the brain level were selected. The search was carried out in the Medline, Latindex, SciELO, and Cochrane Library databases. SYRCLE tool and Newcastle-Ottawa Scale were used for the risk of bias assessment. 23 studies were selected according to the eligibility criteria. Infection with oral pathogens in animals was related to developing neuropathological characteristics of AD and bacteria detection in the brain. In patients with AD, oral bacteria were detected in brain tissues, and increased levels of pro-inflammatory cytokines were also detected. There is evidence of a microbiological susceptibility to develop AD when the most dysbiosis-associated oral bacteria are present. The presence of bacteria in the brain is related to AD's pathological characteristics, suggesting an etiological oral-brain axis.

Assuntos

Doença de Alzheimer , Microbiota , Periodontite , Animais , Humanos , Periodontite/microbiologia , Bactérias , Encéfalo , Disbiose/complicações

RESUMO

Asthma is the most common chronic lung disease, with increasing morbidity and mortality worldwide. Accumulation of peribronchial leukocytes is the hallmark of asthma, in particular, eosinophils, which have been reported as the primary cell associated with the induction of airway hyperresponsiveness. Continued exacerbation and accumulation of other leukocytes, such as neutrophils, Th1, and Th17 cells correlate with many of the long-term effects of asthma, such as airway remodeling. We have patented the TnP family of synthetic cyclic peptides, which is in the preclinical phase of developmental studies for chronic inflammatory diseases. The aim of this work was to investigate whether TnP could show anti-inflammatory activity in a murine model of asthma that includes a mixed phenotype of eosinophilic and neutrophilic inflammation. For this, Balb/c mice, sensitized with OVA and exposed to 1% challenge with OVA aerosol, were submitted to prophylactic treatment, receiving TnP at 0.3 mg/kg orally, 1 h before each challenge. We found that sensitized mice challenged with OVA and treated with TnP showed no airway hyperreactivity or lung remodeling. TnP acts systemically in secondary lymphoid organs and locally in the lung, inhibiting the production of Th2/Th17 cytokines. Furthermore, TnP prevented the infiltration of eosinophils and neutrophils in the BAL and lung tissue, inhibited the production of IgE/IgG1, prevented hyperplasia of mucus-producing cells, and decreased the thickening and deposition of sub-epithelial collagen. Our results showed TnP as a candidate molecule for the treatment of airway remodeling associated with inflammatory diseases, such as asthma.