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1.
Public Health ; 227: 16-23, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38103272

RESUMO

OBJECTIVES: To analyse spatial-temporal changes and spatial association of homicide rates with violence, sociodemographic, public security and human rights indicators in Brazilian municipalities. STUDY DESIGN: An ecological study using homicide estimates from the Global Burden of Disease and population from the Brazilian Ministry of Health, 2000 to 2018. The explanatory variables come from the systems of mortality, notifications of violence and security, and the Brazilian Institute of Geography and Statistics. METHODS: Moran indices and maps identified clusters of high and low risk for homicides in three trienniums (p < 0.05). Multivariate linear and spatial regressions estimated explanatory factors' contributions for the last triennium. RESULTS: Municipalities with high rates of homicides (>34/100,000) doubled, reaching 21.5 %. Those rates were concentrated in big cities, and increased in smaller municipalities. Increases in critical areas were found in the Northeast and North regions: more than 40 % in the states of Sergipe, Bahia, Ceará, Rio Grande do Norte and Roraima. Decreases occurred in the Southeast and Midwest regions: more than 35 % in São Paulo and Rio de Janeiro states. The spatial model, with an 18.9 % higher R2 (0.706), showed a positive association for records of violence, Blacks, low-level education, municipalities >50,000 inhabitants and municipalities with homicide and municipal police. CONCLUSIONS: An increase in and the interiorisation of homicide risk areas in Brazil was observed, with displacement among regions (from the Southeast to the North/Northeast). The level of violence was the main explanatory factor for homicides. Territorial space proved to be important to understand and prevent lethal crime.


Assuntos
Carga Global da Doença , Homicídio , Humanos , Cidades/epidemiologia , Brasil/epidemiologia , Violência
2.
J Reprod Immunol ; 149: 103468, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35007917

RESUMO

During pregnancy, the maternal immune system is challenged to tolerate a semi-allogenic fetus. A shift toward a tolerogenic profile is essential to ensure a healthy fetal and placental development. One of the most important mechanisms involved in the maternal immune tolerance towards the fetal antigens is expressed in the activity of the regulatory T (Treg) and Th17 cells. The behavior and equilibrium of these two T lymphocyte populations were rarely studied in normal healthy pregnancies through the beginning of gestation to the postpartum period. We conducted a prospective longitudinal observational study where peripheral blood lymphocyte subsets were analyzed in each trimester of pregnancy and postpartum period in a group of healthy pregnant women. Our study observed a consistent reduction in peripheric Treg cell count through all pregnancy while the Th17 cell count remained stable. The Th17/Treg ratio increases significantly throughout pregnancy to the postpartum period. These changes could be justified by the migration of the immunotolerant Treg cells to the maternal decidua and lead to the establishment of a systemic pro-inflammatory profile by the end of pregnancy. This data could explain why systemic syndromes like preeclampsia develop in susceptible women during the second half of pregnancy or why many autoimmune disorders flourish in the first weeks postpartum.


Assuntos
Placenta/imunologia , Gravidez/imunologia , Gestantes , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Adulto , Feminino , Voluntários Saudáveis , Humanos , Tolerância Imunológica , Imunidade Celular , Estudos Prospectivos , Adulto Jovem
3.
Public Health ; 201: 78-88, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34798327

RESUMO

OBJECTIVE: To analyze the literature to determine whether autohemotherapy has any effect either clinically or on the immune system on viral diseases on the last ten years. STUDY DESIGN: Systematic review. METHODS: Searches from the year 2010, with at least 5 patients were conducted in PubMed/MEDLINE, Embase, Scopus, Cochrane, LILACS, SciELO, and Web of Science databases. Hand searches were performed in systematic reviews and literature reviews related to autohemotherapy. Unpublished manuscripts were hand-searched in specialized journals. RESULTS: Eight articles were included. Hepatitis B virus, hepatitis C virus, and Coronavirus were evaluated. Autohemotherapy had good results in hepatitis C, hepatitis B, and Coronavirus. CONCLUSION: Autohemotherapy is a safe practice that improves symptoms in the treatment of hepatitis B virus, hepatitis C virus, and Coronavirus. It is necessary to perform more prospective comparative studies with homogeneous protocols.


Assuntos
Infecções por Coronavirus , Viroses , Humanos , Estudos Prospectivos , Viroses/terapia
4.
Curr Pharm Des ; 27(26): 2956-2965, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33106139

RESUMO

BACKGROUND: Cancer is a complex, multifactorial disease, and a major public health problem, as it is a leading cause of morbidity and mortality worldwide. Although treatments have significantly improved, still more effective drugs are searched. One source for these drugs is natural products (NPs). One NP that has shown anticancer activity is Limonene. However, the mechanisms of limonene's antiproliferative, anticancer and antineoplastic activity are not fully understood. OBJECTIVE: The objective of this study is to undertake a systematic review and meta-analysis of the literature on this subject. METHODS: A comprehensive literature search was performed using the Scopus, MEDLINE-PubMed, Web of Science, and Science Direct databases using the keywords: "limonene", "cancer", "neoplasm", and "tumor". The inclusion criteria were: in vivo and in vitro studies on the use of limonene in cancer published in English, Portuguese and Spanish until December 2019. Review articles, meta-analyses, abstracts, conference papers, editorials/ letters and case reports were excluded. RESULTS: The search identified 3568 articles, of which, 126 were selected for full reading, with 11 papers meeting the review criteria. Six more papers were added from the references of the initial 11 texts, giving a total of 17 papers. There was a high level of agreement in inclusion/exclusion (Kappa index > 80%). The risk of bias in the texts was shown to be high. CONCLUSION: The meta-analysis suggests that limonene acts mainly on tumor regression induced apoptosis and is a promising natural product for use in the treatment of several types of cancer.


Assuntos
Projetos de Pesquisa , Bases de Dados Factuais , Limoneno
5.
Artigo em Inglês | MEDLINE | ID: mdl-32376296

RESUMO

Autoimmune hepatitis (AIH) is a rare liver disease of autoimmune aetiology that classically affects women at reproductive age. Diagnosis of AIH is not always straightforward, and other causes of chronic liver disease must be excluded. Pregnancy in patients with AIH is associated with an increased risk of adverse maternal and foetal outcomes. In older studies, the incidence of adverse outcomes was high, with a large number of flare-ups, maternal deaths, and perinatal complications. In the most recent series, improved care based on multidisciplinary surveillance, a larger number of patients treated before and during pregnancy, and reduced incidence of cirrhosis at conception have led to better maternal outcomes and a live-birth rate similar to that in the general population. Nonetheless, AIH is still associated with preterm birth, foetal growth restriction, and unpredictable liver flares, and it represents a group of patients who need close evaluation during pregnancy.


Assuntos
Hepatite Autoimune/diagnóstico , Complicações na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Idoso , Autoanticorpos/sangue , Feminino , Hepatite Autoimune/epidemiologia , Hepatite Autoimune/terapia , Humanos , Recém-Nascido , Testes de Função Hepática , Parto , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/terapia , Resultado da Gravidez , Nascimento Prematuro/etiologia
6.
Clin Neurol Neurosurg ; 194: 105792, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32244037

RESUMO

OBJECTIVE: The risk of progression of multiple sclerosis (MS) related to the association of prognostic factors present at disease onset has rarely been explored. We aimed to construct a clinical risk score for MS long-term progression that could be easily applied in clinical practice. PATIENTS AND METHODS: Among 432 patients with MS, 288 patients were selected as a derivation sample for identification of the knowledge prognostic factors more associated with long-term progression. One point was given to each risk factor identified as statistically significant by the adjusted model, and the sum of the points gave the overall risk score. Subsequently the score was applied to the remaining 144 patients to confirm if those with higher scores had reached MS secondary progression. RESULTS: The prognostic factors identified as independently associated with long-term progression were: no specific MS treatment before EDSS 3, age of onset older than 30 years, pyramidal and cerebellar impairment as the first manifestation of disease, time interval between the first and second relapses less than 2 years, and African ancestry. There was no significant difference between expected and observed number of patients in progression (44 vs. 31, p = 0.966), indicating that the score was able to predict the progression in the validation sample. There was no significant difference between patients with low risk (≤ 2 points) (p = 0.98) and high risk (≥ 3 points) (p = 0.48) in the derivation versus validation samples. In the derivation sample, the patients with three or more points had a 2.8-fold increased risk of progression [hazard ratio (HR): 2.8; 95 % confidence interval (CI): 1.2-6.3; p = 0.014). CONCLUSION: The score proposed was capable of predicting long-term MS progression.


Assuntos
Esclerose Múltipla/patologia , Adulto , Idade de Início , Idoso , População Negra , Brasil , Cerebelo/fisiopatologia , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Prognóstico , Tratos Piramidais/fisiopatologia , Reprodutibilidade dos Testes , Medição de Risco , Adulto Jovem
7.
Oral Maxillofac Surg ; 24(2): 181-187, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32291547

RESUMO

PURPOSE: Major adult maxillary transverse discrepancies are usually treated with surgically assisted rapid maxillary expansion (SARME), utilizing a combination of surgical and orthodontic techniques. Unfortunately, a consensus has not been reached on topics ranging from the best surgical technique that should be performed to the ideal expander type that should be installed. The present study sought to evaluate the efficiency and stability of the maxillary expansion achieved with two types of expanders following the same SARME procedure without pterygomaxillary disjunction (PMD). METHODS: Twenty-four patients with a maxillary transverse deficiency were enrolled in the study. All patients underwent the same SARME, and 12 received a bone-anchored (KLS Martin®) and 12 were installed with a tooth-borne (Hyrax®) expander. Dental impressions were collected both preoperatively and 1 year postoperatively. These casts were scanned and the distances between specific interdental and intergingival points were measured and analyzed. Statistical analyses were performed to assess the effects expander type had on the efficiency of the maxillary expansion and long-term stability. RESULTS: Expansion in the anterior maxillary and premolar regions was found to be similar in both groups. In contrast, the tooth-borne device resulted in a significantly greater expansion in the molar region. CONCLUSION: The SARME technique without PMD is highly effective at treating adults with maxillary transverse deficiencies, and the type of expander selected depends on the location of the larger maxillary constriction region of each patient.


Assuntos
Maxila , Técnica de Expansão Palatina , Adulto , Dente Pré-Molar , Humanos , Dente Molar
8.
Curr Top Med Chem ; 19(28): 2629-2639, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31670621

RESUMO

BACKGROUND: In the last few decades, mycoses caused by opportunistic fungi namely Candida species has gained significant attention. Such infections are very common and present high mortality rates, especially in immunocompromised patients. Currently, a limited number of antifungal drugs are available for the treatment of these infections and are also often related to severe adverse side effects. Therefore, new drugs and innovative technologies for the treatment of this infection are necessary. OBJECTIVE: The aim of this study was to evaluate the development of new drugs, formulations, as well as patents for the treatment of infections caused by Candida spp. METHODS: The present patent review was carried out through a specialized search database Espacenet. The patent selection was based on the following inclusion criteria: Recent patents published in English or Spanish containing candidiasis as the keyword in the title, abstract or full text. This survey was conducted in October and November 2018. RESULTS: As a result of that, 22 patents were selected to the final selection, the most common routes of application were oral (n = 6), vaginal (n = 6), topical (n = 5) and others (n = 5). This fact is related to the clinical manifestations of candidiasis. CONCLUSION: Through this review, it was possible to identify significant improvements and advances in the area of antifungal therapeutic innovation research. In addition, we demonstrated the growing interest of academic and industrial groups in pharmaceutical development and novel formulations for the treatment of candidiasis. New therapeutic options can contribute to improve the quality of patient's life, prevent infections and promote the search for an innovative and effective treatment of Candida infections.


Assuntos
Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Animais , Antifúngicos/administração & dosagem , Humanos
9.
PLoS One ; 14(2): e0211627, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30753197

RESUMO

PURPOSE: To analyze risk factors for recurrent toxoplasmic retinochoroiditis. DESIGN: Single center prospective case series. POPULATION AND METHODS: A total of 230 patients with toxoplasmic retinochoroiditis were prospectively followed to assess recurrences. All patients were treated with a specific drug regime for toxoplasmosis in each episode of active retinochoroiditis. Individuals with chronic diseases and pregnant women were excluded. Survival analysis by extended Cox regression model (Prentice-Williams-Peterson counting process model) was performed to evaluate the time between recurrences according to some potential risk factors: age, number of retinochoroidal lesions at initial evaluation, sex and interferon gamma +874 T/A gene polymorphism. Hazard Ratios (HR) and 95% confidence intervals (CI) were provided to interpret the risk effects. RESULTS: One hundred sixty-two recurrence episodes were observed in 104 (45.2%) patients during follow-up that lasted from 269 to 1976 days. Mean age at presentation was 32.8 years (Standard deviation = 11.38). The risk of recurrence during follow up was influenced by age (HR = 1.02, 95% CI = 1.01-1.04) and number of retinochoroidal lesions at the beginning of the study (HR = 1.60, 95% CI = 1.07-2.40). Heterozygosis for IFN-γ gene polymorphism at position +874 T/A was also associated with recurrence (HR = 1.49, 95% CI = 1.04-2.14). CONCLUSION: The risk of ocular toxoplasmosis recurrence after an active episode increased with age and was significantly higher in individuals with primary lesions, which suggests that individuals with this characteristic and the elderly could benefit from recurrence prophylactic strategies with antimicrobials. Results suggest an association between IFN-γ gene polymorphism at position +874T/A and recurrence.


Assuntos
Coriorretinite/genética , Interferon gama/genética , Polimorfismo Genético/genética , Toxoplasmose Ocular/genética , Adolescente , Anti-Infecciosos/uso terapêutico , Coriorretinite/tratamento farmacológico , Feminino , Humanos , Masculino , Estudos Prospectivos , Recidiva , Fatores de Risco , Análise de Sobrevida , Toxoplasmose Ocular/tratamento farmacológico , Acuidade Visual/genética
10.
J Endocrinol Invest ; 41(9): 1019-1028, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29353393

RESUMO

BACKGROUND: Graves' disease (GD) arising after the treatment of toxic multinodular goitre (TMNG) with radioiodine has long been described but it remained unclear whether GD was in fact iodine induced, its incidence, risk factors, natural history and treatment outcomes. METHODS: A systematic search using The Cochrane Library, Medline and PubMed Central allowed the pooling of data from 3633 patients with thyroid autonomy, 1340 patients with TMNG, to fill gaps in knowledge, regarding the clinical expression of iodine-induced GD (131I-IGD) in adults. RESULTS: 131I-IGD developed in 0-5.3% of those with thyroid autonomy (first year) and in 5-5.4% of those with TMNG, 3-6 months after treatment. Patients with toxic adenoma were less affected. 131I-IGD was more common in patients with pre-treatment direct or indirect signs of autoimmunity: positive anti-TPO (p < 0.05), glandular hypoechogenicity, TRAbs within reference range, diffuse uptake on 99mTc-pertechnetate scans (p < 0.05), findings that may increase the risk tenfold. 131I-IGD manifested 3 months after 131I, justifying 15.4-29% of cases of relapse. The rate of spontaneous remission was 17-20% (6 months) and the rate of relapse after a second 131I treatment 22-25%. The use of an uptake-based administered 131I activity led to a greater proportion of euthyroid patients (78% compared to 25-50% with the mass-based approach). CONCLUSIONS: GD may be triggered by 131I. The incidence of the condition is low. Several risk factors were consistently identified; some have shown to raise the risk significantly. 131I-IGD seems more treatment resistant than iodine-independent GD and the best resolution rates were achieved with uptake-based selected iodine activities.


Assuntos
Bócio Nodular/tratamento farmacológico , Doença de Graves/induzido quimicamente , Radioisótopos do Iodo/efeitos adversos , Estudos de Casos e Controles , Bócio Nodular/diagnóstico , Doença de Graves/diagnóstico , Humanos , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
11.
Theriogenology ; 108: 291-296, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29277069

RESUMO

The objective of this study was to assess the impact of mastitis-causing bacteria and somatic cell count (SCC) on pregnancy per embryo transfer (P/ET) in Holstein-Gir crossbred (Girolando) lactating dairy cows. Cows (n = 1397) were subjected to a timed-embryo transfer protocol. Milk samples were collected two days before embryo transfer for SCC and bacteriological culture analyses. Pregnancy diagnosis was performed on days 31 and 66 after timed-embryo transfer. The animals were grouped according to the National Mastitis Council recommendations: Gram-positive environmental (EV+), Gram-negative environmental (EV-), Gram-positive contagious (C+), coagulase-negative staphylococci (CNS) and control (no bacterial growth). Additional analysis was made by categorizing bacteria based on degree of pathogenicity (Major or Minor). Bacterial growth reduced P/ET (P < .01) at both 31 and 66 days of gestation. The P/ET was lower (P < .05) at 31 days in EV- (30.1%) and EV+ (29.9%) groups and tended (P = .09) to be lower in the C+ group (36.6%) than the control group (44.0%). The P/ET from the Major group at 31 days of gestation was lower (P = .03) compared with the Minor and control groups (32.1 vs 41.1 vs 43.2%, respectively). Cows with SCC > 400,000 cells/mL had lower P/ET (P < .01) than animals with SCC < 200,000 cells/mL at both 31 (30.4% vs 40.8%) and 66 days (24.7% vs 32.2%) of gestation. Pregnancy loss was not different between bacterial isolates and SCC categories. Elevated SCC significantly reduced P/ET, whereas environmental agents and those with Major pathogenicity yielded the greatest reduction in P/ET.


Assuntos
Transferência Embrionária/veterinária , Mastite Bovina/microbiologia , Animais , Bovinos , Feminino , Fertilidade , Infertilidade Feminina/microbiologia , Mastite Bovina/complicações , Leite/citologia , Leite/microbiologia , Gravidez
12.
J Neuroimmunol ; 310: 1-7, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28778431

RESUMO

The aim of this study was to analyze the HLA class II alleles in neuromyelitis optica (NMO) and MS patients from Rio de Janeiro to clarify whether the pattern of genetic predisposition in NMO is different from the one seen in MS or whether it is possible to determine specific alleles of susceptibility or resistance. The DR3 haplotype was over represented in NMO while the DR15 was over represented in MS. The HLA-DRB1*03:01 allele was associated with NMO regardless the NMO-IgG status but did not influence the long term disability. The comparison of the allele and haplotype frequencies significantly discriminated patients with NMO vs. MS.


Assuntos
Cadeias HLA-DRB1/genética , Imunoglobulina G/metabolismo , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Neuromielite Óptica/genética , Neuromielite Óptica/imunologia , Adolescente , Adulto , Idoso , Brasil , Estudos de Casos e Controles , Criança , Análise Mutacional de DNA , Feminino , Genótipo , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Cadeias beta de HLA-DQ/metabolismo , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Neuromielite Óptica/diagnóstico por imagem , Fenótipo , Índice de Gravidade de Doença , Adulto Jovem
13.
Clin Exp Immunol ; 189(3): 318-330, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28542701

RESUMO

Forkhead box P3 (FoxP3)+ regulatory T cells (Tregs ) are functionally deficient in systemic lupus erythematosus (SLE), characterized by reduced surface CD25 [the interleukin (IL)-2 receptor alpha chain]. Low-dose IL-2 therapy is a promising current approach to correct this defect. To elucidate the origins of the SLE Treg phenotype, we studied its role through developmentally defined regulatory T cell (Treg ) subsets in 45 SLE patients, 103 SLE-unaffected first-degree relatives and 61 unrelated healthy control subjects, and genetic association with the CD25-encoding IL2RA locus. We identified two separate, uncorrelated effects contributing to Treg CD25. (1) SLE patients and unaffected relatives remarkably shared CD25 reduction versus controls, particularly in the developmentally earliest CD4+ FoxP3+ CD45RO- CD31+ recent thymic emigrant Tregs . This first component effect influenced the proportions of circulating CD4+ FoxP3high CD45RO+ activated Tregs . (2) In contrast, patients and unaffected relatives differed sharply in their activated Treg CD25 state: while relatives as control subjects up-regulated CD25 strongly in these cells during differentiation from naive Tregs , SLE patients specifically failed to do so. This CD25 up-regulation depended upon IL2RA genetic variation and was related functionally to the proliferation of activated Tregs , but not to their circulating numbers. Both effects were found related to T cell IL-2 production. Our results point to (1) a heritable, intrathymic mechanism responsible for reduced CD25 on early Tregs and decreased activation capacity in an extended risk population, which can be compensated by (2) functionally independent CD25 up-regulation upon peripheral Treg activation that is selectively deficient in patients. We expect that Treg -directed therapies can be monitored more effectively when taking this distinction into account.


Assuntos
Família , Subunidade alfa de Receptor de Interleucina-2/genética , Lúpus Eritematoso Sistêmico/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Feminino , Citometria de Fluxo , Humanos , Interleucina-2/biossíntese , Interleucina-2/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Antígenos Comuns de Leucócito/genética , Antígenos Comuns de Leucócito/imunologia , Antígenos Comuns de Leucócito/metabolismo , Lúpus Eritematoso Sistêmico/fisiopatologia , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Linfócitos T Reguladores/classificação , Regulação para Cima , Adulto Jovem
14.
Clin Neurol Neurosurg ; 151: 24-30, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27756020

RESUMO

BACKGROUND: The natural history of multiple sclerosis (MS) in Brazil has been available in different regions of country. There is no nationwide population-based studies that express general data in Brazil. OBJECTIVE: To review and synthesize available data about MS in Brazil. MATERIAL AND METHODS: Systematic review was performed through a search of medical literature databases to identify Brazilian studies published during 1990-2012. DATA SOURCES: PubMed, SciELO, and Lilacs. KEYWORDS: "Brazil" or "Brazilian" combined with the following terms: "multiple sclerosis", "clinical profile", "demographic profile", "natural history", "clinical course", "pediatric", or "familial form". RESULTS: In total of 45 pediatric and 1922 adult patients, the median age at onset was 10 years in pediatric patients and 32 years in adult patients. Women were more affected. Motor-control complaints and relapsing-remitting phenotype at onset were the most common. Predictors to disability and progression were number of relapses during the first year of disease, older age, male gender and African ancestry. CONCLUSIONS: The profile of the MS in Brazilian seems to correspond to that observed in high-MS-prevalence areas. African ancestry is a risk factor to disability and progression early. In Brazil, factors that limit MS incidence do not interfere with the clinical pattern and outcomes.


Assuntos
Progressão da Doença , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/fisiopatologia , Adulto , Brasil/epidemiologia , Criança , Feminino , Humanos , Masculino
16.
Lupus ; 25(1): 75-80, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26385219

RESUMO

Diffuse alveolar hemorrhage (DAH) is a rare but potentially catastrophic manifestation with a high mortality. Among rheumatologic diseases, it occurs most frequently in patients with systemic lupus erythematosus (SLE) and systemic vasculitis. Despite new diagnostic tools and therapies, it remains a diagnostic and therapeutic challenge. The aim of this work was to characterize the SLE patients with an episode of alveolar hemorrhage followed in our Clinical Immunology Unit (CIU). A retrospective chart review was carried out for all patients with SLE followed in CIU between 1984 and the end of 2013. We reviewed the following data: demographic characteristics, clinical and laboratory data, radiologic investigations, histologic studies, treatment, and outcome. We identified 10 episodes of DAH, corresponding to seven patients, all female. These represent 1.6% of SLE patients followed in our Unit. The age at DAH attack was 42.75 ± 18.9 years. The average time between diagnosis of SLE and the onset of DAH was 7.1 years. Three patients had the diagnosis of SLE and the DAH attack at the same time. Disease activity according to SLEDAI was high, ranging from 15 to 41. All patients were treated with methylprednisolone, 37.5% cyclophosphamide and 28.6% plasmapheresis. The overall mortality rate was 28.6%.


Assuntos
Hemorragia/etiologia , Pneumopatias/etiologia , Lúpus Eritematoso Sistêmico/complicações , Alvéolos Pulmonares , Adolescente , Adulto , Idoso , Feminino , Hemorragia/diagnóstico , Hemorragia/mortalidade , Humanos , Imunossupressores/uso terapêutico , Pneumopatias/diagnóstico , Pneumopatias/mortalidade , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/mortalidade , Lúpus Eritematoso Sistêmico/terapia , Prontuários Médicos , Pessoa de Meia-Idade , Plasmaferese , Portugal , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
17.
Clin Exp Immunol ; 183(3): 480-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26472479

RESUMO

T helper type 17 (Th17) cytokines have been implicated in the pathogenesis of neuromyelitis optica (NMO). As humanized anti-interleukin (IL)-6R (tocilizumab) immunoglobulin (Ig)G has been used as disease-modifying therapy for NMO, the objective of our study was to investigate the role of endogenous IL-6 on NMO-derived CD4(+) T cell behaviour. High production of IL-6, IL-17 and IL-21 by CD4(+) T-cells was detected in NMO patients. Further, IL-21 and IL-6 levels were related directly to the level of neurological disabilities. The addition of anti-IL-6R IgG not only reduced directly the production of these cytokines, but also almost abolished the ability of activated autologous monocytes in enhancing IL-6, IL-17 and IL-21 release by CD4(+) T cells. In contrast, the production of IL-10 was amplified in those cell cultures. Further, anti-IL-6R monoclonal antibodies (mAb) also potentiated the ability of glucocorticoid in reducing Th17 cytokines. Finally, the in-vivo and in-vitro IL-6 levels were significantly higher among those patients who experienced clinical relapse during 2-year follow-up. In summary, our results suggest a deleterious role of IL-6 in NMO by favouring, at least in part, the expansion of corticoid-resistant Th17 cells.


Assuntos
Interleucina-6/fisiologia , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/imunologia , Adulto , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Linfócitos T CD4-Positivos , Resistência a Medicamentos , Feminino , Seguimentos , Humanos , Hidrocortisona/farmacologia , Interleucina-10/sangue , Interleucina-17/sangue , Interleucinas/biossíntese , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-6/metabolismo , Indução de Remissão , Índice de Gravidade de Doença , Células Th17/efeitos dos fármacos , Células Th17/imunologia
18.
Geobiology ; 13(3): 245-66, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25773379

RESUMO

Holocene stromatolites characterized by unusually positive inorganic δ(13) CPDB values (i.e. up to +16‰) are present in Lagoa Salgada, a seasonally brackish to hypersaline lagoon near Rio de Janeiro (Brazil). Such positive values cannot be explained by phototrophic fixation of CO2 alone, and they suggest that methanogenesis was a dominating process during the growth of the stromatolites. Indeed, up to 5 mm methane was measured in the porewater. The archaeal membrane lipid archaeol showing δ(13) C values between -15 and 0‰ suggests that archaea are present and producing methane in the modern lagoon sediment. Moreover, (13) C-depleted hopanoids diplopterol and 3ß-methylated C32 17ß(H),21ß(H)-hopanoic acid (both -40‰) are preserved in lagoon sediments and are most likely derived from aerobic methanotrophic bacteria thriving in the methane-enriched water column. Loss of isotopically light methane through the water column would explain the residual (13) C-enriched pool of dissolved inorganic carbon from where the carbonate constituting the stromatolites precipitated. The predominance of methanogenic archaea in the lagoon is most likely a result of sulphate limitation, suppressing the activity of sulphate-reducing bacteria under brackish conditions in a seasonally humid tropical environment. Indeed, sulphate-reduction activity is very low in the modern sediments. In absence of an efficient carbonate-inducing metabolic process, we propose that stromatolite formation in Lagoa Salgada was abiotically induced, while the (13) C-enriched organic and inorganic carbon pools are due to methanogenesis. Unusually, (13) C-enriched stromatolitic deposits also appear in the geological record of prolonged periods in the Palaeo- and Neoproterozoic. Lagoa Salgada represents a possible modern analogue to conditions that may have been widespread in the Proterozoic, at times when low sulphate concentrations in sea water allowed methanogens to prevail over sulphate-reducing bacteria.


Assuntos
Bactérias/metabolismo , Carbono/química , Sedimentos Geológicos/química , Metano/biossíntese , Brasil , Sedimentos Geológicos/microbiologia , Fenômenos Geológicos
19.
Lupus ; 24(8): 846-53, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25661837

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin, in which both genetic and environmental factors are involved. One such environmental factor is vitamin D, a vital hormone that plays a specific function in the immune system homeostasis, acting through a nuclear receptor (VDR) expressed in all immune cells. Several polymorphisms of the gene that encodes this receptor have been described. Though inconsistently, these polymorphisms have been associated with clinical manifestations and SLE development.The aim of this study was to determine the possible association between VDR gene polymorphisms (BsmI, ApaI, TaqI e FokI) and SLE susceptibility and severity, in a cohort of lupus patients from the north of Portugal.A total of 170 patients (F = 155, M = 15; age = 45 ± 13.4 years) with SLE (diagnosed according the American College of Rheumatology criteria) with at least five years of disease evolution and followed in the Autoimmune Disease Clinical Immunology Unit of Centro Hospitalar do Porto were studied. Patients and 192 ethnicity-matched controls were genotyped for BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) polymorphisms by TaqMan allelic discrimination assay. Disease severity was assessed by SLICC damage score, number of affected organs, number of severe flares and pharmacological history.SLE patients with the CT genotype of FokI polymorphism have a higher SLICC value (p = 0.031). The same result was observed for the group of patients with the TT genotype of TaqI polymorphism (p = 0.046). No differences were observed in VDR genotype between patients and controls. Also, we observed that the other clinical features analysed were not influenced by VDR polymorphisms.Our study confirms a possible role of VDR gene polymorphisms in SLE. A positive association was found between VDR polymorphisms and SLE severity (chronic damage). The presence of CT genotype of FokI and TT genotype of TaqI seems to confer a worse prognosis and may constitute a risk factor for higher long-term cumulative damage in SLE patients.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/genética , Receptores de Calcitriol/classificação , Receptores de Calcitriol/genética , Adulto , Alelos , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Portugal , Fatores de Risco , Deficiência de Vitamina D/etiologia
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