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Hepcidin production is regulated by iron concentration, erythropoietic activity, and inflammation. There is no reference method for determining its levels, but results obtained through various methods strongly correlate and can be compared using recalibration equations. OBJECTIVE: To describe recalibrated serum hepcidin values at different percentiles in schoolchildren, considering age, sex, inflammatory processes, H. pylori infection, and iron status. METHODS: Secondary analysis of data incorporating information on inflammation, H. pylori infection, and iron status of 349 schoolchildren. Hepcidin analysis was performed using a competitive ELISA, and recalibrated hepcidin values were calculated using the inverse of the linear regression model equation obtained by van der Vorm et al. Results: Recalibrated hepcidin values were lower than non-calibrated values. In schoolchildren without infection/inflammation and without iron deficiency, recalibrated values at the 50th percentile (25th-75th) were 4.89 ng/mL (2.68-8.42). For schoolchildren without infection/inflammation but with iron deficiency, recalibrated values were 2.34 ng/mL (1.10-6.58), the lowest hepcidin values observed. The highest values were found in the group with infection/inflammation, regardless of iron deficiency status. CONCLUSIONS: Recalibrated hepcidin values were lower than non-calibrated values. The highest values were observed in schoolchildren with infectious or inflammatory processes, and the lowest values were observed in schoolchildren with iron deficiency but only in the absence of infectious or inflammatory processes. Using recalibrated hepcidin values allows comparison between data obtained using different analytical methods.
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MIC-A and MIC-B are the natural ligands for NKG2D, an activator receptor expressed in NK cells. Soluble isoforms of MIC-A and MIC-B (sMICA, sMICB) have been identified in different malignancies, affecting NK cells' cytotoxicity. The study was performed to determine the levels of sMICA, sMICB, the expression of MIC-A, and MIC-B on tumor tissues, and lymphocyte subpopulations (CD4 + , CD8 + , NK, NKT, Tγδ cells, B cells, monocytes) in 94 patients with non-Hodgkin's lymphoma (NHL) and 72 healthy donors.The most frequent lymphoma was diffuse large B cell lymphoma (48%). Patients with NHL had decreased numbers of CD4 T cells, CD8 T cells, B cells, monocytes, NK cells, type 1 dendritic cells, γδ T cells, and increased iNKT cells. Patients showed higher levels of sMIC-A and similar serum levels of sMIC-B.Survival was poorer in patients having higher LDH values and lower numbers of CD4 T cells, type 1 dendritic cells, gamma-delta T cells, and high levels of sMIC-A.In conclusion, high levels of sMIC and decreased numbers in circulating lymphocyte subsets are related to poor outcomes in NHL.
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Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Prognóstico , Linfoma não Hodgkin/patologia , Subpopulações de Linfócitos , Células Matadoras Naturais/patologia , Linfoma Difuso de Grandes Células B/patologiaRESUMO
Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoma. MIC-A and MIC-B are the natural ligands for NKG2D, a receptor expressed in NK cells. MIC-A soluble isoforms (sMICA) have been described in different malignancies. OBJECTIVES: To analyze lymphocyte subsets and sMIC-A in germinal center DLBCL. MATERIALS AND METHODS: sMICA, sMICB, and peripheral blood lymphocyte subsets (CD4+, CD8+, NK, NKT, γδ T cells, and dendritic cells) were analyzed in 59 patients and 60 healthy donors. RESULTS: Patients had decreased numbers of type 1 and type 2 dendritic cells, NK, iNKT, CD4 T, and CD8 T cells, and higher levels of sMIC-A. The 2-year PFS for high IPI scores and high sMIC-A was 24% and 28%, respectively. The 2-year OS for high IPI scores and high sMIC-A was 42% and 33%. The 2-year PFS and OS for patients not achieving response to treatment were 0% and 10%, respectively. The MICPI score (one point each for high IPI score and high sMIC-A) showed that those patients summing two points had worse PSF and OS. CONCLUSIONS: Patients with DLBCL have decreased numbers of peripheral lymphocyte subsets and high levels of sMIC-A. The addition of sMIC-A to IPI could improve its prognostic relevance.
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Centro Germinativo , Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Prognóstico , Centro Germinativo/patologia , Centro Germinativo/metabolismo , Adulto , Subpopulações de Linfócitos/metabolismo , Subpopulações de Linfócitos/imunologia , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Estadiamento de Neoplasias , Imunofenotipagem , Biomarcadores TumoraisRESUMO
Three-dimensional cell cultures have improved the evaluation of drugs for cancer therapy, due to their high similarity to solid tumors. In melanoma, autophagy appears to show a dual role depending on the progression of the disease. p62 protein has been proposed for the evaluation of autophagic flux since its expression is an indicator of the state of autophagy. Pentoxifylline (PTX) and Norcantharidin (NCTD) are drugs that have been shown to possess anticancer effects. In this work, we used B16F1 mouse melanoma cells in two-dimensional (2D) monolayer cultures and three-dimensional (3D) spheroids to test the effect of PTX and NCTD over the p62 expression. We analyzed the effect on p62 expression through Western blot and immunofluorescence assays. Our results indicate that PTX decreases p62 expression in both cell culture models, while Norcantharidin increases its expression in 3D cultures at 24 h. Therefore, these drugs could have a potential therapeutic use for the regulation of autophagy in melanoma, depending on the state of evolution of the disease.
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Autofagia , Compostos Bicíclicos Heterocíclicos com Pontes , Pentoxifilina , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Animais , Camundongos , Pentoxifilina/farmacologia , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Melanoma Experimental/metabolismo , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Técnicas de Cultura de Células , Proteína Sequestossoma-1/metabolismo , Proteína Sequestossoma-1/genética , Antineoplásicos/farmacologia , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismoRESUMO
The purpose of this study was to describe the changes in iron status indicators at 6 and 12 months of age, controlling by inflammation by measuring alpha-1 acid glycoprotein (AGP). This longitudinal study included 48 healthy-term singleton infants with birth weight ≥ 2500 g, born in hospitals of the Mexican Institute for Social Security. Complete blood count, ferritin, soluble transferrin receptor (sTfR), hepcidin, and AGP were measured in blood at 6 and 12 months of age. sTfR/ferritin ratio and total body iron (TBI) stores were calculated. Hemoglobin and sTfR/ferritin ratio increased with age, while ferritin and TBI decreased. In infants without inflammation, hepcidin, sTfR, and MVC did not show significant changes from 6 to 12 months of age, while ferritin and TBI decreased. In infants with inflammation, hepcidin, TBI, and ferritin levels increased, while hemoglobin and sTfR/ferritin ratio decreased. MVC and sTfR did not change significantly in the presence or absence of inflammation. Hepcidin concentration correlated positively and significantly with ferritin and TBI stores and showed significant negative correlation with sTfR/ferritin ratio. Our study showed that, in absence of inflammation and ID, during the first year of life, physiological changes occur in hemoglobin and ferritin levels as well as in indicators derived from ferritin and sTfR; in contrast, hepcidin and sTfR did not show significant change. However, hepcidin concentration was lower in infants with ID and was higher when inflammation was present, supporting that infants have a functional hepcidin response to changes in iron stores.
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Hepcidinas/sangue , Deficiências de Ferro , Orosomucoide/análise , Anemia Ferropriva/sangue , Anemia Ferropriva/epidemiologia , Anemia Ferropriva/prevenção & controle , Biomarcadores , Contagem de Células Sanguíneas , Feminino , Ferritinas/sangue , Seguimentos , Hemoglobinas/análise , Humanos , Lactente , Inflamação/sangue , Ferro/análise , Ferro/metabolismo , Masculino , México/epidemiologia , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Receptores da Transferrina/sangueRESUMO
Alzheimer disease (AD) is the most common form of dementia in humans. However, to date, the cause of sporadic AD (SAD), which is the most frequent form, is still unknown. Although it has not been possible to determine the origin of this disease, the amyloid hypothesis is one of the most accepted to explain the etiology of AD. This hypothesis proposes that the pathogenesis of AD is derived from the toxic effect produced by the amyloid-ß (Aß) peptide in the brain parenchyma, but it does not make clear how Aß is capable of producing such damage. Furthermore, it has been observed that SAD is accompanied by disruptions in the vascular system, such as damage to the blood-brain barrier. This facilitates the transfer of some systemic proteins, such as fibrinogen, to the brain parenchyma, where Aß is abundant. Therefore, this Aß interacts with fibrinogen, which favors the formation of clots resistant to fibrinolysis, inducing a risk of thrombosis and neuroinflammation. Notably, Aß is not only of neuronal origin; platelets also contribute to high Aß production in the circulation. The Aß present in circulation favors the activation of coagulation factor XII, which leads to the generation of thrombin and bradykinin. In addition to Aß-induced platelet activation, all these events favor the development of inflammatory processes that cause damage to the brain vasculature. This damage represents the beginning of the toxic effects of Aß, which supports the amyloid hypothesis. This review addresses the relationship between alterations in the vascular and hemostatic systems caused by Aß and how both alterations contribute to the progression of SAD.
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Doença de Alzheimer , Peptídeos beta-Amiloides/metabolismo , Fator XII/metabolismo , Fibrinólise/fisiologia , Ativação Plaquetária/fisiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Amiloide/metabolismo , Animais , Encéfalo/patologia , Humanos , InflamaçãoRESUMO
INTRODUCTION: Alloimmunization is caused by exposure to erythrocytes from a donor that expresses blood group antigens other than those of the recipient and is related to processes that alter the balance of the immune system. Knowing the pathophysiology of alloimmunization process is essential to understand clinical complications associated with this process. PATIENTS AND METHODS: From October 2016 to April 2017, irregular antibody screening was performed in 1,434 polytransfused (compatible with the ABO and D system) patients by means of agglutination techniques using erythrocytes of a known phenotype of 44 patients with a positive alloantibody screening. Non-alloimmunized (control) subjects were matched for age, gender, pathology, and treatment group with alloimmunized patients. The subsets of B, T, and Treg lymphocytes were determined by flow cytometry. RESULTS: The results of screening for alloantibodies in patients by specificity of antibodies were as follows: nonspecific (30%), followed by anti-Dia (13%), anti-e (9%), anti-S (9%), anti-I (7%), anti-K (7%), and anti-P (7%). A lower percentage of CD4+ T lymphocytes and an increase of CD8+ T lymphocytes were observed in alloimmunized patients, as well as a low CD4/CD8 ratio (0.7 vs. 1.6, p = 0.003), a higher percentage of B lymphocytes versus the control group (30 vs. 20%, p = 0.003), and a decrease of Treg CD4+ lymphocytes versus the control group (3 vs. 12 cells/µL, p = 0.043). These observations suggest that alloimmunized patients have important alterations in the number of some lymphocyte subsets that can be translated into clinical immune dysregulation. CONCLUSION: A decreased CD4/CD8 ratio, increased B lymphocytes, and Treg lymphocyte deficiency are the most significant changes observed in alloimmunized patients.
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The signaling mediated by small non-proteinogenic molecules, which probably have the capacity to serve as a bridge amongst complex systems is one of the most exiting challenges for the study. In the current report, stem cells differentiation of the immune system in Nile tilapia treated with sub-basal doses of GABA evaluated as c-kit+ and Sca-1+ cells disappearance on pronephros, thymus, spleen and peripheral blood mononuclear cells by flow cytometry was assessed. Explanation of biological response was performed by molecular docking approach and multiparametric analysis. Stem cell differentiation depends on a delicate balance of negative and positive interactions of this neurotransmitter with receptors and transcription factors involved in this process. This in turn depends on the type of interaction with hematopoietic niche to differentiate into primordial, early or late hematopoiesis as well as from the dose delivery. In fish treated with the low doses of GABA (0.1% over basal value) primordial hematopoiesis is regulated by interaction of glutamate (Glu) with the Ly-6 antigen. Early hematopoiesis was influenced by the bond of GABA near or adjacent to turns of FLTR3-Ig-IV domain. During late hematopoiesis, negative regulation by structural modifications on PU.1/IRF-4 complex, IL-7Rα and GM-CSFR mainly prevails. Results of molecular docking were in agreement with the percentages of the main blood cells lineages estimated in pronephros by flow cytometry. Current study provides the first evidences about the role of inhibitory and excitatory neurotransmitters such as GABA and Glu, respectively with the most transcriptional factors and receptors involved on hematopoiesis in adult Nile tilapia.
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Ciclídeos/fisiologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Células-Tronco Hematopoéticas/fisiologia , Animais , Antígenos Ly/genética , Antígenos Ly/imunologia , Diferenciação Celular/fisiologia , Ciclídeos/imunologia , Células-Tronco Hematopoéticas/imunologia , Sistema Imunitário/fisiologia , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/imunologia , Ácido gama-Aminobutírico/farmacologiaRESUMO
Candida glabrata is an emerging opportunistic pathogen that has intrinsic resistance to azoles. During infection or while living as a commensal, it encounters nutritional stresses such as deficiency of carbon or nitrogen sources. Herein, we investigate the expression and activity of PrA, Ape1, Ape3 and CpY vacuolar proteases during these stressful nutrimental conditions. Our findings demonstrate a differential activity profile depending on the addition or lack of carbon, nitrogen or both. Of the four proteases tested, PrA and Ape3 showed a higher activity in the absence of nitrogen. Steady-state RNA levels for all the proteases were also differentially expressed although not always correlated with its activity, suggesting multiple levels of regulation. Microscopy observations of C. glabrata cells subjected to the different conditions showed an increase in the vacuolar volume. Moreover, the presence of ATG8-PE and an increased expression of ATG8 were observed in the yeast under the tested conditions suggesting that C. glabrata is in autophagy stage. Taken together, our results showed that PrA, Ape1, Ape3 and CpY have varying activities and expression depending on whether nitrogen or carbon is added to the media, and that these vacuolar proteases might have a role in the autophagy process.
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Candida glabrata/genética , Candida glabrata/metabolismo , Regulação Fúngica da Expressão Gênica , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , Vacúolos/enzimologia , Vacúolos/genética , Sequência de Aminoácidos , Autofagia , Sítios de Ligação , Biologia Computacional/métodos , Ativação Enzimática , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Fatores de Transcrição/metabolismoRESUMO
OBJECTIVE: Breast cancer is the most common type of cancer in Canadian women and worldwide. Mammographic density is a well-established breast cancer risk. Recent evidence suggested inverse correlations among adiponectin, osteocalcin, and the risk developing breast cancer. The objective of the study was to evaluate the relationship between breast density and adiponectin and osteocalcin concentrations. METHODS: A cross-sectional study was performed in 239 women, age range 40 to 60. Mammographic density, serum adiponectin, and osteocalcin levels were measured. According to the Wolfe method, participants were divided into those with low-risk and high-risk pattern mammograms. RESULTS: The study population included 107 premenopausal and 132 postmenopausal women. Parameters were no different between women with low-risk and high-risk patterns. In obese postmenopausal women, the high-risk pattern mammogram group had significantly higher values of adiponectin and osteocalcin compared with the low-risk pattern group. Multiple linear regression analyses showed that adiponectin and osteocalcin levels were associated with high-risk pattern mammograms. CONCLUSION: Adiponectin and osteocalcin levels were directly associated with high-risk pattern mammograms in obese postmenopausal women. These results do not support the use of adipokines as biomarkers; nevertheless, the most important factor is to assess the risk through breast density.
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Adiponectina/sangue , Densidade da Mama/fisiologia , Mamografia , Osteocalcina/sangue , Pós-Menopausa/fisiologia , Adulto , Estudos Transversais , Feminino , Humanos , Mamografia/classificação , Mamografia/estatística & dados numéricos , México/epidemiologia , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
The gastrointestinal tract is the largest hormone-producing organ in the body due to a specialized cell population called enteroendocrine cells (EECs). The number of EECs increases in the mucosa of inflammatory bowel disease patients; however, the mechanisms responsible for these changes remain unknown. Here, we show that the pro-inflammatory cytokines interferon γ (IFNγ) and tumor necrosis factor α (TNFα) or dextran sulfate sodium (DSS)-induced colitis increase the number of EECs producing chromogranin A (CgA) in the colonic mucosa of C57BL/6J mice. CgA-positive cells were non-proliferating cells enriched with inactive phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and autophagy markers. Moreover, inhibition of Akt and autophagy prevented the increase in CgA-positive cells after IFNγ/TNFα treatment. Similarly, we observed that CgA-positive cells in the colonic mucosa of patients with colitis expressed Akt and autophagy markers. These findings suggest that Akt signaling and autophagy control differentiation of the intestinal EEC lineage during inflammation.
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Cromogranina A/metabolismo , Colo/citologia , Citocinas/farmacologia , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Células Neuroendócrinas/efeitos dos fármacos , Células Neuroendócrinas/metabolismo , Animais , Autofagia/efeitos dos fármacos , Western Blotting , Células CACO-2 , Colite/metabolismo , Imunofluorescência , Humanos , Interferon gama/farmacologia , Interleucina-1beta/farmacologia , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
BACKGROUND: One of the major limitations of umbilical cord blood (UCB) as hematopoietic stem cell source is its restricted cell number. In mothers who are candidates for stem cell donation, there are variables that affect the quantity and quality of UCB units. The aim of this study was to determine if obstetric, maternal, and fetal factors modify the number of lymphocyte subsets in UCB units. STUDY DESIGN AND METHODS: This was a prospective, observational study. In UCB units, the numbers of CD34, NK, NKT, iNKT, Type 1 dendritic cells (DCs), Type 2 DCs, T γδ, T CD4+, T CD8+ lymphocytes, CD4+CD25+FoxP3+, and CD8+CD25+FoxP3+ T regulatory (Treg) cells were quantified by flow cytometry. RESULTS: Fifty-four UCB units were included; the donors' mean weight was 75 kg (range, 52 to 102 kg) and they had a mean body mass index (BMI) of 30 kg/m(2) (range 22 to 40 kg/m(2) ), of which 12 (22%) had a normal BMI, 14 (26%) were overweight, and 28 (52%) were obese. The mean number of CD34+ cells was 4.45 × 10(6) (range, 0.7 × 10(6) to 20.5 × 10(6) ). The number of NKT, CD3+, CD4+, CD8+, and CD8+CD25+FoxP3+ Treg cells was significantly higher in overweight or obese mothers; CD34+ cells were decreased in the same group. The number of iNKT and CD34+ cells was decreased in newborns weighing above the average. CONCLUSIONS: Maternal factors such as BMI, and fetal factors such as weight at birth, should be added to the selection criteria of UCB donors.
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Sangue Fetal/citologia , Contagem de Linfócitos , Obesidade/imunologia , Adolescente , Adulto , Linfócitos T CD8-Positivos/citologia , Seleção do Doador/métodos , Feminino , Humanos , Células T Matadoras Naturais/citologia , Obesidade/sangue , Gravidez , Estudos Prospectivos , Inquéritos e Questionários , Linfócitos T Reguladores/citologia , Adulto JovemRESUMO
Brown algae and its carotenoids have been shown to have a positive influence on obesity and its comorbidities. This study evaluated the effect of Undaria pinnatifida and fucoxanthin on biochemical, physiological and inflammation markers related to obesity and on the expression of genes engaged on white adipose tissue lipid metabolism in a murine model of diet-induced obesity. The treatments improved energy expenditure, ß-oxidation and adipogenesis by upregulating PPARα, PGC1α, PPARγ and UCP-1. Adipogenesis was also confirmed by image analysis of the retroperitoneal adipose tissue, by measuring cell area, perimeter and cellular density. Additionally, the treatments, ameliorated adipose tissue accumulation, insulin resistance, blood pressure, cholesterol and triglycerides concentration in serum, and reduced lipogenesis and inflammation by downregulating acetyl-CoA carboxylase (ACC) gene expression, increasing serum concentration and expression of adiponectin as well as downregulating IL-6 expression. Both fucoxanthin and Undaria pinnatifida may be considered for treating obesity and other diseases related.
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Dieta Vegetariana/métodos , Lipogênese/efeitos dos fármacos , Obesidade/dietoterapia , Phaeophyceae/química , Undaria/química , Xantofilas/farmacologia , Acetil-CoA Carboxilase/metabolismo , Adiponectina/sangue , Adiponectina/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Biomarcadores/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Humanos , Inflamação/dietoterapia , Interleucina-6/metabolismo , Masculino , Síndrome Metabólica/dietoterapia , Obesidade/etiologia , PPAR alfa/metabolismo , PPAR gama/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Ratos Wistar , Proteína Desacopladora 1/metabolismo , Xantofilas/uso terapêuticoRESUMO
FALC cells are natural helper cells producing Th2-type cytokines, which express c-kit, Sca-1, IL7R and CD45 in mouse and human. These cells are involved in allergic responses and contribute to the inflammatory reactions of adipose tissue; however, a lack of information prevails about the presence of these cells in other species. The aim of the study was to identify and characterise FALC cells in the common carp (Cyprinus carpio) using immunohistochemistry and molecular biology techniques as well as to explore their relationships with their microenvironment. Histological description of the FALC was performed using H&E and polyclonal antibodies were used against cell-surface markers such as c-kit, Sca-1 and CD45. Furthermore, gene expression of c-kit, Sca-1 and IL7R was assessed. C. carpio FALC cells express the same surface markers reported in FALC of the mouse at both the pre- and post-transcriptional level. By exposure to the soluble fraction of helminths, FALC cells produce abundant Th2 cytokines (IL-5, IL-6 and IL-13) but do not synthesise IL-1α. Additionally, FALC cells probably participate in vascular remodelling of the intestine vessels, inducing tumours because a malignant haemangiosarcoma in the peritoneal cavity was found. In this tumour, abundant FALC with their characteristic cell-surface markers were detected. The findings of this study suggest the involvement of some proto-oncogenes such as c-kit and Sca-1, and the deregulation of Src kinases modulated by CD45 present in C. carpio FALC with the ontogeny of peritoneal haemangiosarcoma in this fish species.
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Carpas/imunologia , Doenças dos Peixes/imunologia , Hemangiossarcoma/veterinária , Gordura Intra-Abdominal/imunologia , Tecido Linfoide/imunologia , Neoplasias Peritoneais/veterinária , Análise de Variância , Animais , Sequência de Bases , Análise por Conglomerados , Citocinas/biossíntese , Primers do DNA/genética , DNA Complementar/genética , Ensaio de Imunoadsorção Enzimática , Hemangiossarcoma/imunologia , Imuno-Histoquímica/veterinária , Antígenos Comuns de Leucócito/genética , Antígenos Comuns de Leucócito/metabolismo , Funções Verossimilhança , Tecido Linfoide/citologia , Tecido Linfoide/metabolismo , Modelos Genéticos , Dados de Sequência Molecular , Neoplasias Peritoneais/imunologia , Filogenia , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Receptores de Interleucina-7/genética , Receptores de Interleucina-7/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNARESUMO
BACKGROUND: To determine the activity of antithrombin (AT), protein C (PC), and protein S (PS), as well as the frequency of deficiencies of these proteins in a population of healthy Mexican mestizo blood donors. METHODS: AT, PC, and PS were determined from 1,502 plasma samples of healthy blood donors by using commercial kits in a coagulometer 4 STA (Diagnostica Stago, Asnières, France). RESULTS: A total of 741 women and 761 men were under study. They were divided into age range groups (18-24, 25-34, 35-44, 45-54, and 55-64 years). Activity of AT, PC, and PS was determined. For AT, activity values were specific for each age group according to gender when it had to do with PS, as well as when PC was determined. Frequencies of AT, PC, PS, and activated PC resistance activity deficiencies were obtained from reference levels (RLs) and average levels of this study. Differences were found between both frequencies for AT, PC, and PS, and the average levels obtained were used in this study. The frequencies of the activity deficiencies obtained through the values gotten in this population were: AT, 0.6%; PC, 1.06% (which is higher than the one obtained using the RLs described by commercial kits 0.33% and 0.66%, respectively); and PS, 1% (which is less than 4.5%). CONCLUSIONS: It is necessary to know the characteristics and biological behavior of the coagulation proteins in the Mexican population because the RLs used have been established for populations that are genetically different.
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Transtornos da Coagulação Sanguínea/etnologia , Fatores de Coagulação Sanguínea/análise , Coagulação Sanguínea , Doadores de Sangue , Indígenas Norte-Americanos , Adolescente , Adulto , Deficiência de Antitrombina III/sangue , Deficiência de Antitrombina III/diagnóstico , Deficiência de Antitrombina III/etnologia , Proteínas Antitrombina/análise , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Testes de Coagulação Sanguínea , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteína C/análise , Deficiência de Proteína C/sangue , Deficiência de Proteína C/diagnóstico , Deficiência de Proteína C/etnologia , Proteína S/análise , Deficiência de Proteína S/sangue , Deficiência de Proteína S/diagnóstico , Deficiência de Proteína S/etnologia , Adulto JovemRESUMO
BACKGROUND: To identify inherited factors: Protein C (PC), protein S (PS), antithrombin (AT), plasminogen (Plg), the activated PC resistance (APCR), prothrombin (PT) mutation G20210 A (PTG20210 A) and methylenetetrahydrofolate reductase C677 T polymorphism (MTHFR C677 T), as well as acquired-risk factors such as: diabetes mellitus, surgeries, smoking, obesity, hypertension, trauma, alcoholism, family history; and their association, in Mexican patients with diagnostic of thrombophilia. METHODS: Overall, 200 patients diagnosed with thrombophilia and 100 healthy controls. Commercial kits were used for the coagulometric tests and polymerase chain reaction, restriction fragment length polymorphism for molecular alterations. RESULTS: Alterations were found with an estimated prevalence to PC 0.65%, AT 2.04% and Plg 2.5%, APCR 2%, PT 20210 2%, and MTHFR 65%. The C677 T polymorphism of the MTHFR did not associate with acquired-risk factors so we can suppose that it is an independent risk factor. For the patients that only presented acquired-risk factors (21 of 200), the association smoking-alcoholism showed to be the cause of thrombosis with high risk. The following were also associated: smoking with AT, PC, and alcoholism; obesity with Plg; smoking with alcoholism, and PS deficiency. CONCLUSIONS: Risk factors for both primary and secondary and their association were present as a cause of thrombosis in the patients studied, and the possibility to suffer a recurrent thrombosis.
Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação/genética , Plasminogênio/deficiência , Protrombina/genética , Trombofilia/etiologia , Trombose/etiologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , México , Fenótipo , Fatores de Risco , Trombofilia/diagnóstico , Adulto JovemRESUMO
BACKGROUND: PAI-1 is the main inhibitor of fibrinolysis. Increase in PAI-1 levels has been associated with the risk of coronary disease; however, there are few studies on the relationship between subclinical atherosclerosis and PAI-1 levels. OBJECTIVE: The aim of this study was to analyze the relationship between PAI-1 level and carotid intima-media thickness in premenopausal and postmenopausal women without apparent cardiovascular disease. MATERIAL AND METHODS: A cross-sectional study was conducted in 142 women aged 45 to 60 years with no history of cardiovascular disease. Anthropometric and laboratory measurements were performed, including PAI-1 levels. All participants underwent a B-Mode ultrasound to measure intima-media thickness. Subclinical atherosclerosis was considered when intima-media thickness was ≥ 0.7 mm and/or an atheromatous plaque was observed. RESULTS: Postmenopausal women had greater intima-media thickness than premenopausal women (0.688 ± 0.129 vs. 0.621 ± 0.113 mm; p < 0.05). Compared to women with normal intima-media thickness, women with subclinical atherosclerosis had higher PAI-1 levels (23.2 ± 13.7 vs. 30.4 ± 20.7 ng/ml; p < 0.05). In all participants, intima-media thickness correlated with PAI-1 (r = 0.302; p = 0.01) and with age (r = 0.358; p = 0001). CONCLUSIONS: An increase in intima-media thickness was observed in postmenopausal women compared with premenopausal women. Asymptomatic women with increased intima-media thickness had higher PAI-1 levels. These findings suggest that fibrinolytic activity is low in the subclinical stage of atherosclerosis.
Assuntos
Aterosclerose/patologia , Espessura Intima-Media Carotídea , Inibidor 1 de Ativador de Plasminogênio/sangue , Pós-Menopausa , Aterosclerose/epidemiologia , Estudos Transversais , Feminino , Fibrinólise/fisiologia , Humanos , Pessoa de Meia-Idade , Pré-MenopausaRESUMO
INTRODUCTION: Thrombosis is one of the leading causes of morbidity and mortality worldwide. Venous thromboembolic disease (VTD) is considered a new epidemic. FXII deficiency is supposed to be a cause of thrombosis. To search for unknown causes of thrombosis in our population, our aim was to determine if FXII deficiency can be considered a risk factor for VTD. METHODS: Young adult Mexican patients with at least one VTD episode and healthy controls were included in this prospective, observational, controlled study. Liver and renal function tests, blood cytometry, and blood coagulation assays were performed. Plasma FXII activity and its concentration were evaluated. RESULTS: Over a two-year period, 250 patients and 250 controls were included. FXII activity was significantly lower in the control group compared to patients with VTD (p = 0.005). However, percentage of patients and controls with FXII deficiency was 8.8 and 9.2%, respectively (p = 1.000). No significant association was found between FXII deficiency and VTD (p = 1.0). FXII plasma concentration was lower in controls vs. patients with VTD: 4.05 vs. 6.19 ng/mL (p <0.001). Percentage of patients with low FXII plasma concentration was 1.6% and 6.0% in patients and controls, respectively (p = 0.010). CONCLUSIONS: FXII deficiency is a frequent finding in patients with VTD and controls in Mexico. Some patients with FXII deficiency had normal APTT result, an effect not described above. FXII plasma concentration was lower in patients with low activity.
Assuntos
Deficiência do Fator XII , Trombose , Humanos , Adulto Jovem , Deficiência do Fator XII/complicações , Deficiência do Fator XII/epidemiologia , México/epidemiologia , Prevalência , Estudos Prospectivos , Fator XII/metabolismoRESUMO
Legg-Calve-Perthes disease (LCPD) is an idiopathic avascular necrosis of the pediatric femoral head. Bone remodeling and bone structural genes have the potential to contribute to the progression of LCPD when there is disequilibrium between bone resorption and bone formation. A case-control study was performed to search for associations of several common polymorphisms in the genes Receptor Activator for Nuclear Factor κappa B (RANK), Receptor Activator for Nuclear Factor κappa B Ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, and type 1 collagen (COL1A1) with LCPD susceptibility in Mexican children. A total of 23 children with LCPD and 46 healthy controls were genotyped for seven polymorphisms (rs3018362, rs12585014, rs2073618, rs1800795, rs1800796, rs1800012, and rs2586498) in the RANK, RANKL, OPG, IL-6, and COL1A1 genes by real-time polymerase chain reaction with TaqMan probes. The variant allele (C) of IL-6 rs1800795 was associated with increased risk of LCPD (odds ratio [OR]: 3.8, 95% confidence interval [CI]: [1.08-13.54], p = 0.033), adjusting data by body mass index (BMI) and coagulation factor V (FV), the association with increased risk remained (OR: 4.9, 95% CI: [1.14-21.04], p = 0.025). The OPG polymorphism rs2073618, specifically GC-GG carriers, was associated with a more than fourfold increased risk of developing LCPD (OR: 4.34, 95% CI: [1.04-18.12], p = 0.033) when data were adjusted by BMI-FV. There was no significant association between RANK rs3018362, RANKL rs12585014, IL-6 rs1800796, COL1A1 rs1800012, and rs2586498 polymorphisms and LCPD in a sample of Mexican children. The rs1800975 and rs2037618 polymorphisms in the IL-6 and OPG genes, respectively, are informative markers of increased risk of LCPD in Mexican children.
Assuntos
Remodelação Óssea , Predisposição Genética para Doença , Interleucina-6 , Doença de Legg-Calve-Perthes , Osteoprotegerina , Polimorfismo de Nucleotídeo Único , Ligante RANK , Humanos , Osteoprotegerina/genética , Doença de Legg-Calve-Perthes/genética , Interleucina-6/genética , Masculino , Feminino , México , Criança , Estudos de Casos e Controles , Remodelação Óssea/genética , Ligante RANK/genética , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I/genética , Pré-Escolar , Receptor Ativador de Fator Nuclear kappa-B/genéticaRESUMO
BACKGROUND: Legg-Calvé-Perthes disease (LCPD) is a pediatric disorder that occurs due to the avascular necrosis of the femoral head and affects the range of motion of the hip in various degrees. Its etiology is still unknown, although it has been associated with coagulation abnormalities, however, the lack of reproducibility in the results in various studies has created a controversy as to whether hemostasis disorders are related to LCPD. On the other hand, there is little information on laboratory studies that could facilitate the diagnosis and treatment of LCPD. METHODS: Blood and plasma samples were tested from 25 patients with LCPD and 50 healthy controls, matched by sex and age. Cellular markers were evaluated through complete blood count, as well as coagulation times, coagulation factors activity, antithrombotic proteins, and homocysteine concentration. RESULTS: After assessing activity value frequencies in each group, the results showed more significant activity in some of the biological risk markers of thrombophilia, presenting a substantial difference in prothrombin timeâ, FVâ, FVIIIâ, FIXâ, and Hcyâ. These values imply that there may be hypercoagulable states in patients, which can cause thrombotic events. CONCLUSIONS: Diminished prothrombin time and increase in FV activity, FVIII, FIX, and Hcy concentration support the hypothesis that microthrombi formation in small-caliber vessels could be causing avascularity and femoral necrosis, which are traits of LCPD. In addition, based on our results, we believe that the laboratory studies carried out are very useful in the diagnosis and treatment of LCPD.