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BACKGROUND: Circulating T follicular helper (cTfh) and T peripheral helper (Tph) subpopulations are shown to be higher in systemic lupus erythematosus (SLE) patients and have been involved in promoting extrafollicular B cell responses. However, a possible association with the B cell activating factor (BAFF), a cytokine mainly related to B cell responses and disease activity in SLE, has not been investigated. Therefore, this study aimed to evaluate the association of cTfh and Tph subpopulations with the BAFF system expression and clinical activity in SLE patients. METHODS: This study included 43 SLE patients and 12 healthy subjects (HS). The identification of cTfh (CD4+CXCR5+PD-1+), Tph (CD4+CXCR5-PD-1+) cells, expression of membrane-bound BAFF (mBAFF), BAFFR, TACI, BCMA, and intracellular IL-21 was performed by flow cytometry. Serum levels of IL-21, CXCL13, and BAFF were analyzed using ELISA. The SLEDAI-2K score was used to evaluate disease activity in SLE patients. RESULTS: Compared with HS, SLE patients showed a significantly increased percentage of cTfh and Tph cells, higher in patients with clearly active disease. SLE patients had markedly higher IL-21-producing cTfh and Tph cells than HS. Both subpopulations were positively correlated with the disease activity in SLE patients. Tph cells were negatively correlated with CD19+CXCR5+ B cells and positively correlated with CD19+CXCR5- B cells. A low expression of mBAFF and their receptors TACI and BCMA was found on cTfh and Tph cells in SLE patients and HS. However, SLE patients with clearly active disease showed decreased expression of BAFFR on cTfh and Tph subpopulations than patients with mildly active/nonactive disease. Serum IL-21, CXCL13, and BAFF levels were higher in SLE patients than in HS. Levels of CXCL13 were correlated with disease activity. Non-significant correlations were observed among T cell subpopulations and IL-21, CXCL13, and BAFF levels. CONCLUSIONS: This study emphasizes the importance of cTfh and Tph cells in SLE pathogenesis. Besides the importance of IL-21, our results suggest that BAFFR could play a role in cTfh and Tph subpopulations in the autoimmunity context.
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Lupus Eritematoso Sistémico , Humanos , Antígeno de Maduración de Linfocitos B , Linfocitos T CD4-Positivos , Receptor de Muerte Celular Programada 1/metabolismo , Receptores CXCR5/metabolismo , Linfocitos T Colaboradores-InductoresRESUMEN
BACKGROUND: CD40 is a transmembrane protein mainly expressed on the antigen-presenting cells surface. CD40 plays a crucial role in immunoglobulin class switching and antibodies production. Genetic polymorphisms in the CD40 gene have been associated with increased risk of systemic lupus erythematosus (SLE) in several populations. This study aimed to evaluate the association of CD40 polymorphisms (-1 C > T, rs1883832 and 6,048 G > T, rs4810485) with SLE susceptibility, as well as with mRNA expression and soluble CD40 (sCD40) levels. METHODS: The study included 293 patients with SLE and 294 control subjects (CS). Genotyping was performed by PCR-RFLP method. CD40 mRNA expression was determined by quantitative real-time PCR, and ELISA quantified sCD40 levels. RESULTS: The CD40 polymorphisms -1 C > T and 6,048 G > T were associated with SLE susceptibility. There was no difference between CD40 mRNA expression and CD40 polymorphisms. The sCD40 levels were lower in SLE patients with TT haplotype, whereas higher sCD40 levels were associated with damage and impaired renal function according to SLICC and KDIGO. The sCD40 levels were negatively correlated with eGFR. CONCLUSION: The CD40 gene polymorphisms increase the risk of SLE in the western Mexican population. The sCD40 levels are associated with -1 C > T polymorphism and chronic kidney disease.
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Antígenos CD40/genética , Lupus Eritematoso Sistémico/genética , Polimorfismo Genético , Insuficiencia Renal Crónica/genética , Adulto , Antígenos CD40/metabolismo , Regulación hacia Abajo , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Lupus Eritematoso Sistémico/metabolismo , Masculino , México , Persona de Mediana Edad , Insuficiencia Renal Crónica/metabolismoRESUMEN
BACKGROUND: CD40 is a costimulatory molecule for B cells, and CD154 is a marker of CD4+ T cells activation. CD40-CD154 interaction promotes pro-inflammatory cytokines secretion and autoantibodies production. PTPN22 gene encodes LYP protein, an inhibitor of T- and B-cell activation. PTPN22 1858C>T polymorphism confers rheumatoid arthritis (RA) susceptibility. Hence, we evaluate the relationship between 1858C>T polymorphism with CD40 and CD154 expression and IFN-γ secretion in RA patients. METHODS: PTPN22 1858C>T polymorphism was genotyped in 315 RA patients and 315 control subjects (CS) using PCR-RFLP method. Later, we selected only ten anti-CCP-positive RA patients, naïve to disease-modifying antirheumatic drugs and ten CS, all with known 1858C>T PTPN22 genotype. The CD40 and CD154 membrane expressions were determined by flow cytometry in peripheral B and T cells, correspondingly. RESULTS: The B cells percentage and mCD40 expression were similar between RA and CS (P > 0.05) and we did not find an association between these variables and the 1858C>T polymorphism. The CD4+ T cells percentage was higher in RA patients than CS (P = 0.003), and in the RA group, the CD4+ T cells percentage and mCD154 expression were higher in the 1858 T allele carriers (P = 0.008 and P = 0.032, respectively). The IFN-γ levels were lower in RA patients carrying the PTPN22 risk allele (P = 0.032). CONCLUSION: The PTPN22 1858 T risk allele is associated with increased CD4+ T cells percentage and high mCD154 expression in RA patients, which could favor the pro-inflammatory cytokine release and the establishment of the inflammatory response at the seropositive RA.
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Artritis Reumatoide/genética , Linfocitos T CD4-Positivos/inmunología , Ligando de CD40/genética , Predisposición Genética a la Enfermedad/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Adulto , Anciano , Artritis Reumatoide/epidemiología , Ligando de CD40/análisis , Ligando de CD40/metabolismo , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Humanos , Interferón gamma/sangre , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
BACKGROUND: Systemic lupus erythematosus (SLE) is the prototype of systemic autoimmune disease, characterized by loss of immune tolerance against self-antigens where autoantibody production is the hallmark of disease. B-cell-activating factor (BAFF) and A proliferation-inducing ligand (APRIL) are cytokines that promote autoreactive cell survival, immunoglobulin-class switching and autoantibody responses in human and mouse SLE models. BAFF and APRIL exert their functions through interactions with their receptors BAFF-R and TACI that are differentially expressed in B lymphocyte subsets, monocytes, dendritic cells and T lymphocytes. BAFF stimulation favors T lymphocyte activation and cytokine production through BAFF-R, which could contribute to the Th1, Th17 and/or Th2 response dysregulation observed in SLE patients. OBJECTIVE: To evaluate the expression of the cytokines BAFF and APRIL and their association with the receptors BAFF-R and TACI on CD3+ T cells and to evaluate Th1/Th2/Th17 cytokine profile in patients with SLE. METHODS: Fifteen healthy controls (HC) and 36 SLE patients were included, and their demographic and clinical data were assessed. The disease activity index (Mex-SLEDAI) and damage index (SLICC) were applied to the SLE patients. BAFF-R and TACI expression on CD3+ T cells were evaluated by flow cytometry. Serum BAFF and APRIL concentrations were measured by enzyme-linked immunosorbent assays (ELISA). Cytokine levels of Th1 (IL-12, IL-2, IFN-γ, TNF-α), Th2 (IL-4, IL-6, IL-10, IL-13) and Th17 (IL-1ß e IL-17) were quantified with a multiplex assay (MAGPIX). Statistical analysis was performed using PASW Statistics v.20 and GraphPad Prism v.6 software. RESULTS: No differences in BAFF-R or TACI expression on the CD3+ T cells of SLE and HC were observed. BAFF-R expression correlates inversely with disease activity (râ¯=â¯-0.538, pâ¯<â¯0.01), while TACI correlates with disease activity (râ¯=â¯0.530, pâ¯<â¯0.05). Serum BAFF and APRIL levels were high in SLE patients and correlated with the disease activity index Mex-SLEDAI (râ¯=â¯0.621, pâ¯<â¯0.01 and râ¯=â¯0.416, pâ¯<â¯0.05). SLE patients were found to have significantly higher levels of IL-12, IFN-γ, TNF-α, IL-6, IL-10, IL-13, IL-1ß and IL-17 compared to HC (pâ¯<â¯0.05). Cytokines IL-17 (râ¯=â¯0.526) and TNF-α (râ¯=â¯0.410) correlate with disease activity (pâ¯<â¯0.05), while APRIL (râ¯=â¯0.477), IL-10 (râ¯=â¯0.426) and IFN-γ (râ¯=â¯0.440) levels were associated with organ damage (pâ¯<â¯0.01). Serum BAFF expression levels correlate with IL-4 (râ¯=â¯0.424; pâ¯<â¯0.05), IL-6 (râ¯=â¯0.420; pâ¯<â¯0.05) and IL-10 (râ¯=â¯0.459; pâ¯<â¯0.01), whereas APRIL levels correlate with IL-2 (râ¯=â¯0.666; pâ¯<â¯0.01), IL-12 (râ¯=â¯0.611; pâ¯<â¯0.01) and TNF-α (râ¯=â¯0.471; pâ¯<â¯0.05) cytokines. A subgroup of SLE patients with high serum BAFF levels (>2â¯ng/mL) also showed increased APRIL, IL-2, IL-6 and IL-10 levels (pâ¯<â¯0.05). Finally, BAFF, IL-4 and TNF-α serum levels were associated with high titers of antinuclear antibodies. CONCLUSIONS: The study demonstrates an imbalance in the Th1/Th2 cytokine profile, with increased proinflammatory cytokines, as well as BAFF and APRIL serum levels. Associations of BAFF with Th2 profile cytokines and disease activity, as well as APRIL with Th1 profile cytokines and organ damage, suggest that BAFF and APRIL generated in the autoimmunity context could through still unknown mechanisms, modulate the microenvironment, and perpetuate the inflammatory response, autoantibody production and organ damage observed in SLE patients.
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Factor Activador de Células B/metabolismo , Receptor del Factor Activador de Células B/metabolismo , Citocinas/sangre , Lupus Eritematoso Sistémico/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Proteína Activadora Transmembrana y Interactiva del CAML/metabolismo , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Adulto , Autoanticuerpos/sangre , Complejo CD3/metabolismo , Femenino , Humanos , Lupus Eritematoso Sistémico/sangre , Persona de Mediana Edad , Adulto JovenRESUMEN
Introduction: Prolactin (PRL) is a 23-kDa protein that can be synthesized and secreted by pituitary and extrapituitary tissues such as immune cells due to its expression being regulated by two independent promoter regions. The promoter which is responsible for extrapituitary expression contains the single nucleotide polymorphism (SNP) -1149 G/T previously associated with autoimmune diseases in various populations. This study evaluates the relationship of PRL -1149 G/T polymorphism with PRL serum levels and clinical characteristics in systemic lupus erythematosus (SLE) patients from western Mexico. Material and methods: One hundred and sixty-three SLE patients classified according to the 1982 American College of Rheumatology (ACR) SLE classification criteria and 326 unrelated control subjects (CS), both from western Mexico, were included. The PRL -1149 G/T polymorphism was genotyped using the polymerase chain reaction restriction fragment length polymorphism technique, and both PRL serum levels and autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA). Results: We found an association between the PRL -1149 TT genotype and SLE according to the recessive genetic model (OR = 2.26, 95% CI: 1.01-5.08, p = 0.04). The TT genotype was associated with anti-RNP antibodies (p = 0.04) and with higher scores of the Mex-SLEDAI (p = 0.02). Moreover, SLE patients showed elevated PRL serum levels (12.4 ng/ml; p < 0.01), and this condition was associated with renal activity and the presence of anti-RNP antibodies. Conclusions: PRL -1149 TT genotype is associated with susceptibility to SLE in a Mexican-Mestizo population, and high PRL serum levels are associated with anti-RNP antibodies and renal activity.
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Resumen: Objetivo: Evaluar la precisión de Raypex 6 para localizar el foramen y ubicarse en la zona cemento dentina conducto (CDC) en conductos de molares inferiores por medio de diafanización. Material y métodos: 52 conductos permeables de 20 molares inferiores extraídos inmersos en alginato fueron utilizados. Se realizó abertura coronaria, localización, permeabilización e irrigación con hipoclorito de sodio al 5.25%. Con el localizador electrónico Raypex 6 se obtuvo conductometría electrónica. Se introdujo lima tipo K #15 o 20 en cada muestra que tenía el clip labial inserto en alginato. La pantalla del dispositivo indicó la posición del foramen apical en la barra roja y se procedió a reajustar la posición de la lima K en las dos primeras barras amarillas y la lima se fijó con resina acrílica. Los dientes se diafanizaron por medio de la técnica de ácido nítrico y se mantuvieron en salicilato de metilo. Las muestras se analizaron con microscopio clínico a 16x y de manera subjetiva se asignó el valor de preciso, si la punta de la lima se ubicó entre 0 a -0.5 mm, fuera o positivo (+) si la lima estuvo +0.1 mm o más y corto o negativo (-) si fue de -0.51 mm o menos con respecto al foramen apical. Resultados: De las 52 muestras analizadas, se encontraron 40 precisas, siete largas y cinco cortas. La estadística descriptiva demostró 76.9% de precisión. Conclusión: La longitud de trabajo electrónica con Raypex 6 mostró una adecuada precisión en conductos mesiales de molares inferiores.
Abstract: Objective: To assess precision of Raypex 6 to locate foramen and establish placement in the canal -dentin-cement (CDC) area in lower molar canals by means of diaphanization. Material and methods: 52 permeable canals from 20 extracted lower molars immersed in alginate were used. Crown opening, location, permeabilization and irrigation with 5.25% sodium hypochlorite were performed. Electronic conductometry was obtained with Raypex 6 electronic locator. A K #15/20 file type was inserted in all samples which had labial clip inserted in alginate. The device's screen indicated position of the apical foramen in the red bar, K files position was readjusted in the first two yellow bars, the file was then fixated with acrylic resin. Teeth were diaphanized by means of the nitric acid technique; teeth were kept in methyl salicylate. Samples were analyzed with clinical microscope at 16x, they were subjectively assigned a value called precise when the tip of the file was located at 0-0.5 mm, external or positive (+), when the file was +0.1 mm or more, and short or negative (-) when it was -0.51 mm or less with respect to the apical foramen. Results: Of the 52 analyzed samples, 40 were found to be precise, seven long and five short. Descriptive statistics showed 76.9% precision. Conclusion: Electronic working length with Raypex 6 showed suitable precision in mesial canals of lower molars.
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Prolactin (PRL) is associated with different types of cancer, such as cervical cancer. Recombinant PRL has antiapoptotic effect on cervical cancer cells, and it can also induce cytokine production on macrophages. A 60 kDa variant of PRL is produced by cervical cancer cells. The aim of the present study was to evaluate this variant's bioactivity, to test its effect on cervical cancer cell apoptosis, and to assess its ability to induce cytokine production on THP-1 macrophages. First, 60 kDa PRL was isolated and used to stimulate Nb2 cells. Later, apoptosis was measured after exposure to 60 kDa PRL. Finally, cytokines were measured on THP-1 stimulated supernatants. Our results show that 60 kDa PRL increased Nb2 cell proliferation. Apoptosis was decreased after stimuli with 60 kDa PRL in cervical cancer cells. IL-1ß and TNF-α are produced by THP-1 macrophages after stimuli. These results suggest that 60 kDa PRL produced by cervical cancer cells is able to reduce apoptosis in HeLa, SiHa and C-33A cells and induce IL-1ß and TNF-α production by THP-1 macrophages.
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Apoptosis , Citocinas/biosíntesis , Prolactina/fisiología , Neoplasias del Cuello Uterino/metabolismo , Animales , Línea Celular , Línea Celular Tumoral , Femenino , Células HeLa , Humanos , Interleucina-1beta/biosíntesis , Macrófagos/inmunología , Prolactina/aislamiento & purificación , Prolactina/metabolismo , Isoformas de Proteínas/aislamiento & purificación , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/fisiología , Ratas , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Introduction: The precise localization of the apical foramen and the odontometry determination is an important stage since it locates the apical limit for instrumentation and filling. Objective: To compare the accuracy of Root-ZX Mini and Raypex 6 in locating apical foramen in extracted molars. Material and methods: 80 mesial and buccal canals from 40 mandibular and maxillary human molars were used. A size #15 K-file was introduced to canal, until the locator indicated the apical foramen (red bar/line in both devices). With the file in position, it was re-adjusted for Root-ZX II Mini on the green bar and on the two yellow bars for Raypex 6. All the samples were measured from the tip of the file to the apical foramen with radiovisiograph and the Sidexis software. The apical third of the root was shaved until exposure of the file. The distance from the file tip to the most coronal border of the apical foramen was obtained and it was measured with a clinical microscope at 16-fold magnification. The measured lengths with the radiovisiograph and the clinical microscope were analyzed with the statistical Student's T-test. Results: The average length from the tip of the file to the apical foramen using Root-ZX Mini was 0.695 mm and 0.543 mm with Raypex 6. There was no significant difference. Conclusion: Two devices were accurate in locating apical foramen with an adequate level of reliability.
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AIM: The case of a lower molar with apical periodontitis, which had previous root canal treatment and a fractured instrument in the distal root beyond the foramen, is presented. BACKGROUND: The simultaneous presence of a foreign body (endodontic instrument or material) in periapical tissues and microorganisms in the root canal, are etiological factors in the formation or maintenance of a periapical lesion, and can lead to failure in endodontic treatment. CASE DESCRIPTION: This instrument was removed through the staging platform technique, by using ultrasound and an Instrument removal system (IRS) microtube under microscope visual amplification. All the canals were re-instrumented, irrigated with sodium hypochlorite and passive ultrasonic irrigation, removal of smear layer and intracanal medication with calcium hydroxide for 8 days, after which they were filled. The symptoms disappeared and clinical and radiograph 2-year follow-up shows healing of periapical tissues. CONCLUSION: The combined use of visual magnification microscope, ultrasound and the IRS system by staging platform technique, allowed the removal of an endodontic instrument beyond the foramen, which made it possible to apply a conventional disinfection protocol. CLINICAL SIGNIFICANCE: Endodontic re-treatment by conservative approach of complicated cases it is an option with good clinical prognosis, before apical surgery or extraction.
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Cuerpos Extraños/terapia , Tejido Periapical/patología , Preparación del Conducto Radicular/instrumentación , Adulto , Hidróxido de Calcio/uso terapéutico , Falla de Equipo , Femenino , Estudios de Seguimiento , Gutapercha/uso terapéutico , Humanos , Microcirugia/métodos , Absceso Periapical/terapia , Periodontitis Periapical/terapia , Retratamiento , Materiales de Obturación del Conducto Radicular/uso terapéutico , Irrigantes del Conducto Radicular/uso terapéutico , Preparación del Conducto Radicular/efectos adversos , Hipoclorito de Sodio/uso terapéutico , Diente no Vital/terapia , Terapia por Ultrasonido/instrumentación , Terapia por Ultrasonido/métodosRESUMEN
Introdução: estabelecer o comprimento de trabalho durante o tratamento do canal radicular e muito importante, uma vez que permite que os procedimentos clínicos sejam realizados respeitando os limites do canal. Objetivo: o objetivo deste artigo e relatar cinco casos nos quais o tratamento do canal radicular foi realizado por meio de um método eletrônico sem radiografia transoperatória. Métodos: trés molares superiores e dois molares inferiores foram diagnosticados com pulpite irreversível ou necrose pulpar. Os casos foram tratados na Clinica de Endodontia do Hospital Militar Regional de Guadalajara, México, mediante assinatura de consentimento livre e esclarecido, por parte dos pacientes. O comprimento de trabalho do canal radicular foi determinado com a ajuda de um localizador apical Raypex 6 sem tomada radiográfica. Todos os canais radiculares foram preparados por meio do sistema de instrumentação Reciproc e obturados por meio da técnica hibrida de Tagger. Resultados: no controle radiográfico pós-operatório, observou-se que o nível de preenchimento do canal radicular, em 12 dos 14 canais, foi de 0 a 2 mm do ápice apical. Conclusão: os resultados do presente estudo sugerem que condutimetria e um método confiável para determinar o comprimento de trabalho, alem de reduzir o numero de tomadas radiográficas durante o tratamento do canal radicular.
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Humanos , Adulto Joven , Endodoncia , Preparación del Conducto Radicular/instrumentación , Obturación del Conducto Radicular , Tratamiento del Conducto Radicular , Tecnología OdontológicaRESUMEN
Introdução: fusão dentária é uma anomalia de desenvolvimentoem que dois germes dentários unem-se umao outro em níveis diferentes. Objetivo: relatar um casode canino inferior e incisivo lateral inferior com coroasseparadas e fusão de raiz, com seus canais radicularesconectados e periodontite apical. Métodos: um anoantes, a paciente recebeu tratamento de canal no canino,porém, não houve remissão dos sintomas. O tratamentoendodôntico foi realizado com reinstrumenta-ção, irrigação ultrassônica passiva com hipoclorito desódio, remoção de smear layer e medicação intracanalcom hidróxido de cálcio. Uma semana depois, os sintomasdesapareceram e os canais foram obturados comguta-percha e Sealapex, utilizando a técnica híbrida deTagger. Resultados: após dois anos e dois meses, o pacienteapresentou cicatrização dos tecidos periapicais.Conclusão: a detecção e manejo adequado dos casosde anomalias do desenvolvimento dentário são obrigatóriospara o sucesso do tratamento.
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Humanos , Femenino , Adulto , Dientes Fusionados/terapia , Retratamiento , Anomalías DentariasRESUMEN
INTRODUCTION: During chemomechanical instrumentation, several liquid or paste substances are used to ease the action of the files and to eliminate debris and the smear layer. The aim of this study was to evaluate whether the use of a paste containing EDTA during cleaning and shaping of the root canal helps to eliminate debris. METHODS: Twenty root canals in dog teeth were instrumented by a crown-down technique by using nickel-titanium rotary files. In 10 root canals (group A), sodium hypochlorite was used during instrumentation, followed by a final irrigation with 17% liquid EDTA. In another 10 canals (group B), sodium hypochlorite was again used as the irrigating solution, but Glyde File Prep paste was used with every instrument, and a final irrigation with EDTA was also carried out. Two additional teeth were used as positive and 2 as negative controls. The jaws were prepared for histologic evaluation. RESULTS: In group A where Glyde was not used during cleaning and shaping, little or no debris was found in the apical third of the instrumented root canals; however; in group B in which Glyde File Prep paste was used during chemomechanical instrumentation, moderate to high accumulation of debris was observed in the apical third. CONCLUSIONS: The use of Glyde File Prep paste during rotary mechanical instrumentation favors the accumulation of debris in the apical third of the root canals. Irrigation with NaOCl and a final flush with EDTA by means of a small-gauge needle with simultaneous aspiration led to less accumulation of debris than in the Glyde File Prep group (P < .05).
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Cavidad Pulpar/patología , Irrigantes del Conducto Radicular/uso terapéutico , Preparación del Conducto Radicular/métodos , Capa de Barro Dentinario/patología , Hipoclorito de Sodio/uso terapéutico , Ápice del Diente/patología , Animales , Aleaciones Dentales/química , Cavidad Pulpar/efectos de los fármacos , Perros , Ácido Edético/administración & dosificación , Ácido Edético/uso terapéutico , Diseño de Equipo , Masculino , Agujas , Níquel/química , Pomadas , Distribución Aleatoria , Irrigantes del Conducto Radicular/administración & dosificación , Preparación del Conducto Radicular/instrumentación , Capa de Barro Dentinario/tratamiento farmacológico , Soluciones , Succión/instrumentación , Titanio/químicaRESUMEN
INTRODUCTION: Autoantibodies to RNA helicase A (RHA) were reported as a new serological marker of systemic lupus erythematosus (SLE) associated with early stage of the disease. Anti-RHA and other autoantibodies in Mexican SLE patients and their correlation with clinical and immunological features were examined. METHODS: Autoantibodies in sera from 62 Mexican SLE patients were tested by immunoprecipitation of 35S-labeled K562 cell extract and enzyme-linked immunosorbent assay (anti-U1RNP/Sm, ribosomal P, beta2GPI, and dsDNA). Anti-RHA was screened based on the immunoprecipitation of the 140-kDa protein, the identity of which was verified by Western blot using rabbit anti-RHA serum. Clinical and immunological characteristics of anti-RHA-positive patients were analyzed. RESULTS: Anti-RHA was detected in 23% (14/62) of patients, a prevalence higher than that of anti-Sm (13%, 8/62). Prevalence and levels of various autoantibodies were not clearly different between anti-RHA (+) vs. (-) cases, although there was a trend of higher levels of anti-RHA antibodies in patients without anti-U1RNP/Sm (P = 0.07). Both anti-RHA and -Sm were common in cases within one year of diagnosis; however, the prevalence and levels of anti-RHA in patients years after diagnosis did not reduce dramatically, unlike a previous report in American patients. This suggests that the high prevalence of anti-RHA in Mexican patients may be due to relatively stable production of anti-RHA. CONCLUSIONS: Anti-RHA was detected at high prevalence in Mexican SLE patients. Detection of anti-RHA in races in which anti-Sm is not common should be clinically useful. Racial difference in the clinical significance of anti-RHA should be clarified in future studies.
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Autoanticuerpos/sangre , ARN Helicasas DEAD-box/inmunología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Proteínas de Neoplasias/inmunología , Adulto , Edad de Inicio , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Western Blotting , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoprecipitación , México , Persona de Mediana Edad , Prevalencia , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Systemic lupus erythematosus in some cases is characterized for development of thrombotic events with a significantly increased risk of mortality. The frequencies and clinical associations of Ser(413)/Cys(413) PAI-2 polymorphism in 40 systemic lupus erythematosus, 50 rheumatoid arthritis patients, and 100 healthy subjects were investigated. The Ser(413)/Ser(413) genotype frequency was 53% (lupus), 36% (rheumatoid arthritis), and 35% (healthy subjects). The Ser(413) allele was associated with systemic lupus erythematosus (P = .04, odds ratio = 1.76, 95% confidence interval = 1.01-3.06). In all, 4 patient carriers of Ser(413)/Ser(413) genotype, developed thrombotic events. The lupus patients identified with Ser( 413)/Ser(413) genotype showed an increased damage (57%), compared with Ser(413)/Cys(413) and Cys(413)/Cys(413) genotypes, with significant difference (P = .03). These findings suggest an association of Ser( 413) /Ser( 413) genotype with greater damage index score and Ser( 413) allele with systemic lupus erythematosus. Besides, PAI-2 polymorphism could be related with thrombotic phenomena in systemic lupus erythematosus.
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Lupus Eritematoso Sistémico/genética , Inhibidor 2 de Activador Plasminogénico/genética , Adolescente , Adulto , Anciano , Alelos , Artritis Reumatoide/sangre , Artritis Reumatoide/genética , Artritis Reumatoide/patología , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/patología , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Oxidized low-density lipoprotein (oxLDL) interacts with beta2-glycoprotein I (beta2-GPI) via oxLDL-derived specific ligands (oxLig-1) forming complexes. The prevalence and significance of oxLDL/alpha2-GPI complexes and antibodies to oxLig-1/alpha2-GPI were evaluated in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). The oxLDL/beta2-GPI complex was 69% positive (above mean + 3 SD of control subjects) in 97 consecutive patients with SLE, 62% in 40 patients with SLE with secondary APS, and 60% in 50 control patients with SLE without APS. IgG anti-oxLig-1/beta2-GPI antibody was positive in 31 (32%) of 97 consecutive patients with SLE, in 26 (65%) of 40 patients with SLE with secondary APS, and in 6 (19%) of 32 control patients with SLE. Anti-oxLig-1/beta2-GPI antibodies were 93.7% specific with a positive predictive value of 90.0% for APS, better than anticardiolipin antibodies (80.0% specific, 71.4% predictive value). These results confirm that oxLDL/beta2-GPI complexes are common in SLE and suggest a possible immunogenic role in APS. In contrast, IgG anti-oxLig-1/beta2-GPI antibodies not only are associated with but also are clinically useful risk factors for APS.