RESUMO
It remains unexplored in the field of fear memory whether functional neuronal connectivity between two brain areas is necessary for one sex but not the other. Here, we show that chemogenetic silencing of centromedial (CeM)-Tac2 fibers in the lateral posterior BNST (BNSTpl) decreased fear memory consolidation in male mice but not females. Optogenetic excitation of CeM-Tac2 fibers in the BNSTpl exhibited enhanced inhibitory postsynaptic currents in males compared to females. In vivo calcium imaging analysis revealed a sex-dimorphic fear memory engram in the BNSTpl. Furthermore, in humans, the single-nucleotide polymorphism (SNP) in the Tac2 receptor (rs2765) (TAC3R) decreased CeM-BNST connectivity in a fear task, impaired fear memory consolidation, and increased the expression of the TAC3R mRNA in AA-carrier men but not in women. These sex differences in critical neuronal circuits underlying fear memory formation may be relevant to human neuropsychiatric disorders with fear memory alterations such as posttraumatic stress disorder.
Assuntos
Medo , Memória , Caracteres Sexuais , Medo/fisiologia , Animais , Feminino , Masculino , Humanos , Camundongos , Memória/fisiologia , Polimorfismo de Nucleotídeo Único , AdultoRESUMO
Background: The Disability of the Arm, Shoulder and Hand (DASH) questionnaire assesses the impact of upper extremity disorders on quality of life. However, its use in the Mexican population has not been formally validated. Objective: To conduct a cultural adaptation and validation of the DASH questionnaire to evaluate the perspective of patients with neurogenic disorders of the upper extremity regarding the impact on their quality of life. Method: We performed an adaptation of the Spanish version of the DASH questionnaire to the Mexican vocabulary and applied it to 478 volunteers. Ceiling effect, floor effect, item-total correlation, descriptive statistics of items and total score, internal consistency, precision, cross-sectional and longitudinal validity were estimated by comparing healthy controls and affected individuals with different disability levels. Results: Our DASH questionnaire version was equivalent to those previously approved and showed homogeneity of the items with respect to the total value of the questionnaire (Cronbach's alpha > 0.96). In addition, it showed an accuracy of 7.25 points and the crosssectional and longitudinal validity was documented with significant differences between groups and subgroups with distinct disability levels. Conclusions: The DASH questionnaire can be used with a high level of confidence in the Mexican population.
Antecedentes: El cuestionario de discapacidad de brazo, hombro y mano (DASH, Disabilities of the Arm, Shoulder and Hand) mide el impacto de patologías del miembro superior en la calidad de vida. Sin embargo, su uso en la población mexicana no ha sido formalmente validado. Objetivo: Realizar la adaptación cultural y validación del cuestionario DASH para conocer la perspectiva de pacientes con trastornos neurogénicos del miembro superior respecto al impacto en su calidad de vida. Método: Se realizó una adaptación al vocabulario mexicano de la versión española del cuestionario DASH y se aplicó en 478 voluntarios. Se estimaron el efecto techo, el efecto suelo, la correlación ítem-total, las medidas de tendencia central de ítems y el puntaje total, la consistencia interna, la precisión y la validez transversal y longitudinal mediante la comparación de individuos sanos y enfermos con diferente nivel de discapacidad. Resultados: Nuestra versión del cuestionario DASH resultó equivalente a las previamente aprobadas y mostró homogeneidad de los ítems respecto al valor total del cuestionario (alfa de Cronbach > 0.96). Además, tuvo una precisión de 7.25 puntos y se documentó la validez transversal y longitudinal con diferencias significativas entre grupos y subgrupos con diferente nivel de discapacidad. Conclusiones: El cuestionario DASH puede ser empleado con un nivel de confianza alto en la población mexicana.
RESUMO
BACKGROUND: Phrenic nerve injury (PNI) is a complication of lung transplantation related to the surgical procedure and associated with increased morbidity. However, the incidence and risk factors, specifically regarding surgical techniques, have not been adequately studied. METHODS: We conducted a prospective single-center study over 4-years, in recipients of lung transplantation with a normal pretransplant phrenic nerve conduction study (PNCS). Diaphragm ultrasound and PNCS were performed in the first 21 postoperative days and PNI was defined when both tests were abnormal. Patients were followed up until hospital discharge. The association between transplant characteristics and PNI was analyzed by using logistic regression models. RESULTS: Two hundred eleven lung grafts implanted in 127 patients were included in the study. After lung transplantation, PNI was diagnosed in 43.3% of the subjects and 29% of the operated hemithorax. Regression logistic model showed that the variables related to PNI were female gender (p = 0.02), bilateral lung transplantation (BLT) (p = 0.001), right lung graft (p = 0.003), clamshell incision (p = 0.01), mediastinal adhesions (p = 0.002), longer operative time (p = 0.003), intraoperative extracorporeal support (p = 0.02), and blood transfusion (p = 0.003). Conversely, age >61 years (p = 0.008) and higher thoracic diameter (p = 0.04) were protective factors. The use of electrocautery, cardiac mechanical retractors, and diaphragmatic traction was not associated with PNI. Morbidity was increased without any difference in mortality. CONCLUSIONS: PNI is a frequent complication after lung transplantation, associated with higher morbidity. Mainly risk factors were age, BLT, female gender, and variables related to surgical difficulties. Lung graft in the right hemithorax and mediastinal adhesiolysis were the most relevant technical variables.
Assuntos
Complicações Intraoperatórias/epidemiologia , Transplante de Pulmão/métodos , Nervo Frênico/lesões , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal and rapidly progressive form of dementia caused by the spread of a prion protein within the brain. Its real incidence is unknown since its definitive diagnosis requires histopathological analysis of brain specimens. However, novel tests that detect prion proteins in cerebrospinal fluid samples, such as the real-time quaking-induced conversion (RT-QuIC) technique, now allow the pre-mortem diagnosis of sCJD. Here, we report the first case of sCJD confirmed by RT-QuIC in Latin America, providing evidence of its diagnostic performance and clinical correlation.
Assuntos
Síndrome de Creutzfeldt-Jakob , Príons , Encéfalo/diagnóstico por imagem , Síndrome de Creutzfeldt-Jakob/diagnóstico , Humanos , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: Reports of dermatological manifestations in patients with COVID-19 suggest a possible cutaneous tropism of SARS-CoV-2; however, the capacity of this virus to infect the skin is unknown. OBJECTIVE: To determine the susceptibility of the skin to SARS-CoV-2 infection based on the expression of viral entry factors ACE2 and TMPRSS2 in this organ. METHOD: A comprehensive analysis of human tissue gene expression databases was carried out looking for the presence of the ACE2 and TMPRSS2 genes in the skin. mRNA expression of these genes in skin-derived human cell lines was also assessed. RESULTS: The analyses showed high co-expression of ACE2 and TMPRSS2 in the gastrointestinal tract and kidney, but not in the skin. Only the human immortalized keratinocyte HaCaT cell line expressed detectable levels of ACE2, and no cell line originating in the skin expressed TMPRSS2. CONCLUSIONS: Our results suggest that cutaneous manifestations in patients with COVID-19 cannot be directly attributed to the virus. It is possible that cutaneous blood vessels endothelial damage, as well as the effect of circulating inflammatory mediators produced in response to the virus, are the cause of skin involvement.
INTRODUCCIÓN: Reportes de manifestaciones dermatológicas en pacientes con COVID-19 sugieren un posible tropismo cutáneo del virus SARS-CoV-2; sin embargo, se desconoce la capacidad de este virus para infectar la piel. OBJETIVO: Determinar la susceptibilidad de la piel a la infección por SARS-CoV-2 con base en la expresión de los factores de entrada viral ACE2 y TMPRSS2 en dicho órgano. MÉTODO: Se buscaron los genes ACE2 y TMPRSS2 en la piel, para lo cual se realizó un análisis extenso de las bases de datos de expresión genética en tejidos humanos. Asimismo, se evaluó la expresión de dichos genes en líneas celulares humanas derivadas de la piel. RESULTADOS: Los análisis mostraron alta expresión conjunta de ACE2 y TMPRSS2 en el tracto gastrointestinal y en los riñones, pero no en la piel. Solo la línea celular de queratinocitos humanos inmortalizados HaCaT expresó niveles detectables de ACE2 y ninguna línea celular de origen cutáneo expresó TMPRSS2. CONCLUSIONES: Los resultados sugieren que las manifestaciones dermatológicas en pacientes con COVID-19 no pueden ser atribuidas directamente al virus; es posible que sean originadas por el daño endotelial a los vasos sanguíneos cutáneos y el efecto de los mediadores inflamatorios circulantes producidos en respuesta al virus.
Assuntos
Infecções por Coronavirus/complicações , Peptidil Dipeptidase A/genética , Pneumonia Viral/complicações , Serina Endopeptidases/genética , Dermatopatias Virais/virologia , Enzima de Conversão de Angiotensina 2 , Betacoronavirus/isolamento & purificação , COVID-19 , Linhagem Celular , Infecções por Coronavirus/genética , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Pandemias , Pneumonia Viral/genética , SARS-CoV-2 , Pele/virologia , Dermatopatias Virais/genética , Tropismo Viral/fisiologia , Internalização do VírusRESUMO
Abstract Introduction: Reports of dermatological manifestations in patients with COVID-19 suggest a possible cutaneous tropism of SARS-CoV-2; however, the capacity of this virus to infect the skin is unknown. Objective: To determine the susceptibility of the skin to SARS-CoV-2 infection based on the expression of viral entry factors ACE2 and TMPRSS2 in this organ. Method: A comprehensive analysis of human tissue gene expression databases was carried out looking for the presence of the ACE2 and TMPRSS2 genes in the skin. mRNA expression of these genes in skin-derived human cell lines was also assessed. Results: The analyses showed high co-expression of ACE2 and TMPRSS2 in the gastrointestinal tract and kidney, but not in the skin. Only the human immortalized keratinocyte HaCaT cell line expressed detectable levels of ACE2, and no cell line originating in the skin expressed TMPRSS2. Conclusions: Our results suggest that cutaneous manifestations in patients with COVID-19 cannot be directly attributed to the virus. It is possible that cutaneous blood vessels endothelial damage, as well as the effect of circulating inflammatory mediators produced in response to the virus, are the cause of skin involvement.
Resumen Introducción: Reportes de manifestaciones dermatológicas en pacientes con COVID-19 sugieren un posible tropismo cutáneo del virus SARS-CoV-2; sin embargo, se desconoce la capacidad de este virus para infectar la piel. Objetivo: Determinar la susceptibilidad de la piel a la infección por SARS-CoV-2 con base en la expresión de los factores de entrada viral ACE2 y TMPRSS2 en dicho órgano. Método: Se buscaron los genes ACE2 y TMPRSS2 en la piel, para lo cual se realizó un análisis extenso de las bases de datos de expresión genética en tejidos humanos. Asimismo, se evaluó la expresión de dichos genes en líneas celulares humanas derivadas de la piel. Resultados: Los análisis mostraron alta expresión conjunta de ACE2 y TMPRSS2 en el tracto gastrointestinal y en los riñones, pero no en la piel. Solo la línea celular de queratinocitos humanos inmortalizados HaCaT expresó niveles detectables de ACE2 y ninguna línea celular de origen cutáneo expresó TMPRSS2. Conclusiones: Los resultados sugieren que las manifestaciones dermatológicas en pacientes con COVID-19 no pueden ser atribuidas directamente al virus; es posible que sean originadas por el daño endotelial a los vasos sanguíneos cutáneos y el efecto de los mediadores inflamatorios circulantes producidos en respuesta al virus.
Assuntos
Humanos , Pneumonia Viral/complicações , Serina Endopeptidases/genética , Dermatopatias Virais/virologia , Infecções por Coronavirus/complicações , Peptidil Dipeptidase A/genética , Pneumonia Viral/genética , Pele/virologia , Linhagem Celular , Regulação da Expressão Gênica , Infecções por Coronavirus/genética , Predisposição Genética para Doença , Internalização do Vírus , Tropismo Viral/fisiologia , Pandemias , Betacoronavirus/isolamento & purificação , Enzima de Conversão de Angiotensina 2 , SARS-CoV-2 , COVID-19RESUMO
Approximately one third of individuals who experience a severe traumatic event will develop posttraumatic stress disorder (PTSD). It is crucial to identify what factors may be associated with increased or decreased risk for PTSD. We conducted an umbrella review of systematic reviews and meta-analyses of risk/protective factors for PTSD and assessed and graded the evidence of the association between each factor and PTSD. Thirty-three systematic reviews and meta-analyses were included and 130 potential risk factors were identified. Of those, 57 showed a significant association with PTSD. Being female or being indigenous people of the Americas, among the sociodemographic factors; history of physical disease and family history of psychiatric disorder, among the pretrauma factors; and cumulative exposure to potentially traumatic experiences, trauma severity, and being trapped during an earthquake, among the peritrauma factors, showed convincing or highly suggestive evidence of an association with PTSD. Data from prospective studies were less conclusive. Our results have the potential of helping refine PTSD prediction models and contributing to the design of prevention strategies.
Assuntos
Transtornos de Estresse Pós-Traumáticos/etiologia , Humanos , Metanálise como Assunto , Literatura de Revisão como Assunto , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/psicologiaRESUMO
INTRODUCTION: Our objective was to evaluate the pulmonary hypertension (PH) data for Spanish patients with systemic sclerosis (SSc), define the PH types and determine the associated factors. METHOD: Descriptive study of PH-related data from the multicentre RESCLE registry. Estimated systolic pulmonary artery pressure (esPAP), measured via echocardiogram was considered elevated if ≥ 35 mmHg. Left heart disease (LHD) and interstitial lung disease (ILD) were identified. When performed, data from right heart catheterisation (RHC) were collected. RESULTS: esPAP was elevated in 350 of 808 patients (43.3%). One hundred and forty-four patients (17.8%) were considered to have PH (88 via RHC and the rest due to elevated esPAP along with evidence of significant LHD or ILD): PAH 3.7%, secondary to ILD 8.3%, secondary to LHD 2.8% and unclassified 3%. Prevalence of elevated esPAP was greater in diffuse SSc (dSSc) than in limited scleroderma (lSSc) (50.5 vs. 42.2%, p 0.046). In the group with elevated esPAP, a lower prevalence of anti-centromere antibodies (41.9% vs. 52.3%, p 0.006) and a greater prevalence of anti-topoisomerase-1 antibodies (ATA) (25.1% vs. 18.6%, p 0.04) were observed compared to the group with normal esPAP. Patients with elevated esPAP had a lower rate of digital ulcers (50.6% vs. 60.2%, p 0.007) and esophageal involvement (83.6% vs. 88.7%, p 0.07) and higher rate of renal crisis (4.6% vs. 1.8%, p 0.066). CONCLUSIONS: Prevalence of PAH was lower than expected (3.7%). Probability of having elevated esPAP was higher among patients with dSSc and among those with ATA.
Assuntos
Hipertensão Pulmonar/epidemiologia , Escleroderma Sistêmico/epidemiologia , Adulto , Idoso , Anticorpos Antinucleares , Centrômero/imunologia , Comorbidade , Feminino , Humanos , Hipertensão Pulmonar/imunologia , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros , Escleroderma Sistêmico/imunologia , Espanha/epidemiologiaRESUMO
Extra-cardiac abdominal complications are common in left-side infective endocarditis (LS-IE). The aim of this work was to study whether patients with LS-IE presenting splenic, renal, or liver (SRL) involvement seen in abdominal computed tomography (CT) had different clinical features, therapeutic plans, and outcome than those without these findings on CT.From January 2008 to April 2010, multidisciplinary teams have prospectively collected all consecutive cases of IE, diagnosed according to the Duke criteria, in which abdominal CT was performed.A total of 147 patients with LS-IE had abdominal CT. Fifty (34%) had SRL lesions: 46 splenic, 15 renal, 1 liver infarct, and 2 liver abscesses. Patients with SRL lesions were mainly men (Pâ=â.01), had liver disease (Pâ=â.001) with natural valve (Pâ=â.050) and mitro-aortic valve involvement (Pâ=â.042), splenomegaly (Pâ=â.001), nonabdominal emboli (Pâ=â.001), and a greater number and larger vegetation (>15âmm, Pâ=â.049) in the mitro-aortic valves (Pâ=â.051) than patients with normal abdominal CT. The site of acquisition, clinical characteristics, microbiology, surgical treatment, days of hospitalization, hospital death, and 1-year mortality were similar in patients with and without SRL emboli on CT. In the stepwise logistic regression analysis, male gender (odds ratio [OR]â=â3.6, 95% confidence interval [CI] = 1.4-9.1), liver disease (ORâ=â8.3, 95% CIâ=â2.1-31.8), and nonabdominal emboli (ORâ=â5.2, 95% CIâ=â2.3-11.7) were independently associated with SRL lesions.Male patients with native LS-IE who had liver disease and nonabdominal emboli had more frequent abdominal lesions seen on CT. The presence of SRL infarcts on abdominal CT scan performed on patients with LS-IE seems to have poor practical implications, and as a consequence, its realization should only be considered when there are symptoms or signs that suggest them.
Assuntos
Endocardite/complicações , Infarto/diagnóstico por imagem , Rim/irrigação sanguínea , Fígado/irrigação sanguínea , Infarto do Baço/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Endocardite/diagnóstico por imagem , Feminino , Humanos , Infarto/microbiologia , Rim/diagnóstico por imagem , Rim/microbiologia , Fígado/diagnóstico por imagem , Fígado/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Baço/irrigação sanguínea , Baço/diagnóstico por imagem , Baço/microbiologia , Infarto do Baço/microbiologiaRESUMO
Context: Early life cortisol plays an important role in bone, muscle, and fat mobilization processes, which could influence body composition, affecting anthropometric indicators such as weight and height. Objective: To explore the association between diurnal cortisol levels and growth indexes in children from 12 to 48 months of age. Design: This study includes data from 404 children from the Programming Research in Obesity, Growth, Environment and Social Stressors Mexican birth cohort. Cortisol was measured in eight saliva samples collected at four time points during the day (from wakeup to bedtime), over 2 days, when the child was either 12, 18, or 24 months old. Total daytime cortisol levels were calculated by averaging the area under the curve (AUC) for the 2 days. Height and weight were measured from 12 to 48 months of age. Growth indexes were constructed according to z scores following World Health Organization standards: weight-for-age z score (Z-WFA), height/length-for-age z score, weight-for-height/length z score (Z-WFH), and body mass index-for-age z score (Z-BMIFA). Mixed models were used to analyze the association between cortisol AUC quartiles and growth indexes. Results: Cortisol showed an inverted U-shaped association with the four growth indexes. Compared with the first quartile, all quartiles had a positive association with indexes that include weight, with the second quartile having the strongest association, resulting in an average change of ß (95% CI) 0.38 (0.13-0.64) for Z-WFA, 0.36 (0.10-0.62) for Z-WFH, and 0.43 (0.17-0.69) for Z-BMIFA. Conclusions: Results suggest that early life daytime cortisol levels, as a reflection of hypothalamic-pituitary-adrenal axis development, might influence growth in early infancy.
Assuntos
Estatura/fisiologia , Índice de Massa Corporal , Peso Corporal/fisiologia , Hidrocortisona/análise , Antropometria , Área Sob a Curva , Pré-Escolar , Ritmo Circadiano , Cidades , Estudos de Coortes , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Lactente , Masculino , México , Sistema Hipófise-Suprarrenal/crescimento & desenvolvimento , Saliva/metabolismoRESUMO
OBJECTIVES: To determine the ability of Coronary Artery Calcification Score (CACS) and carotid ultrasonography (US) to detect high cardiovascular (CV) risk axial spondyloarthritis (ax-SpA) patients. METHODS: CACS and carotid plaques were assessed in 66 consecutive ax-SpA patients (51 fulfilling criteria for ankylosing spondylitis and 15 for non-radiological ax-SpA) without history of CV events. The Systematic Coronary Risk Evaluation (SCORE) calculated using total cholesterol (TC-SCORE) was assessed in 64 patients without diabetes mellitus or chronic kidney disease. RESULTS: The mean age of the patients and the median disease duration since the onset of symptoms were 49.3 and 14.5 years. HLA-B27 was positive in 47 (75%) patients. CV risk was categorised according to the TC-SCORE as low (<1%; n=33), moderate (≥1% and<5%; n=30) and high/very high risk (≥5%; n=1). Most patients with low TC-SCORE (27/33; 82%) had normal CACS (zero), and only 1/33 had CACS >100. However, carotid plaques were observed in patients with CACS=0 (12/37; 32%) and CACS 1-100 (10/16; 62%). The sensitivity to detect high/very high CV risk using only the TC-SCORE was very low as the algorithm only detected 1/33 (3%) of patients with high/very high CV risk. Ten of 33 (30%) high/very high CV risk patients were identified using a chart TC-SCORE risk ≥5% plus the presence of CACS ≥100 in patients with moderate TC-SCORE. The replacement of CACS with carotid US identified a higher number of high/very high CV risk patients (22/33; 67%). CONCLUSIONS: Carotid US is more sensitive than CACS for the detection of high CV risk in ax-SpA patients.
Assuntos
Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Espondilite Anquilosante/complicações , Calcificação Vascular/diagnóstico por imagem , Adulto , Doenças Assintomáticas , Doenças das Artérias Carótidas/etiologia , Doença da Artéria Coronariana/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Espondilite Anquilosante/diagnóstico , Calcificação Vascular/etiologiaRESUMO
Hereditary haemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber syndrome, is a dominant genetic vascular disorder. In HHT, blood vessels are weak and prone to bleeding, leading to epistaxis and anaemia, severely affecting patients' quality of life. Development of vascular malformations in HHT patients is originated mainly by mutations in ACVRL1/ALK1 (activin receptor-like kinase type I) or Endoglin (ENG) genes. These genes encode proteins of the TGF-ß signalling pathway in endothelial cells, controlling angiogenesis. Haploinsufficiency of these proteins is the basis of HHT pathogenicity. It was our objective to study the efficiency of Bazedoxifene, a selective estrogen receptor modulator (SERM) in HHT, looking for a decrease in epistaxis, and understanding the underlying molecular mechanism. Plasma samples of five HHT patients were collected before, and after 1 and 3 months of Bazedoxifene treatment. ENG and ALK1 expression in activated mononuclear cells derived from blood, as well as VEGF plasma levels, were measured. Quantification of Endoglin and ALK1 mRNA was done in endothelial cells derived from HHT and healthy donors, after in vitro treatment with Bazedoxifene. Angiogenesis was also measured by tubulogenesis and wound healing assays. Upon Bazedoxifene treatment, haemoglobin levels of HHT patients increased and the quantity and frequency of epistaxis decreased. Bazedoxifene increased Endoglin and ALK1 mRNA levels, in cells derived from blood samples and in cultured endothelial cells, promoting tube formation. In conclusion, Bazedoxifene seems to decrease bleeding in HHT by partial compensation of haploinsufficiency. The results shown here are the basis of a new orphan drug designation for HHT by the European Medicine Agency (EMA).
Assuntos
Indóis/uso terapêutico , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Receptores de Activinas Tipo II/genética , Idoso , Células Cultivadas , Endoglina/genética , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Hemorragia/sangue , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Humanos , Pessoa de Meia-Idade , Neovascularização Fisiológica/efeitos dos fármacos , Produção de Droga sem Interesse Comercial , Projetos Piloto , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/genética , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/genética , Cicatrização/efeitos dos fármacosRESUMO
OBJECTIVE: Results of a recent study suggested that the excess cardiovascular (CV) risk observed in patients with rheumatoid arthritis (RA) could be partially explained by the presence of immune complexes of antibodies against citrullinated proteins that locally promote and perpetuate inflammation and progression of atherosclerotic plaques. The present study was undertaken to attempt to replicate one of the observations supporting this hypothesis, i.e., association between anti-citrullinated fibrinogen (anti-Cit-fibrinogen) positivity and subclinical atherosclerosis. METHODS: Three surrogate markers of atherosclerosis were assessed in 124 RA patients with no previous history of CV events: carotid intima-media thickness (CIMT) assessed by carotid ultrasonography, carotid plaques assessed by carotid ultrasonography, and Coronary Artery Calcification Score (CACS) determined by multidetector computed tomography (CT) scanning. We analyzed the relationship of these 3 subclinical atherosclerosis markers to the presence and levels of autoantibodies, including anti-Cit-fibrinogen, anti-cyclic citrullinated peptide 2 (anti-CCP-2), and rheumatoid factor (RF). RESULTS: Carotid plaques and CIMT >0.90 mm were present in 69.4% and 15.3%, of the patients, respectively, and the CACS was moderate or high in 21.0%. None of these surrogate markers of atherosclerosis showed a significant association with positivity for or the level of anti-Cit-fibrinogen antibodies (either against the whole protein [present in 33.9% of the patients] or against an immunodominant peptide [present in 23.4%]), anti-CCP-2 (present in 60.7%), or RF (present in 58.1%) in this series of patients with RA. CONCLUSION: Our results do not support the notion that there is a relationship between anti-Cit-fibrinogen antibodies and subclinical atherosclerosis in RA, thus calling into question the claim that these antibodies have a role in the increased risk of CV disease observed in patients with RA.
Assuntos
Artrite Reumatoide/complicações , Aterosclerose/complicações , Autoanticorpos/sangue , Fibrinogênio/imunologia , Peptídeos Cíclicos/imunologia , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Aterosclerose/sangue , Aterosclerose/imunologia , Espessura Intima-Media Carotídea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fator Reumatoide/sangueRESUMO
OBJECTIVE: To determine the ability of Coronary Artery Calcification Score (CACS) and carotid ultrasonography in detecting subclinical atherosclerosis in rheumatoid arthritis (RA). METHODS: A set of 104 consecutive RA patients without history of cardiovascular (CV) events were studied to determine CACS, carotid intima-media thickness (cIMT) and plaques. Systematic Coronary Risk Evaluation (SCORE) modified according to the EULAR recommendations (mSCORE) was also assessed. RESULTS: The mean disease duration was 10.8 years, 72.1% had rheumatoid factor and/or anti-CCP positivity and 16.4% extra-articular manifestations. Nine were excluded because they had type 2 diabetes mellitus or chronic kidney disease. CV risk was categorised in the remaining 95 RA patients according to the mSCORE as follows: low (n=21), moderate (n=60) and high/very high risk (n=14). Most patients with low mSCORE (16/21; 76.2%) had normal CACS (zero), and none of them CACS>100. However, a high number of patients with carotid plaques was disclosed in the groups with CACS 0 (23/40; 57.5%) or CACS 1-100 (29/38; 76.3%). 72 (75.8%) of the 95 patients fulfilled definitions for high/very high CV as they had an mSCORE ≥5% or mSCORE <5% plus one of the following findings: severe carotid ultrasonography findings (cIMT>0.9 mm and/or plaques) or CACS>100. A CACS>100 showed sensitivity similar to mSCORE (23.6% vs 19.4%). In contrast, the presence of severe carotid ultrasonography findings allowed identifying most patients who met definitions for high/very high CV risk (70/72; sensitivity 97.2% (95% CI 90.3 to 99.7)). CONCLUSIONS: Carotid ultrasonography is more sensitive than CACS for the detection of subclinical atherosclerosis in RA.
Assuntos
Artrite Reumatoide/complicações , Doenças Cardiovasculares/diagnóstico , Doenças das Artérias Carótidas/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico , Calcificação Vascular/diagnóstico , Idoso , Doenças Assintomáticas , Doenças Cardiovasculares/complicações , Doenças das Artérias Carótidas/complicações , Espessura Intima-Media Carotídea , Doença da Artéria Coronariana/complicações , Vasos Coronários/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Calcificação Vascular/complicaçõesRESUMO
Thromboangiitis obliterans (also known as Buerger's disease) is an inflammatory vascular disorder that affects small and medium-sized arteries and veins in the extremities. There is no specific treatment and the only effective intervention is absolute cessation of tobacco use. Endothelial dysfunction appears to be of relevance to this condition and a report has even found that high serum levels of endothelin correlate with the presence of necrosis. We report two cases of digital necrosis showing a very satisfactory response to treatment with bosentan, a dual endothelin receptor antagonist.