ABSTRACT
OBJECTIVE: This study aimed to assess the influence of smoking on the subgingival metatranscriptomic profile of young patients affected by stage III/IV and generalized periodontal disease. METHODOLOGY: In total, six young patients, both smokers and non-smokers (n=3/group), who were affected by periodontitis were chosen. The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for case-control reporting were followed. Periodontal clinical measurements and subgingival biofilm samples were collected. RNA was extracted from the biofilm and sequenced via Illumina HiSeq. Differential expression analysis used Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and differentially expressed genes were identified using the Sleuth package in R, with a statistical cutoff of ≤0.05. RESULTS: This study found 3351 KEGGs in the subgingival biofilm of both groups. Smoking habits altered the functional behavior of subgingival biofilm, resulting in 304 differentially expressed KEGGs between groups. Moreover, seven pathways were modulated: glycan degradation, galactose metabolism, glycosaminoglycan degradation, oxidative phosphorylation, peptidoglycan biosynthesis, butanoate metabolism, and glycosphingolipid biosynthesis. Smoking also altered antibiotic resistance gene levels in subgingival biofilm by significantly overexpressing genes related to beta-lactamase, permeability, antibiotic efflux pumps, and antibiotic-resistant synthetases. CONCLUSION: Due to the limitations of a small sample size, our data suggest that smoking may influence the functional behavior of subgingival biofilm, modifying pathways that negatively impact the behavior of subgingival biofilm, which may lead to a more virulent community.
Subject(s)
Biofilms , Smoking , Humans , Pilot Projects , Male , Female , Adult , Smoking/adverse effects , Periodontitis/microbiology , Case-Control Studies , Young Adult , Gene Expression Profiling , Gingiva/microbiology , TranscriptomeABSTRACT
Abstract This study aimed to assess the influence of smoking on the subgingival metatranscriptomic profile of young patients affected by stage III/IV and generalized periodontal disease. Methodology In total, six young patients, both smokers and non-smokers (n=3/group), who were affected by periodontitis were chosen. The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for case-control reporting were followed. Periodontal clinical measurements and subgingival biofilm samples were collected. RNA was extracted from the biofilm and sequenced via Illumina HiSeq. Differential expression analysis used Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and differentially expressed genes were identified using the Sleuth package in R, with a statistical cutoff of ≤0.05. Results This study found 3351 KEGGs in the subgingival biofilm of both groups. Smoking habits altered the functional behavior of subgingival biofilm, resulting in 304 differentially expressed KEGGs between groups. Moreover, seven pathways were modulated: glycan degradation, galactose metabolism, glycosaminoglycan degradation, oxidative phosphorylation, peptidoglycan biosynthesis, butanoate metabolism, and glycosphingolipid biosynthesis. Smoking also altered antibiotic resistance gene levels in subgingival biofilm by significantly overexpressing genes related to beta-lactamase, permeability, antibiotic efflux pumps, and antibiotic-resistant synthetases. Conclusion Due to the limitations of a small sample size, our data suggest that smoking may influence the functional behavior of subgingival biofilm, modifying pathways that negatively impact the behavior of subgingival biofilm, which may lead to a more virulent community.
ABSTRACT
Background: The pandemic of COVID-19 raised the urgent need for safe and efficacious vaccines against SARS-CoV-2. We evaluated the efficacy and safety of a new SARS-CoV-2 virus receptor-binding domain (RBD) vaccine. Methods: A phase 3, multicentre, randomised, double-blind, placebo-controlled trial was carried out at 18 clinical sites in three provinces of the south-eastern region of Cuba. Subjects (healthy or those with controlled chronic diseases) aged between 19 and 80 years, who gave written informed consent were eligible. Subjects were randomly assigned (1:1, in blocks) to two groups: placebo, and 50 µg RBD vaccine (Abdala). The product was administered intramuscularly, 0.5 mL in the deltoid region, in a three-dose immunization schedule at 0-14-28 days. The organoleptic characteristics and presentations of the vaccine and placebo were identical. All participants (subjects, clinical researchers, statisticians, laboratory technicians, and monitors) remained blinded during the study period. The main endpoint was to evaluate the efficacy of the Abdala vaccine in the prevention of symptomatic COVID-19. The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000359. Findings: Between March 22 to April 03, 2021, 48,290 subjects were included (24,144 and 24,146 in the placebo and Abdala groups, respectively) in the context of predominant D614G variant circulation. The evaluation of the main efficacy outcomes occurred during May-June 2021, starting at May 3rd, in the context of high circulation of mutant viruses, predominantly VOC Beta. The incidence of adverse reactions for individuals in the placebo and Abdala vaccine groups were 1227/24,144 (5.1%) and 1621/24,146 (6.7%), respectively. Adverse reactions were mostly mild, and from the injection site, which resolved in the first 24-48 h. No severe adverse events with demonstrated cause-effect relationship attributable to the vaccine were reported. Symptomatic COVID-19 disease was confirmed in 142 participants in the placebo group (78.44 incidence per 1000 person-years, 95% confidence interval [CI], 66.07-92.46) and in 11 participants in Abdala vaccine group (6.05 incidence per 1000 person years; 95% CI 3.02-10.82). The Abdala vaccine efficacy against symptomatic COVID-19 was 92.28% (95% CI 85.74-95.82). Moderate/serious forms of COVID-19 occurred in 30 participants (28 in the placebo group and only 2 in the Abdala vaccine group) for a vaccine efficacy of 92.88% (95% CI 70.12-98.31). There were five critical patients (of which four died), all in the placebo group. Interpretation: The Abdala vaccine was safe, well tolerated, and highly effective, fulfilling the WHO target product profile for COVID-19 vaccines. Those results, along with its immunization schedule and the advantage of easy storage and handling conditions at 2-8 °C, make this vaccine an option for the use in immunization strategies as a key tool for the control of the pandemic. Funding: Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.
ABSTRACT
Introducción: La diabetes mellitus se encuentra entre las enfermedades crónicas no transmisibles más comunes en el mundo, y se estima que para el 2030 será diagnosticada en 7,7 % de la población mayor de 18 años, es decir, en 430 millones de individuos. Objetivo: Caracterizar a pacientes diabéticos que presentaron infarto agudo de miocardio con elevación del segmento ST, según variables clinicoepidemiológicas, electrocardiográficas, ecocardiográficas y terapéuticas. Métodos: Se realizó un estudio descriptivo, desde enero hasta diciembre de 2019, de 137 pacientes con antecedente de diabetes mellitus que presentaron infarto agudo de miocardio con elevación del segmento ST, atendidos en el Servicio de Cardiología del Hospital Provincial Clínico-Quirúrgico Docente Saturnino Lora de Santiago de Cuba. Entre las variables analizadas figuraron la edad, el sexo, la clase funcional, las complicaciones, la función sistólica y la diastólica del ventrículo izquierdo, la terapia de reperfusión empleada y el estado del paciente al egreso. Resultados: En la serie predominaron el sexo masculino y el grupo etario mayor de 60 y más años. Se observó que el infarto agudo de miocardio en la topografía anterior presentara más complicaciones, así como mayor número de pacientes con tratamiento trombolítico y combinado. Asimismo, la mayoría de los pacientes egresaron vivos, lo cual se correspondió, además, con que recibieran terapia trombolítica. Al analizar a los pacientes con alteraciones segmentarias en el estudio ecocardiográfico, se obtuvo una primacía de los fallecidos en ese grupo en cuestión. Conclusiones: Los pacientes diabéticos que presentan infarto agudo de miocardio con elevación del segmento ST constituyen un grupo independiente con especificidades clínicas y ecocardiográficas y mayor riesgo de complicaciones mortales.
Introduction: Diabetes mellitus is not among the most common chronic non communicable diseases in the world, and is considered that by 2030 it will be diagnosed in the 7.7 % of the population over 18 years, that is to say, in 430 million individuals. Objective: To characterize diabetic patients that presented acute heart attack with elevation of the ST segment, according to clinical epidemiological, electrocardiographic, echocardiographic and therapeutic variables. Methods: A descriptive study was carried out from January to December, 2019 of 137 patients with history of diabetes mellitus that presented acute heart attack with elevation of the ST segment, assisted in the Cardiology Service of Saturnino Lora Teaching Clinical-Surgical Provincial Hospital in Santiago de Cuba. Among the analyzed variables figured the age, sex, functional class, complications, systolic and dyastolic function of the left ventricle, the therapy of reperfusion used and the state of the patient when discharged from the hospital. Results: In the series there was a prevalence of the male sex and the 60 and over age group. It was observed that the acute heart attack in the previous topography presented more complications, as well as higher number of patients with thrombolitic and combined treatment. Also, most of the patients were alive when discharged from the hospital, which also corresponded with the thrombolitic therapy received. When analyzing the patients with segmental alterations in the echocardiographic study, a primacy of the deceaseds was obtained in that group. Conclusions: The diabetic patients that present acute heart attack with elevation of the ST segment constitute an independent group with clinical and echocardiographic specificities, and more risk of mortal complications.
Subject(s)
Diabetes Mellitus , Myocardial Infarction , Echocardiography , ST Elevation Myocardial InfarctionABSTRACT
OBJECTIVE: Periodontitis in younger patients can cause severe periodontal destruction, and cases are usually more numerous in members of the same family due to the sharing of susceptibility factors. Thus, the use of a familial study design could improve our understanding of initial alterations in periodontal tissue. This observational study aimed to evaluate the salivary inflammatory pattern in descendants of periodontitis patients and identify any correlation with the clinical periodontal condition. STUDY DESIGN: Fifteen children of Generalized Aggressive Periodontitis (GAgP) patients and 15 children with periodontally healthy parents were evaluated for their plaque index (PI), gingival index (GI), bleeding on probing (BoP), and probing depth (PD). The concentrations of interferon (IFN)-γ, interleukin (IL)-10, IL-17, IL-1ß, IL-4, and tumor necrosis factor (TNF)-α were measured in unstimulated saliva using the Luminex MAGPix platform. RESULTS: Children from the GAgP group presented higher probing depth (PD) and bleeding on probing (BoP) (p<0.05) and lower release of IL-4 in saliva (p<0.05) than the periodontally healthy group. The cytokines IL-10, IFN-γ, IL-17, and IL-4 were negatively correlated with the gingival index, while IL-4 was negatively correlated with BoP. A regression analysis revealed that salivary IL-4 and plaque were predictors of BoP. CONCLUSIONS: Children of GAgP parents presented lower salivary IL-4 and higher BoP and PD than children from periodontally healthy families. Additionally, salivary IL-4 was a predictor of bleeding on probing in the children, suggesting that the lower presence of this anti-inflammatory cytokine is related to higher clinical inflammation.
Subject(s)
Aggressive Periodontitis , Interleukin-17 , Child , Cytokines , Dental Plaque Index , Humans , Interleukin-17/analysis , Interleukin-4 , Periodontal Index , Saliva/chemistry , Tumor Necrosis Factor-alpha/analysisABSTRACT
Aggressive periodontitis is a disease that causes severe destruction of periodontal tissues, showing early development and rapid progression in both primary and permanent dentitions. Due to familial aggregation, children of parents with periodontitis are considered to be at higher risk for disease occurrence, which suggests that they should be evaluated and monitored as early as possible. The purpose of this case report is to describe aspects related to early diagnosis of periodontitis in two children and their relationship with the parent's periodontal condition, exploring the familial component as a crucial factor that can lead to an early diagnosis and better clinical management in their offspring.
Subject(s)
Aggressive Periodontitis , Gingival Diseases , Aggressive Periodontitis/diagnosis , Aggressive Periodontitis/drug therapy , Aggressive Periodontitis/genetics , Anti-Bacterial Agents/therapeutic use , Child , Dentition, Permanent , HumansABSTRACT
RESUMEN La tuberculosis es una de las principales causas de mortalidad en el mundo, a pesar de los múltiples controles y estrategias del tratamiento. La forma diseminada corresponde al 5 % de las presentaciones. Reportamos el primer caso en la literatura de una paciente adolescente con diabetes mellitus tipo 1 y tuberculosis diseminada quien presentó síntomas constitucionales asociados con un dolor lumbar, inicialmente interpretado como sacroileítis no infecciosa y una probable enfermedad inflamatoria intestinal.
SUMMARY Tuberculosis is one of the leading causes of mortality in the world despite multiple control and treatment strategies. Disseminated tuberculosis corresponds to 5% of cases. We report the first case in literature of an adolescent patient with type 1 diabetes mellitus and disseminated tuberculosis, who had constitutional symptoms associated with low back pain and was initially, interpreted initially as noninfectious sacroiliitis and a probable inflammatory bowel disease.
Subject(s)
Humans , Adolescent , Tuberculosis , Diabetes Mellitus, Type 1ABSTRACT
Se describe el caso clínico de un paciente de 18 años de edad, seropositivo al VIH, quien fue atendido en el Hospital Provincial de Luena, provincia angolana de Moxico, por presentar dolor lumbar. Se le realizó tomografía axial computarizada, la cual mostró gran destrucción vertebral y colecciones paravertebrales bilaterales. El paciente mantuvo una evolución desfavorable y falleció 20 días después de realizado el diagnóstico.
The case report of an 18 years patient, HIV seropositive is described. He was assisted at Luena Provincial Hospital, angolan province of Moxico due to a lumbar pain. A computerized axial tomography was carried out, which showed great vertebral destruction and bilateral paravertebral collections. The patient maintained an unfavorable clinical course and died 20 days after the diagnosis.
Subject(s)
Tuberculosis, Spinal , Adolescent , Mycobacterium tuberculosis , HIV SeropositivityABSTRACT
BACKGROUND AND AIMS: Advances in cancer treatment have improved survival; however, local recurrence and metastatic disease-the principal causes of cancer mortality-have limited the ability to achieve durable remissions. Local recurrences arise from latent tumor cells that survive therapy and are often not detectable by conventional clinical imaging techniques. Local recurrence after transarterial embolization (TAE) of hepatocellular carcinoma (HCC) provides a compelling clinical correlate of this phenomenon. In response to TAE-induced ischemia, HCC cells adapt their growth program to effect a latent phenotype that precedes local recurrence. APPROACH AND RESULTS: In this study, we characterized and leveraged the metabolic reprogramming demonstrated by latent HCC cells in response to TAE-induced ischemia to enable their detection in vivo using dynamic nuclear polarization (DNP) magnetic resonance spectroscopic imaging (MRSI) of 13 carbon-labeled substrates. Under TAE-induced ischemia, latent HCC cells demonstrated reduced metabolism and developed a dependence on glycolytic flux to lactate. Despite the hypometabolic state of these cells, DNP-MRSI of 1-13 C-pyruvate and its downstream metabolites, 1-13 C-lactate and 1-13 C-alanine, predicted histological viability. CONCLUSIONS: These studies provide a paradigm for imaging latent, treatment-refractory cancer cells, suggesting that DNP-MRSI provides a technology for this application.
Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/therapy , Embolization, Therapeutic , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/therapy , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy , Animals , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Disease Models, Animal , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Male , Rats , Rats, WistarABSTRACT
Resumo: Introdução: A empatia é um atributo valorizado como competência médica que influencia positivamente a relação médico-paciente e repercute na adesão ao tratamento e na melhora clínica. Estudos prévios indicam que há correlação entre personalidade e empatia em estudantes de Medicina, mas não existem, até o momento, dados referentes na literatura nacional. Este estudo teve como objetivos analisar a capacidade de empatia e os domínios de personalidade e investigar a correlação entre empatia e personalidade em estudantes de Medicina brasileiros. Métodos: Aplicaram-se dois instrumentos em estudantes do primeiro ano do curso de Medicina, nos anos de 2015 e 2017, para avaliar empatia e personalidade por meio das seguintes escalas: Jefferson Scale Empathy - Students version (JSE-S) e NEO-Five Factor Inventory (NEO-FFI). Foi realizada análise descritiva dos dados contendo média, escores mínimo e máximo, correlação e regressão linear de personalidade e empatia. Resultados: Preencheram os instrumentos 164 (96,4%) estudantes, sendo 50,5% do sexo feminino. A média do escore global da JSE-S foi de 117,6 ± 10,9, sendo a média feminina (119,5 ± 10,5) e masculina (115,7 ± 11) com diferença significativa (p < 0,01). No NEO-FFI, a conscienciosidade obteve a maior média global (29,1 ± 3,8), e coube ao neuroticismo a menor média (21,7 ± 4,7). No grupo feminino, a maior média foi encontrada em conscienciosidade (29,4 ± 3,8); e a menor, em abertura para experiência (20,6 ± 3,3). No grupo masculino, conscienciosidade (29,4±3,9) e neuroticismo (21,6±4,2) obtiveram as maiores e menores médias. Constatou-se diferença significativa entre os sexos no escore global da JSE-S, em abertura para experiência e socialização. As correlações encontradas entre empatia e personalidade foram fracas, e nenhuma delas foi estatisticamente significativa. Conclusão: As médias dos domínios de personalidade diferem entre os sexos, e, no presente estudo, em avaliação transversal, não houve correlação forte da personalidade e empatia em estudantes de Medicina. Estudos com abordagem longitudinal são necessários para elucidar modulações na empatia e personalidade, nos diferentes momentos da formação médica.
Abstract: Introduction: Empathy is a valuable attribute for a physician, as it positively influences the doctor-patient relationship. Previous studies indicate that there is a correlation between personality and empathy in medical students, but there is no data available in the Brazilian literature so far. This study aimed to analyze the empathy and personality traits of Brazilian medical students, and investigate their association. Methods: First year medical students from the 2015 and 2017 cohorts had their empathy and personality traits evaluated by two instruments using the following scales, respectively: Jefferson Scale of Empathy - Students version (JSE-S) and NEO-Five Factor Inventory (NEO-FFI). A descriptive analysis comprised mean, minimum and maximum scores, correlation coefficients and linear regression of personality and empathy. Results: 164 (96.4%) students completed the surveys, and 50.5% were women. The mean global score of the JSE-S was 117.6 ± 10.9; stratification by gender showed scores of 119.5 ± 10.5 and 115.7 ± 11.0, respectively in women and men (p<0.01). In the NEO-FFI, the domain of 'conscientiousness' had the highest global mean (29.1 ± 3.8) and 'neuroticism', the lowest (21.7 ± 4.7). In women, the highest mean was observed in 'conscientiousness' (29.4 ± 3.8) and the lowest in 'open to new experiences' (20.6 ± 3.3). In men, the highest and the lowest scores were respectively in the domains 'conscientiousness' (29.4 ± 3.9) and 'neuroticism' (21.6 ± 4.2). There was a significant difference between men and women in the global score of the JSE-S, and in the personality domains of 'open to new experiences' and 'socialization'. Correlations between empathy and personality were found to be weak and not statistically relevant. Conclusion: The personality traits differed between men and women, but there was no significant correlation between empathy and personality among medical students enrolled in this cross-sectional study. Further investigations are needed to examine how empathy and personality modulate during medical studies using longitudinal approaches.
ABSTRACT
The objective was to determine the prevalence of molar incisor hypomineralization (MIH) among individuals between 7 and 15 years old infected or noninfected with human immunodeficiency virus (HIV). The study was conducted with 33 HIV-infected individuals (study group; SG) and 66 non-HIV-infected schoolchildren (control group; CG), paired by gender and age. Data collection was based on medical records (SG), a questionnaire for caregivers and oral examination for diagnosis of MIH (European Academy of Pediatric Dentistry criteria) and caries (DMFT index and ICDAS). Data were analyzed with Mann-Whitney, chi-square, and Fisher's exact tests and logistic regression. In SG, MIH (45.5%) and caries (87.9%) had higher prevalence. MIH was associated with use of protease inhibitors in SG (OR: 2.14; 95% CI: 1.21 to 3.77) and incubator need in CG (OR: 2.80; 95% CI: 1.71 to 9.10). HIV-infected patients had a higher prevalence of MIH and dental caries in the permanent dentition.
Subject(s)
Dental Enamel Hypoplasia/epidemiology , Dental Enamel Hypoplasia/etiology , HIV Infections/complications , Adolescent , Brazil/epidemiology , Case-Control Studies , Child , DMF Index , Female , Humans , Incisor , Male , Molar , Prevalence , Risk Factors , Socioeconomic FactorsABSTRACT
Los traumatismos del sistema arterial carotideo son raros y tienen alta mortalidad. Se presenta un caso de trombosis de la arteria carótida interna derecha por una herida por arma de fuego a nivel del cuello con el objetivo de evidenciar en la práctica médica la utilidad de la ecografía Doppler para el diagnóstico temprano de estas lesiones, a pesar de reportarse en la literatura la angiografía, la resonancia magnética nuclear y la angiorresonancia como estudios de elección. Con este caso se pudo afirmar que la trombosis carotidea traumática tiene una incidencia baja, pero no descartable en los traumas de la región cervical. Por esta causa, son frecuentes las complicaciones neurológicas dadas por la oclusión arterial y la ecografía Doppler resultó muy útil en el diagnóstico temprano del paciente(AU)
Carotid artery system traumas are rare and show high mortality rates. The case of right internal carotid artery thrombosis caused by a gunshot injury in the neck was presented in this report to show evidence of the usefulness of Doppler echography in the medical practice for the early diagnosis of these lesions in spite of the fact that literature highlights angiography, nuclear magnetic resonance and angioresonance as the imaging studies of choice. This case confirmed that carotid thrombosis due to trauma has low incidence but it can not be ignored in the cervical regi¥n traumas. For these reasons, the neurological complications stemming from artery occlusion are frequent and Doppler echography turned to be very useful for the early diagnosis of this illness in a patient(AU)
Subject(s)
Humans , Male , Adult , Carotid Artery Thrombosis/diagnosis , Echocardiography, Doppler/methods , Magnetic Resonance Spectroscopy/methods , Coronary Occlusion/complications , Angiography/adverse effectsABSTRACT
Los traumatismos del sistema arterial carotideo son raros y tienen alta mortalidad. Se presenta un caso de trombosis de la arteria carótida interna derecha por una herida por arma de fuego a nivel del cuello con el objetivo de evidenciar en la práctica médica la utilidad de la ecografía Doppler para el diagnóstico temprano de estas lesiones, a pesar de reportarse en la literatura la angiografía, la resonancia magnética nuclear y la angiorresonancia como estudios de elección. Con este caso se pudo afirmar que la trombosis carotidea traumática tiene una incidencia baja, pero no descartable en los traumas de la región cervical. Por esta causa, son frecuentes las complicaciones neurológicas dadas por la oclusión arterial y la ecografía Doppler resultó muy útil en el diagnóstico temprano del paciente.
Carotid artery system traumas are rare and show high mortality rates. The case of right internal carotid artery thrombosis caused by a gunshot injury in the neck was presented in this report to show evidence of the usefulness of Doppler echography in the medical practice for the early diagnosis of these lesions in spite of the fact that literature highlights angiography, nuclear magnetic resonance and angioresonance as the imaging studies of choice. This case confirmed that carotid thrombosis due to trauma has low incidence but it can not be ignored in the cervical región traumas. For these reasons, the neurological complications stemming from artery occlusion are frequent and Doppler echography turned to be very useful for the early diagnosis of this illness in a patient.
Subject(s)
Humans , Male , Angiography/adverse effects , Magnetic Resonance Spectroscopy/methods , Echocardiography, Doppler/methods , Carotid Artery Thrombosis/diagnosis , Coronary Occlusion/complicationsABSTRACT
OBJECTIVES: Patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) have increased IL-1ß levels. IL-1ß and other pro-inflammatory cytokines have a modulating activity on cardiac ion channels and have been associated with increased arrhythmic risk in rheumatoid arthritis patients. Likewise, adult patients with connective tissue diseases (CTDs) may have prolonged QTc intervals associated with the presence of anti-Ro/SSA antibodies. Our objective was to evaluate the presence of serum IL-1ß in subjects with CTDs, in relation to the presence of anti-Ro/SSA antibodies and QTc interval duration. METHODS: 12-lead electrocardiograms (ECG) were performed and blood was withdrawn, measuring electrolytes, IL-1ß anti-Ro/SSA antibodies by ELISA in 73 patients with CTDs. RESULTS: 55 patients were anti-Ro/SSA positive and 18 were anti-Ro/SSA negative. Patients with anti-Ro/SSA positive antibodies had a significantly greater median IL-1ß serum level: 7.29 (range: 0.17-17.3 pg/ml) compared to patients with anti-Ro/SSA negative antibodies whose median was: 1.67 (range 0.55-4.12 pg/ml) p<0.001. The mean QTc interval values obtained in both groups were not significantly different (417.7±23.1 vs. 414.7±21.2, p=0.63). The QTc interval was prolonged in 11 (20%) patients, who were all anti-Ro/SSA positive versus 0 (0 %) in anti-Ro/SSA negative patients p=0.05. Median IL-1ß levels were: 8.7 (range: 2.69-15.1 pg/ml) in patients with prolonged QTc interval versus median: 5.0 (range: 0.17-17.3 pg/ml) in those with normal QTc interval values (<440ms) p=0.006. CONCLUSIONS: IL-1ß is elevated in patients with CTDs that have both anti-Ro/SSA antibodies and prolonged QTc intervals.
Subject(s)
Antibodies, Antinuclear/blood , Arrhythmias, Cardiac/blood , Connective Tissue Diseases/blood , Heart Conduction System/physiopathology , Interleukin-1beta/blood , Action Potentials , Adult , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/immunology , Arrhythmias, Cardiac/physiopathology , Biomarkers/blood , Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/immunology , Electrocardiography , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Risk Factors , Up-RegulationABSTRACT
BACKGROUND: We demonstrate that serum immunoglobulin G (IgG) directed against glandular M3 muscarinic acetylcholine receptors (M3mAChR) and pilocarpine triggers the increment of superoxide dismutase (SOD) and catalase (CAT) and the production of nitric oxide (NO) and prostaglandin E2(PGE2). METHODS: Enzyme-linked immunosorbent assay (ELISA) was performed in the presence of the human M2mAChR synthetic peptide as antigen to detect in serum of pSS patients the autoantibodies. Further, SOD and CAT specific activity and NO were determined chemically in the presence of anti-M3mAChR IgG and pilocarpine. The level of PGE2generation in the presence of autoantibody and pilocarpine was determined by ELISA. RESULTS: An association between anti-M2mAChR autoantibodies and pilocarpine given the increment of the specific activity of SOD and CAT in the serum of pSS patients and in the rat submandibular gland was observed. As a result of this action, M3synthetic peptide and atropine abrogated the stimulatory action. The L-type calcium channel, calcium/calmodulin complex and COX-2 inhibitors selectively blocked the increment of the specific activity of SOD and CAT in the rat submandibular gland. An increased production of NO and PGE2by the cholinergic autoantibody and pilocarpine was also detected. CONCLUSION: On the basis of these results, the increment of the specific activity of SOD and CAT in pSS patients as compared to control healthy individuals may be seen as a defensive reaction to the increment of the amount of ROS, which becoming uncontrollable, leads to irreversible cellular and tissue damage.
Subject(s)
Antioxidants/metabolism , Immunoglobulin G/pharmacology , Receptor, Muscarinic M3/immunology , Sjogren's Syndrome/enzymology , Sjogren's Syndrome/immunology , Submandibular Gland/enzymology , Acetylcholine , Adult , Amino Acid Sequence , Animals , Autoantibodies/blood , Autoantibodies/pharmacology , Catalase/blood , Cyclooxygenase 2 Inhibitors/pharmacology , Dinoprostone/biosynthesis , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Molecular Sequence Data , Nitric Oxide/metabolism , Pilocarpine/pharmacology , Rats , Rats, Wistar , Receptors, IgG/metabolism , Sjogren's Syndrome/therapy , Submandibular Gland/drug effects , Superoxide Dismutase/bloodABSTRACT
An anti-ß(1)-adrenergic antibody from the sera of periodontitis patients (anti-ß(1)-AR IgG) against the second extracellular loop of the human ß(1)-adrenoceptor (ß(1)-AR) has been shown to cause rat atria apoptosis. The anti-ß(1)-AR IgG binds and activates atria ß(1)-AR, increasing the intracellular calcium concentration, which, in turn, activates caspases-3, -8, and -9. The ß(1)-AR and the post-receptor activation of calcium/calmodulin (CaM) lead to increased inducible nitric oxide synthase (iNOS) activity, with an increase in cyclic GMP (cGMP) accumulation as well as increased JNK phosphorylation and cyclic AMP (cAMP) production. We also observed an apoptotic effect of anti-ß(1)-AR IgG, with increased generation of PGE(2). Comparatively, xamoterol, an authentic ß(1)-AR agonist, mimicked the autoantibody effect on rat atria ß(1)-AR apoptosis. Our results suggest that autoantibodies from the sera of periodontitis patients bind and interact with rat atria ß(1)-AR, provoking apoptosis. This implicates a series of modulatory cardiac signaling events that could alter normal heart function and may occur with chronic stimulation of the atria ß(1)-AR, which could lead to heart failure. These results suggest an important link between periodontitis and cardiovascular disease.
Subject(s)
Apoptosis/physiology , Immunoglobulin G/pharmacology , Periodontitis/therapy , Receptors, Adrenergic, beta-1/immunology , Adult , Animals , Caspases/genetics , Caspases/metabolism , Dinoprostone/metabolism , Female , Gene Expression Regulation/immunology , Heart Atria/drug effects , Heart Atria/metabolism , Humans , Immunoglobulin G/immunology , MAP Kinase Kinase 4/genetics , MAP Kinase Kinase 4/metabolism , Male , Middle Aged , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase/metabolism , Nucleotides, Cyclic/metabolism , RatsABSTRACT
Primary Sjögren's syndrome (pSS) is an autoimmune disease that targets salivary and lachrymal glands, characterized by anti-cholinergic autoantibodies directed against the M(3) muscarinic acetylcholine receptor (mAChR). The aim of this work was to evaluate if cholinergic autoantibodies contained in IgG purified from Sjögren sera could trigger apoptosis of A253 cell line. We also determined if caspase-3 and matrix metalloproteinase-3 (MMP-3) are involved in the induction of A253 cell death. Our results demonstrated that anti-cholinergic autoantibodies stimulate apoptosis and inositol phosphate (InsP) accumulation accompanied by caspase-3 activation and MMP-3 production. All of these effects were blunted by atropine and J104794, indicating that M(3) mAChRs are impacted by the anti-cholinergic autoantibodies. The intracellular pathway leading to autoantibody-induced biological effects involves phospholipase C (PLC), calcium/calmodulin (CaM) and extracellular calcium as demonstrated by treatment with U-73122, W-7, verapamil, BAPTA and BAPTA-AM, all of which blocked the effects of the anti-cholinergic autoantibodies. In conclusion, anti-cholinergic autoantibodies in IgG purified from pSS patient's sera mediates apoptosis of the A253 cell line in an InsP, caspase-3 and MMP-3 dependent manner.
Subject(s)
Apoptosis , Immunoglobulin G/immunology , Receptor, Muscarinic M3/immunology , Sjogren's Syndrome/immunology , Adult , Cell Line, Tumor , Female , Humans , Immunoglobulin G/isolation & purification , Middle Aged , Peptide Fragments/immunology , Sjogren's Syndrome/blood , Sjogren's Syndrome/pathologyABSTRACT
In this paper, we demonstrate that circulating antibodies from chronic periodontitis patients reacting with atrial ß(1)-adrenoceptors (ß(1)-ARs) act as an inducer of soluble CD40 ligand (sCD40L) release and prostaglandin E(2) (PGE(2)) generation. By enzyme-linked immunosorbent assay using ß(1) synthetic peptide (with an amino acid sequence identical to the second loop of human myocardial ß(1)-ARs) as a coating antigen, we demonstrated reactivity against the second extracellular loop on human myocardial ß(1)-ARs. This autoantibody present in the serum of chronic periodontitis patients was significantly correlated with the release of sCD40L and PGE(2). The release of sCD40L was blunted by atenolol, SP600125 and ß(1) synthetic peptide, and PGE(2) generation was inhibited by DuP 697 and slightly by FR122049. The effects of the antibody incubated with isolated rat atria upregulated sCD40L release with an increase of PGE(2) production and c-Jun N-terminal kinase phosphorylation. These results indicate that in chronic periodontitis patients, there is a positive association between sCD40L release and PGE(2) generation via the action of ß(1)-AR antibodies.
Subject(s)
Autoantibodies/immunology , CD40 Ligand/immunology , Chronic Periodontitis/immunology , Dinoprostone/immunology , Receptors, Adrenergic, beta-1/immunology , Adult , Animals , Autoantibodies/blood , CD40 Ligand/blood , Chronic Periodontitis/blood , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin G/isolation & purification , JNK Mitogen-Activated Protein Kinases/immunology , Male , Middle Aged , Myocardium/immunology , Rats , Rats, WistarABSTRACT
Experimental and clinical investigations have revealed that statins can down-regulate acute and chronic inflammatory processes. Whether statins express anti-inflammatory activities in the salivary glands in patients with primary Sjögren's syndrome (pSS) is not known. The in vitro and in vivo effect of atorvastatin on rat submandibular gland treated with anti-M(3) peptide IgG purified from SS patients was studied. The anti-inflammatory effects of atorvastatin were assessed by measuring the levels of IL-1ß, PGE(2) and MMP-3 by ELISA. Atorvastatin inhibited the increase in the production of IL-1ß, PGE(2) and MMP-3 in submandibular glands treated with anti-M(3) peptide IgG. A positive correlation between IL-1ß production with accumulation of PGE(2) and MMP-3 was observed. Rats pre-treated orally with atorvastatin (30 mg kg(-1)) or vehicle (phosphate-buffered solution) once a day for three consecutive days impaired the increment in the production of IL-1ß, PGE(2) and MMP-3 in the submandibular gland in the presence of anti-M(3) peptide IgG. In conclusion, the anti-inflammatory effects of atorvastatin are dependent upon inhibition of production of a pro-inflammatory cytokine (IL-1ß) and pro-inflammatory mediators such as PGE(2) and MMP-3. These data suggest that atorvastatin may constitute an anti-inflammatory effect in SS.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Heptanoic Acids/pharmacology , Immunoglobulin G/pharmacology , Peptide Fragments/pharmacology , Pyrroles/pharmacology , Receptor, Muscarinic M3/antagonists & inhibitors , Sjogren's Syndrome/immunology , Submandibular Gland/drug effects , Adult , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Atorvastatin , Autoantibodies/immunology , Autoantibodies/pharmacology , Dinoprostone/biosynthesis , Dinoprostone/blood , Dinoprostone/immunology , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay , Female , Heptanoic Acids/administration & dosage , Humans , Immunoglobulin G/immunology , In Vitro Techniques , Interleukin-1beta/biosynthesis , Interleukin-1beta/blood , Interleukin-1beta/immunology , Male , Matrix Metalloproteinase 3/biosynthesis , Matrix Metalloproteinase 3/blood , Matrix Metalloproteinase 3/immunology , Middle Aged , Peptide Fragments/immunology , Pyrroles/administration & dosage , Rats , Receptor, Muscarinic M3/immunology , Submandibular Gland/immunologyABSTRACT
BACKGROUND: The presence of serum autoantibodies against ß(1) adrenoreceptors (ß(1)-ARs) in human gingival fibroblast from patients with periodontitis inhibits primary cell-specific growth and induces over-expression of pro-inflammatory mediators. Serum ß(1)-AR autoantibodies from patients with periodontitis react with myocardium and modify cardiac contractility. The relationship between the presence of serum ß(1)-AR autoantibodies and alterations in heart rate variability (HRV) was also studied. METHODS: An enzyme-linked immunosorbent assay (ELISA) using cardiac and gingival fibroblast membranes or synthetic peptides corresponding to the second extracellular loop of human ß(1)-AR was used to detect serum autoantibodies. The HRV was assessed from RR interval files generated from 22:00 to 08:00 hours. The autoantibody effects on contractility were measured on spontaneous rat isolated atria. RESULTS: Circulating autoantibodies from 36 patients with periodontitis and 20 healthy individuals (controls) interacted with fibroblasts, the cardiac surface, and ß(1)-AR synthetic peptides. The distributions of serum antibodies against gingival and myocardium membranes and ß(1)-AR synthetic peptide were 88.8%, 77.7%, and 92.8%, respectively. Moreover, 88.5% of patients with periodontitis whose sera were positive against ß(1)-AR synthetic peptide had decreased HRV. The corresponding affinity-purified anti-ß(1)-AR peptide IgG displayed partial agonist-like activity modifying the isolated atria contractility. CONCLUSION: This manuscript describes that patients with periodontitis showed increased levels of serum IgG with reactive activity against ß(1)-AR. Those patients demonstrated decrease in heart rate, and IgG derived from their sera induced aberrant contractility of heart atrium. We propose that periodontitis increases the risk of cardiovascular diseases, although it increases anti-ß(1)-AR autoantibody that alters myocardial contractility.