RESUMEN
The hypothesis that physiological changes in women can affect periodontal tissues is the subject of this study, and inflammatory markers such as matrix metalloproteinase-8 can measure susceptibility to inflammation. The study aimed to analyze MMP-8 levels in periodontal sites of postpartum women and women without a history of pregnancy, comparing health parameters and periodontal disease. This is a case-control study with 40 participants, 20 cases (women in the postpartum period) and 20 controls (women without any pregnancy), who underwent clinical periodontal examination and the collection of crevicular gingival fluid. The ELISA test was used to detect MMP-8 levels. Postpartum women had worse periodontal parameters, such as bleeding index on probing, number of sites with CAL ≥ 3, and fewer teeth present. In the group of women without a history of pregnancy, a significantly lower MMP-8 level was observed in healthy sites and a higher one was observed in periodontal pockets (p < 0.01). In contrast, in postpartum women, MMP-8 levels were elevated in both healthy sites and periodontal pockets (p > 0.01). The MMP-8 levels in gingival fluid appear to be related to periodontal clinical parameters and may be a possible marker of enzymatic changes involved in periodontal tissue destruction in postpartum women.
Asunto(s)
Líquido del Surco Gingival , Metaloproteinasa 8 de la Matriz , Periodo Posparto , Humanos , Femenino , Metaloproteinasa 8 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/análisis , Adulto , Estudios de Casos y Controles , Líquido del Surco Gingival/enzimología , Embarazo , Enfermedades Periodontales/enzimología , Biomarcadores/metabolismo , Adulto JovenRESUMEN
Patients with COVID-19 predominantly have a respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung infection is associated with hyper-inflammation and tissue damage. Matrix metalloproteinases (MMPs) contribute to tissue destruction in many pathological situations, and the activity of MMPs in the lung leads to the release of bioactive mediators with inflammatory properties. We sought to characterize a scenario in which MMPs could influence the lung pathogenesis of COVID-19. Although we observed high diversity of MMPs in lung tissue from COVID-19 patients by proteomics, we specified the expression and enzyme activity of MMP-2 in tracheal-aspirate fluid (TAF) samples from intubated COVID-19 and non-COVID-19 patients. Moreover, the expression of MMP-8 was positively correlated with MMP-2 levels and possible shedding of the immunosuppression mediator sHLA-G and sTREM-1. Together, overexpression of the MMP-2/MMP-8 axis, in addition to neutrophil infiltration and products, such as reactive oxygen species (ROS), increased lipid peroxidation that could promote intensive destruction of lung tissue in severe COVID-19. Thus, the inhibition of MMPs can be a novel target and promising treatment strategy in severe COVID-19.
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COVID-19 , Metaloproteinasa 2 de la Matriz , Antígenos HLA-G , Humanos , Inmunidad , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Estrés Oxidativo , SARS-CoV-2RESUMEN
Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients (n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.
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Biomarcadores/sangre , COVID-19/diagnóstico , COVID-19/mortalidad , Leucocitos/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Índice de Severidad de la Enfermedad , Receptor Activador Expresado en Células Mieloides 1/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Femenino , Humanos , Inflamación , Interleucina-10/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Estudios Prospectivos , SARS-CoV-2 , Receptor Activador Expresado en Células Mieloides 1/metabolismo , Adulto JovenRESUMEN
OBJECTIVES: The aim of this study is to investigate the expression of sTREM-1 and its ligand PGLYRP1, as well as the expression of MMP-8 and its inhibitor TIMP-1, in peri-implant diseases. As a secondary aim, we analyzed the influence of the concomitant existence of periodontitis in the expression of these biomarkers. MATERIALS AND METHODS: This study included 77 patients (29 males and 48 females; mean age 55.0 ± 11.5), 18 having gingivitis, 16 having periodontitis, 20 having mucositis, and 23 having peri-implantitis. Patients were clinically examined, and unstimulated whole saliva was collected. sTREM-1, PGLYRP1, MMP-8, TIMP-1, and MMP-8/TIMP1 ratio were determined by ELISA. RESULTS: The periodontitis group presented higher probing depth (PD) mean, and higher clinical attachment loss, compared with the other groups. The peri-implantitis group presented higher PD mean in implants compared to the mucositis group. Patients with PD ≥ 6 mm showed significantly higher levels of PGLYRP1, MMP-8, and MMP-8/TIMP-1 ratio than patients with PD < 6 mm. When all four markers were assessed, there were no significant differences between mucositis and peri-implantitis groups. Concomitant periodontitis resulted in higher significant levels of MMP-8 in patients with peri-implant disease. CONCLUSION: We did not observe significant differences in the levels of the sTREM-1/PGLYRP1/MMP-8 axis between patients with periodontal and peri-implant diseases, suggesting that these markers are also involved in the inflammatory process around implants. Besides, the presence of periodontitis may affect the levels of MMP-8 in patients with peri-implant disease. CLINICAL RELEVANCE: The sTREM-1/PGLYRP1/MMP-8 axis could be useful as potent markers in periodontal and peri-implant diseases.
Asunto(s)
Citocinas/metabolismo , Implantes Dentales , Metaloproteinasa 8 de la Matriz/metabolismo , Periimplantitis/metabolismo , Periodontitis/metabolismo , Receptor Activador Expresado en Células Mieloides 1/metabolismo , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidor Tisular de Metaloproteinasa-1/metabolismoRESUMEN
OBJECTIVE: In utero fetal surgery to correct incomplete closure of the spinal cord lessens the extent of permanent damage but is associated with preterm prelabour rupture of membranes (PPROM). We determined whether compounds in amniotic fluid collected at the time of surgery predicted subsequent development of PPROM. DESIGN: Prospective study. SETTING: Hospitals in Sao Paulo, Brazil. POPULATION: Twenty-four consecutive pregnant women at 24-26 weeks of gestation seen between February and October 2017 with a singleton pregnancy underwent in utero surgery to correct an open spinal defect in their fetus. METHODS: Amniotic fluid was tested for lactic acid, matrix metalloproteinase 2 (MMP-2), MMP-8, MMP-9 and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay. Clinical data were collected after completion of all laboratory studies. MAIN OUTCOME MEASURE: Amniotic fluid concentration of compounds in women with or without PPROM. RESULTS: Preterm prelabour rupture of membranes occurred in seven (29.2%) women. There were no differences in maternal age, gravidity, parity, race, history of caesarean sections or fetal gender between women with or without PPROM. Length of surgery, days of wound healing and length of hospital stay were also indistinguishable. The median concentrations of MMP-8 (1.7 versus 0.6 ng/ml; P = 0.0041) and lactic acid (7.1 versus 5.9 mm; P = 0.0181) were higher in women with PPROM. The amniotic fluid MMP-8 level was also negatively correlated with gestational age at delivery (Spearman r = -0.4217, P = 0.0319). CONCLUSION: Differences in susceptibility to develop PPROM are present before fetal surgery. An increase in anaerobic glycolysis, evidenced by the intra-amniotic lactic acid level, may enhance MMP-8 production and weaken maternal and fetal membranes. TWEETABLE ABSTRACT: Matrix metalloproteinase-8 and lactic acid in amniotic fluid predict preterm prelabour rupture of membranes.
Asunto(s)
Líquido Amniótico/metabolismo , Rotura Prematura de Membranas Fetales/metabolismo , Ácido Láctico/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Columna Vertebral/cirugía , Biomarcadores/metabolismo , Femenino , Terapias Fetales , Edad Gestacional , Humanos , Interleucina-6/metabolismo , Proyectos Piloto , Embarazo , Estudios Prospectivos , Columna Vertebral/anomalíasRESUMEN
Periodontal disease is characterized as a disorder of the oral microbiota resulting in an immune response which, in turn, leads to the destruction of periodontal tissue. Matrix metalloproteinase-8 (MMP-8) has been reported as the major metalloproteinase involved in periodontal disease, being present at high levels in gingival crevicular fluid and salivary fluid (SF). The aim of this systematic review was to evaluate the scientific literature regarding the expression of MMP-8 in gingival crevicular fluid and SF in patients with periodontal disease, analyzing its validity as a possible biomarker in the diagnosis of periodontal disease. A systematic review of the literature was performed using the PubMed/Medline, CENTRAL and Science Direct databases. Studies concerning the use of MMP-8 in the diagnosis of periodontal disease that evaluated its effectiveness as a biomarker for periodontal disease were selected. The search strategy provided a total of 6483 studies. After selection, six articles met all the inclusion criteria and were included in the present systematic review. The studies demonstrated significantly higher concentrations of MMP-8 in patients with periodontal disease compared with controls, as well as in patients presenting more advanced stages of periodontal disease. The findings on higher MMP-8 concentrations in patients with periodontal disease compared with controls imply the potential adjunctive use of MMP-8 in the diagnosis of periodontal disease.
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Biomarcadores , Metaloproteinasa 8 de la Matriz/análisis , Metaloproteinasa 8 de la Matriz/metabolismo , Enfermedades Periodontales/diagnóstico , Enfermedades Periodontales/inmunología , Factores de Edad , Bases de Datos Factuales , Índice de Placa Dental , Líquido del Surco Gingival/inmunología , Gingivitis/diagnóstico , Gingivitis/inmunología , Humanos , Pérdida de la Inserción Periodontal , Índice Periodontal , Bolsa Periodontal , Periodontitis/diagnóstico , Periodontitis/inmunología , Saliva/inmunología , Factores SexualesRESUMEN
Background:Neisseria gonorrhoeae (Ngo) is the etiological agent of gonorrhea, a sexually transmitted infection that initially infects the female lower genital tract. In untreated women, the bacteria can ascend to the upper genital reproductive tract and infect the fallopian tube (FTs), which is associated with salpingitis and can lead to impaired FT function and infertility. The extracellular matrix (ECM) plays an important role in cell migration and differentiation in the female genital tract, and some pathogens modify the ECM to establish successful infections. The ECM is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), their endogenous inhibitors; MMP deregulation causes pathological conditions in a variety of tissues. Results: The aim of this work was to analyze the expression and localization of MMP-3, MMP-8, MMP-9, and TIMP-1 in FT explants during Ngo infection using real-time PCR, immunohistochemistry, zymography and ELISA. No significant variations in MMP-3, MMP-9, and TIMP-1 transcript levels were observed. In contrast, a significant increase (p < 0.05) was observed for MMP-8 expression and was accompanied by stromal immunoreactivity in infected explants. ELISA results supported these findings and showed that MMP-8 release increased upon gonococcal infection. Conclusions: Our results indicate that gonococcal infection induces increased MMP-8 expression, which might contribute to FT damage during infection.
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Trompas Uterinas/metabolismo , Gonorrea/inmunología , Metaloproteinasa 8 de la Matriz/metabolismo , Neisseria gonorrhoeae/patogenicidad , Adulto , Trompas Uterinas/citología , Trompas Uterinas/microbiología , Trompas Uterinas/patología , Femenino , Humanos , Inmunohistoquímica , Metaloproteinasa 3 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Técnicas de Cultivo de Órganos , ARN Mensajero/análisis , Inhibidor Tisular de Metaloproteinasa-1/metabolismoRESUMEN
á : Matrix metalloproteinases can modulate the inflammatory response through processing of cyto- and chemokines. Among them, MMP-14 is a non-dispensable collagenase responsible for the activation of other enzymes, triggering a proteolytic cascade. To identify the role of MMP-14 during the pro-inflammatory response, wildtype and Mmp14 -/- mice were challenged with lipopolysaccharide. MMP-14 levels decreased after endotoxemia. Mutant animals showed 100% mortality, compared to 50% in wildtype mice. The increased mortality was related to a more severe lung injury, an impaired lung MMP-2 activation, and increased levels of the alarmin S100A9. There were no differences in the expression of other mediators including Il6, Cxcl2, Tgfb, Il10, or S100a8. A similar result was observed in lung explants of both genotypes cultured in presence of lipopolysaccharide. In this ex vivo model, exogenous activated MMP-2 ameliorated the observed increase in alarmins. Samples from septic patients showed a decrease in serum MMP-14 and activated MMP-2 compared to non-septic critically ill patients. These results demonstrate that the MMP-14-MMP-2 axis is downregulated during sepsis, leading to a proinflammatory response involving S100A9 and a more severe lung injury. This anti-inflammatory role of MMP-14 could have a therapeutic value in sepsis. KEY MESSAGES: ⢠MMP-14 levels decrease in lungs from endotoxemic mice and serum from septic patients. ⢠Mmp14 -/- mice show increased lung injury and mortality following endotoxemia. ⢠Absence of Mmp14 decreases activated MMP-2 and increases S100A9 levels in lung tissue. ⢠MMP-14 ameliorates inflammation by promoting S100A9 cleavage by activated MMP-2.
Asunto(s)
Endotoxemia/enzimología , Endotoxemia/metabolismo , Metaloproteinasa 14 de la Matriz/metabolismo , Anciano , Anciano de 80 o más Años , Animales , Endotoxemia/inducido químicamente , Femenino , Genotipo , Humanos , Lipopolisacáridos/toxicidad , Pulmón/efectos de los fármacos , Pulmón/enzimología , Pulmón/metabolismo , Masculino , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 14 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/genética , Metaloproteinasa 8 de la Matriz/metabolismo , Ratones , Ratones Mutantes , Persona de Mediana Edad , Sepsis/enzimología , Sepsis/metabolismoRESUMEN
BACKGROUND AND OBJECTIVE: No previous study has directly compared the levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) between smokers and individuals with diabetes mellitus (DM) with periodontitis. Therefore, the aim of this study was to evaluate the gene expression of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 in tissues with chronic periodontitis (ChP) of smokers and individuals with type 2 DM. MATERIAL AND METHODS: Gingival biopsies were harvested from: non-smokers and non-diabetic individuals with ChP (n = 18) (ChP group); non-diabetic smokers (≥ 10 cigarettes per day for at least the past 5 years) with ChP (n = 18) (SChP group); non-smoking individuals with type 2 diabetes (glycated hemoglobin levels ≥ 7.5%) and ChP (n = 18) (DMChP group). The tissue levels of mRNA of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 were evaluated by quantitative real-time polymerase chain reaction. RESULTS: The MMP-8 expression was the lowest in the ChP group (p < 0.05). The DMChP group presented increased mRNA levels of MMP-2 and MMP-9, when compared to the SChP group (p < 0.05). MMP-1 expression and the MMP-1/TIMP-1, MMP-2/TIMP-1, MMP-8/TIMP-1, MMP-9/TIMP-1, MMP-1/TIMP-2 and MMP-2/TIMP-2 ratios were higher in the DMChP group than in the ChP and SChP groups (p < 0.05). The DMChP group presented lower mRNA levels of TIMP-1 than the ChP group (p < 0.05). The MMP-8/TIMP-2 ratio was the highest in the SChP group (p < 0.05). CONCLUSION: Uncontrolled type 2 DM upregulates the ratio of MMP/TIMPs in sites with ChP more than smoking, which may contribute to a greater extracellular matrix degradation and periodontal breakdown in DM-related periodontitis.
Asunto(s)
Periodontitis Crónica/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Metaloproteinasas de la Matriz/metabolismo , Fumar/efectos adversos , Adulto , Periodontitis Crónica/enzimología , Periodontitis Crónica/metabolismo , Diabetes Mellitus Tipo 2/enzimología , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Encía/enzimología , Encía/metabolismo , Humanos , Masculino , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismoRESUMEN
BACKGROUND: Matrix metalloproteinases (MMPs) are responsible for the breakdown of the extracellular matrix and play an important role in the inflammatory processes of pleural exudates. The imbalance between MMPs and their inhibitors (TIMPs) is present in various pathological processes. OBJECTIVE: To evaluate the profile of MMPs and TIMPs in pleural effusions of different etiologies correlated with inflammatory markers. METHODS: The patients with pleural effusion due to tuberculosis (TB), cancer (CA) or transudate were prospectively evaluated. Pleural fluid was submitted to cytological, biochemical, cytokines, MMP, and TIMP analysis. Statistical analysis was performed using ANOVA and Spearman's correlation, and p < 0.05 was considered significant. RESULTS: One hundred and fourteen patients were enrolled, 80 exudates (41 TB and 39 CA) and 34 transudates. The levels of MMP-8 and MMP-9 were higher in exudates compared to transudates. The level of MMP-8 was significantly higher in TB than in CA. TIMP-1 levels were higher in exudates. IL-6, VEGF, and TGF-ß1 showed differences between exudates and transudates. However, IL-6 level was higher in TB than in CA. We found a significant correlation between MMPs and TIMPs with inflammation markers. MMP-1 was correlated with LDH levels. MMP-8 was correlated with LDH, total cell count, neutrophils, and ADA as well as MMP-1 levels. MMP-9 was correlated with IL-6, TGF-ß1, and VEGF. TIMP-1 was correlated with MMP-9 and IL-6. CONCLUSIONS: MMPs and TIMPs are expressed in pleural fluid of different etiologies and correlate with inflammatory mediators. MMPs may be useful in determining the cause of fluid, but more studies are needed to determine the spectrum of diseases associated with the various isoforms of MMPS and TIMPs.
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Exudados y Transudados/enzimología , Metaloproteasas/metabolismo , Derrame Pleural Maligno/enzimología , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Tuberculosis Pulmonar/enzimología , Adenosina Desaminasa/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Exudados y Transudados/metabolismo , Femenino , Humanos , Inflamación , Interleucina-6/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Recuento de Leucocitos , Masculino , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Neutrófilos , Derrame Pleural Maligno/etiología , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/patología , Estudios Prospectivos , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto JovenRESUMEN
The extracellular matrix (ECM) is the major macromolecule in skeletal muscle, which affects meat quality greatly. The remodeling of the ECM is mainly regulated by matrix metalloproteinases (MMPs). The expression patterns of MMP-1, -2, and -8 in longissimus dorsi muscle were explored using quantitative real-time polymerase chain reaction. The results show that the expression of MMP-1, -2, and -8 decreased significantly from 135 days of pregnancy to postnatal 30 months. While the expression of MMP-1, -2, and -8 showed no significant relationships with intramuscular fat contents, MMP-1 and -2 showed significant negative correlations with the shearing force of the longissimus dorsi muscle in cattle. The expression of MMP-1 also showed a significant negative correlation with cooking loss and a positive correlation with water holding capacity. The expression levels of MMP-1 and -2 were usually higher in fat than in skeletal muscle tissue. The expression of MMP-8 was significantly higher in the mammary fat pad and the longissimus dorsi muscle than in all other tissues. This study indicates that the remodeling of the ECM has important effects both on the development of postnatal skeletal muscle and on meat quality.
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Calidad de los Alimentos , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Músculos Paraespinales/metabolismo , Carne Roja , Animales , Bovinos , Desarrollo Fetal , Expresión Génica , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 8 de la Matriz/genética , Músculos Paraespinales/embriología , Músculos Paraespinales/crecimiento & desarrollo , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: We aimed to investigate the acute systemic and tissue inflammatory response associated with carotid endarterectomy (CEA) and analyze the association between serum and tissue biomarkers and histological features of carotid plaques between symptomatic and asymptomatic patients. METHODS: We studied 11 patients (6 symptomatic and 5 asymptomatic) with ≥70% internal carotid stenosis treated with CEA. Serum expression of interleukin (IL) 1ß, IL-4, IL-6, IL-8, IL-10, metalloproteinase (MMP) 8, MMP-9, tumor necrosis factor-α (TNF-α), high-sensitive C-reactive protein (hs-CRP), and vascular endothelial growth factor (VEGF) were measured in the preoperative period and 1, 6 and 24 hours after CEA. Assessment of tissue biomarkers (IL-1ß, IL-4, IL-6, IL-8, IL-10, MMP-8, MMP-9, TNF-α, and VEGF) and histological analyses were performed on carotid plaques. RESULTS: Peak serum values for MMP-8, MMP-9, IL-6, and IL 10 were observed 6 hours after CEA, whereas for hs-CRP, TNF-α, and VEGF, they were identified 24 hours after the procedure. Symptomatic patients exhibited higher serum concentrations of MMP-8, MMP-9, IL-1ß, IL-4, IL-8, hs-CRP and TNF-α and higher tissue concentrations of MMP-8, MMP-9, IL-1ß, IL-6 and VEGF than asymptomatic patients. Significant difference was found between symptomatic and asymptomatic patients in tissue IL-6 levels (30.95 pg/mL and 9.33 pg/mL, respectively; P=0.028). CONCLUSIONS: Systemic and tissue inflammatory response occurs even after CEA, being observed important activity of inflammatory and anti-inflammatory cytokines at 6 and 24 hours after CEA. Symptomatic patients show higher concentrations of serum and tissue biomarkers in comparison to asymptomatic patients.
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Estenosis Carotídea/cirugía , Citocinas/metabolismo , Endarterectomía Carotidea/efectos adversos , Inflamación/metabolismo , Anciano , Brasil , Proteína C-Reactiva/análisis , Femenino , Humanos , Masculino , Metaloproteinasa 8 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: The study of MMPs' behavior in carious lesions contributes to the understanding of the mechanisms involved in dentin reorganization after restoration. AIM: To compare the abundance and localization of MMPs 2, 8, and 9 in infected dentin before and after restoration. DESIGN: The sample consisted of 23 young permanent molars with active deep carious lesions. Infected carious dentin samples were collected from the same tooth at baseline and 60 days after cavity lining with GIC and composite resin restoration and processed for immunohistochemistry assays. After digital images were obtained, two calibrated operators analyzed the samples according to the immunostaining intensity and the MMPs' localization. Chi-square test was used for statistical analysis. RESULTS: The intensity of immunostaining for MMP-8 was reduced after 60 days (P = 0.02), and no difference was observed for MMP-2 (P = 0.32) and MMP-9 (P = 0.14). The MMPs' distribution was generalized in the intertubular dentin and absent or located in the intratubular dentin, regardless of the period. CONCLUSION: The sealing of infected carious dentin in young permanent molars reduced the expression of MMP-8, which is consistent with the initial remodeling process of the dentin matrix.
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Caries Dental/metabolismo , Caries Dental/patología , Caries Dental/terapia , Dentina/patología , Cementos de Ionómero Vítreo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Adolescente , Brasil , Niño , Resinas Compuestas , Dentición Permanente , Femenino , Humanos , Técnicas para Inmunoenzimas , Masculino , Diente MolarRESUMEN
OBJECTIVE: The impact of polypropylene mesh implantation on vaginal collagen and elastin metabolism was analyzed using a nonhuman primate model to further delineate the mechanism of mesh induced complications. STUDY DESIGN: Forty-nine middle-aged parous rhesus macaques underwent surgical implantation of 3 synthetic meshes via sacrocolpopexy. Gynemesh PS (n = 12) (Ethicon, Somerville, NJ) and 2 lower-weight, higher-porosity, lower-stiffness meshes (UltraPro [n = 19] [Ethicon] and Restorelle [n = 8] [Coloplast, Minneapolis, MN]) were implanted, in which UltraPro was implanted with its blue orientation lines perpendicular (low stiffness direction, n = 11) and parallel (high stiffness direction, n = 8) to the longitudinal axis of the vagina. Sham-operated animals were used as controls (n = 10). Twelve weeks after surgery, the mesh-tissue complex was excised and analyzed. RESULTS: Relative to sham, Gynemesh PS had a negative impact on the metabolism of both collagen and elastin-favoring catabolic reactions, whereas UltraPro induced an increase only in elastin degradation. Restorelle had the least impact. As compared with sham, the degradation of collagen and elastin in the vagina implanted with Gynemesh PS was increased with a simultaneous increase in active matrix metalloproteinase (MMP)-1, -8, -13, and total MMP-2 and -9 (all P < .05). The degradation of elastin (tropoelastin and mature elastin) was increased in the UltraPro-implanted vagina with a concomitant increase of MMP-2, and -9 (all P < .05). Collagen subtype ratio III/I was increased in Gynemesh PS and UltraPro perpendicular groups (P < .05). CONCLUSION: Following implantation with the heavier, less porous, and stiffer mesh, Gynemesh PS, the degradation of vaginal collagen and elastin exceeded synthesis, most likely as a result of increased activity of MMPs, resulting in a structurally compromised tissue.
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Colágeno/metabolismo , Elastina/metabolismo , Matriz Extracelular/metabolismo , Polipropilenos , Mallas Quirúrgicas/efectos adversos , Prolapso Uterino/cirugía , Vagina/metabolismo , Animales , Western Blotting , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Electroforesis en Gel de Poliacrilamida , Femenino , Macaca mulatta , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Procolágeno/metabolismo , Tropoelastina/metabolismoRESUMEN
OBJECTIVE: Do metabolites in vaginal samples vary between women with different vaginal disorders. DESIGN: Cross-sectional study. SETTING: Campinas, Brazil. SAMPLE: Seventy-seven women (39.9%) with no vaginal disorder, 52 women (26.9%) with vulvovaginal candidiasis (VVC), 43 women (22.3%) with bacterial vaginosis (BV), and 21 women (10.9%) with cytolytic vaginosis (CTV). METHOD: Concentrations of D- and L-lactic acid, extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinase-8 (MMP-8), and the influence of Candida albicans on EMMPRIN production by cultured vaginal epithelial cells, were determined by enzyme-linked immunosorbent assay (ELISA). Associations were determined by the Mann-Whitney U-test and by Spearman's rank correlation test. MAIN OUTCOME MEASURES: Metabolite levels and their correlation with diagnoses. RESULTS: Vaginal concentrations of D- and L-lactic acid were reduced from control levels in BV (P < 0.0001); L-lactic acid levels were elevated in CTV (P = 0.0116). EMMPRIN and MMP-8 concentrations were elevated in VVC (P < 0.0001). EMMPRIN and L-lactic acid concentrations (P ≤ 0.008), but not EMMPRIN and D-lactic acid, were correlated in all groups. EMMPRIN also increased in proportion with the ratio of L- to D-lactic acid in controls and in women with BV (P ≤ 0.009). Concentrations of EMMPRIN and MMP-8 were correlated in controls and women with VVC (P ≤ 0.0002). Candida albicans induced EMMPRIN release from vaginal epithelial cells. CONCLUSIONS: Vaginal secretions from women with BV are deficient in D- and L-lactic acid, women with VVC have elevated EMMPRIN and MMP-8 levels, and women with CTV have elevated L-lactic acid levels. These deviations may contribute to the clinical signs, symptoms, and sequelae that are characteristic of these disorders.
Asunto(s)
Basigina/metabolismo , Candidiasis Vulvovaginal/metabolismo , Ácido Láctico/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Vagina/microbiología , Vaginosis Bacteriana/metabolismo , Adulto , Líquidos Corporales/metabolismo , Brasil , Candidiasis Vulvovaginal/microbiología , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Células Epiteliales , Femenino , Humanos , Vaginosis Bacteriana/microbiologíaRESUMEN
The aim of this study was to investigate the adjunctive effect of antimicrobial photodynamic therapy (aPDT) to scaling and root planing (SRP) in smokers with chronic periodontitis. Twenty subjects had two contralateral teeth randomly assigned to receive SRP (SRP group) or SRP + a single episode of aPDT (SRP + aPDT group), with a diode laser and a phenothiazine photosensitizer. Plaque index, bleeding on probing, probing depth (PD), clinical attachment level (CAL), and gingival recession were recorded, and gingival crevicular fluid was collected for assay of IL-1ß and matrix metalloproteinase (MMP)-8 levels. There was a significant PD reduction (SRP 1.81 ± 0.52 mm/SRP + aPDT 1.58 ± 1.28 mm; p < 0.001) and a significant CAL gain (SRP 1.60 ± 0.92 mm/SRP + aPDT 1.41 ± 1.58 mm; p < 0.001) for both groups. Significant differences were not observed in between-group comparisons. IL-1ß level in gingival crevicular fluid was higher in SRP group after 1 week (SRP 24.65 ± 18.85 pg/µL/SRP + aPDT 34.07 ± 24.81 pg/µL; p = 0.048), and MMP-8 level was higher in SRP group after 12 weeks (SRP 303.31 ± 331.62 pg/µL/SRP + aPDT 534.23 ± 647.37 pg/µL; p = 0.024). There were no statistically significant differences in intragroup comparisons. The adjunctive effect of aPDT did not warrant improvements on clinical parameters in smokers. However, it resulted in a suppression of IL-1ß and MMP-8 when compared with SRP alone.
Asunto(s)
Antiinfecciosos/administración & dosificación , Periodontitis/terapia , Fotoquimioterapia/métodos , Aplanamiento de la Raíz/métodos , Fumar/efectos adversos , Adulto , Periodontitis Crónica/terapia , Terapia Combinada/métodos , Índice de Placa Dental , Raspado Dental/métodos , Femenino , Líquido del Surco Gingival/metabolismo , Recesión Gingival/tratamiento farmacológico , Humanos , Interleucina-1beta/metabolismo , Láseres de Semiconductores/uso terapéutico , Masculino , Metaloproteinasa 8 de la Matriz/metabolismo , Persona de Mediana Edad , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
Protease-activated receptor 2 (PAR2) is implicated in the pathogenesis of chronic inflammatory diseases, including periodontitis; it can be activated by gingipain and produced by Porphyromonas gingivalis and by neutrophil protease 3 (P3). PAR2 activation plays a relevant role in inflammatory processes by inducing the release of important inflammatory mediators associated with periodontal breakdown. The effects of periodontal treatment on PAR2 expression and its association with levels of proinflammatory mediators and activating proteases were investigated in chronic periodontitis patients. Positive staining for PAR2 was observed in gingival crevicular fluid cells and was reflective of tissue destruction. Overexpression of PAR2 was positively associated with inflammatory clinical parameters and with the levels of interleukin-6 (IL-6), IL-8, tumor necrosis factor alpha, matrix metalloprotease 2 (MMP-2), MMP-8, hepatocyte growth factor, and vascular endothelial growth factor. Elevated levels of gingipain and P3 and decreased levels of dentilisin and the protease inhibitors secretory leukocyte protease inhibitor and elafin were also associated with PAR2 overexpression. Healthy periodontal sites from individuals with chronic periodontitis showed diminished expression of PAR2 mRNA and the PAR2 protein (P < 0.05). Furthermore, periodontal treatment resulted in decreased PAR2 expression and correlated with decreased expression of inflammatory mediators and activating proteases. We concluded that periodontal treatment resulted in decreased levels of proteases and that proinflammatory mediators are associated with decreased PAR2 expression, suggesting that PAR2 expression is influenced by the presence of periodontal infection and is not a constitutive characteristic favoring periodontal inflammation.
Asunto(s)
Líquido del Surco Gingival/citología , Periodontitis/metabolismo , Periodontitis/terapia , Receptor PAR-2/metabolismo , Adhesinas Bacterianas/metabolismo , Adulto , Proteínas Bacterianas , Quimotripsina/metabolismo , Cisteína Endopeptidasas/metabolismo , Elafina/metabolismo , Femenino , Cisteína-Endopeptidasas Gingipaínas , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Persona de Mediana Edad , Mieloblastina/metabolismo , Péptido Hidrolasas , Bolsa Periodontal/inmunología , Periodontitis/inmunología , Porphyromonas gingivalis/metabolismo , ARN Mensajero/biosíntesis , Receptor PAR-2/biosíntesis , Receptor PAR-2/genética , Inhibidor Secretorio de Peptidasas Leucocitarias/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases with an important role in physiological and pathological remodeling. Their activity is regulated by tissue inhibitors of matrix metalloproteinases (TIMPs). Excess MMPs and myeloperoxidase (MPO) activity have been associated with loss of tooth supporting tissues in periodontal disease (PD). We investigate the changes in salivary MMP-8, MMP-9, TIMP-1, TIMP-2, and MPO concentrations during PD treatment and compare results with plasma levels. METHODS: MMP-8, MMP-9, TIMP-1 and TIMP-2 were analyzed by ELISA. Gelatinolytic activity of MMP-9 forms was determined by zymography, and the MPO activity was determined by colorimetric assay. RESULTS: Subjects were divided into 2 groups: PD and control, which were further divided into 2 subgroups each, namely PD before (PB) and after 3 months (PA) of non-surgical periodontal therapy, and healthy volunteers at baseline (CB) and 3months after baseline (CA). Subgroup PA presented lower gelatinolytic activity and MMP-8 and TIMP-2 concentrations in the saliva compared with PB (p<0.05). The MPO activity was higher in PB compared with CB (p<0.05). There were significant correlations between the gelatinolytic activity of the saliva and MMP-8 and MMP-9 plasma levels. There was a significant correlation between plasma and saliva TIMP-2 levels. CONCLUSION: These results suggest attenuation of some inflammatory markers in the saliva and plasma after PD treatment. Moreover, correlations between salivary and plasma levels exist for some of these markers.
Asunto(s)
Metaloproteinasa 8 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Periodontitis/metabolismo , Peroxidasa/metabolismo , Proteínas y Péptidos Salivales/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Adulto , Estudios de Casos y Controles , Raspado Dental , Femenino , Expresión Génica , Humanos , Masculino , Metaloproteinasa 8 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Persona de Mediana Edad , Periodontitis/genética , Periodontitis/patología , Periodontitis/terapia , Peroxidasa/genética , Saliva/química , Proteínas y Péptidos Salivales/genética , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-2/genéticaRESUMEN
BACKGROUND: Anastomotic dehiscence is the most severe complication of colorectal surgery and its incidence increases in the presence of infection. It has been reported that immune factors or the activity of matrix metalloproteinases (MMP) may mediate the loss of anastomotic strength in the first postoperative days. In this study, we investigated the effects of abdominal sepsis on the MMP and interleukin (IL) gene expression in left colonic anastomoses in rats. MATERIALS AND METHODS: Forty rats were divided into two groups of 20 animals according to the presence (group S) or absence (group N) of sepsis induction by cecal ligation and perforation during left colonic anastomosis. Each group was divided into subgroups for euthanasia on the third (N3 and S3) or seventh (N7 and S7) postoperative day (POD). A colonic segment containing anastomosis was removed for analysis of the expression of MMP1a, MMP8, MMP13, IL1ß, IL6, IL10, TNFα, and IFNγ genes. RESULTS: The anastomoses with abdominal sepsis showed increased MMP1a gene expression and decreased MMP8 gene expression both on the third and seventh POD. There was no change in the expression of MMP13. There was an increase in the expression of IL10 only on the third POD and a negative modulation of IL1ß, IFNγ, and IL6 genes on both periods. The TNFα gene expression was negatively modulated on the third POD and became not modulated on the seventh POD. CONCLUSION: Abdominal sepsis induced a specific inflammatory pattern with increased MMP1a and IL10 gene expression and negative modulation of MMP8, IL1ß, IFNγ, and TNFα gene expression in left colonic anastomoses in rats.
Asunto(s)
Anastomosis Quirúrgica , Colon/metabolismo , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Sepsis/metabolismo , Animales , Ciego/lesiones , Colon/cirugía , Modelos Animales de Enfermedad , Interferón gamma/metabolismo , Ligadura/efectos adversos , Masculino , Punciones/efectos adversos , Ratas , Ratas Wistar , Sepsis/etiología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
This randomized split-mouth study aimed to examine the levels of matrix metalloproteinases (MMPs) -1, -2, -3, -7, -8, -12, and -13 in the gingival crevicular fluid (GCF) at different time points during orthodontic tooth movement. A total of 16 healthy orthodontic subjects (7 females, 9 males; mean age, 17.7 years) who needed their first upper premolars extracted were enrolled. One randomly chosen maxillary canine was subjected to a distalizing force and was considered to be the test side. The contralateral canine, which was not subjected to any force but was included in the orthodontic appliance, was used as a control side. GCF sampling was performed at both the mesial (tension) and distal (pressure) test and control sites at baseline, immediately before applying the orthodontic appliance, and after 1 and 24 hours and 7, 14, and 21 days. A multiplexed bead immunoassay was used to analyse the GCF samples. The mean levels of the MMP-1, -2, -3, -7, -8, -12, and -13 were not significantly different between the test and control groups in each time showed. The comparisons between the tension and pressure sites were also not significantly different at each individual time. A few variations focused on MMP-1 and -3, but the expression of MMP-8 was higher than that of the other MMPs. MMPs are released in sufficient quantities such that tooth movement occurs but with no significant increase in GCF levels.