Fluid Matrix Metalloproteinase-8 Research Articles

The earlier the gestational age, the greater the intensity of the intra-amniotic inflammatory response in women with preterm premature rupture of membranes and amniotic fluid infection by Ureaplasma species.

Objectives To determine the relationship between the intensity of the intra-amniotic inflammatory response and the gestational age at the time of diagnosis in cases with preterm premature rupture of membranes (PROM) and intra-amniotic infection caused by Ureaplasma spp. Methods A retrospective cohort study was conducted which included 71 women with preterm PROM and a positive amniotic fluid culture with Ureaplasma spp. Women with mixed intra-amniotic infections were excluded. The study population was classified into three groups according to gestational age: group 1, <26 weeks (extreme preterm PROM, n = 17); group 2, 26.0-33.9 weeks (moderate preterm PROM, n = 39); group 3, 34.0-36.9 weeks (late preterm PROM, n = 15). The intensity of the intra-amniotic and maternal inflammatory response was compared among the three groups. The intensity of the intra-amniotic inflammatory response was assessed by the concentration of amniotic fluid matrix metalloproteinase-8 (MMP-8) and white blood cell (WBC) count. The maternal inflammatory response was assessed by the concentration of C-reactive protein (CRP) and WBC count in maternal blood at the time of amniocentesis. Results (1) The median values of amniotic fluid MMP-8 concentration and WBC count were the highest in the extreme preterm PROM group and the lowest in the late preterm PROM group (P < 0.001 and P = 0.01, respectively); (2) the intensity of the maternal inflammatory response measured by maternal blood WBC count and CRP concentration was not significantly associated with gestational age at the time of diagnosis. Conclusion The earlier the gestational age at the time of PROM, the higher the intensity of the intra-amniotic inflammatory response in women with preterm PROM and intra-amniotic infection caused by Ureaplasma spp.

The evaluation of probiotic as an adjunct to scaling and root planing in chronic periodontitis patients - A clinical, microbiological and biochemical study

Introduction: As probiotics are emerging as an essential treatment modality for chronic periodontitis its role is not well established. This study aimed to evaluate the efficacy of probiotic as an adjunct to Scaling and Root Planing (SRP) in chronic periodontitis. The clinical parameters, the levels of Matrix Metalloproteinases 8 in gingival crevicular fluid and the presence & reduction of Porphyromonas gingivalis in subgingival plaque samples were determined. Materials and Methods: This clinical study was conducted for 6 weeks with a single evaluator to investigate the effect of probiotic as an adjunct to SRP in chronic periodontitis. The clinical parameters were analyzed at baseline, 3 weeks and 6 weeks. This study also evaluated the effect of Probiotic on Matrix metalloproteinase 8 levels in GCF and on the existence of Porphyromonas gingivalis in subgingival plaque after 3 weeks. Results: Clinical parameters, gingival crevicular fluid Matrix Metalloproteinase 8 and Subgingival plaque levels of Porphyromonas gingivalis were reduced in Control (Group I) and Probiotic study (Group II) at baseline and 6 weeks. On comparing the groups, Group II had a significant decrease in clinical, microbiological and biochemical parameters than Group I, post treatment. Conclusion: Probiotics have great potential in arena of periodontics in terms of plaque formation, altering anaerobic bacterial colonization, reduction in Pocket Depth, gingival bleeding and clinical attachment level and in treating halitosis. Probiotics can be used as an effective adjunctive therapy to conventional non-surgical periodontal treatment in Chronic Periodontitis patients. Keywords: Chronic periodontitis, Probiotics, Scaling and root planing, Gingival bleeding, Halitosis.

A high concentration of fetal fibronectin in cervical secretions increases the risk of intra-amniotic infection and inflammation in patients with preterm labor and intact membranes

Objective To determine whether the risk of intra-amniotic infection/inflammation and spontaneous preterm delivery (SPTD) varies as a function of the concentration of cervical fetal fibronectin (fFN) in patients with preterm labor and intact membranes. Methods This prospective study included 180 patients with preterm labor and intact membranes who had a sample collected for quantitative fFN measurement and underwent amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. Results (1) The prevalence of intra-amniotic infection/inflammation and SPTD within 7 days was 32.2% (58/180) and 33.9% (61/178), respectively; (2) The higher the fFN concentration, the greater the risk of intra-amniotic infection/inflammation and SPTD within 7 days (P<0.001, respectively); (3) An fFN concentration 150 ng/mL had a better diagnostic performance than an fFN 50 ng/mL in the identification of intra-amniotic infection/inflammation and SPTD within 7 days; (4) Among the patients with an fFN <50 ng/mL, intra-amniotic infection/inflammation was identified in 7.6% (6/79) of patients and 66.7% (4/6) delivered within 7 days. Conclusion The higher the concentration of fFN, the greater the risk of intra-amniotic infection/inflammation and SPTD in patients with preterm labor and intact membranes.

Meta-analysis of the association between serum and gingival crevicular fluid matrix metalloproteinase-9 and periodontitis

BackgroundThe authors of this meta-analysis evaluated whether there is a difference in the levels of serum and gingival crevicular fluid (GCF) matrix metalloproteinase (MMP)-9 between patients with periodontitis and periodontally healthy control participants. Types of Studies ReviewedThe authors searched PubMed, Embase, the Cochrane Library, and the China Biology Medicine disk databases for eligible studies in which the investigators reported the relationships between MMP-9 levels in serum and GCF and periodontitis. The authors pooled the standardized mean differences (SMDs) and 95% confidence intervals (CIs) from each study to evaluate the difference in the serum and GCF MMP-9 levels between patients with periodontitis and periodontally healthy control participants. ResultsResults of a meta-analysis of 6 case-control studies including a total of 923 healthy control participants and 557 patients with periodontitis indicated that serum MMP-9 levels were significantly higher in patients with periodontitis than in periodontally healthy control participants (SMD, 1.60; 95% CI, 0.17 to 3.03; P < .05). Results of a separate meta-analysis of 6 case-control studies including a total of 153 healthy control participants and 189 patients with periodontitis indicated that GCF MMP-9 levels were significantly higher in patients with periodontitis than in periodontally healthy control participants (SMD, 1.96; 95% CI, 0.76 to 3.16; P < .01). Conclusions and Practical ImplicationsThe results of the meta-analysis revealed statistically significant differences in the MMP-9 levels in serum and GCF between patients with periodontitis and periodontally healthy control participants. These results cannot be used to confirm causality because the included studies were all case-control studies in which the investigators reported associations. Moreover, readers should view the results with caution because of the considerable heterogeneity among the studies included in the meta-analysis.

Wound Fluid Matrix Metalloproteinase-9 as a Potential Predictive Marker for the Poor Healing Outcome in Diabetic Foot Ulcers.

Background and Objective Evidence for the roles of matrix metalloproteinases-9 (MMP-9) in the healing process of diabetic foot ulcers has remained unclear. We therefore aimed to demonstrate the relationship of MMP-9 with the wound healing process and determine its potential usefulness in predicting the wound healing outcome. Methods Twenty-two patients with diabetic foot ulcer were recruited. The wound size was determined, and the wound fluid was collected for the measurement of MMP-9 levels using an ELISA during the 12-week follow-up period regularly. The patients were categorized as good healers and poor healers when the wound area reduction was ≥ 50% and < 50% at week 4 when compared to the initial wound size at week 0. Results Median wound fluid MMP-9 levels in the poor healer group were shown to be significantly higher than those in the good healer group (1.03 pg/µg protein vs. 0.06 pg/µg protein, p = 0.001), and the levels fluctuated throughout the 12-week follow-up period. In contrast to the poor healer group, the MMP-9 levels were demonstrated to be constantly low throughout the follow-up period in the good healer group. ROC analysis showed that the MMP-9 level of 0.38 pg/µg protein was able to predict the wound healing outcome with the sensitivity of 81.8%, the specificity of 64.6%, and the area under the curve of 0.901 (CI 0.78-1.03, p = 0.001). Conclusion These findings suggested that determination of wound fluid MMP-9 levels might become a promising biomarker predicting wound healing outcomes and a novel potential therapeutic target for diabetic foot ulcers.

Cervical and Amniotic Fluid Matrix Metalloproteinase-8 and Interleukin-6 Concentrations in Preterm Pregnancies with or without Preterm Premature Rupture of Membranes

Introduction: Intra-amniotic inflammation is defined by elevated inflammatory biomarkers in the amniotic fluid (AF), either due to microbial invasion of the amniotic cavity (MIAC) or sterile inflammation. Amniocentesis being an invasive procedure, we wanted to investigate whether elevated matrix metalloproteinase-8 (MMP-8) or interleukin-6 (IL-6) concentrations could be detected from cervical fluid samples. Materials and Methods: This prospective study included 67 women with singleton nondiabetic pregnancies with or without preterm premature rupture of membranes (PPROM) between 22⁺⁰ and 37⁺⁰ weeks of gestation. Simultaneous AF and cervical samples were obtained. Results: In women without PPROM, cervical MMP-8 concentrations correlated with AF MMP-8 concentrations (r_S = 0.466, p = 0.002), but cervical IL-6 did not correlate with AF IL-6 (r_S = 0.277, p = 0.076). In PPROM cases no correlations were found. Women with MIAC had higher concentrations of AF MMP-8 and AF IL-6 compared to women without MIAC regardless of membrane status. However, only women without PPROM had higher concentrations of cervical MMP-8 in proven MIAC. Conclusion: In women without PPROM, cervical MMP-8 concentration reflects the magnitude of AF MMP-8, thus potentially guiding the selection of patients benefitting from amniocentesis.

The analysis of matrix metalloproteinase-8 in gingival crevicular fluid and periodontal diseases

Periodontal disease, also generally called periodontitis or gum disease, is a chronic infection-induced inflammatory disease that causes tooth loss if not properly treated, and is considered as a modifying factor in systemic health. Gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) is an inflammatory marker found in periodontal pathologic conditions. Gingivitis, a nondestructive type of periodontal disease, can progress to periodontitis if left untreated. Therefore, assessing the level of MMP-8 with comfortable methods and no tissue intervention can determine the progression of the periodontal disease for a better treatment. The purpose of the present study is to determine the relationship between MMP-8 in GCF and periodontal disease. This is a cross-sectional study that took place in West Sumatra, Indonesia from June to December 2013. This study involves 60 respondents who are divided into three groups based on the periodontal disease index. The samples consist of 20 healthy individuals, 20 with mild gingivitis, and 20 periodontitis initial. GCF was collected from each group. MMP8 level in GCF was tested by using ELISA technique. Data were analyzed with SPSS version 17 Software. ANOVA test was used to determine the differences in average levels of MMP-8. Bonferroni post hoc test was used to discover which spesific means differed. The level of MMP-8 is significantly different between the healthy group and mild gingivitis group, between the healthy group with mild periodontitis group, and also between groups with mild gingivitis and mild periodontitis (P < 0.05). The findings of this study can be used by practitioners of dentistry to establish a proper diagnosis and appropriate treatment of periodontal disease by measuring the scale of MMP-8, to prevent or to minimize further complication in periodontitis patients.

Impact of Pregnancy History and 17-Hydroxyprogesterone Caproate on Cervical Cytokines and Matrix Metalloproteinases.

The objective of this study was to evaluate the impact of pregnancy history and 17-hydroxyprogesterone caproate (17-OHPC) treatment on cervical fluid cytokines and matrix metalloproteinases (MMPs). Cervical fluid was obtained between 160/7 and 246/7 weeks from women with only prior term births (controls, n = 26), women with one or more prior spontaneous preterm births (SPTBs) choosing to receive 17-OHPC (17-OHPC, n = 24), or to not receive 17-OHPC (refusers, n = 12). Cervical fluid collections were repeated 2, 4, and 8 weeks after the first sample and concentrations of MMPs and cytokines were measured by multiplex immune assay. Among women whose earliest prior delivery occurred between 16 and 23 weeks, cervical fluid concentration of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α at baseline were significantly elevated when compared with cervical cytokines of women whose earliest delivery occurred between 32 and 36 weeks (relative risk ratio was 3.37 for IL-6 [95% confidence interval, CI, 1.08-10.53, p < 0.05], 2.81 for IL-10 [95% CI, 1.39-5.70, p < 0.05], and 6.34 for TNF-α [95% CI, 2.19-18.68, p < 0.001]). Treatment with 17-OHPC had no significant impact on these cytokines. The cervical fluid of women with a history of an early prior SPTB is characterized by inflammation that is unaffected by 17-OHPC.

Cerebrospinal fluid matrix metalloproteinase 9 levels, blood-brain barrier permeability, and treatment outcome in tuberculous meningitis

ObjectivesTuberculous meningitis is characterized by elevated levels of matrix metalloproteinase 9 (MMP9) in the cerebrospinal fluid (CSF). However, it is unclear whether elevated MMP9 levels are associated with poor treatment outcome. We tested the hypothesis that pretreatment MMP9 levels in the CSF would be higher in tuberculous meningitis patients experiencing a poor treatment outcome.MethodsWe prospectively assessed the treatment outcome in a consecutive sample of human immunodeficiency virus-negative patients with tuberculous meningitis. We defined good outcome as survival without severe neurological disability (modified Rankin scale scores 0–2). We estimated levels of MMP9 and its tissue inhibitor (TIMP1) on pretreatment CSF samples. We used albumin index to assess blood-brain barrier permeability.ResultsWe studied 40 patients (23 males [58%]) with tuberculous meningitis. Sixteen patients (40%) had stage 3 disease. On follow-up, 18 (45%) patients had a poor treatment outcome—15 patients died and 3 had severe neurological disability. Pretreatment MMP9 levels were not associated with treatment outcome (median [interquartile range], 254 [115–389] vs. 192 [60–383] ng/mL in good vs. poor outcome groups; P = 0.693). MMP9 levels did not correlate with the albumin index (Spearman’s rho = 0.142; P = 0.381). However, MMP9 levels significantly correlated with CSF glucose levels (rho = −0.419; P = 0.007) and admission Glasgow coma scale score (rho = 0.324; P = 0.032). Likewise, TIMP1 levels also did not differ by treatment outcome (1239 [889–1511] vs. 1522 [934–1949] ng/mL; P = 0.201). MMP9/TIMP1 ratio that reflects net proteolytic activity was also not different between the two groups (0.191 [0.107–0.250] vs. 0.163 [0.067–0.34]; P = 0.625).ConclusionOur findings do not support the hypothesis that pretreatment levels of MMP9 would be higher in tuberculous meningitis patients experiencing a poor treatment outcome. Further, MMP9 levels in the CSF did not correlate with blood-brain barrier permeability in patients with tuberculous meningitis.

The combined exposure to intra-amniotic inflammation and neonatal respiratory distress syndrome increases the risk of intraventricular hemorrhage in preterm neonates.

To evaluate the impact of combined exposure to intra-amniotic inflammation and neonatal respiratory distress syndrome (RDS) on the development of intraventricular hemorrhage (IVH) in preterm neonates. This retrospective cohort study includes 207 consecutive preterm births (24.0-33.0 weeks of gestation). Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. According to McMenamin's classification, IVH was defined as grade II or higher when detected by neurosonography within the first weeks of life. (1) IVH was diagnosed in 6.8% (14/207) of neonates in the study population; (2) IVH was frequent among newborns exposed to intra-amniotic inflammation when followed by postnatal RDS [33% (6/18)]. The frequency of IVH was 7% (8/115) among neonates exposed to either of these conditions - intra-amniotic inflammation or RDS - and 0% (0/64) among those who were not exposed to these conditions; and (3) Neonates exposed to intra-amniotic inflammation and postnatal RDS had a significantly higher risk of IVH than those with only intra-amniotic inflammation [odds ratio (OR) 4.6, 95% confidence interval (CI) 1.1-19.3] and those with RDS alone (OR 5.6, 95% CI 1.0-30.9), after adjusting for gestational age. The combined exposure to intra-amniotic inflammation and postnatal RDS markedly increased the risk of IVH in preterm neonates.

Matrix metalloproteinase activity and prostaglandin E2 are elevated in the synovial fluid of meniscus tear patients

ABSTRACTPurpose: Meniscus tears are a common knee injury and are associated with the development of post-traumatic osteoarthritis (OA). The purpose of this study is to evaluate potential OA mediators in the synovial fluid and serum of meniscus tear subjects compared to those in the synovial fluid of radiographic non-OA control knees. Materials and methods: Sixteen subjects with an isolated unilateral meniscus injury and six subjects who served as reference controls (knee Kellgren-Lawrence grade 0-1) were recruited. Twenty-one biomarkers were measured in serum from meniscus tear subjects and in synovial fluid from both groups. Meniscus tear subjects were further stratified by tear type to assess differences in biomarker levels. Results: Synovial fluid total matrix metalloproteinase (MMP) activity and prostaglandin E2 (PGE2) were increased 25-fold and 290-fold, respectively, in meniscus tear subjects as compared to reference controls (p < 0.05). Synovial fluid MMP activity and PGE2 concentrations were positively correlated in meniscus tear subjects (R = 0.83, p < 0.0001). In meniscus tear subjects, synovial fluid levels of MMP activity, MMP-2, MMP-3, sGAG, COMP, IL-6, and PGE2 were higher than serum levels (p < 0.05). Subjects with complex meniscus tears had higher synovial fluid MMP-10 (p < 0.05) and reduced serum TNFα and IL-8 (p < 0.05) compared to other tear types. Conclusions: Given the degradative and pro-inflammatory roles of MMP activity and PGE2, these molecules may alter the biochemical environment of the joint. Our findings suggest that modulation of PGE2 signaling, MMP activity, or both following a meniscus injury may be targets to promote meniscus repair and prevent OA development.

Twenty-four percent of patients with clinical chorioamnionitis in preterm gestations have no evidence of either culture-proven intraamniotic infection or intraamniotic inflammation

Recent studies on clinical chorioamnionitis at term suggest that some patients with this diagnosis have neither intraamniotic infection nor intraamniotic inflammation. A false-positive diagnosis of clinical chorioamnionitis in preterm gestation may lead to unwarranted preterm delivery. We sought to determine the frequency of intraamniotic inflammation and microbiologically proven amniotic fluid infection in patients with preterm clinical chorioamnionitis. Amniocentesis was performed in singleton pregnant women with preterm clinical chorioamnionitis (<36 weeks of gestation). Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas and assayed for matrix metalloproteinase-8 concentration. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture; intraamniotic inflammation was defined as an elevated amniotic fluid matrix metalloproteinase-8 concentration of >23 ng/mL. Nonparametric and survival techniques were used for analysis. Among patients with preterm clinical chorioamnionitis, 24% (12/50) had neither microbiologic evidence of intraamniotic infection nor intraamniotic inflammation. Microbial invasion of the amniotic cavity was present in 34% (18/53) and intraamniotic inflammation in 76% (38/50) of patients. The most common microorganisms isolated from the amniotic cavity were the Ureaplasma species. Finally, patients without microbial invasion of the amniotic cavity or intraamniotic inflammation had significantly lower rates of adverse outcomes (including lower gestational age at delivery, a shorter amniocentesis-to-delivery interval, acute histologic chorioamnionitis, acute funisitis, and significant neonatal morbidity) than those with microbial invasion of the amniotic cavity and/or intraamniotic inflammation. Among patients with preterm clinical chorioamnionitis, 24% had no evidence of either intraamniotic infection or intraamniotic inflammation, and 66% had negative amniotic fluid cultures, using standard microbiologic techniques. These observations call for a reexamination of the criteria used to diagnose preterm clinical chorioamnionitis.

The Effects of Body Mass Index on Second-Trimester Amniotic Fluid Cytokine and Matrix Metalloproteinase Levels

Aim: The aim of this study was to determine the effects of obesity on amniotic fluid (AF) inflammatory markers in second-trimester AF, testing the hypothesis that there is a relationship between maternal body mass index (BMI) and fetal inflammatory exposure. Methods: AF was obtained from 84 singleton pregnant women undergoing elective amniocentesis for karyotype analysis at 16-24 weeks of gestation between April 2014 and May 2016. The cell-free AF was used to analyze interleukin (IL)-1β and IL-6, and matrix metalloproteinase (MMP)-1, MMP-6, and MMP-13. Results: IL-1β levels were significantly higher in class II-III obese patients than in class I obese, overweight, and normal weight patients (14.68 ± 1.37 vs. 13.34 ± 1.86 vs. 13.00 ± 2.22 vs. 10.78 ± 1.92, respectively; p < 0.05). IL-6 levels were lowest in the normal weight group and highest in class II-III obese patients. MMP-1, MMP-6, and MMP-13 levels were also significantly higher in class II-III obese patients than in the other groups. Conclusion: This study demonstrated that the fetuses of class II-III obese women are exposed in utero to higher cytokine and MMP levels than fetuses of lean women. Modification of current cutoff levels of intra-amniotic cytokines and MMPs according to the BMI could improve the accuracy of the prenatal diagnosis of intra-amniotic infection and inflammation.

Cerebrospinal Fluid Matrix Metalloproteinase-9 Level in Children with Bacterial Meningitis

Cerebrospinal Fluid Matrix Metalloproteinase-9 Level in Children with Bacterial Meningitis

Increased cerebrospinal fluid metalloproteinase-2 and interleukin-6 are associated with albumin quotient in neuromyelitis optica: Their possible role on blood–brain barrier disruption

Background: Inflammation in neuromyelitis optica (NMO) is triggered by a serum antibody against the aquaporin-4 (AQP4). This process requires antibody penetration of the blood–brain barrier (BBB), but the mechanisms for BBB disruption in NMO remain unknown. Objective: We examined whether changes in cerebrospinal fluid (CSF) and serum matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and cytokines are associated with BBB disruption in NMO. Methods: The concentrations 9 MMPs, 4 TIMPs, and 14 cytokines were measured by multiplex assay in CSF and serum samples from 29 NMO patients, 29 relapsing-remitting multiple sclerosis (MS) patients, and 27 patients with other neurological disorders. We also performed immunohistochemistry for MMP-2 and TIMP-1 expression in post-mortem brain tissues from NMO patients. Results: NMO patients exhibited significantly elevated MMP-2, TIMP-1, interleukin-6, and MMP-2/TIMP-2 ratio in CSF (but not sera) than the other groups. The CSF/serum albumin ratio, an index of BBB permeability, was most strongly correlated with CSF MMP-2 concentration, which in turn correlated with CSF interleukin-6 levels. Immunohistochemistry revealed MMP-2- and TIMP-1-positive cells surrounding vessels in NMO lesions. Conclusion: In NMO, increased CSF MMP-2, likely induced by interleukin-6 signaling, may disrupt the BBB and enable serum anti-AQP-4 antibodies migration into the central nervous system (CNS).

Comparison of amniotic fluid matrix metalloproteinase-8 and cathelicidin in the diagnosis of intra-amniotic infection.

To evaluate the association of amniotic fluid (AF) matrix metalloproteinase-8 (MMP-8) and cathelicidin concentrations with microbial invasion of the amniotic cavity (MIAC) in pregnancies with preterm prelabor rupture of the membranes or intact membranes. Amniocentesis was performed in 54 singleton pregnancies between 22+0 and 34+2 gestational weeks with suspected intra-amniotic infection. AF-MMP-8 was analysed by immunoassay and AF-cathelicidin by commercial ELISA. Standard biochemical methods, molecular microbiology and culture techniques were used. MIAC was present in 18 (33%) women. The cutoff value for the diagnosis of MIAC was 41.5 ng ml-1 for AF-MMP-8, and 11.6 ng ml-1 for AF-cathelicidin. With these cutoff values AF-MMP-8 had a sensitivity of 100%, specificity of 69%, positive predictive value of 62% and negative predictive value of 100% for MIAC. The corresponding values for AF-cathelicidin were 89, 81, 70 and 94%. The performance of AF-cathelicidin in the prediction of MIAC is comparable to AF-MMP-8.

Early- or mid-trimester amniocentesis biomarkers for predicting preterm delivery: a meta-analysis

Objective: To determine the value of early- or mid-trimester amniotic fluid levels of interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8), and glucose for predicting preterm delivery.Methods: Randomized controlled trials and two-arm prospective, retrospective, cohorts, and case-controlled studies in which patients received early- or mid-trimester amniocentesis for karyotyping, and biomarker testing of the amniotic fluid was performed and delivery data were available were included in the analysis.Results: Outcome measures were the associations of amniotic fluid IL-6, MMP-8, and glucose levels with preterm delivery. Differences in means with 95% confidence intervals (CIs) were calculated. Of 288 articles identified, 14 were included in the meta-analysis with a total of 675 patients who had preterm birth and 2518 patients who had term births. The preterm-delivery group had significantly higher amniotic fluid IL-6 and MMP-8 levels, and a significantly lower glucose level than the term delivery group (IL-6: difference in means = 0.32, 95% CI: 0.22–0.43, p < 0.001; MMP-8: difference in means = 4.47, 95% CI: 0.83–8.11), p = 0.016; glucose: difference in means = −5.22, 95% CI: −8.19 to −2.26, p = 0.001)Conclusion: Early- or mid-trimester amniotic fluid IL-6, MMP-8, and glucose levels are useful for predicting the risk of preterm delivery.KEY MESSAGESMedian amniotic fluid ferritin and IL-6 levels, and mean amniotic fluid ALP levels were higher in the preterm group.The preterm-delivery group had significantly higher amniotic fluid IL-6 and MMP-8 levels, and a significantly lower glucose level than the term-delivery group.

Oral fluid matrix metalloproteinase (MMP)-8 as a diagnostic tool in chronic periodontitis

Oral fluid matrix metalloproteinase (MMP)-8 as a diagnostic tool in chronic periodontitis Patricia Hernández-Ríos,1 Marcela Hernández,2,3 Mauricio Garrido,1 Taina Tervahartiala,4 Jussi M Leppilahti,4 Heidi Kuula,4 Anna Maria Heikkinen,4 Päivi Mäntylä,4 Nilminie Rathnayake,5 Solomon Nwhator,6 Timo Sorsa4,5 1Department of Conservative Dentistry, 2Department of Pathology and Oral Medicine, 3Laboratory of Periodontal Biology, Department of Conservative Dentistry, Faculty of Dentistry, University of Chile, Santiago, Chile; 4Department of Oral and Maxillofacial Diseases, Institute of Dentistry, Helsinki University and Helsinki University Central Hospital, Helsinki, Finland; 5Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden; 6Department of Preventive and Community Dentistry, Faculty of Dentistry, College of Health Sciences, Obafemi Awolowo University, Ife, Nigeria Abstract: Periodontal diseases that affect the marginal and apical periodontium result from the interaction between bacterial biofilm and the host response. Oral fluid biomarkers might aid clinical diagnosis. Matrix metalloproteinases (MMPs) are a family of 24 proteases that act in physiological and pathological conditions. They can degrade almost all extracellular matrix constituents and regulate inflammatory processes. They are mainly inhibited by tissue inhibitors of metalloproteinases. The aim of this study was to perform a current literature review with a special reference on the diagnostic and clinical utility of oral fluid MMPs, especially MMP-8, and their inhibitors in periodontal and oral diseases. MMP-8 is the main collagenolytic MMP detected in oral fluids, such as saliva, oral mouthrinse, gingival crevicular fluid, and peri-implant fluid. MMP-8, and potentially MMP-9, in oral fluids represent strong biomarker candidates associated especially with periodontal disease diagnosis, severity, progression, and follow-up. Additionally, they show diagnostic potential for systemic conditions, such as pregnancy, myocardial infarction, and smoking. A commercially available mouthrinse, active MMP-8 chair-side/point-of-care lateral flow immunoassay, shows enough sensitivity and specificity to detect clinical signs of periodontitis. The current literature supports that high MMP-8 levels reflect the loss of periodontal supporting tissues rather than inflammation, representing a potentially useful side-diagnostic point-of-care oral disease biomarker, especially in periodontal diseases. Keywords: gingival crevicular fluid, saliva, biomarkers

GDF15/MIC1 and MMP9 Cerebrospinal Fluid Levels in Parkinson's Disease and Lewy Body Dementia.

Based on animal and ex-vivo experiments, Growth/Differentiation Factor-15 (GDF15, also called Macrophage Inhibitory Cytokine-1, MIC1), a member of the transforming growth factor-beta family, and Matrix Metalloproteinase-9 (MMP9), a member of the matrix metalloprotease family may be potential markers for Lewy body disorders, i.e. Parkinson’s disease with (PDD) and without dementia (PDND) and Lewy body dementia (DLB). GDF15 has a prominent role in development, cell proliferation, differentiation, and repair, whereas MMP9 degrades, as a proteolytic enzyme, components of the extracellular matrix. In this study, cerebrospinal fluid GDF15 and MMP9 levels of 59 PDND, 17 PDD and 23 DLB patients, as well as of 95 controls were determined, and associated with demographic, clinical and biochemical parameters. Our analysis confirmed the already described association of GDF15 levels with age and gender. Corrected GDF15 levels were significantly higher in PDD than in PDND patients, and intermediate in DLB patients. Within Lewy body disorders, GDF15 levels correlated positively with age at onset of Parkinsonism and dementia, Hoehn & Yahr stage and cerebrospinal fluid t-Tau and p-Tau levels, and negatively with the Mini Mental State Examination. Remarkably, it does not relevantly correlate with disease duration. MMP9 was not relevantly associated with any of these parameters. Cerebrospinal GDF15, but not MMP9, may be a potential marker of and in Lewy body disorders.

The plasma and peritoneal fluid concentrations of matrix metalloproteinase-9 are elevated in patients with endometriosis.

Enzyme matrix metalloproteinase-9 is a member of the matrix metalloproteinase family, which is critical to normal tissue remodelling during embryogenesis and wound healing. In patients with endometriosis, increased expression and activity of matrix metalloproteinase-9 have been observed in ectopic endometrium, but the plasma and peritoneal fluid concentrations of matrix metalloproteinase-9 in patients with endometriosis and their relation to disease severity have not been clear. The aim of the study was to investigate the concentrations of matrix metalloproteinase-9 in plasma and peritoneal fluid of patients with endometriosis. A prospective case-control study was conducted in Jinan Military General Hospital between January 2010 and December 2013. Fifty patients with proven endometriosis and 26 endometriosis-free controls were enrolled in this study. Patients with endometriosis were evaluated and divided into moderate/severe endometriosis group (stage I-II, n = 26) and minimal/mild endometriosis group (stage III-IV, n = 24) according to the revised criteria of the American Society for Reproductive Medicine. Blood samples and peritoneal fluid were obtained from both patients and controls. Matrix metalloproteinase-9 was measured using enzyme-linked immunosorbent assay in plasma and peritoneal fluid. The concentration of matrix metalloproteinase-9 between different groups was compared and its correlation to disease severity was analysed. Plasma and peritoneal fluid concentrations of matrix metalloproteinase-9 in patients with endometriosis were higher than that in controls. In addition, those patients with moderate/severe endometriosis had significantly higher plasma and peritoneal fluid concentrations of matrix metalloproteinase-9 compared to those with minimal/mild endometriosis. Matrix metalloproteinase-9 concentrations in plasma and peritoneal fluid were both positively correlated with severity of endometriosis and plasma matrix metalloproteinase-9 concentrations had a positive correlation with peritoneal fluid matrix metalloproteinase-9 concentrations in patients with endometriosis. Increased concentrations of plasma and peritoneal fluid concentrations of matrix metalloproteinase-9 appear to be associated with disease severity of endometriosis and may serve as an alternative biomarker to determine disease severity of endometriosis.