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Background To explore the soluble Neuropilin-1 (sNRP-1) concentrations in gingival crevicular fluid (GCF) and the periodontal clinical status of patients with Rheumatoid Arthritis (RA). Materials and methods We conducted an exploratory study with 40 study participants, 20 with RA, and 20 healthy controls. Clinical and periodontal data were recorded, and GCF samples were obtained. sNRP-1 levels in GCF were determined by ELISA assay. Descriptive statistics, Mann–Whitney U test, Unpaired t-test, logistic regression model, and Area Under Receiver Operating Characteristic Curve (AUC-ROC) were made to explore the diagnostic performance accuracy. Results RA patients had significantly higher levels of sNRP-1 in GCF (p ​= ​0.0447). The median levels of GCF-sNRP-1 were 208.85 ​pg/μl (IQR 131.03) in the RA group compared to 81.46 ​pg/μl (IQR 163.73) in the control group. We observed an association between the GCF-sNRP-1 concentrations and the RA diagnosis (OR:1.009; CI 1.00–1.001; p ​= ​0.047). The diagnosis of chronic periodontitis was also associated with RA (OR: 6.9; CI 1.52–31.37; p ​= ​0.012). Moreover, the AUC-ROC of GCF-sNRP-1 concentrations combined with periodontal clinical parameters such as periodontal probing depth and periodontal inflamed surface area was 0.80. Conclusion This exploratory case-control study shows that RA patients had significantly higher levels of sNRP-1 in GCF. New longitudinal studies are necessary to evaluate the role of NRP-1 in periodontal tissues and consider it an oral biomarker with clinical value in RA.

BACKGROUND To explore the diagnostic usefulness of extracellular vesicles (EVs), and their subpopulations (micro-vesicles and exosomes), and microRNAs (miRNA-21-3p, miRNA-150-5p, and miRNA-26a-5p) in peri-implant crevicular fluid (PICF) of subjects with healthy, peri-implant mucositis and peri-implantitis implants. METHODS A total of 54 patients were enrolled into healthy, peri-implant mucositis, and peri-implantitis groups. PICF samples were collected, EVs subpopulations (MVs and Exo) were isolated and characterized by nanoparticle tracking analysis and transmission electron microscopy. The expression of miRNA-21-3p, miRNA-150-5p and miRNA-26a-5p was quantified by qRT-PCR. Logistic regression models and accuracy performance tests were estimated. RESULTS PICF samples show the presence of EVs delimited by a bi-layered membrane, in accordance with the morphology and size (

Peri-implantitis is one of the leading causes of implant failure and loss, and its early diagnosis is not currently feasible due to the low sensitivity of currents methods. In the current exploratory cross-sectional study, we explored the diagnostic potential of lymphocyte B and Th17-chemotactic cytokine levels in peri-implant crevicular fluid (PICF) in 54 patients with healthy, peri-mucositis, or peri-implantitis implants. Peri-implant crevicular fluid was collected, and the levels of the molecules under study were quantified by Luminex assay. The concentrations of CCL-20 MIP-3 alpha, BAFF/BLYS, RANKL and OPG concentration in PICF were analyzed in the context of patient and clinical variables (smoking status, history of periodontitis, periodontal diagnosis, implant survival, suppuration, bleeding on probing, periodontal probing depth, clinical attachment level, mean of implant probing depth, and plaque index). Patients with peri-implantitis, appear to have an overregulation of the RANKL/BAFF-BLyS axis. This phenomenon needs to be investigated in depth in further studies with a larger sample size.

To explore a set of inflammatory biomarkers obtained from dentinal fluid (DF) from patients with symptomatic irreversible pulpitis (IP), reversible pulpitis (RP) and normal pulp (NP).A cross-sectional exploratory study was performed, recruiting 64 patients on the basis of their respective pulp condition. DF samples were obtained from all patients (23, from IP patients; 20, from RP patients; and 21, from NP patients). Quantification of biomarkers was performed using a Luminex® MAGPIX platform system and multiplex assay kits. The Kruskal-Wallis test was used for comparisons with regard to pulp state. A simple logistic regression model and the odds ratio (OR) with a 95% level of confidence (P = 0.05) were used to evaluate associations between biomarker levels and pulpal diagnosis. The performance discrimination of the biomarkers was evaluated through the construction of a receiver operating characteristic (ROC) curve by calculating the area under the curve (AUC) for IP versus RP after logistic regression modelling. Youden criteria were used to establish cut-off points for biomarkers alone with AUC 70 and P-value 0.05, or estimated probabilities from the multivariable logistic model.The biomarkers that had significantly higher values in participants with IP versus RP were IL-1α, VEGF-α and FGF acid (P 0.05). FGF acid (OR: 12.62; P = 0.0085; CI 95% 1.91-83.29) and VEGF-α (OR: 2.61; P = 0.0252; CI 95% 1.13-6.03) were associated with pulp diagnoses of IP versus RP. The AUC-ROC curve for FGF acid was 0.79. The model containing FGF acid, IL-1α, IL-6 and TIMP-1 had an AUC-ROC of 0.92 for IP versus RP with a significant difference from the FGF acid ROC curve (P = 0.0231).Dentinal fluid could be used to assay pulpal mediators in the molecular diagnosis of pulpitis. Despite the limitation of the clinical diagnostics used in the present study, it was possible to detect a difference between irreversible symptomatic pulpitis and reversible pulpitis associated with the following combined biomarkers: FGF acid + IL-6 + IL-1α, +TIMP-1.

Rheumatoid arthritis (RA) and chronic periodontitis (CP) may be related due to a bidirectional etiology. The evidence shows that CP could alter the clinical course of RA. We performed a systematic search to determine if CP alters the morbidity of RA, analyzing its clinical and molecular aspects. Of 552 initial articles found, 16 were selected for a thorough review. There is a greater prevalence of CP in patients with RA. Patients with RA have significantly higher values of periodontal clinical parameters than healthy controls. Arthritis activity is significantly greater in patients who suffer from CP and decreases with nonsurgical periodontal treatment. There is a significant relationship between the severity of CP and RA activity.

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Periodontitis is a host-mediated bacterial disease that affects the tooth attachment apparatus. Metalloproteinase-8 (MMP-8), a validated biomarker, could aid in clinical diagnosis. This study aimed to evaluate the diagnostic performance of active (a) MMP-8 immunotest versus total (t) MMP-8 ELISA for quantitative real-time diagnosis and assessment of periodontitis severity at the site level. Gingival crevicular fluid (GCF) was sampled from 30 healthy, 42 mild, and 59 severe periodontitis sites from thirty-one volunteers. MMP-8 concentrations were determined by time-resolved immunofluorometric assay (IFMA) and enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using the STATA package. Both active and total MMP-8-based methods discriminated among sites according to periodontal diagnosis and severity, with a positive correlation between the two tests (p < 0.001). (a) MMP-8 models showed the best performance in receiver operating characteristic (ROC) curves to discriminate between healthy and periodontitis sites (area under the curve [AUC] = 0.89), while (t) MMP-8 demonstrated a high diagnostic precision in the detection of mild from severe periodontitis sites (AUC ≥ 0.80). The use of (a) MMP-8 and (t) MMP-8 could represent a useful adjunctive tool for periodontitis diagnosis and severity. These results support the applicability of new point-of-care methods in the monitoring of high-risk periodontal patients.

Early and innovative diagnostic strategies are required to predict the risk of developing pre-eclampsia (PE). The purpose of this study was to evaluate the performance of gingival crevicular fluid (GCF) placental alkaline phosphatase (PLAP) concentrations to correctly classify women at risk of PE. A prospectively collected, retrospectively stratified cohort study was conducted, with 412 pregnant women recruited at 11–14 weeks of gestation. Physical, obstetrical, and periodontal data were recorded. GCF and blood samples were collected for PLAP determination by ELISA assay. A multiple logistic regression classification model was developed, and the classification efficiency of the model was established. Within the study cohort, 4.3% of pregnancies developed PE. GCF-PLAP concentration was 3- to 6-fold higher than in plasma samples. GCF-PLAP concentrations and systolic blood pressure were greater in women who developed PE (p = 0.015 and p &lt, 0.001, respectively). The performance of the multiparametric model that combines GCF-PLAP concentration and the levels of systolic blood pressure (at 11–14 weeks gestation) showed an association of systolic blood pressure and GCF-PLAP concentrations with the likelihood of developing PE (OR:1.07, 95% CI 1.01–1.11, p = 0.004 and OR:1.008, 95% CI 1.000–1.015, p = 0.034, respectively). The model had a sensitivity of 83%, a specificity of 72%, and positive and negative predictive values of 12% and 99%, respectively. The area under the receiver operating characteristic (AUC-ROC) curve was 0.77 and correctly classified 72% of PE pregnancies. In conclusion, the multivariate classification model developed may be of utility as an aid in identifying pre-symptomatic women who subsequently develop PE.

Biomarkers represent promising aids in periodontitis, host-mediate diseases of the tooth-supporting tissues. We assessed the diagnostic potential of matrix metalloproteinase-8 (MMP-8), tartrate-resistant acid phosphatase-5 (TRAP-5), and osteoprotegerin (OPG) to discriminate between healthy patients&rsquo, mild and severe periodontitis sites. Thirty-one otherwise healthy volunteers with and without periodontal disease were enrolled at the Faculty of Dentistry, University of Chile. Periodontal parameters were examined and gingival crevicular fluid was sampled from mild periodontitis sites (M, n = 42), severe periodontitis sites (S, n = 59), and healthy volunteer sites (H, n = 30). TRAP-5 and OPG were determined by commercial multiplex assay and MMP-8 by the immunofluorometric (IFMA) method. STATA software was used. All biomarkers showed a good discrimination performance. MMP-8 had the overall best performance in regression models and Receiver Operating Characteristic (ROC) curves, with high discrimination of healthy from periodontitis sites (area under the curve (AUC) = 0.901). OPG showed a very high diagnostic precision (AUC &ge, 0.95) to identify severe periodontitis sites (S versus H + M), while TRAP-5 identified both healthy and severe sites. As conclusions, MMP-8, TRAP-5, and OPG present a high precision potential in the identification of periodontal disease destruction, with MMP-8 as the most accurate diagnostic biomarker.

Background Soluble Neuropilin-1 (sNRP-1) is a glycoprotein with angiogenic and immune regulatory functions, which correspond to processes deeply involved with periodontal diseases. This study’s objective was to determine the concentration of sNRP-1 in gingival crevicular fluid (GCF) samples of severe periodontitis (stages III-IV) compared to mild-moderate (stages I-II) periodontitis patients. Materials and methods An exploratory cross-sectional study was conducted, including 36 adults subjected to a complete periodontal exam, which recorded the following periodontal parameters: periodontal probing depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), gingival index (GI) and periodontal inflamed surface area (PISA). Periodontitis was defined by two periodontists using the case definition proposed by the 2017 World Workshop for periodontal diseases. GCF samples were collected to determine the levels of sNRP-1 via ELISA. The results were analyzed using descriptive statistics, Mann-Whitney, Kruskal Wallis, and Spearman tests. Results The levels of sNRP-1 in patient’s GCF with periodontitis in stages III-IV showed a median of 38.385 ​ng/mL (iqr 30.98), in comparison with 20.085 ​ng/mL (iqr 12.74) for stages I-II (p ​= ​0.202). Regardless of the periodontitis stage, we observed a positive correlation between the levels of sNRP-1 in BOP (Rho: 0.45; p ​= ​0.0048), PISA (Rho: 0.50; p ​= ​0.0019), PD (Rho: 0.3; p ​= ​0.015) and GI (Rho: 0.37; p ​= ​0.02). Conclusions The GCF-sNRP-1 concentration was positively related to periodontal clinical inflammatory parameters and probably could be involved in pro-inflammatory and angiogenic mechanisms observed in periodontitis. Additional studies are necessary to confirm these preliminary results.

Background Gestational diabetes mellitus (GDM) affects around 7% to 10% of all pregnancies. Early detection of predisposition to GDM is the first step in developing efficacious preventive treatment. The objective of the present study was to establish the utility of placental proteins presents in oral fluids (gingival crevicular fluid [GCF] and saliva), and periodontal disease status as early pregnancy predictors of GDM. Methods A nested case control within a prospective cohort was conducted. Pregnant systemically healthy women, aged between 18 and 40 years at 11 to 14 weeks gestation were included. Samples of oral fluids were collected and a complete maternal/obstetric and periodontal history was obtained. The concentration of placental growth factor (PlGF) and soluble Fms-like tyrosine kinase 1 (sFlt-1) were measured by enzyme-linked immunosorbent assay in a nested case control sample of the prospective cohort. Multiple logistic regression models assessed the association. The evaluation of the diagnostic accuracy of the biomarkers was performed through receiver operating characteristic (ROC) curves by calculating the area under the curve (AUC). Results There were recruited 212 pregnant women at 11 to 14 weeks of pregnancy, of these, 14 women (i.e., 6.6%) developed GDM, and displayed significant greater bleeding on probing (BOP) [P = 0.0003]; periodontal probing depth (PD) [P = 0.0028]; clinical attachment level (AL) [P = 0.0008] and periodontal inflamed surface area (PISA) [P = 0.0001]. Similarly, initial glycemia and GCF-PlGF concentrations were significantly greater in women with GDM [P = 0.0012, and P = 0.0019, respectively]. When data were subjected to ROC curve analysis, the combination of initial glycemia and GCF-PlGF concentration delivered an area under the ROC curve of 0.897. Multiple logistic regression analyses demonstrate an association between glycemia (OR 1.21, 95% confidence interval [CI] 1.06 to 1.38; P = 0.005) and GCF-PlGF concentrations in women who developed GDM (OR 1.68, CI 1.05 to 2.68 P = 0.03). Conclusions Within the limitations of the present study, the results support that first trimester maternal glycemia combined with GCF-PlGF concentrations could be a surrogate biomarker for the future development of GDM in pre-symptomatic women.

Workshops are an integral component of the annual International Federation of Placenta Association (IFPA) meeting, allowing for networking and focused discussion related to specialized topics on the placenta. At the 2015 IFPA meeting (Brisbane, Australia) twelve themed workshops were held, three of which are summarized in this report. These workshops focused on various aspects of placental function, particularly in cases of placenta-mediated disease. Collectively, these inter-connected workshops highlighted the role of the placenta in fetal programming, the use of various biomarkers to monitor placental function across pregnancy, and the clinical impact of novel diagnostic and surveillance modalities in instances of late onset fetal growth restriction (FGR).

Objectives: The objectives of this study are to explore the feasibility of measuring endothelial and placental biomarkers in saliva and gingival crevicular fluid (GCF) and to determine if patients with preeclampsia (PE) have a different profile of these biomarkers in oral fluids. Method: A case-control study was conducted, including patients with PE (n=10) and a control group with normal pregnancies randomly selected (n=20) admitted at the Sotero del Rio Hospital in Santiago, Chile. A complete periodontal and obstetric history that involved the collection of oral fluids was performed at the same gestational age. Levels of Cd63 extracellular vesicles, placental alkaline phosphatase (PLAP), placental growth factor (PlGF), and sFlt-1 levels were determined by ELISA assays. Data analysis was performed with chi-square or Fisher's exact test, and Mann-Whitney U-test for continuous variables. The association was assessed using a multiple logistic regression model. Results: sFlt-1 concentrations in saliva and GCF were significantly higher in patients with PE (p=0.045 and p=0.033 respectively). Concentrations of PLAP were elevated in GCF of patients with PE (p=0.049). The PLAP/CD63 ratio in GCF of patients with PE was significantly higher (p=0.0008). No differences in PlGF levels were observed. Conclusion(s): GCF of patients with PE concentrates higher levels of biomarkers related with the PE development.

Background: Statins are drugs used for the treatment of dyslipidemia. However, statins have multiple actions, including anti-inflammatory and immunomodulatory effects, as well as the ability to stimulate new bone formation. Such features could be beneficial for periodontal pathology therapy. Methods: A literature review was conducted using filtered electronic databases (Cochrane and Trip) and unfiltered databases (Medline/PubMed, Scielo and Google Scholar). The articles chosen were controlled and randomized clinical trials that performed local delivery of statins to humans and assessed the effects of immunomodulation and bone regeneration on periodontal disease between 2010 and 2017. All of the studies were blind or double-blind and were written in English. Results: The inclusion criteria were applied to a total of 79 identified articles, and 10 studies were ultimately chosen. The results show that an injected dose of statins or the local delivery of atorvastatin (ATV) leads to a significant improvement in clinical and radiographic periodontal parameters. Moreover, rosuvastatin (RSV) induced stronger beneficial effects when administered systemically, whereas ATV and simvastatin (SMV) had better results following topical delivery. Conclusions: Statins can affect periodontal status, increasing the gain in clinical attachment and decreasing gingival bleeding, probing depth and the magnitude of bone defects. For this reason, statins represent an excellent support measure for conventional periodontal therapy. Specifically, positive effects are seen for local delivery of statins as an adjunct treatment to scaling and root planing (SRP) at doses of 1.2 to 2%. Statins could be administered through topical delivery via direct injection in the periodontal pocket or by brushing with medicated dentifrices. More studies with appropriate designs should evaluate the short and long term clinical benefit of statins inpatients with periodontal pathology. These studies should determine the appropriate dose, timing side effects and ideal vehicles for delivery.

AimTo isolate and characterize oral extracellular vesicles from gingival crevicular fluid at 11-14 weeks and evaluate their capacity to identify patients at risk of developing gestational diabetes mellitus.MethodsA case-control study was conducted, including patients who developed gestational diabetes mellitus (n = 11) and healthy pregnant controls (n = 23). Obstetric and periodontal histories were recorded at 11-14 weeks of gestation, and samples of gingival crevicular fluid obtained. Extracellular vesicles were isolated from gingival crevicular fluid by ExoQuick. Nanoparticle tracking analysis, ELISA and transmission electron microscopy were used to characterize extracellular vesicles.ResultsTotal extracellular vesicles isolated from gingival crevicular fluid were significantly higher in patients who developed gestational diabetes mellitus later in pregnancy compared to normoglycemic pregnant women (6.3x109 vs 1.7 x1010, p value = 0.0026), and the concentration of the extracellular vesicles delivered an area under the ROC curve of 0.81. The distribution size of extracellular vesicles obtained using ExoQuick was around 148 ± 57 nm. There were no significant differences in the periodontal status between cases and controls. The exosome transmembrane protein CD63 was also detected in the extracellular vesicles of gingival crevicular fluid.ConclusionWe were able to isolate extracellular vesicles from gingival crevicular fluid using a method that is suitable to be applied in a clinical setting. Our results provide an insight into the potential capacity of first trimester oral extracellular vesicles as early biomarkers for the prediction of gestational diabetes mellitus in pre-symptomatic women.

Introduction The aim of this study was to assess whether apical lesions are associated with inflammatory serum markers of cardiovascular risk, especially high-sensitivity C-reactive protein (hsCRP), in young adults. Methods In this cross-sectional study, otherwise healthy individuals with apical lesions of endodontic origin (ALEOs) and a clinical diagnosis of asymptomatic apical periodontitis and controls aged between 18 and 40 years were included. Patients’ sociodemographic characteristics, medical history, and classic cardiovascular risk factors were recorded, and the pathobiological determinants of atherosclerosis in youth score was calculated. Oral clinical and radiographic examinations were performed. Blood samples were collected to determine the lipid profile, glycated hemoglobin, hsCRP, immunoglobulin G, interleukin (IL)-6, IL-10, IL-12p70, matrix metalloproteinase 8, soluble vascular cellular adhesion molecule-1, soluble intercellular adhesion molecule-1, and soluble E-selectin. Bivariate and multivariate analyses adjusting for oral and classic cardiovascular risk factors were performed. Results hsCRP levels were significantly higher in ALEO patients versus controls (median = 2.54 vs 0.78), whereas the pathobiological determinants of atherosclerosis in youth score was comparable among the groups. Also, the levels of IL-6, matrix metalloproteinase 8, and soluble E-selectin were significantly higher in ALEO patients. hsCRP, IL-6, and IL-12 correlated with soluble adhesion molecules. Bivariate analysis based on hsCRP serum concentrations ≥1 mg/L showed an odds ratio (OR) = 6.8, and the risk increased 3.3 times for an additional ALEO. In multivariate analysis, ALEO was significantly associated with hsCRP levels ≥1 mg/L (OR = 5.1–12.8) independently of the adjustment model. ALEO also associated with CRP levels >3 mg/L, which was significant after the adjustment for covariates (OR = 4.0). Conclusions ALEO is associated with the systemic inflammatory burden and cardiovascular risk determined by hsCRP, supporting a mechanistic link for cardiovascular diseases in young adults.

ResumenObjetivosDescribir los cambios del estado clínico periodontal de pacientes según el consumo sistémico de estatinas por indicación del cardiólogo.Material y métodoSe realizó un estudio descriptivo en el cual se reclutaron pacientes con periodontitis crónica derivados desde cardiología de la Clínica Dávila. Un grupo de ellos iniciaría terapia de estatinas. Se realizaron mediciones clínicas periodontales de profundidad al sondaje (PS), nivel de inserción clínico, índice de sangrado, área de superficie periodontal inflamada, e índice gingival, al inicio (antes de comenzar la terapia de estatinas) y 6 meses después. Los datos fueron analizados utilizando estadística descriptiva.ResultadosDiez pacientes participaron del estudio, 5 con indicación de estatinas. El grupo con estatinas en comparación con el grupo sin estatinas presentó una disminución en promedio: de PS (0,4mm versus 0,13mm); porcentaje de sitios con PS≥5mm (4,16% versus 1,09%); de nivel de inserción clínico (0,5mm versus 0,2mm), índice de sangrado (27,16% versus 8,8%) y área de superficie periodontal inflamada (305,68 mm2 versus 121,35).ConclusionesEstos resultados sugieren que pacientes con periodontitis crónica podrían obtener beneficios de la terapia sistémica con estatinas. Se requiere de estudios clínicos con asignación aleatoria y el óptimo tamaño muestral que comprueben el efecto e impacto de las estatinas sobre el estado periodontal.AbstractObjectiveTo describe changes in periodontal clinical status of patients according to systemic statin use prescribed by a cardiologist.Material and methodsA descriptive study was performed on patients with chronic periodontitis referred from the Department of Cardiovascular Diseases of Dávila Clinic. A group of them began statin therapy. Clinical measurements of periodontal probing depth (PD), clinical attachment level, bleeding index, periodontal inflamed surface area, and gingival index, were performed at baseline (before starting statin therapy) and 6 months later. Data were analyzed using descriptive statistics.ResultsA total of 10 patients participated in the study, and five of them received statin therapy. The statin group compared to the group without statins, showed a mean decrease in: PD (0.4mm versus 0.13mm); percentage of PS sites≥5mm (4.16% versus 1.09%); clinical attachment level (0.5mm versus 0.2mm), bleeding index (27.16% versus 8.8%), and periodontal inflamed surface area (305.68 versus 121.35 mm2).ConclusionsThese results suggest that patients with chronic periodontitis may benefit from systemic therapy with statins. Randomized clinical trials with optimal sample size are required to check the effect and impact of statins on the periodontal status.

AIM: To evaluate the impact of two non-surgical periodontal treatment modalities on metabolic and periodontal clinical parameters in subjects with type 2 diabetes mellitus (T2DM) and poor glycaemic control and chronic periodontitis. MATERIAL AND METHODS: A randomized controlled clinical trial was conducted. Ninety-three T2DM subjects with glycosylated haemoglobin (HbA1c) > 7% were randomly assigned to one of two groups receiving scaling with root planing in multiple sessions quadrant-by-quadrant (Q by Q) or within 24 hr (one stage). Periodontal parameters, HbA1c, glycaemia blood levels (FPG) and C-reactive protein (CRP) values were assessed at baseline and at 3 and 6 months post-therapy. RESULTS: At 6 months, HbA1c had decreased by 0.48% in the Q by Q group and by 0.18% in the one-stage group (p = 0.455). After therapy, subjects with an initial HbA1c 9% regardless of treatment modality. Both modalities resulted in significant improvements in periodontal parameters. ispartof: JOURNAL OF CLINICAL PERIODONTOLOGY vol:45 issue:9 pages:1098-1106 ispartof: location:United States status: published

ResumenObjetivoDeterminar si la condición clínica periodontal materna, el índice de masa corporal (IMC) y su variación durante el embarazo, se asocian con marcadores de inflamación sistémica: interleuquina-6 (IL-6), factor de necrosis tumoral alfa (TNF-α) y proteína C reactiva (PCR) a nivel plasmático.Material y MétodoEstudio clínico que analizó una cohorte de 56 embarazadas entre 18 y 38 años de edad (promedio 27.9±7.04 años), derivadas de la unidad de medicina perinatal en el centro de salud docente asistencial (CESA) de la Universidad de los Andes. Todas ellas consintieron voluntariamente su participación en el estudio. En cada trimestre de embarazo, se les realizó un examen periodontal completo, consistente en la determinación de los niveles de inserción clínica, profundidad al sondaje, índice de higiene y sangrado en seis sitios por cada pieza dentaria, excluyendo terceros molares. Adicionalmente, en cada control se obtuvieron muestras de sangre periférica para la determinación de los mediadores proinflamatorios mediante técnica de ELISA. El diagnóstico periodontal y los niveles de mediadores inflamatorios fueron relacionados con la variación del IMC durante el embarazo.ResultadosLas embarazadas con periodontitis crónica presentaron una mayor variación y aumento del índice de masa corporal (p=0.039) y niveles de IL-6 (p=0.026) en comparación con las mujeres embarazadas con gingivitis.ConclusionesEn esta serie de pacientes, se demostró una asociación entre el diagnóstico clínico de periodontitis durante el embarazo con un aumento plasmático de IL-6, así como también una asociación entre un aumento del IMC con los niveles plasmáticos de PCR.AbstractObjectiveTo determine if maternal periodontal clinical status, body mass index (BMI) and its variation during pregnancy are associated with increased levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and C-reactive protein (CRP) in plasma.Material and MethodsThis clinical study included a total of 56 pregnant women between 18 and 38 years old (mean 27.9±7.04 years), referred from perinatal medicine unit at health care center Universidad de los Andes. All pregnant patients consented to voluntarily participate in the study. In each trimester of pregnancy, they underwent a complete periodontal examination, involving the determination of clinical attachment levels, probing depth, bleeding and hygiene index at six sites of each tooth, excluding third molars. Additionally, in each clinical check, peripheral blood samples were taken for determination of pro-inflammatory mediators with ELISA immunoassay. Periodontal diagnosis and inflammatory mediators were the variables analyzed in relation to changes in BMI during pregnancy.ResultsPregnant women with chronic periodontitis had an increase and more variation of BMI (p=0.039) and higher levels of IL-6 (p=0.026) in comparison with pregnant women with gingivitis.ConclusionsIn this series of pregnant patients the clinical diagnosis of periodontitis, with an increase in BMI are associated with increased plasma levels of IL-6 and CRP.

Epidemiologic and randomized controlled studies have shown that periodontal diseases may be associated with preterm labor and delivery of infants with low birth weights. The purpose of the present study was to determine the presence of microbial invasion of the amniotic cavity by periodontopathic bacteria in pregnant women with a diagnosis of threatened premature labor.A periodontal examination and collection of amniotic fluid and subgingival plaque samples were performed on women identified as having threatened premature labor (preterm premature rupture of membranes without clinical infection or labor and preterm labor with intact membranes) and a gestational age ranging between 24 and 34 weeks. Samples collected from amniotic fluid and from the four deepest periodontal pockets in each patient were pooled in prereduced transport fluid and cultured. Porphyromonas gingivalis was identified primarily by colony morphology under stereoscopic microscope and rapid biochemical tests. Amniotic fluid or plaque samples were homogenized, DNA was extracted, and polymerase chain reaction (PCR) amplification of 16S rRNA with specific and universal primers was carried out.Twenty-six women with threatened premature labor were included: eight with preterm premature rupture of membranes and 18 with preterm labor with intact membranes. Eight women presented with gingivitis, 12 with chronic periodontitis, and six without periodontal disease. Microbial invasion of the amniotic cavity as detected by P. gingivalis PCR was 30.8% (eight of 26 patients). In these eight patients, P. gingivalis was present in both the subgingival samples and the respective amniotic fluid sample.The presence of microbial invasion of the amniotic cavity by P. gingivalis could indicate a role for periodontal pathogenic bacteria in pregnant women with a diagnosis of threatened premature labor.

Background and aims Interleukin-17 (IL-17) is a T-cell-derived cytokine that may play an important role in the initiation or maintenance of the pro-inflammatory response and has recently been found to stimulate osteoclastic resorption. The purpose of the present study was to determine the presence of IL-17 in gingival crevicular fluid (GCF) samples and in the culture supernatants of gingival cells from patients with chronic periodontitis. Method GCF samples were collected during 30 s from two sites in 16 patients from periodontally affected sites (probing depth > or =5 mm, attachment loss > or =3 mm). The comparison with healthy controls was carried out by collecting GCF samples from eight healthy volunteers. GCF was collected using a paper strip and ELISA was performed to determine the total amount of IL-17. Supernatant cellular cultures of gingival cells were obtained from periodontal biopsies taken from 12 periodontitis patients and from eight healthy control subjects during the surgical removal of wisdom teeth. Spontaneous and phytohaemagglutinin (PHA)-stimulated levels of IL-17 were determined by ELISA. Results The total amount of cytokine IL-17 was significantly higher in the periodontitis group than the control group (45.9 versus 35.6 pg, p=0.005). Significantly higher GCF volume and amount of total proteins were obtained from periodontitis patients as compared with control subjects (0.98 versus 0.36 microl, p=0.0005; 0.12 versus 0.05 microg, p=0.0005, respectively). A higher concentration of IL-17 was detected in culture supernatants from periodontitis patients compared with healthy subjects, either without stimulation (36.28+/-8.39 versus 28.81+/-1.50 microg/ml, p=0.011) or with PHA stimulation (52.12+/-14.56 versus 39.00+/-4.90 microg/ml, p=0.012). Treatment with PHA induced a significant increase in the production of IL-17 in healthy subjects and periodontitis patients (p=0.001 and 0.003). Conclusions The total amount of cytokine IL-17 in GCF samples and in the culture supernatants of gingival cells are significantly increased in periodontal disease.

Periodontal disease is one of the most common conditions affecting humans, and current treatment strategies, which focus on the removal and long-term control of dental plaque, are generally successful in eliminating active disease and promoting tissue repair. However, regeneration of the supporting structures of the tooth remains an elusive goal and a challenge. The formation of new bone and cementum with supportive periodontal ligament is the ultimate objective, but current regeneration therapies are incapable of achieving this in a predictable way. The regeneration of periodontal tissue requires a combination of fundamental events, such as appropriate level and sequencing of regulatory signals, the presence of progenitor cells, an extracellular matrix or carrier and an adequate blood supply. Based on tissue-engineering concepts, the regeneration process may be modulated by manipulating the signaling pathways of regulatory molecules, the extracellular matrix or scaffold, or the cellular components. The identification of mesenchymal stem cells from bone marrow started a new era in regenerative medicine. Tissue engineering using mesenchymal stem cells became a therapeutic option with several advantages, including high-quality regeneration of damaged tissues without the formation of fibrous tissue, minimal donor-site morbidity compared with autografts and a low risk of autoimmune rejection and disease transmission. The aim of this review was to describe the main sources of mesenchymal stem cells from tissues in the oral cavity and the potential of these cells in regenerative therapy. Special attention is paid to gingival tissue-derived mesenchymal stem cells because they represent the most accessible source of stem cells in the human mouth.

Introduction Preeclampsia (PE) is a pregnancy-specific disorder that complicates 5–7% of all pregnancies. In recent years, many methods have attempted to predict PE but they do not achieve detection rates good enough to be considered a screening test and used in a clinical setting. The placenta is crucial in pathogenesis of PE, and one of the hormone that is produced and released by the placenta is the human placental lactogen (hPL). hPL mRNA can be detected in plasma in all three trimester of pregnancy. Objective The objective of this study was to evaluate if the addition of hPL cell free mRNA (hPL cfmRNA) as a placental dysfunction biomarker improves the prediction of PE during the first trimester of pregnancy. Method A nested case-control study was conducted from a prospective cohort of pregnant women attending our institution for prenatal care at 11–14 weeks. From a total of 627 patients, cases (moderate PE (mPE) and severe PE (sPE)) and controls were selected. Clinical characteristic such as maternal age, history of hypertension, blood pressure and uterine artery pulsatility index (UtAPI) were measured. Total mRNA and protein from plasma samples at 11–14 weeks of gestation were purified. hPL cfmRNA levels were measured by quantitative reverse transcription PCR. Placental growth factor (PIGF) levels were measured by ELISA. Results Women with a normal pregnancy (control group 14) presented similar clinical characteristic in the first trimester of pregnancy compared with women who afterward developed mPE (4 patients). However, women who subsequently developed sPE were significantly older, had higher maternal weight, and higher blood pressure in comparison with women in the control group at 11–14 weeks ( p -value p -value p Conclusion The levels of hPL cfmRNA decrease at 11–14 weeks in patient that will develop PE. Addition of hPL cfmRNA could improve the prediction of PE at the first trimester of pregnancy when included in multiparametric models.

Introduction PE increases the prevalence of morphologic and functional alterations of the left ventricle. These changes can persist after pregnancy and would increase the risk of patients to develop chronic hypertension. A commonly used tool in prediction of cardiovascular disease is transthoracic echocardiography (TT-EC). Using TT-EC, patients with early asymptomatic ventricular dysfunction can be identified, which is useful because these patients have benefit with pharmacologic therapy despite being asymptomatic. A new technique for TT-EC (Speckle Tracking) has been developed that is more sensitive to evaluate cardiac functional alterations before they become clinically recognizable. There are currently no studies that evaluate heart function at short or long term after birth in patients with history of PE using speckle tracking. Objective To evaluate if the Speckle Tracking technique can identify early asymptomatic ventricular dysfunction in patients with past history of PE. Method A pilot case-control study was performed in Clinica Davila. 14 patients that had their delivery in our institution were recruited. 6 patients diagnosed with severe preeclampsia (sPE), 4 moderate preeclampsia (mPE) and 4 controls. One year after their delivery a Speckle Tracking index (ST index) using transthoracic echocardiography was performed. Results Our analysis show that patients with history of PE decrease the ST index in comparison with women without history of PE but without statistical significance (p = 0.0729). Dividing by severity of PE the data show significantly difference in the ST index of women with mPE (p = 0.0286), but not in woman with sPE (p = 0.3905), in comparison with the controls. Conclusion Women with history of PE and with asymptomatic ventricular dysfunction showed decrease of the ST index. Speckle tracking analysis could be a good technique to identify if women with history of PE can develop cardiac dysfunction.

Chaparro A, Sanz A, Quintero A, Inostroza C, Ramirez V, Carrion F, Figueroa F, Serra R, Illanes SE. Increased inflammatory biomarkers in early pregnancy is associated with the development of pre-eclampsia in patients with periodontitis: a case control study. J Periodont Res 2013; 48: 302-307. (C) 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Aim(s) To explore the relationship between biomarkers of systemic inflammation in plasma and gingival crevicular fluid in early pregnancy and the subsequent development of pre-eclampsia in patients with periodontitis. Materials and Methods A case-control study was performed.From a cohort composed of 126 pregnant women, 43 normotensive healthy pregnant women were randomly selected, and 11 cases of preeclampsia were identified. Plasmatic and gingival crevicular fluid (GCF) samples were collected in early pregnancy (1114wk gestation). The levels of interleukin-6 (IL-6) and tumour necrosis factor- (TNF-) were measured in the plasma and GCF samples, whereas the level of C-reactive protein (CRP) was measured in plasma samples. Biomarkers were determined by ELISAassays. The data were analysed usingdescriptive statistics, and the association between variables was estimated through logistic regression models. Results There was observed an association between pre-eclampsia and plasmatic levels of CRP (OR: 1.07; p=0.003). Additionally, pre-eclampsia also was associated withIL-6 levels in GCF samples in early pregnancy (OR: 1.05; p=0.039).Amultiple logistic regression model suggests thatincreased levels of IL-6 in GCF (OR=1.06; p=0.02; CI 95% 1.0071.117) in early pregnancy increase the riskof developing pre-eclampsia. Conclusion(s) Pregnant women with periodontitis who later development pre-eclampsia, shows increased levels of IL-6 in GCF and CRP in plasma during early pregnancy. Periodontal disease could contribute to systemic inflammation in early pregnancy via a local increase of IL-6 and the systemic elevation of CRP. Therefore, both inflammatory markers could be involved in the relationship between periodontal disease and pre-eclampsia.

Background: Tissue engineering using mesenchymal stem cells (MSCs) is a recent therapeutic modality that has several advantages. MSCs have high proliferation potential and may be manipulated to permit differentiation before being transplanted, suggesting they may be an ideal candidate for regenerative procedures. Precise identification of cells capable of regenerating the periodontium is valuable because no predictable regeneration procedure has yet been described. The purpose of this study is to determine the presence of MSCs in human gingival connective tissue and their morphologic and functional characteristics. Methods: Gingival connective tissue samples were obtained from five healthy students. The samples were deepithelialized, leaving only connective tissue. The explants were minced and cultured on tissue culture dishes for 3 to 4 weeks, after which cells were characterized by flow cytometry. Differentiation into osteogenic, chondrogenic, and adipogenic lineages was induced and evaluated by culture staining. An immunoregulation assay was also performed. Results: The results show that gingival tissue cells fulfill the minimal criteria proposed by the International Society for Cellular Therapy to be defined as MSCs. Cell characterization was consistently positive for CD90, CD105, CD73, CD44, and CD13 markers and negative for hematopoietic markers CD34, CD38, CD45, and CD54. We observed differentiation in positive staining of adipogenic, chondrogenic, and osteogenic lineages. Furthermore, gingival cells showed immunomodulative capacity. Conclusion: Gingival connective tissue could be a reservoir of MSCs that could be used in regenerative procedures based on tissue engineering. J Periodontol 2010;81:917-925.

Objetivo: Determinar la relacion entre enfermedad periodontal, infeccion bacteriana ascendente y patologia placentaria, con parto prematuro. Pacientes y Metodos: Participaron embarazadas entre 24 y 34 semanas de gestacion, con trabajo de parto prematuro sin causa clinica evidente y membranas intactas o con el diagnostico de rotura prematura de membranas (RPM), sin trabajo de parto y sin corioamnionitis clinica. Todas las embarazadas tuvieron estudio periodontal clinico y evaluacion microbiologica de la placa subgingival, del liquido amniotico (LA) y cervicovaginal. R ecibieron corticoesteroides, antibioticos, tocolisis (casos con membranas intactas) y manejo expectante hasta las 35 semanas (casos con RPM) . Las placentas se enviaron a estudio y se diagnostico corioamnionitis, funisitis y vellositis. Se definio invasion microbiana de la cavidad amniotica ( IMCA) el cultivo positivo del liquido amniotico. Infeccion cervicovaginal (ICV) se diagnostico con vaginosis bacteriana (VB) o cultivo positivo para bacteria patogena u oportunista en cervix o vagina, con incremento significativo de los leucocitos polimorfonucleares. Se considero como infeccion bacteriana ascendente (IBA) la presencia de IMCA por bacterias ascendentes y/o ICV. Resultados: Se incluyeron 59 pacientes, 42 con membranas intactas y 17 con RPM . La frecuencia de la enfermedad periodontal fue 93.2%. La IMCA fue 27.1% Se aislaron bacterias patogenas periodontales del LA en el 18.6% y de la placa subgingival en el 71.2% de los casos. La IBA fue 83.1%. La asociacion IBA con enfermedad periodontal fue 72.9%. El parto prematuro ( 82.1% p=0.03 y con la presencia conjunta de infeccion bacteriana ascendente y enfermedad periodontal 74.4% p=0.03. Los casos con nacimiento prematuro y enfermedad periodontal generalizada tuvieron significativa mayor frecuencia de corioamnionitis y funisitis histologica 69.6% p=0.04. Conclusiones : L a enfermedad periodontal generalizada y la presencia conjunta de infeccion bacteriana ascendente y enfermedad periodontal se asocian con parto prematuro . En estos casos, son frecuentes l os marcadores histologicos placentarios de infeccion ascendente .

7 páginas, 3 figuras, 3 tablas -- PAGS nros. 283-289, OBJECTIVES: The cytokine receptor activator of nuclear factor kappaB-ligand (RANKL) has been involved in both the physiological and pathological regulation of osteoclast life span and bone metabolism. Periapical granuloma is a periradicular lesion characterized by periapical bone destruction. The aims of this study were to associate the RANKL mRNA levels to periapical granulomas using the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) technique and to determine the specific cell involved in RANKL synthesis. METHODS: In eight periapical granuloma and eight periodontal ligament samples from periodontally healthy volunteers, RANKL mRNA was detected by real-time RT-PCR. Expression of RANKL on infiltrate leukocytes was further investigated by flow cytometry in six periapical granulomas. RESULTS: Receptor activator of nuclear factor kappaB-ligand mRNA levels were higher in periapical granulomas than in healthy periodontal ligament as its RANKL mRNA cycle threshold (Ct) and DeltaCt were significantly lower than that of controls (33.07 +/- 1.24 vs 36.96 +/- 1.69 and 11.58 +/- 3.02 vs 15.60 +/- 3.31, respectively). A 16.2-fold (2.0-131.6) higher RANKL gene expression was detected in the granulomas compared with the control tissues. We determined by flow cytometry that lymphocytes were the predominant leukocyte cells (53.31%), and monocytes and dendritic cells were the main RANKL synthesizers in granuloma lesions. CONCLUSIONS: These data indicate that monocytes synthesized RANKL in periapical granulomas and suggest that RANKL is involved in bone loss associated with periapical lesions, This research was supported by grant 1050518 of Fondo de Investigación Científica y Tecnológica (FONDECYT), grant 01/0073-01 of Fondo de Investigaciones Sanitarias (FIS), and grant PG/2503 of Vicerrectoría Académica y Departamento de Posgrado y Postítulo of Universidad de Chile. The authors are grateful to Dr Raúl Sáez from Dental Service of Barros Luco Hospital

Background: Receptor activator of nuclear factor κB ligand (RANK-L) is a cytokine involved in the regulation of osteoclastogenesis in bone remodeling and inflammatory osteolysis. One of the major causes of tooth loss in humans is bone destruction. The aim of our study was to determine the presence of RANK-L in gingival crevicular fluid (GCF) samples from adult patients with untreated chronic periodontitis and in healthy controls. We also identified the RANK-L present in lesions undergoing episodic attachment loss from GCF. Methods: GCF samples were collected from two periodontally affected sites (probing depth ≥5 mm, attachment loss ≥3 mm) in 20 patients (N = 40). After monitoring for 4 months, seven patients showed active periodontal disease, and GCF samples were collected from one active and one inactive site (N = 14 samples). The comparison with healthy controls was carried out by collecting GCF samples from 12 healthy volunteers (N = 24 samples). GCF was collected using a paper strip, and enzymelinked immunosorbent assay (ELISA) was performed to determine the total amount of RANK-L. Results: RANK-L was found in a higher proportion (85%) of samples from patients than from controls (46%). The total amount of RANK-L was significantly higher in patients (115.53 ± 78.18 picograms [pg]) than in healthy subjects (63.08 ± 55.08 pg) (P = 0.003). Active sites, presumably associated with tissue destruction, had significantly higher levels of RANK-L than their inactive counterparts (125.95 pg versus 91.80 pg, P = 0.007). Conclusion: GCF total amount of RANK-L is significantly increased in periodontal disease, supporting its role in the alveolar bone loss developed in this disease. J Periodontol 2004;75: 1586-1591.