Endogenous nitric oxide formation correlates negatively with circulating matrix metalloproteinase (MMP)-2 and MMP-9 levels in black subjects

Deficient formation of endogenous nitric oxide (NO) contributes to cardiovascular diseases, and this may be associated with increased circulating levels of matrix metalloproteinase-9 (MMP-9), as previously shown in white subjects. Because interethnic differences exist with respect to risk factors, prevalence, and severity of cardiovascular diseases, we designed this study to examine whether the circulating levels of nitrites (a marker of endogenous NO formation) are associated with the plasma levels of MMP-9 and MMP-2 in healthy black subjects. We studied 198 healthy subjects self-reported as blacks not taking any medications. Venous blood samples were collected and plasma and whole blood nitrite levels were measured using an ozone-based chemiluminescence assay. Plasma MMP-2 and MMP-9 levels were determined by gelatin zymography. We found a positive correlation between plasma MMP-9 and MMP-2 levels (P < 0.0001, rs = 0.556). Interestingly, we found a negative relationship between the plasma MMP-9 levels and the plasma or whole blood nitrites levels (P = 0.04, rs = -0.149; and P < 0.0001, rs = -0.349, respectively). In parallel, we found similar negative relationships between plasma MMP-2 levels and plasma or whole blood nitrites levels (P = 0.02, rs = -0.172; and P < 0.0001, rs = -0.454, respectively). This is the first study to show that endogenous nitric oxide formation correlates negatively with the circulating levels of both MMP-2 and MMP-9 in black subjects. Our findings suggest a mechanistic link between deficient NO formation and increased MMPs levels, which may promote cardiovascular diseases.

A bayesian network meta-analysis on comparisons of enamel matrix derivatives, guided tissue regeneration and their combination therapies

Aims: Guided tissue regeneration (GTR) and enamel matrix derivatives (EMD) are two popular regenerative treatments for periodontal infrabony lesions. Both have been used in conjunction with other regenerative materials. We conducted a Bayesian network meta-analysis of randomized controlled trials on treatment effects of GTR, EMD and their combination therapies. Material and Methods: A systematic literature search was conducted using the Medline, EMBASE, LILACS and CENTRAL databases up to and including June 2011. Treatment outcomes were changes in probing pocket depth (PPD), clinical attachment level (CAL) and infrabony defect depth. Different types of bone grafts were treated as one group and so were barrier membranes. Results: A total of 53 studies were included in this review, and we found small differences between regenerative therapies which were non-significant statistically and clinically. GTR and GTR-related combination therapies achieved greater PPD reduction than EMD and EMD-related combination therapies. Combination therapies achieved slightly greater CAL gain than the use of EMD or GTR alone. GTR with BG achieved greatest defect fill. Conclusion: Combination therapies performed better than single therapies, but the additional benefits were small. Bayesian network meta-analysis is a promising technique to compare multiple treatments. Further analysis of methodological characteristics will be required prior to clinical recommendations.

STATISTICAL TEST FOR GENOTYPE AND ENVIRONMENT CONTRIBUTION IN THE GENOTYPES x ENVIRONMENTS INTERACTION MATRIX

The objective of the present work was to propose a method for testing the contribution of each level of the factors in a genotypes x environments (GxE) interaction using multi-environment trials analyses by means of an F test. The study evaluated a data set, with twenty genotypes and thirty-four environments, in a block design with four replications. The sum of squares within rows (genotypes) and columns (environments) of the GxE matrix was simulated, generating 10000 experiments to verify the empirical distribution. Results indicate a noncentral chi-square distribution for rows and columns of the GxE interaction matrix, which was also verified by the Kolmogorov-Smirnov test and Q-Q plot. Application of the F test identified the genotypes and environments that contributed the most to the GxE interaction. In this way, geneticists can select good genotypes in their studies.

The influence of pore size on osteoblast phenotype expression in cultures grown on porous titanium

This study investigated the effect of pore size on osteoblastic phenotype development in cultures grown on porous titanium (Ti). Porous Ti discs with three different pore sizes, 312 mu m (Ti 312), 130 mu m (Ti 130) and 62 mu m (Ti 62) were fabricated using a powder metallurgy process. Osteoblastic cells obtained from human alveolar bone were cultured on porous Ti samples for periods of up to 14 days. Cell proliferation was affected by pore size at day 3 (p = 0.0010), day 7 (p = 0.0005) and day 10 (p = 0.0090) in the following way: Ti 62 < Ti 130 < Ti 312. Gene expression of bone markers evaluated at 14 days was affected, RUNX2 (p = 0.0153), ALP (p = 0.0153), BSP (p = 0.0156), COL (p = 0.0156), and OPN (p = 0.0156) by pore size as follows: Ti 312 < Ti 130 < Ti 62. Based on these results, the authors suggest that porous Ti surfaces with pore sizes near 62 mu m, compared with those of 312 mu m and 130 mu m, yield the highest expression of osteoblast phenotype as indicated by the lower cell proliferation rate and higher gene expression of bone markers.

Bone tissue, cellular, and molecular responses to titanium implants treated by anodic spark deposition

A myriad of titanium (Ti) surface modifications has been proposed to hasten the osseointegration. In this context, the aim of this study was to perform histomorphometric, cellular, and molecular analyses of the bone tissue grown in close contact with Ti implants treated by anodic spark deposition (ASD-AK). Acid-etched (AE) Ti implants either untreated or submitted to ASD-AK were placed into dog mandibles and retrieved at 3 and 8 weeks. It was noticed that both implants, AE and ASD-AK, were osseointegrated at 3 and 8 weeks. Histomorphometric analysis showed differences between treatments only for bone-to-implant contact, being higher on AE implants. Although not backed by histomorphometric results, gene expression of key bone markers was higher for bone grown in close contact with ASD-AK and for cells harvested from these fragments and cultured until subconfluence. Cell proliferation at days 7 and 10 and alkaline phosphatase activity at day 10 was higher on AE surfaces. No statistical significant difference was noticed for extracellular matrix mineralization at 17 days. Our results have shown that the Ti fixtures treated by ASD-AK allowed in vivo osseointegration and induced higher expression of key markers of osteoblast phenotype, suggesting that this surface treatment could be considered to produce implants for clinical applications. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:30923098, 2012.

Matrix metalloproteinase-9 polymorphisms affect plasma MMP-9 levels and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy

Abnormal matrix metalloproteinase (MMP)-9 levels may have a role in hypertensive disorders of pregnancy. We examined whether MMP-9 genetic polymorphisms (g.-1562C>T and g.-90(CA)(13-25)) modify plasma MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 levels and the responses to antihypertensive therapy in 214 patients with preeclampsia (PE), 185 patients with gestational hypertension (GH) and a control group of 214 healthy pregnant (HP). Alleles for the g.-90(CA)(13-25) polymorphism were grouped L (low) (<21 CA repeats) or H (high) (>= 21 CA repeats). Plasma MMP-9 and TIMP-1 concentrations were measured by enzyme-linked immunosorbent assay. Plasma MMP-9 concentrations were not affected by genotypes or haplotypes in HP and PE groups, except for the g.-90(CA)(13-25) polymorphism: GH patients with the LH genotype for this polymorphism have higher MMP-9 levels than those with other genotypes. The T allele for the g.-1562C>T polymorphism and the H4 haplotype (combining T and H alleles) are associated with GH and lack of responsiveness to antihypertensive therapy in GH. The H2 haplotype (combining C and H alleles) was associated with lack of responsiveness to antihypertensive therapy in PE, but not in GH. In conclusion, our results show that MMP-9 genetic variants are associated with GH and suggest that MMP-9 haplotypes affect the responsiveness to antihypertensive therapy in hypertensive disorders of pregnancy. The Pharmacogenomics Journal (2012) 12, 489-498; doi: 10.1038/tpj.2011.31; published online 19 July 2011

Circulating matrix metalloproteinases and their endogenous inhibitors in patients with erectile dysfunction

Erectile dysfunction (ED) may reflect vascular alterations associated with imbalanced matrix metalloproteinases (MMPs) activities. However, no previous study has compared MMPs levels in ED patients with those found in healthy subjects. We measured the circulating MMP-2, MMP-9, TIMP-1 and TIMP-2 levels in ED patients, with or without diabetes mellitus (DM), and in healthy controls. We studied 28 healthy men (control group), 35 men with ED (ED group), and 33 men with ED and DM (ED/DM group). MMP-2, MMP-9, TIMP-1 and TIMP-2 plasma levels were measured by enzyme-linked immunosorbent assay and zymography. We found no differences in MMP-9 levels (P>0.05) among groups. However, while patients in the ED group had similar TIMP-1 levels compared with those found in the control group, we found higher TIMP-1 levels and lower MMP-9/TIMP-1 ratios in the ED/DM group compared with controls (P<0.05). While both groups of patients (ED and ED/DM) had slightly lower MMP-2 levels compared with controls (P<0.05), we found no differences in TIMP-2 levels among the study groups (P>0.05), and no differences in MMP-2/TIMP-2 ratios (P>0.05). We found evidence indicating lack of significant alterations in circulating net MMP-9 and MMP-2 activities in patients with ED, and lower net MMP-9 activity in diabetic patients with ED. International Journal of Impotence Research (2012) 24, 38-43; doi:10.1038/ijir.2011.44; published online 15 September 2011

Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese children

Objective: Matrix metalloproteinase-9 (MMP-9) is involved in the atherosclerotic process and functional polymorphisms in the MMP-9 gene affect MMP-9 expression/activity, and are associated with cardiovascular diseases. However, no study has tested the hypothesis that functional MMP-9 polymorphisms could affect MMP-9 levels in obese children. We investigated whether three MMP-9 gene polymorphisms (C-1562T (rs3918242), 90(CA)((14-24)) (rs2234681) and Q279R (rs17576)), or haplotypes, affect MMP-9 levels in obese children. Methods: We studied 175 healthy control children and 127 obese children. Plasma MMP-9, tissue inhibitor of MMPs (TIMP)-1 and adiponectin concentrations were measured using enzyme-linked immunosorbent assay. Results: We found similar MMP-9 genotypes, allelic and haplotypes distributions in the two study groups (P > 0.05). However, we found lower plasma MMP-9 concentrations in obese subjects carrying the CC or the QQ genotypes for the C-1562T and the Q279R polymorphisms, respectively, in obese children compared with children with the other genotypes, or with non-obese children with the same genotypes (all P < 0.05). Moreover, we found lower MMP-9 levels and lower MMP-9/TIMP-1 ratios (which reflect net MMP-9 activity) in obese children carrying the H2 haplotype (which combines the C, H and Q alleles for the three polymorphisms, respectively) when compared with obese children carrying the other haplotypes, or with non-obese children carrying the same haplotype (P < 0.05). Conclusions: Our findings show that MMP-9 genotypes and haplotypes affect MMP-9 levels in obese children and adolescents, and suggest that genetic factors may modify relevant pathogenetic mechanisms involved in the development of cardiovascular complications associated with obesity in childhood. International Journal of Obesity (2012) 36, 69-75; doi:10.1038/ijo.2011.169; published online 16 August 2011

Magnetic and optical investigation of 40SiO(2)center dot 30Na(2)O center dot 1Al(2)O(3)center dot(29-x) B2O3 center dot xFe(2)O(3) glass matrix

Samples of 40SiO(2)center dot 30Na(2)O center dot 1Al(2)O(3)center dot(29 - x)B2O3 center dot xFe(2)O(3) (mol%), with 0.0 <= x <= 17.5, were prepared by the fusion method and investigated by electron paramagnetic resonance (EPR), optical absorption (OA) and Mossbauer spectroscopy (MS). The EPR spectra of the as-synthesized samples exhibit two well-defined EPR signals around g = 4.27 and g = 2.01 and a visible EPR shoulder around g = 6.4, assigned to isolated Fe3+ ion complexes (g = 4.27 and g = 6.4) and Fe3+-based clusters (g = 2.01). Analyses of both EPR line intensity and line width support the model picture of Fe3+-based clusters built in from two sources of isolated ions, namely Fe2+ and Fe3+; the ferrous ion being used to build in iron-based clusters at lower x-content (below about x = 2.5%) whereas the ferric ion is used to build in iron-based clusters at higher x-content (above about x = 2.5%). The presence of Fe2+ ions incorporated within the glass template is supported by OA data with a strong band around 1100 nm due to the spin-allowed E-5(g)-T-5(2g) transition in an octahedral coordination with oxygen. Additionally, Mossbauer data (isomer shift and quadrupole splitting) confirm incorporation of both Fe2+ and Fe3+ ions within the template, more likely in tetrahedral-like environments. We hypothesize that ferrous ions are incorporated within the glass template as FeO4 complex resulting from replacing silicon in non-bridging oxygen (SiO3O-) sites whereas ferric ions are incorporated as FeO4 complex resulting from replacing silicon in bridging-like oxygen silicate groups (SiO4). (C) 2012 Elsevier Masson SAS. All rights reserved.

Matrix metalloproteinases, tissue inhibitors of metalloproteinases, and growth factors regulate the aggressiveness and proliferative activity of keratocystic odontogenic tumors

Objective. The objective of this preliminary study was to evaluate the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and growth factors in keratocystic odontogenic tumors (KOTs). Study Design. The expression of MMPs, TIMPs, growth factors, and the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway were assessed by immunohistochemistry in 15 cases of KOT and 4 cases of calcifying cystic odontogenic tumor (CCOT). Results. KOT samples expressed significantly higher amounts of MMPs, TIMPs, growth factors, epidermal growth factor receptor (EGFR), and ERK compared with CCOT samples, with the exception of MMP-2 and TIMP-1. Conclusions. MMP-9, TIMP-2, EGF and transforming growth factor alpha act together and likely regulate the proliferation and aggressiveness of KOT. ERK-1/2 serves as the transducer of signals generated by these proteins, which signal through the common receptor, EGFR. This process may be related to the increased proliferation and aggressiveness observed in KOT. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:487-496)

The r-matrix of the Alday-Arutyunov-Frolov model

We investigate the classical integrability of the Alday-Arutyunov-Frolov model, and show that the Lax connection can be reduced to a simpler 2 x 2 representation. Based on this result, we calculate the algebra between the L-operators and find that it has a highly non-ultralocal form. We then employ and make a suitable generalization of the regularization technique proposed by Mail let for a simpler class of non-ultralocal models, and find the corresponding r- and s-matrices. We also make a connection between the operator-regularization method proposed earlier for the quantum case, and the Mail let's symmetric limit regularization prescription used for non-ultralocal algebras in the classical theory.

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

We examined whether two functional polymorphisms (g.-1306 C> T and g.-735 C>T) in matrix metalloproteinase (MMP)-2 gene are associated with preeclampsia (PE) or gestational hypertension (GH), and whether they modify MMP-2 or tissue inhibitor of metalloproteinase (TIMP)-2 plasma concentrations in these hypertensive disorders of pregnancy. We studied 130 healthy pregnant (HP), 130 pregnant with GH, and 133 pregnant with PE. Genomic DNA was extracted from whole blood and genotypes for g.-1306 C>T and g.-735 C>T polymorphisms were determined by Real Time-PCR, using Taqman allele discrimination assays. Haplotypes were inferred using the PHASE program. Plasma MMP-2 and TIMP-2 concentrations were measured by ELISA. The main findings were that pregnant with PE have higher plasma MMP-2 and TIMP-2 concentrations than HP (P<0.05), although the MMP-2/TIMP-2 ratios were similar (P>0.05). Moreover, pregnant with GH have elevated plasma MMP-2 levels and MMP-2/TIMP-2 ratios compared to HP (P<0.05). While MMP-2 genotypes and haplotypes are not linked with hypertensive disorders of pregnancy, MMP-2 genotypes and haplotypes are associated with significant alterations in plasma MMP-2 and TIMP-2 concentrations in preeclampsia (P<0.05). Our findings may help to understand the relevance of MMP-2 and its genetic polymorphisms to the pathophysiology of hypertensive disorders of pregnancy. It is possible that patients with PE and the MMP-2 haplotype combining the C and T alleles for the g.-1306 C>T and g.-735 C>T polymorphisms may benefit from the use of MMPs inhibitors such as doxycycline. However, this possibility remains to be determined. (C) 2012 Elsevier Inc. All rights reserved.

A Single Statistic for Monitoring the Covariance Matrix of Bivariate Processes

In this article, we present a new control chart for monitoring the covariance matrix in a bivariate process. In this method, n observations of the two variables were considered as if they came from a single variable (as a sample of 2n observations), and a sample variance was calculated. This statistic was used to build a new control chart specifically as a VMIX chart. The performance of the new control chart was compared with its main competitors: the generalized sampled variance chart, the likelihood ratio test, Nagao's test, probability integral transformation (v(t)), and the recently proposed VMAX chart. Among these statistics, only the VMAX chart was competitive with the VMIX chart. For shifts in both variances, the VMIX chart outperformed VMAX; however, VMAX showed better performance for large shifts (higher than 10%) in one variance.

Extracellular matrix composition in COPD

Extracellular matrix (ECM) composition has an important role in determining airway structure. We postulated that ECM lung composition of chronic obstructive pulmonary disease (COPD) patients differs from that observed in smoking and nonsmoking subjects without airflow obstruction. We determined the fractional areas of elastic fibres, type-I, -III and -IV collagen, versican, decorin, biglycan, lumican, fibronectin and tenascin in different compartments of the large and small airways and lung parenchyma in 26 COPD patients, 26 smokers without COPD and 16 nonsmoking control subjects. The fractional area of elastic fibres was higher in non-obstructed smokers than in COPD and nonsmoking controls, in all lung compartments. Type-I collagen fractional area was lower in the large and small airways of COPD patients and in the small airways of non-obstructed smokers than in nonsmokers. Compared with nonsmokers, COPD patients had lower versican fractional area in the parenchyma, higher fibronectin fractional area in small airways and higher tenascin fractional area in large and small airways compartments. In COPD patients, significant correlations were found between elastic fibres and fibronectin and lung function parameters. Alterations of the major ECM components are widespread in all lung compartments of patients with COPD and may contribute to persistent airflow obstruction.

Effect of dental tissue conditioners and matrix metalloproteinase inhibitors on type I collagen microstructure analyzed by Fourier transform infrared spectroscopy

This study aimed to evaluate the chemical interaction of collagen with some substances usually applied in dental treatments to increase the durability of adhesive restorations to dentin. Initially, the similarity between human dentin collagen and type I collagen obtained from commercial bovine membranes of Achilles deep tendon was compared by the Attenuated Total Reflectance technique of Fourier Transform Infrared (ATR-FTIR) spectroscopy. Finally, the effects of application of 35% phosphoric acid, 0.1M ethylenediaminetetraacetic acid (EDTA), 2% chlorhexidine, and 6.5% proanthocyanidin solution on microstructure of collagen and in the integrity of its triple helix were also evaluated by ATR-FTIR. It was observed that the commercial type I collagen can be used as an efficient substitute for demineralized human dentin in studies that use spectroscopy analysis. The 35% phosphoric acid significantly altered the organic content of amides, proline and hydroxyproline of type I collagen. The surface treatment with 0.1M EDTA, 2% chlorhexidine, or 6.5% proanthocyanidin did not promote deleterious structural changes to the collagen triple helix. The application of 6.5% proanthocyanidin on collagen promoted hydrogen bond formation. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.