Circulating matrix metalloproteinase-8 (MMP-8) and MMP-9 are increased in chronic periodontal disease and decrease after non-surgical periodontal therapy

Background: Periodontal disease shares risk factors with cardiovascular diseases and other systemic inflammatory diseases. The present study was designed to assess the circulating matrix metalloproteinases (MMPs) from chronic periodontal disease patients and, subsequently, after periodontal therapy. Methods: We compared the plasma concentrations of MMP-2. MMP-3, MMP-8, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2, and total gelatinolytic activity in patients with periodontal disease (n =28) with those of control subjects (n = 22) before and 3 months after non-surgical periodontal therapy. Results: Higher plasma MMP-3, MMP-8, and MMP-9 concentrations were found in periodontal disease patients compared with healthy controls (all P<0.05), whereas MMP-2, TIMP-1, and TIMP-2 levels were not different. Treatment decreased plasma MMP-8 and MMP-9 concentrations by 35% and 39%, respectively (both P<0.02), while no changes were found in controls. MMP-2, MMP-3, TIMP-1, and TIMP-2 remained unaltered in both groups. Plasma gelatinolytic activity was higher in periodontal disease patients compared with controls (P<0.001) and decreased after periodontal therapy (P<0.05). Conclusions: This study showed increased circulating MMP-8 and MMP-9 levels and proteolytic activity in periodontal disease patients that decrease after periodontal therapy. The effects of periodontal therapy suggest that it may attenuate inflammatory chronic diseases. (C) 2009 Published by Elsevier B.V.

Analysis of proximal femur DXA scans in growing children: Comparisons of different protocols for cross-sectional 8-month and 7-year longitudinal data

Dual-energy X-ray absorptiometry (DXA) is a widely used method for measuring bone mineral in the growing skeleton. Because scan analysis in children offers a number of challenges, we compared DXA results using six analysis methods at the total proximal femur (PF) and five methods at the femoral neck (FN), In total we assessed 50 scans (25 boys, 25 girls) from two separate studies for cross-sectional differences in bone area, bone mineral content (BMC), and areal bone mineral density (aBMD) and for percentage change over the short term (8 months) and long term (7 years). At the proximal femur for the short-term longitudinal analysis, there was an approximate 3.5% greater change in bone area and BMC when the global region of interest (ROI) was allowed to increase in size between years as compared with when the global ROI was held constant. Trend analysis showed a significant (p < 0.05) difference between scan analysis methods for bone area and BMC across 7 years. At the femoral neck, cross-sectional analysis using a narrower (from default) ROI, without change in location, resulted in a 12.9 and 12.6% smaller bone area and BMC, respectively (both p < 0.001), Changes in FN area and BMC over 8 months were significantly greater (2.3 %, p < 0.05) using a narrower FN rather than the default ROI, Similarly, the 7-year longitudinal data revealed that differences between scan analysis methods were greatest when the narrower FN ROI was maintained across all years (p < 0.001), For aBMD there were no significant differences in group means between analysis methods at either the PF or FN, Our findings show the need to standardize the analysis of proximal femur DXA scans in growing children.

Ni-II and Zn-II complexes of the hexadentate macrocyclic ligand cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetra- decane-6,13-diamine

The title pendent-arm macrocyclic hexaamine ligand binds stereospecifically in a hexadentate manner, and we report here its isomorphous Ni-II and Zn-II complexes (both as perchlorate salts), namely (cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine-kappa(6)N)nickel(II) diperchlorate, [Ni(C12H30N6)](ClO4)(2), and (cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine-kappa(6)N)zinc(II) diperchlorate, [Zn(C-12 H30N6)](ClO4)(2). Distortion of the N-M-N valence angles from their ideal octahedral values becomes more pronounced with increasing metal-ion size and the present results are compared with other structures of this ligand.

Halogenated terpenoids. XXXII - Pentabromides from limonene two 1,2,8,9,9-pentabromo-p-menthanes

The problems of structure in diastereomers where one chiral centre is remote from another are further investigated in the 1,2,8,9,9-pentabromo-p-menthane series.

trans-Cyano(6-methyl-1,4,8,11-tetraazacyclotetradecan-6-amine)cobalt(III) bis(perchlorate) hydrate and trans-hydroxo(6-methyl-1,4,8,11-tetraazacyclotetradecan-6-amine)cobalt(III) bis(perchlorate)

The crystal structures of a pair of closely related macrocyclic cyano- and hydroxopentaaminecobalt(III) complexes, as their perchlorate salts, are reported. Although the two complexes, [Co(CN)(C11H27N5)](ClO4)2.H2O and [Co(OH)(C11H27N5)](ClO4)(2), exhibit similar conformations, significant differences in the Co-N bond lengths arise from the influence of the sixth ligand (cyano as opposed to hydroxo). The ensuing hydrogen-bonding patterns are also distinctly different. Disorder in the perchlorate anions was clearly resolved and this was rationalized on the basis of distinct hydrogen-bonding motifs involving the anion O atoms and the N-H and O-H donors.

Unraveling the Na,K-ATPase alpha(4) Subunit Assembling Induced by Large Amounts of C(12)E(8) by Means of Small-Angle X-ray Scattering

In the current work, we studied the effect of the nonionic detergent dodecyloctaethyleneglycol, C(12)E(8), on the structure and oligomeric form of the Na,K-ATPase membrane enzyme (sodium-potassium pump) in aqueous suspension, by means of small-angle X-ray scattering (SAXS). Samples composed of 2 mg/mL of Na,K-ATPase, extracted from rabbit kidney medulla, in the presence of a small amount of C(12)E(8) (0.005 mg/mL) and in larger concentrations ranging from 2.7 to 27 mg/mL did not present catalytic activity. Under this condition, an oligomerization of the alpha subunits is expected. SAXS data were analyzed by means of a global fitting procedure supposing that the scattering is due to two independent contributions: one coming from the enzyme and the other one from C(12)E(8) micelles. In the small detergent content (0.005 mg/mL), the SAXS results evidenced that Na,K-ATPase is associated into aggregates larger than (alpha beta)(2) form. When 2.7 mg/mL of C(12)E(8) is added, the data analysis revealed the presence of alpha(4) aggregates in the solution and some free micelles. Increasing the detergent amount up to 27 mg/mL does not disturb the alpha(4) aggregate: just more micelles of the same size and shape are proportionally formed in solution. We believe that our results shed light on a better understanding of how nonionic detergents induce subunit dissociation and reassembling to minimize the exposure of hydrophobic residues to the aqueous solvent.

Pregnancy outcome in juvenile systemic lupus erythematosus: A Brazilian multicenter cohort study

Objective. To determine pregnancy outcome and fetal loss risk factors in patients with juvenile systemic lupus erythematosus (JSLE). Methods. A total of 315 female patients with JSLE followed in 12 Brazilian pediatric rheumatology centers were consecutively selected. Menarche was observed in 298 (94.6%) patients. Patients` medical records were reviewed for pregnancy outcomes and demographic, clinical, and therapeutic data. Results. A total of 24 unplanned pregnancies occurred in 298 (8%) patients. The outcomes were 5 (21%) early fetal losses (prior to 16 wks gestation), 18 (75%) live births, and 1 (4%) death due to preeclampsia and premature birth. The frequencies of active diffuse proliferative glomerulonephritis, proteinuria >= 0.5 g/day, and arterial hypertension at the beginning of pregnancy were higher in pregnancies resulting in fetal losses than in live births [60% vs 5% (p = 0.02), 60% vs 5% (p = 0.02), 60% vs 5% (p = 0.02), respectively]. JSLE pregnancies with fetal losses had a significantly higher mean SLE Disease Activity Index 2000 (SLEDAI-2K) at the start of pregnancy compared with those with live births (9.40 +/- 7.47 vs 3.94 +/- 6.00; p = 0.049). Four pregnancies were inadvertently exposed to intravenous cyclophosphamide therapy for renal involvement despite contraceptive prescriptions, resulting in fetal loss in 3 (p = 0.02). In multivariate analysis only intravenous cyclophosphamide use at start of pregnancy (OR 25.50, 95% CI 1.72-377.93, p = 0.019) remained as an independent risk factor for fetal loss. Conclusion. We identified immunosuppressive therapy as the major contributing factor for fetal loss in JSLE, reinforcing the importance of contraception.

Nitrogen- and carbon-based isomerism in the copper(II) complexes of 6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine

A number of N- and C-based diastereomeric copper(II) complexes of the pendant-arm macrocyclic hexaamines trans- and cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine (L-1 and L-2) have been isolated and characterised. The crystal structures of the complexes RRSS-[CuL1(OH2)(2)][ClO4](2), SSRR-[Cu(H2L1)(OClO3)(2)]-[ClO4](2) . 2H(2)O RSRS-[CuL1(OClO3)]ClO4, RSRS-[CuL2(OClO3)]ClO4 and RRSS-[Cu(H2L2)(OClO3)(2)][ClO4](2) have been determined. Some unusual structural and spectroscopic variations are found across this series of diastereomers. The protonation constants of the pendant primary amines are dependent on the relative dispositions of the adjacent macrocyclic secondary amine H atoms, which is indicative of intramolecular hydrogen-bonding interactions.

Effects of Optimal Medical Treatment With or Without Coronary Revascularization on Angina and Subsequent Revascularizations in Patients With Type 2 Diabetes Mellitus and Stable Ischemic Heart Disease

Background-In the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, an initial strategy of coronary revascularization and optimal medical treatment (REV) compared with an initial optimal medical treatment with the option of subsequent revascularization (MED) did not reduce all-cause mortality or the composite of cardiovascular death, myocardial infarction, and stroke in patients with type 2 diabetes mellitus and stable ischemic heart disease. In the same population, we tested whether the REV strategy was superior to the MED strategy in preventing worsening and new angina and subsequent coronary revascularizations. Methods and Results-Among the 2364 men and women (mean age, 62.4 years) with type 2 diabetes mellitus, documented coronary artery disease, and myocardial ischemia, 1191 were randomized to the MED and 1173 to the REV strategy preselected in the percutaneous coronary intervention (796) and coronary artery bypass graft (377) strata. Compared with the MED strategy, the REV strategy at the 3-year follow-up had a lower rate of worsening angina (8% versus 13%; P < 0.001), new angina (37% versus 51%; P = 0.001), and subsequent coronary revascularizations (18% versus 33%; P < 0.001) and a higher rate of angina-free status (66% versus 58%; P = 0.003). The coronary artery bypass graft stratum patients were at higher risk than those in the percutaneous coronary intervention stratum, and had the greatest benefits from REV. Conclusions-In these patients, the REV strategy reduced the occurrence of worsening angina, new angina, and subsequent coronary revascularizations more than the MED strategy. The symptomatic benefits were observed particularly for high-risk patients.

Altered Ex Vivo Expression of Caspase 8, Caspase 9, and Bcl-2 Is Associated with T-Cell Hyporeactivity in Patients with Paracoccidioidomycosis

To better understand the T-cell hyporesponsiveness of patients with paracoccidioidomycosis, we tested the hypothesis that the T cells were committed to apoptosis. We show here that T cells of patients with paracoccidioidomycosis overexpress caspase 9 and caspase 8 but express low Bcl-2 levels and that interleukin-2 was unable to revert the hyporesponsiveness. These data suggest that the T cells would in vivo be driven to a tolerant state and apoptosis.

Health in Brazil 4 Chronic non-communicable diseases in Brazil: burden and current challenges

Non-communicable diseases (NCDs) have become a major health priority in Brazil-72% of all deaths were attributable to NCDs in 2007. They are also the main source of disease burden, with neuropsychiatric disorders being the single largest contributor. Morbidity and mortality due to NCDs are greatest in the poor population. Although the crude NCD mortality increased 5% between 1996 and 2007, age-standardised mortality declined by 20%. Declines were primarily for cardiovascular and chronic respiratory diseases, in association with the successful implementation of health policies that lead to decreases in smoking and the expansion of access to primary health care. Of note, however, the prevalence of diabetes and hypertension is rising in parallel with that of excess weight; these increases are associated with unfavourable changes of diet and physical activity. Brazil has implemented major policies for the prevention of NCDs, and its age-adjusted NCD mortality is falling by 1.8% per year. However, the unfavourable trends for most major risk factors pose an enormous challenge and call for additional and timely action and policies, especially those of a legislative and regulatory nature and those providing cost-effective chronic care for individuals affected by NCDs.

Decreased immunoexpression of survivin could be a potential marker in human non-alcoholic fatty liver disease progression?

Background/aim Regulation of apoptosis in non-alcoholic fatty liver disease (NAFLD) has been a theme of growing debate. Although no other study assessed the role of survivin in NAFLD, its expression has been reported in hepatic carcinogenesis because of other aetiological factors with relevant discrepancies. The aim of this study was to assess the pattern of survivin immunoexpression by tissue microarray along the whole spectrum of NAFLD, including non-alcoholic steatohepatitis (NASH)-related hepatocelular carcinoma (HCC). Methods Liver biopsies from 56 patients with NAFLD were evaluated: 18 with steatosis, 21 non-cirrhotic NASH, 10 NASH-related cirrhosis, seven NASH-related HCC, as compared with 71 HCC related to other causes and with 12 normal livers. Results Survivin immunoexpression in NAFLD was restricted to cytoplasm and was found to be progressively lower in advanced stages, including cirrhosis and HCC: steatosis vs NASH-related cirrhosis (P=0.0243); steatosis vs NASH-related HCC (P=0.0010); NASH vs NASH-related cirrhosis (P=0.0318); and NASH vs NASH-related HCC (P=0.0007), thus suggesting a deregulation of apoptosis from NAFLD towards HCC. Interestingly, survivin immunoreactivity in NASH-related HCC was also found to be significantly lower than in HCC related to other causes (P < 0.05). Remarkably, nuclear staining for survivin was not detected in any case of NAFLD, contrasting to its presence in all other cases of HCC. Conclusions Survivin immunoexpression in NASH-related HCC is herein originally found substantially different than in HCC related to other causes, thus requiring further studies to elucidate the role of survivin in human NAFLD progression.