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.

Deconstructing Tick Saliva NON-PROTEIN MOLECULES WITH POTENT IMMUNOMODULATORY PROPERTIES

Dendritic cells (DCs) are powerful initiators of innate and adaptive immune responses. Ticks are blood-sucking ectoparasite arthropods that suppress host immunity by secreting immunomodulatory molecules in their saliva. Here, compounds present in Rhipicephalus sanguineus tick saliva with immunomodulatory effects on DC differentiation, cytokine production, and costimulatory molecule expression were identified. R. sanguineus tick saliva inhibited IL-12p40 and TNF-alpha while potentiating IL-10 cytokine production by bone marrow-derived DCs stimulated by Toll-like receptor-2, -4, and -9 agonists. To identify the molecules responsible for these effects, we fractionated the saliva through microcon filtration and reversed-phase HPLC and tested each fraction for DC maturation. Fractions with proven effects were analyzed by micro-HPLC tandem mass spectrometry or competition ELISA. Thus, we identified for the first time in tick saliva the purine nucleoside adenosine (concentration of similar to 110pmol/mu l) as a potent anti-inflammatory salivary inhibitor of DC cytokine production. We also found prostaglandin E(2) (PGE(2) similar to 100 nM) with comparable effects in modulating cytokine production by DCs. Both Ado and PGE(2) inhibited cytokine production by inducing cAMP-PKA signaling in DCs. Additionally, both Ado and PGE(2) were able to inhibit expression of CD40 in mature DCs. Finally, flow cytometry analysis revealed that PGE(2), but not Ado, is the differentiation inhibitor of bone marrow-derived DCs. The presence of non-protein molecules adenosine and PGE(2) in tick saliva indicates an important evolutionary mechanism used by ticks to subvert host immune cells and allow them to successfully complete their blood meal and life cycle.

Who chooses to inflation target?

In this article, we seek what are the factors behind a country`s decision to move to Inflation Targeting. We find that high past inflation, low debt levels and the absence of a nominal exchange rate anchor increase the probability that a country will end up opting for it. (C) 2007 Elsevier B.V. All rights reserved.

Non-Spatial Government Policies and Regional Income Inequality in Brazil

Silveira Neto R. Da M. and Azzoni C. R. Non-spatial government policies and regional income inequality in Brazil, Regional Studies. This paper uses both macro- and micro-data to analyse the role of social programmes in the recent reduction in Brazilian regional income inequality. Convergence indicators are presented for different sources of regional income in the period 1995-2006. A decomposition of the Gini indicator allows the identification of the role of each of these income sources with respect to the reduction of regional inequality during the period. The results point out that both labour productivity and government non-spatial policies - mainly minimum wage changes and income transference programmes - do have a role in explaining regional inequality reduction during the period. [image omitted] Silveira Neto R. Da M. et Azzoni C. R. Les politiques gouvernementales non-spatiales et l`ecart des revenus regionaux au Bresil, Regional Studies. Cet article emploie des donnees a la fois macroeconomiques et microeconomiques afin d`analyser le role des programmes d`actions sociales quant a la baisse recente de l`ecart des revenus regionaux au Bresil. On presente des indicateurs de convergence pour diverses sources des revenus regionaux pour la periode allant de 1995 a 2006. Une decomposition du coefficient de Gini permet d`identifier le role de chacune de ces sources des revenus par rapport a la baisse de l`ecart des revenus pendant cette periode. Les resultats indiquent que la productivite du travail et les politiques gouvernementales non-spatiales - notamment la modification du salaire minimum et les programmes visant le transfert des revenus - ont un role a jouer pour expliquer la baisse de l`ecart des revenus regionaux pendant la periode en question. Convergence Productivite du travail Transfert des revenus Salaire minimum Effets spatiaux des politiques non-spatiales Silveira Neto R. Da M. und Azzoni C. R. Nicht raumliche Regierungspolitiken und das regionale Einkommensungleichgewicht in Brasilien, Regional Studies. In diesem Beitrag analysieren wir mit Hilfe von Makro- und Mikrodaten die Rolle von sozialen Programmen bei der unlangst erzielten Verringerung des regionalen Einkommensungleichgewichts in Brasilien. Wir stellen Konvergenz-Indikatoren fur verschiedene regionale Einkommensquellen im Zeitraum von 1995 bis 2006 vor. Eine Dekomposition des Gini-Indikators ermoglicht die Identifizierung der jeweiligen Rolle dieser Einkommensquellen fur die Verringerung des regionalen Ungleichgewichts im betreffenden Zeitraum. Die Ergebnisse weisen darauf hin, dass sowohl die Produktivitat der Arbeitskrafte als auch die nicht raumlichen Regierungspolitiken - in erster Linie Veranderungen beim Mindestlohn und Programme fur Einkommenstransfers - als Grunde fur die Verringerung des regionalen Ungleichgewichts in dieser Periode durchaus eine Rolle spielen. Konvergenz Arbeitsproduktivitat Einkommenstransfer Mindestlohn Raumliche Auswirkungen nicht raumlicher Politiken Silveira Neto R. Da M. y Azzoni C. R. Politicas gubernamentales no espaciales y desigualdades de ingresos regionales en Brasil, Regional Studies. En este articulo utilizamos datos macro y micro para analizar el papel de los programas sociales en la reciente reduccion en las desigualdades de ingresos regionales de Brasil. Presentamos los indicadores de convergencia para diferentes fuentes de ingresos regionales en el periodo de 1995 a 2006. Una descomposicion del indice Gini permite identificar el papel de cada una de estas fuentes de ingresos con respecto a la reduccion de las desiguadades regionales durante este periodo. Los resultados destacan que tanto la productividad laboral como las politicas no espaciales del gobierno - principalmente los cambios de salario minimo y los programas de transferencias de ingresos - desempenan una funcion a la hora de explicar la reduccion de las desigualdades regionales durante este periodo. Convergencia Productividad laboral Transferencias de ingresos Salario minimo Efectos espaciales de politicas no espaciales.

The Controllership Relevance or Risk Management in non-Financial Companies: a study of risk managers` and controllers` perceptions

The purpose of this study is to analyze the Controllership relevance as support risk management in non-financial companies. Risk management is a widely discussed and disseminated subject amongst financial institutions. It is obvious that economic uncertainties and, consequently, prevention and. control must also exist in non-financial companies. To enable managers to take safe-decisions, it is essential for them to be able to count on instrumental support that provides timely and adequate information, to ensure lower levels of mistakes and risk exposure. However, discussion concerning risk management in non-financial companies is still in its early stages in Brazil. Considering this gap, this study aims at assessing how Controllership has been acting in? companies under the insight of risk and how it can contribute to risk management in non-financial companies. To achieve the proposed goal, a field research was. carried-out with non-financial companies that are located in the city Sao Paulo and listed in the Sao Paulo Stock Exchange (Bovespa). The research was carried out using questionnaires, which were sent do Risk Officers and Controllers of those companies with the purpose of evaluating their perception on the subject. The results,of the research allow us to conclude that Controllership offers support to risk management, through information that contributes to the mitigation of the risks in non-financial companies.

Non-linear pathways of corporate environmental management: a survey of ISO 14001-certified companies in Brazil

A study was conducted to verify whether the theory on the evolution of corporate environmental management (CEM) is applicable to organizations located in Brazil. Some of the most important proposals pertaining to the evolution of CEM were evaluated in a systematic fashion and integrated into a typical theoretical framework containing three evolutionary stages: reactive, preventive and proactive. The validity of this framework was tested by surveying 94 companies located in Brazil with ISO 14001 certification. Results indicated that the evolution of CEM tends to occur in a manner that is counter to what has generally been described in the literature. Two evolutionary stages were identified: 1) synergy for eco-efficiency and 2) environmental legislation view, which combine variables that were initially categorized into different theoretical CEM stages. These data, obtained from a direct study of Brazilian companies, suggest that the evolution of environmental management in organizations tends to occur in a non-linear fashion, requiring a re-analysis of traditional perceptions of CEM development, as suggested by Kolk and Mauser (2002). (C) 2010 Elsevier Ltd. All rights reserved.

Colonization sequence of non-pollinating fig wasps associated with Ficus citrifolia in Brazil

Mutualisms, such as the fig-agaonid wasp association, are susceptible to colonization by parasitic species, which exploit the resources involved therein. In most cases, they oviposit into the figs from outside without providing any pollination service. In this study, we used several different methods (adhesive traps and direct standardized field observations) to assess the colonization sequence of a diverse fig wasp fauna associated with Ficus citrifolia, section Americana, in Brazil. They consistently showed a temporal partitioning in colonization among non-pollinating fig wasp species. Idarnes species belonging to the flavicollis and incerta groups colonized figs just before or during the fig receptive phase. In contrast, Idarnes females belonging to the carme group oviposited one to three weeks later, mainly in the middle of the inter-floral phase. Eurytoma, Heterandrium, Physothorax and Torymus were later colonizers, and laid eggs either in the middle or during the late inter-floral phase. The results suggest that these Neotropical fig wasps have different strategies of resource exploitation, even among species belonging to the same genus.

Non-ribosomal peptides produced by Brazilian cyanobacterial isolates with antimicrobial activity

Cyanobacterial strains isolated from terrestrial and freshwater habitats in Brazil were evaluated for their antimicrobial and siderophore activities. Metabolites of fifty isolates were extracted from the supernatant culture media and cells using ethyl acetate and methanol, respectively. The extracts of 24 isolates showed antimicrobial activity against several pathogenic bacteria and one yeast. These active extracts were characterized by Q-TOF/MS. The cyanobacterial strains Cylindrospermopsis raciborskii 339-T3, Synechococcus elongatus PCC7942, Microcystis aeruginosa NPCD-1, M. panniformis SCP702 and Fischerella sp. CENA19 provided the most active extracts. The 50 cyanobacterial strains were also screened for the presence of non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) genes and microcystin production. Putative fragment genes coding for NRPS adenylation domains and PKS keto-synthase domains were successfully PCR amplified from 92% and 80% of cyanobacterial strains, respectively. The potential therapeutical compounds siderophores were detected in five cyanobacterial isolates. Microcystin production was detected by ELISA test in 26% of the isolates. Further a protease inhibitor substance was detected by LC-MS/MS in the M. aeruginosa NPLJ-4 extract and the presence of aeruginosin and cyanopeptolin was confirmed by PCR amplification using specific primers, and sequenced. This screening study showed that Brazilian cyanobacterial isolates are a rich source of natural products with potential for pharmacological and biotechnological applications. (C) 2010 Elsevier GmbH. All rights reserved.

Reduced pH induces an inactive non-native conformation of the monomeric bothropstoxin-I (Lys49-PLA(2))

Bothropstoxin-I (BthTx-I), a Lys49-PLA(2) from Bothrops jararacussu venom, permeabilizes membranes by a non-hydrolytic Ca(2+)-independent mechanism. The BthTx-I showed activity against liposomes including 10% and 50% negatively charged lipids at pH 7.0, but not at pH 5.0. Nevertheless, ultracentrifugation and FRET demonstrated that at pH 5.0 the BthTx-I is bound to 50% negatively charged membranes. ANS binding identified a non-native monomeric conformation at pH 5.0, suggesting that tertiary structure alterations result in activity loss of the BthTx-I at low pH. (C) 2009 Elsevier Ltd. All rights reserved.

THE ANTERIOR CINGULATE CORTEX IS A TARGET STRUCTURE FOR THE ANXIOLYTIC-LIKE EFFECTS OF BENZODIAZEPINES ASSESSED BY REPEATED EXPOSURE TO THE ELEVATED PLUS MAZE AND FOS IMMUNOREACTIVITY

Prior experience with the elevated plus maze (EPM) increases the avoidance of rodents to the open arms and impairs the anxiolytic-like effects of benzodiazepines on the traditional behaviors evaluated upon re-exposure to the maze, a phenomenon known as one-trial tolerance. Risk assessment behaviors are also sensitive to benzodiazepines. During re-exposure to the maze, these behaviors reinstate the information-processing initiated during the first experience, and the detection of danger generates stronger open-arm avoidance. The present study investigated whether the benzodiazepine midazolam alters risk assessment behaviors and Fos protein distribution associated with test and retest sessions in the EPM. Naive or maze-experienced Wistar rats received either saline or midazolam (0.5 mg/kg i.p.) and were subjected to the EPM. Midazolam caused the usual effects on exploratory behavior, increasing exploratory activity of naive rats in the open arms and producing no effects on these conventional measures in rats re-exposed to the maze. Risk assessment behaviors, however, were sensitive to the benzodiazepine during both sessions, indicating anxiolytic-like effects of the drug in both conditions. Fos immunohistochemistry showed that midazolam injections were associated with a distinct pattern of action when administered before the test or retest session, and the anterior cingulate cortex, area 1 (Cg1), was the only structure targeted by the benzodiazepine in both situations. Bilateral infusions of midazolam into the Cg1 replicated the behavioral effects of the drug injected systemically, suggesting that this area is critically involved in the anxiolytic-like effects of benzodiazepines, although the behavioral strategy adopted by the animals appears to depend on the previous knowledge of the threatening environment. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

Occasion setting in Pavlovian ambiguous target discriminations

Rats were trained in a Pavlovian serial ambiguous target discrimination, in which a target cue was reinforced if it was preceded by one stimulus (P -> T+) but was not reinforced if it was preceded by another stimulus (N -> T-). Test performance indicated that stimulus control by these features was weaker than that acquired by features trained within separate serial feature positive (P -> T+, T-) and serial feature negative (N -> W-, W+) discriminations. The form of conditioned responding and the patterns of transfer observed suggested that the serial ambiguous target discrimination was solved by occasion setting. The data are discussed in terms of the use of retrospective coding strategies when solving Pavlovian serial conditional discriminations, and the acquisition of special properties by both feature and target stimuli. (C) 2008 Published by Elsevier B.V.

C(alpha)-HOLDER CLASSICAL SOLUTIONS FOR NON-AUTONOMOUS NEUTRAL DIFFERENTIAL EQUATIONS

In this paper we discuss the existence of alpha-Holder classical solutions for non-autonomous abstract partial neutral functional differential equations. An application is considered.

Twelve-month Outcomes After Coronary Stenting With the Genous (TM) Bio-Engineered R Stent (TM) in Diabetic Patients from the e-HEALING Registry

Objectives: We compared 12-month outcomes, regarding ischemic events, repeat intervention, and ST, between diabetic and nondiabetic patients treated with the Genous (TM) EPC capturing R stent (TM) during routine nonurgent percutaneous coronary intervention (PCI) using data from the multicenter, prospective worldwide e-HEALING registry. Background: Diabetic patients have an increased risk for restenosis and stent thrombosis (ST). Methods: In the 4,996 patient e-HEALING registry, 273 were insulin requiring diabetics (IRD), 963 were non-IRD (NIRD), and 3,703 were nondiabetics. The 12-month primary outcome was target vessel failure (TVF), defined as target vessel-related cardiac death or myocardial infarction (MI) and target vessel revascularization. Secondary outcomes were the composite of cardiac death, MI or target lesion revascularization (TLR), and individual outcomes including ST. Cumulative event rates were estimated with the Kaplan-Meier method and compared with a log-rank test. Results: TVF rates were respectively 13.4% in IRD, 9.0% in NIRD, and 7.9% in nondiabetics (P < 0.01). This was mainly driven by a higher mortality hazard in IRD (P < 0.001) and NIRD (P = 0.07), compared with nondiabetics. TLR rates were comparable in NIRD and nondiabetics, but significantly higher in IRD (P = 0.04). No difference was observed in ST. Conclusion: The 1-year results of the Genous stent in a real-world population of diabetics show higher TVF rates in diabetics compared with nondiabetics, mainly driven by a higher mortality hazard. IRD is associated with a significant higher TLR hazard. Definite or probable ST in all diabetic patients was comparable with nondiabetics. (J Interven Cardiol 2011;24:285-294)

Early Control of PTH and FGF23 in Normophosphatemic CKD Patients: A New Target in CKD-MBD Therapy?

Background and objectives: Levels of parathyroid hormone (PTH) and the phosphaturic hormone FGF23, a fibroblast growth factor (FGF) family member, increase early in chronic kidney disease (CKD) before the occurrence of hyperphosphatemia. This short-term 6-wk dose titration study evaluated the effect of two phosphate binders on PTH and FGF23 levels in patients with CKD stages 3 to 4. Design, setting, participants, and measurements: Patients were randomized to receive over a 6-wk period either calcium acetate (n = 19) or sevelamer hydrochloride (n = 21). Results: At baseline, patients presented with elevated fractional excretion of phosphate, serum PTH, and FGF23. During treatment with both phosphate binders there was a progressive decline in serum PTH and urinary phosphate, but no change in serum calcium or serum phosphate. Significant changes were observed for FGF23 only in sevelamer-treated patients. Conclusions: This study confirms the positive effects of early prescription of phosphate binders on PTH control. Prospective and long-term studies are necessary to confirm the effects of sevelamer on serum FGF23 and the benefits of this decrease on outcomes. Clin J Am Soc Nephrol 5: 286-291, 2010. doi: 10.2215/CJN.05420709

Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia

Purpose Dasatinib is a BCR-ABL inhibitor, 325-fold more potent than imatinib against unmutated BCR-ABL in vitro. Phase II studies have demonstrated efficacy and safety with dasatinib 70 mg twice daily in chronic-phase (CP) chronic myelogenous leukemia (CML) after imatinib treatment failure. In phase I, responses occurred with once-daily administration despite only intermittent BCR-ABL inhibition. Once-daily treatment resulted in less toxicity, suggesting that toxicity results from continuous inhibition of unintended targets. Here, a dose-and schedule-optimization study is reported. Patients and Methods In this open-label phase III trial, 670 patients with imatinib-resistant or -intolerant CP-CML were randomly assigned 1: 1: 1: 1 between four dasatinib treatment groups: 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. Results With minimum follow-up of 6 months (median treatment duration, 8 months; range, = 1 to 15 months), marked and comparable hematologic (complete, 86% to 92%) and cytogenetic (major, 54% to 59%; complete, 41% to 45%) response rates were observed across the four groups. Time to and duration of cytogenetic response were similar, as was progression-free survival (8% to 11% of patients experienced disease progression or died). Compared with the approved 70-mg twice-daily regimen, dasatinib 100 mg once daily resulted in significantly lower rates of pleural effusion (all grades, 7% v 16%; P = .024) and grade 3 to 4 thrombocytopenia (22% v 37%; P = .004), and fewer patients required dose interruption (51% v 68%), reduction (30% v 55%), or discontinuation (16% v 23%). Conclusion Dasatinib 100 mg once daily retains the efficacy of 70 mg twice daily with less toxicity. Intermittent target inhibition with tyrosine kinase inhibitors may preserve efficacy and reduce adverse events.