Nitrite or sildenafil, but not BAY 41-2272, blunt acute pulmonary embolism-induced increases in circulating matrix metalloproteinase-9 and oxidative stress

Introduction: Inhibition of matrix metalloproteinases (MMPs) improves the hemodynamics during acute pulmonary embolism (APE) and oxidative stress upregulates MMPs. We compared the effects of different NO-cGMP pathway activators on APE-induced increases in MMPs. Materials and Methods: Hemodynamic and biochemical evaluations were performed in non-embolized dogs treated with saline (N = 5), and in microspheres embolized dogs receiving saline (n = 9), or nitrite (6.75 mu mol/kg i.v. over 15 min followed by 0.28 mu mol/kg/min; n = 5), or sildenafil (0.25 mg/kg; n = 5), or BAY 41-2272 (0.03, 0.1, 0.3, and 1 mg/kg/h; n = 5). Plasma thiobarbituric acid reactive substances (TBARS) concentrations were determined. Zymograms of plasma samples were performed, and in vitro antioxidant effects or inhibition of MMPs by these drugs were examined. Results: APE increased mean pulmonary artery pressure by similar to 25 mmHg. Nitrite, BAY 41-2272, or sildenafil reversed this increase by similar to 40% (P < 0.05). Similar effects were seen on the pulmonary vascular resistance. While both nitrite and sildenafil produced no systemic effects, the highest dose of BAY 41-2272 produced systemic hypotension (P<0.05). While nitrite and sildenafil blunted the increases in plasma pro-MMP-9 levels and TBARS (all P < 0.05), BAY 41-2272 produced no such effects. Nitrite and sildenafll produced in vitro antioxidant effects and inhibited MMPs only at high concentrations. BAY 41-2272 produced no such effects. Conclusions: Activation of the NO-cGMP pathway with nitrite or sildenafil, but not with BAY 41-2272, attenuates APE-induced oxidative stress and increased MMP-9 levels. These findings are consistent with the idea that NO-cGMP pathway activators with antioxidant effects prevent the release of MMP-9 during APE. (c) 2008 Elsevier Ltd. All rights reserved.

A Nationwide Population-Based Study of Tension-Type Headache in Brazil

To estimate the 1-year prevalence of tension-type headache (TTH) and the degree of the association of TTH with some sociodemographic characteristics of a representative sample of the adult population of Brazil. This was an observational, cross-sectional, population-based study. We conducted telephone interviews on 3848 people, aged 18-79 years, randomly selected from the 27 states of Brazil. Trained lay interviewers administered the structured questionnaire. It included questions about the sociodemographic characteristics of the population, as well as questions about headache. The degree of the association was calculated through prevalence ratios, adjusted with Poisson regression by gender, age, years of education, marital status, household income, job status, body mass index (BMI), and physical exercise. The estimated 1-year gender- and-age-adjusted prevalence of TTH was 13.0% (95% CI: 11.8-14.2%); 15.4% in males and 9.5% in females. The prevalence of probable TTH was 22.6% (95% CI: 21.1-24.1%). Most (86.2%) subjects reported episodic TTH; 6.4% had chronic TTH. The prevalence was higher at 18-29 years of age (16.2%). TTH was 1.6 times more prevalent in men, and 1.54 times more in subjects with more than 11 years of education. There was no significant association of TTH with marital or job status, household income, BMI, and physical activity. This is the first nationwide epidemiological study of TTH in Brazil. The overall prevalence of TTH in Brazil is low, at 13%. TTH is significantly more prevalent in males and subjects with higher education level.

Chronic daily headache in Brazil: a nationwide population-based study

The objectives of this study were to estimate the 1-year prevalence of chronic daily headache (CDH) and the degree of the association of CDH with some sociodemographic characteristics of the adult population of Brazil. This was a cross-sectional, population-based study. We conducted telephone interviews with 3848 people, aged 18-79 years, randomly selected from the 27 States of Brazil. The degree of the association was calculated through prevalence ratios, adjusted with Poisson regression by gender, age and some sociodemographic factors. The estimated 1-year gender- and age-adjusted prevalence of CDH was 6.9%. CDH was 2.4 times more prevalent in women, 1.72 times more in unemployed, 1.63 times more in subjects with high household income and two times greater in those who did not exercise. The overall prevalence of CDH in Brazil is high. CDH is significantly more prevalent in women, the unemployed, subjects with higher income, and in those who do not exercise.

Prevention of ""Risky"" drinking among students at a Brazilian University

Aim: The aim of this paper was to compare the quantity and frequency of alcohol use and its associated negative consequences between two groups of college students who were identified as being ""risky drinkers."" Subjects were randomly allocated in a clinical trial to intervention or control groups. Methods: Risky drinking use was defined as Alcohol Use Disorders Identification Test (AUDIT) >= 8 and/or Rutgers Alcohol Problem Index (RAPI) >= 5 problems in the previous year. Students who had undergone the Brief Alcohol Screening and Intervention for College Students (BASICS) (N = 145 at baseline; 142 at 12 months, and 103 at 24 months, loss of 29.7%) were compared with a control group (N = 121 at baseline; 121 at 12 months and 113 at 24 months, loss of 9.3%), the nonintervention group. Variables included drinking frequency, quantity and peak consumption, dependence assessment, and family and friends` abuse assessment. Results: Treated students at a 24-month follow-up decreased quantity of alcohol use per occasion and lowered AUDIT and RAPI scores. Conclusions: This is the first brief intervention work on risky drinking with college students in Brazil and the results are encouraging. However, it is difficult to conduct individual prevention strategies in a country where culture fosters heavy drinking through poor public policy on alcohol and lack of law enforcement.

Impact of implementing an exclusively dedicated respiratory isolation room in a Brazilian tertiary emergency department

Background Occupational risk due to airborne disease challenges healthcare institutions. Environmental measures are effective but their cost-effectiveness is still debatable and most of the capacity planning is based on occupational rates. Better indices to plan and evaluate capacity are needed. Goal To evaluate the impact of installing an exclusively dedicated respiratory isolation room (EDRIR) in a tertiary emergency department (ED) determined by a time-to-reach-facility method. Methods A group of patients in need of respiratory isolation were first identified-group I (2004; 29 patients; 44.1 +/- 3.4 years) and the occupational rate and time intervals (arrival to diagnosis, diagnosis to respiratory isolation indication and indication to effective isolation) were determined and it was estimated that adding an EDRIR would have a significant impact over the time to isolation. After implementing the EDRIR, a second group of patients was gathered in the same period of the year-group II (2007; 50 patients; 43.4 +/- 1.8 years) and demographic and functional parameters were recorded to evaluate time to isolation. Cox proportional hazard models adjusted for age, gender and inhospital respiratory isolation room availability were obtained. Results Implementing an EDRIR decreased the time from arrival to indication of respiratory isolation (27.5 +/- 9.3 X 3.7 +/- 2.0; p = 0.0180) and from indication to effective respiratory isolation (13.3 +/- 3.0 X 2.94 +/- 1.06; p = 0.003) but not the respiratory isolation duration and total hospital stay. The impact on crude isolation rates was very significant (8.9 X 75.4/100.000 patients; p < 0.001). The HR for effective respiratory isolation was 26.8 (95% CI 7.42 to 96.9) p < 0.001 greater for 2007. Conclusion Implementing an EDRIR in a tertiary ED significantly reduced the time to respiratory isolation.

Matrix metalloproteinase 9 gene haplotypes affect left ventricular hypertrophy in hypertensive patients

Background: Matrix metalloproteinases (MMPs) are involved in cardiac remodeling and are encoded by genes showing genetic polymorphisms that have functional implications. We examined whether MMP-9 genetic polymorphisms are associated with hypertension and with left ventricular (LV) remodeling in hypertensive patients. Methods: We studied 173 hypertensive patients and 137 age, race and gender matched healthy controls. Heart echocardiography was performed in all patients and the following MMP-9 genetic polymorphisms were analyzed: C-(1562)T (rs3918242). -90 (CA)(14-24) (rs2234681) and Q279R (rs17576). Haplo.stats analysis was used to assess whether MMP-9 haplotypes are associated with hypertension. Linear regression analysis was performed to assess whether MMP-9 haplotypes affect LV mass index (LVMI) and other echocardiography parameters. Results: MMP-9 90 (CA)14-24 ""HH"" genotype (H allele defined by number of CA repeats >= 21) was associated with hypertension (P = 0.0085; OR = 2.321, 95% confidence interval = 1.250 to 4.309). While one MMP-9 haplotype (""C. H, Q"") protects against LVMI and end-diastolic diameter increases due to remodeling (P = 0.0490 and P = 0.0367), another MMP-9 haplotype apparently has detrimental effects over both parameters in hypertensive patients (""T, H. Q"", P = 0.0015 and P = 0.0057. respectively). Conclusion: Genetic polymorphisms in MMP-9 gene may modify the susceptibility of hypertensive patients to LV remodeling. Further studies are necessary to examine whether these polymorphisms affect clinical events in hypertensive patients. (C) 2010 Elsevier B.V. All rights reserved.

Differential expression of HDAC3, HDAC7 and HDAC9 is associated with prognosis and survival in childhood acute lymphoblastic leukaemia

Altered expression of histone deacetylases (HDACs) is a common feature in several human malignancies and may represent an interesting target for cancer treatment, including haematological malignancies. We evaluated the mRNA gene expression profile of 12 HDAC genes by quantitative real-time polymerase chain reaction in 94 consecutive childhood acute lymphoblastic leukaemia (ALL) samples and its association with clinical/biological features and survival. ALL samples showed higher expression levels of HDAC2, HDAC3, HDAC8, HDAC6 and HDAC7 when compared to normal bone marrow samples. HDAC1 and HDAC4 showed high expression in T-ALL and HDAC5 was highly expressed in B-lineage ALL. Higher than median expression levels of HDAC3 were associated with a significantly lower 5-year event-free survival (EFS) in the overall group of patients (P = 0.03) and in T-ALL patients (P = 0.01). HDAC7 and HADC9 expression levels higher than median were associated with a lower 5-year EFS in the overall group (P = 0.04 and P = 0.003, respectively) and in B-lineage CD10-positive patients (P = 0.009 and P = 0.005, respectively). Our data suggest that higher expression of HDAC7 and HDAC9 is associated with poor prognosis in childhood ALL and could be promising therapeutic targets for the treatment of refractory childhood ALL.