Effects of vitamin C supplementation on acute phase Chagas disease in experimentally infected mice with Trypanosoma cruzi QM1 strain

The tissue changes that occur in Chagas disease are related to the degree of oxidative stress and antioxidant capacity of affected tissue. Studies with vitamin C supplementation did not develop oxidative damage caused by Chagas disease in the host, but other studies cite the use of peroxiredoxins ascorbate - dependent on T. cruzi to offer protection against immune reaction. Based on these propositions, thirty "Swiss" mice were infected with T. cruzi QM1 strain and treated with two different vitamin C doses in order to study the parasitemia evolution, histopathological changes and lipid peroxidation biomarkers during the acute phase of Chagas disease. The results showed that the parasite clearance was greater in animals fed with vitamin C overdose. There were no significant differences regarding the biomarkers of lipid peroxidation and inflammatory process or the increase of myocardium in animals treated with the recommended dosage. The largest amount of parasite growth towards the end of the acute phase suggests the benefit of high doses of vitamin C for trypomastigotes. The supplementation doesn't influence the production of free radicals or the number of amastigote nests in the acute phase of Chagas disease.

Clinical evolution of patients hospitalized due to the first episode of Acute Coronary Syndrome

AIM: to assess the clinical evolution of patients hospitalized due to the first episode of Acute Coronary Syndrome (ACS) according to its clinical manifestation. METHODS: data were collected from 234 patients, hospitalized between May 2006 and July 2009 due to the first episode of an ACS, by consulting their medical records. RESULTS: 234 patients were hospitalized, 140 (59.8%) due to Acute Myocardial Infarction (AMI). In the group with AMI, 19.3% presented complications, against 12.8% in the group with Unstable Angina (UA) (p=0.19). Angioplasty levels were higher among patients with AMI than with UA (p=0.02) and coronary artery bypass graft surgery was more frequent among UA patients (p=0.03). The majority (227; 97%) survived after the coronary event. Among the seven patients who died during the hospitalization, four had AMI (2.9%) and three UA (3.2%). CONCLUSIONS: A larger number of complications were found among infarction victims and the accomplishment of coronary artery bypass graft surgery differed between the groups.

Fluoxetine exposure during pregnancy and lactation: effects on acute stress response and behavior in the novelty-suppressed feeding are age and gender-dependent in rats

Fluoxetine (FLX) is commonly used to treat anxiety and depressive disorders in pregnant women. Since FLX crosses the placenta and is excreted in milk, maternal treatment with this antidepressant may expose the fetus and neonate to increased levels of serotonin (5-HT). Long-term behavioral abnormalities have been reported in rodents exposed to higher levels of 5-HT during neurodevelopment. In this study we evaluated if maternal exposure to FLX during pregnancy and lactation would result in behavioral and/or stress response disruption in adolescent and adult rats. Our results indicate that exposure to FLX influenced restraint stress-induced Fos expression in the amygdala in a gender and age-specific manner. In male animals, a decreased expression was observed in the basolateral amygdala at adolescence and adulthood; whereas at adulthood, a decrease was also observed in the medial amygdala. A lack of FLX exposure effect was observed in females and also in the paraventricular nucleus of both genders. Regarding the behavioral evaluation, FLX exposure did not induce anhedonia in the sucrose preference test but decreased the latency to feed of both male and female adolescent rats evaluated in the novelty-suppressed feeding test. In conclusion, FLX exposure during pregnancy and lactation decreases acute amygdalar stress response to a psychological stressor in males (adolescents and adults) as well as influences the behavior of adolescents (males and females) in a model that evaluates anxiety and/or depressive-like behavior. Even though FLX seems to be a developmental neurotoxicant, the translation of these findings to human safe assessment remains to be determined since it is recognized that not treating a pregnant or lactating woman may also impact negatively the development of the descendants.

Adaptive immunity is related to coronary artery disease severity after acute coronary syndrome in subjects with metabolic syndrome

Metabolic syndrome (MetS) is an inflammatory state associated with high coronary disease risk. Inflammation and adaptive immunity modulate atherosclerosis and plaque instability. We examined early changes in anti-oxidized lowdensity lipoprotein (LDL) (anti-oxLDL) autoantibodies (Abs) in patients with MetS after an acute coronary syndrome (ACS). Patients of both genders (n=116) with MetS were prospectively included after an acute yocardial infarction (MI) or hospitalization due to unstable angina. Anti-oxLDL Abs (IgG class) were assayed at baseline, three and six weeks after ACS. The severity of coronary disease was evaluated by the Gensini score. We observed a decrease in anti-oxLDL Abs titers (p<0.002 vs. baseline), mainly in males (p=0.01), in those under 65 y (p=0.03), and in subjects with Gensini score above median (p=0.04). In conclusion, early decrease in circulating anti-oxLDL Abs is associated with coronary disease severity among subjects with MetS.

Periodontitis: a future risk of acute coronary syndrome? A follow-up study over 3 years

BACKGROUND: Periodontitis has been associated with cardiovascular disease. We assess if the recurrence of acute coronary syndrome (ACS) could be predicted by preceding medical and periodontal conditions. METHODS: A total of 165 consecutive subjects with ACS and 159 medically healthy, matched control subjects were examined and followed for 3 years. Periodontitis was defined by alveolar bone loss. Subgingival microbial samples were studied by the checkerboard DNA-DNA hybridization method. RESULTS: The recurrence of ACS was found in 66 of 165 (40.0%) subjects, and a first ACS event was found in seven of 159 (4.4%) subjects among baseline control subjects. Subjects who later had a second ACS event were older (P <0.001). Significantly higher serum levels of high-density lipoprotein (P <0.05), creatinine (P <0.01), and white blood cell (WBC) counts (P <0.001) were found in subjects with future ACS. Periodontitis was associated with a first event of ACS (crude odds ratio [OR]: 10.3:1; 95% confidence interval [CI]: 6.1 to 17.4; P <0.001) and the recurrence of ACS (crude OR: 3.6:1; 95% CI: 2.0 to 6.6; P <0.001). General linear modeling multivariate analysis, controlling for age and the prediction of a future ACS event, identified that WBC counts (F = 20.6; P <0.001), periodontitis (F = 17.6; P <0.001), and serum creatinine counts (F = 4.5; P <0.05) were explanatory of a future ACS event. CONCLUSIONS: The results of this study indicate that recurrent ACS events are predicted by serum WBC counts, serum creatinine levels, and a diagnosis of periodontitis. Significantly higher counts of putative pathogens are found in subjects with ACS, but these counts do not predict future ACS events.

Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial

OBJECTIVE: Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid (ASA) is superior to ASA alone in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. We sought to determine whether clopidogrel plus ASA conferred benefit on limb outcomes over ASA alone in patients undergoing below-knee bypass grafting. METHODS: Patients undergoing unilateral, below-knee bypass graft for atherosclerotic peripheral arterial disease (PAD) were enrolled 2 to 4 days after surgery and were randomly assigned to clopidogrel 75 mg/day plus ASA 75 to 100 mg/day or placebo plus ASA 75 to 100 mg/day for 6 to 24 months. The primary efficacy endpoint was a composite of index-graft occlusion or revascularization, above-ankle amputation of the affected limb, or death. The primary safety endpoint was severe bleeding (Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries [GUSTO] classification). RESULTS: In the overall population, the primary endpoint occurred in 149 of 425 patients in the clopidogrel group vs 151 of 426 patients in the placebo (plus ASA) group (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.78-1.23). In a prespecified subgroup analysis, the primary endpoint was significantly reduced by clopidogrel in prosthetic graft patients (HR, 0.65; 95% CI, 0.45-0.95; P = .025) but not in venous graft patients (HR, 1.25; 95% CI, 0.94-1.67, not significant [NS]). A significant statistical interaction between treatment effect and graft type was observed (P(interaction) = .008). Although total bleeds were more frequent with clopidogrel, there was no significant difference between the rates of severe bleeding in the clopidogrel and placebo (plus ASA) groups (2.1% vs 1.2%). CONCLUSION: The combination of clopidogrel plus ASA did not improve limb or systemic outcomes in the overall population of PAD patients requiring below-knee bypass grafting. Subgroup analysis suggests that clopidogrel plus ASA confers benefit in patients receiving prosthetic grafts without significantly increasing major bleeding risk.

Sudden cardiac arrest during acute coronary occlusion - who is at risk?

Many people with acute myocardial infarction die from sudden cardiac arrest before reaching the hospital. The current clinical understanding of the mechanisms and risk factors surrounding sudden cardiac death is limited. However, 2 factors related to sudden death, namely the occluded coronary vessel (right coronary, left circumflex, or left anterior descending artery) and the extent of collateral circulation, are of potential relevance. Recent data suggest that the risk differs between the different coronary arteries and that coronary collateral circulation seems to have an important protective 'antiarrhythmic' effect. This editorial will address possible mechanisms and potential implications in clinical practice.

Impact of Retrievable Stents on Acute Ischemic Stroke Treatment

Retrievable stents combine the high recanalization rate of stents and the capability of removing the thrombus offered by mechanical thrombectomy devices. We hypothesized that retrievable stents shorten time to recanalization in the multimodal approach for endovascular stroke treatment.

Ascending thoracic aorta dimension and outcomes in acute type B dissection (from the International Registry of Acute Aortic Dissection [IRAD])

It is not well known if the size of the ascending thoracic aorta at presentation predicts features of presentation, management, and outcomes in patients with acute type B aortic dissection. The International Registry of Acute Aortic Dissection (IRAD) database was queried for all patients with acute type B dissection who had documentation of ascending thoracic aortic size at time of presentation. Patients were categorized according to ascending thoracic aortic diameters ≤4.0, 4.1 to 4.5, and ≥4.6 cm. Four hundred eighteen patients met inclusion criteria; 291 patients (69.6%) were men with a mean age of 63.2 ± 13.5 years. Ascending thoracic aortic diameter ≤4.0 cm was noted in 250 patients (59.8%), 4.1 to 4.5 cm in 105 patients (25.1%), and ≥4.6 cm in 63 patients (15.1%). Patients with an ascending thoracic aortic diameter ≥4.6 cm were more likely to be men (p = 0.01) and have Marfan syndrome (p <0.001) and known bicuspid aortic valve disease (p = 0.003). In patients with an ascending thoracic aorta ≥4.1 cm, there was an increased incidence of surgical intervention (p = 0.013). In those with an ascending thoracic aorta ≥4.6 cm, the root, ascending aorta, arch, and aortic valve were more often involved in surgical repair. Patients with an ascending thoracic aorta ≤4.0 were more likely to have endovascular therapy than those with larger ascending thoracic aortas (p = 0.009). There was no difference in overall mortality or cause of death. In conclusion, ascending thoracic aortic enlargement in patients with acute type B aortic dissection is common. Although its presence does not appear to predict an increased risk of mortality, it is associated with more frequent open surgical intervention that often involves replacement of the proximal aorta. Those with smaller proximal aortas are more likely to receive endovascular therapy.

Distress related to myocardial infarction and cardiovascular outcome: a retrospective observational study

Background During acute coronary syndromes patients perceive intense distress. We hypothesized that retrospective ratings of patients' MI-related fear of dying, helplessness, or pain, all assessed within the first year post-MI, are associated with poor cardiovascular outcome. Methods We studied 304 patients (61 ± 11 years, 85% men) who after a median of 52 days (range 12-365 days) after index MI retrospectively rated the level of distress in the form of fear of dying, helplessness, or pain they had perceived at the time of MI on a numeric scale ranging from 0 ("no distress") to 10 ("extreme distress"). Non-fatal hospital readmissions due to cardiovascular disease (CVD) related events (i.e., recurrent MI, elective and non-elective stent implantation, bypass surgery, pacemaker implantation, cerebrovascular incidents) were assessed at follow-up. The relative CVD event risk was computed for a (clinically meaningful) 2-point increase of distress using Cox proportional hazard models. Results During a median follow-up of 32 months (range 16-45), 45 patients (14.8%) experienced a CVD-related event requiring hospital readmission. Greater fear of dying (HR 1.21, 95% CI 1.03-1.43), helplessness (HR 1.22, 95% CI 1.04-1.44), or pain (HR 1.27, 95% CI 1.02-1.58) were significantly associated with an increased CVD risk without adjustment for covariates. A similarly increased relative risk emerged in patients with an unscheduled CVD-related hospital readmission, i.e., when excluding patients with elective stenting (fear of dying: HR 1.26, 95% CI 1.05-1.51; helplessness: 1.26, 95% CI 1.05-1.52; pain: HR 1.30, 95% CI 1.01-1.66). In the fully-adjusted models controlling for age, the number of diseased coronary vessels, hypertension, and smoking, HRs were 1.24 (95% CI 1.04-1.46) for fear of dying, 1.26 (95% CI 1.06-1.50) for helplessness, and 1.26 (95% CI 1.01-1.57) for pain. Conclusions Retrospectively perceived MI-related distress in the form of fear of dying, helplessness, or pain was associated with non-fatal cardiovascular outcome independent of other important prognostic factors.

Multicentre evaluation of a new point-of-care test for the determination of NT-proBNP in whole blood

BACKGROUND: The Roche CARDIAC proBNP point-of-care (POC) test is the first test intended for the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in whole blood as an aid in the diagnosis of suspected congestive heart failure, in the monitoring of patients with compensated left-ventricular dysfunction and in the risk stratification of patients with acute coronary syndromes. METHODS: A multicentre evaluation was carried out to assess the analytical performance of the POC NT-proBNP test at seven different sites. RESULTS: The majority of all coefficients of variation (CVs) obtained for within-series imprecision using native blood samples was below 10% for both 52 samples measured ten times and for 674 samples measured in duplicate. Using quality control material, the majority of CV values for day-to-day imprecision were below 14% for the low control level and below 13% for the high control level. In method comparisons for four lots of the POC NT-proBNP test with the laboratory reference method (Elecsys proBNP), the slope ranged from 0.93 to 1.10 and the intercept ranged from 1.8 to 6.9. The bias found between venous and arterial blood with the POC NT-proBNP method was < or =5%. All four lots of the POC NT-proBNP test investigated showed excellent agreement, with mean differences of between -5% and +4%. No significant interference was observed with lipaemic blood (triglyceride concentrations up to 6.3 mmol/L), icteric blood (bilirubin concentrations up to 582 micromol/L), haemolytic blood (haemoglobin concentrations up to 62 mg/L), biotin (up to 10 mg/L), rheumatoid factor (up to 42 IU/mL), or with 50 out of 52 standard or cardiological drugs in therapeutic concentrations. With bisoprolol and BNP, somewhat higher bias in the low NT-proBNP concentration range (<175 ng/L) was found. Haematocrit values between 28% and 58% had no influence on the test result. Interference may be caused by human anti-mouse antibodies (HAMA) types 1 and 2. No significant influence on the results with POC NT-proBNP was found using volumes of 140-165 muL. High NT-proBNP concentrations above the measuring range of the POC NT-proBNP test did not lead to false low results due to a potential high-dose hook effect. CONCLUSIONS: The POC NT-proBNP test showed good analytical performance and excellent agreement with the laboratory method. The POC NT-proBNP assay is therefore suitable in the POC setting.

Bacterial profile and burden of periodontal infection in subjects with a diagnosis of acute coronary syndrome

BACKGROUND: Periodontitis has been identified as a potential risk factor in cardiovascular diseases. It is possible that the stimulation of host responses to oral infections may result in vascular damage and the inducement of blood clotting. The aim of this study was to assess the role of periodontal infection and bacterial burden as an explanatory variable to the activation of the inflammatory process leading to acute coronary syndrome (ACS). METHODS: A total of 161 consecutive surviving cases admitted with a diagnosis of ACS and 161 control subjects, matched with cases according to their gender, socioeconomic level, and smoking status, were studied. Serum white blood cell (WBC) counts, high- and low-density lipoprotein (HDL/LDL) levels, high-sensitivity C-reactive protein (hsC-rp) levels, and clinical periodontal routine parameters were studied. The subgingival pathogens were assayed by the checkerboard DNA-DNA hybridization method. RESULTS: Total oral bacterial load was higher in the subjects with ACS (mean difference: 17.4x10(5); SD: 10.8; 95% confidence interval [CI]: 4.2 to 17.4; P<0.001), and significant for 26 of 40 species including Porphyromonas gingivalis, Tannerella forsythensis, and Treponema denticola. Serum WBC counts, hsC-rp levels, Streptococcus intermedius, and Streptococcus sanguis, were explanatory factors to acute coronary syndrome status (Nagelkerke r2=0.49). CONCLUSION: The oral bacterial load of S. intermedius, S. sanguis, Streptococcus anginosus, T. forsythensis, T. denticola, and P. gingivalis may be concomitant risk factors in the development of ACS.