Chronic Trypanosoma cruzi-elicited cardiomyopathy: from the discovery to the proposal of rational therapeutic interventions targeting cell adhesion molecules and chemokine receptors - how to make a dream come true

One hundred years ago, Carlos Chagas discovered a new disease, the American trypanosomiasis. Chagas and co-workers later characterised the disease's common manifestation, chronic cardiomyopathy, and suggested that parasitic persistence coupled with inflammation was the key underlying pathogenic mechanism. Better comprehension of the molecular mechanisms leading to clinical heart afflictions is a prerequisite to developing new therapies that ameliorate inflammation and improve heart function without hampering parasite control. Here, we review recent data showing that distinct cell adhesion molecules, chemokines and chemokine receptors participate in anti-parasite immunity and/or detrimental leukocyte trafficking to the heart. Moreover, we offer evidence that CC-chemokine receptors may be attractive therapeutic targets aiming to regain homeostatic balance in parasite/host interaction thereby improving prognosis, supporting that it is becoming a non-phantasious proposal.

Acute experimental Trypanosoma cruzi infection: establishing a murine model that utilises non-invasive measurements of disease parameters

Trypanosoma cruzi infection has a large public health impact in Latin American countries. Although the transmission rates via blood transfusions and insect vectors have declined sharply in the past 20 years due to policies of the Southern Cone countries, a large number of people are still at risk for infection. Currently, no accepted experimental model or descriptions of the clinical signs that occur during the course of acute murine infection are available. The aim of this work was to use non-invasive methods to evaluate the clinical signs of Balb/c mice infected with the Y strain of T. cruzi. The infected mice displayed evident clinical changes beginning in the third week of infection. The mice were evaluated based on physical characteristics, spontaneous activity, exploratory behaviour and physiological alterations. We hope that the results presented in this report provide parameters that complement the effective monitoring of trypanocidal treatment and other interventions used to treat experimental Chagas disease.

Hyperalgesic effect induced by barbiturates, midazolam and ethanol: pharmacological evidence for GABA-A receptor involvement

The involvement of GABA-A receptors in the control of nociception was studied using the tail-flick test in rats. Non-hypnotic doses of the barbiturates phenobarbital (5-50 mg/kg), pentobarbital (17-33 mg/kg), and thiopental (7.5-30 mg/kg), of the benzodiazepine midazolam (10 mg/kg) or of ethanol (0.4-1.6 g/kg) administered by the systemic route reduced the latency for the tail-flick response, thus inducing a 'hyperalgesic' state in the animals. In contrast, non-convulsant doses of the GABA-A antagonist picrotoxin (0.12-1.0 mg/kg) administered systemically induced an increase in the latency for the tail-flick response, therefore characterizing an 'antinociceptive' state. Previous picrotoxin (0.12 mg/kg) treatment abolished the hyperalgesic state induced by effective doses of the barbiturates, midazolam or ethanol. Since phenobarbital, midazolam and ethanol reproduced the described hyperalgesic effect of GABA-A-specific agonists (muscimol, THIP), which is specifically antagonized by the GABA-A antagonist picrotoxin, our results suggest that GABA-A receptors are tonically involved in the modulation of nociception in the rat central nervous system

Role of non-nitric oxide non-prostaglandin endothelium-derived relaxing factor(s) in bradykinin vasodilation

The most conspicuous effect of bradykinin following its administration into the systemic circulation is a transient hypotension due to vasodilation. In the present study most of the available evidence regarding the mechanisms involved in bradykinin-induced arterial vasodilation is reviewed. It has become firmly established that in most species vasodilation in response to bradykinin is mediated by the release of endothelial relaxing factors following the activation of B2-receptors. Although in some cases the action of bradykinin is entirely mediated by the endothelial release of nitric oxide (NO) and/or prostacyclin (PGI2), a large amount of evidence has been accumulated during the last 10 years indicating that a non-NO/PGI2 factor accounts for bradykinin-induced vasodilation in a wide variety of perfused vascular beds and isolated small arteries from several species including humans. Since the effect of the non-NO/PGI2 endothelium-derived relaxing factor is practically abolished by disrupting the K+ electrochemical gradient together with the fact that bradykinin causes endothelium-dependent hyperpolarization of vascular smooth muscle cells, the action of such factor has been attributed to the opening of K+ channels in these cells. The pharmacological characteristics of these channels are not uniform among the different blood vessels in which they have been examined. Although there is some evidence indicating a role for KCa or KV channels, our findings in the mesenteric bed together with other reports indicate that the K+ channels involved do not correspond exactly to any of those already described. In addition, the chemical identity of such hyperpolarizing factor is still a matter of controversy. The postulated main contenders are epoxyeicosatrienoic acids or endocannabinoid agonists for the CB1-receptors. Based on the available reports and on data from our laboratory in the rat mesenteric bed, we conclude that the NO/PGI2-independent endothelium-dependent vasodilation induced by BK is unlikely to involve a cytochrome P450 arachidonic acid metabolite or an endocannabinoid agonist.

Morphologic and biochemical changes in male rat lung after surgical and pharmacological castration

The morphology of the rat lung was studied by light microscopy in different situations: after surgical and pharmacological castration and after administration of testosterone to the castrated rat to determine if the androgen is required to maintain the normal morphology of the lung. We also determined the effect of flutamide on the phospholipid composition of both the surfactant and microsomes of the lung. Rats were separated into five groups: I - control non-castrated rats, II - castrated rats sacrificed 21 days after castration, III - castrated rats that received testosterone daily from day 2 to day 21 after castration, IV - castrated rats that received testosterone from day 15 to day 21 after castration, and V - control rats injected with flutamide for 7 days. The amount of different phospholipids in the surfactant and microsomes of the lung was measured in group I and V rats. At the light microscopy level, the surgical and pharmacological castration provoked alterations in the morphology of the lung, similar to that observed in human lung emphysema. The compositions of surfactant and microsomes of the lung were similar to those previously reported by us for the surgically castrated rats. These results indicate that androgens are necessary for the normal morphology as well as for some metabolic aspects of the lung.

Interests and Values in Obama's foreign Policy: Leading from Behind?

Abstract This study will exam the relative importance of values and interests in Obama's foreign policy, focusing on crucial cases: the military actions related to Afghanistan, Iraq, Libya, Non-Syria, Al-Qaeda and ISIL. We will argue that his "leading from behind" strategy is not very distant from the foreign and defense strategies of his post-Cold War predecessors, by which democracy is seen as an assurance to security. According to Obama's strategy, Americans will only provide support for the building of democracy in the target countries, while this task should be performed by the locals themselves. Americans will provide military training to the new governments as well so they can be responsible for their own security, including preventing regrouping of terrorists in their soil. If Obama opposes the imposing of democracy by the use of force, empirical data shows that his administration is "not prepared to accept" any option that threats US security or American liberal-democratic values, bringing in this way values and interests very close to each other.

Feeding non-preference by Spodoptera frugiperda and Spodoptera eridania on tomato genotypes

Larvae of the genus Spodoptera spp. are highly polyphagous and can cause economical losses in several agricultural crops. Given their growing importance in the tomato crop, especially for industry, this work aimed to evaluate the feeding non-preference by larvae of Spodoptera frugiperda (J. E. Smith, 1797) and Spodoptera eridania (Cramer, 1782) on tomato genotypes and classify them by the levels of resistance. The commercial cultivar Santa Clara was set as the susceptible standard and line PI 134417 as the resistant standard to evaluate the lines PI 134418, PI 126931, LA 462 and LA 716. Feeding non-preference tests were performed under non-choice and free-choice conditions to evaluate the genotype attractiveness to larvae at predetermined times after their release, as well as the leaf area consumed. Overall, the genotypes LA 716 and PI 126931 were the least attractive to S. frugiperda, whereas Santa Clara was the most attractive and consumed. For S. eridania, the genotypes PI 126931, LA 462, LA 716 and PI 134418 were the least preferred for feeding, and Santa Clara and PI 134417 were the most attractive and consumed. The genotypes LA 716 and PI 126931 are moderately resistant to S. frugiperda and S. eridania; PI 134418 and LA 462 are moderately resistant to S. eridania; PI 134417 is susceptible to S. frugiperda and S. eridania; and Santa Clara is highly susceptible to both S. frugiperda and S. eridania.

Mortality among patients with non-affective functional psychoses in a metropolitan area of South-Eastern Brazil

High mortality rates among those suffering from schizophrenia and related psychoses have been consistently described in developed societies. However, to date there is a lack of data on this matter in Brazil. In order to examine this issue, a prospective 2-year follow-up study was carried out in S. Paulo. The sample consisted of 120 consecutive admissions to psychiatric hospitals in a defined catchment area, aged 18 to 44 years old, with clinical diagnoses of non-affective functional psychoses according to the ICD-9. After 2 years, 116 (96.7%) subjects were traced. During the study period there were 7 deaths (6.0% of those traced), 5 (4.3%) due to suicide. All but one of the suicides occurred in the first year after discharge from hospital. Age and sex Standardised Mortality Ratios (relative to rates for the population of the city of Sao Paulo) were 8.4 for overall mortality (95% confidence interval: 4.0-15.9) and 317.9 for deaths due to suicide (95% confidence interval: 125.2-668.3). These results are in agreement with previous studies, and show that in Brazil non-affective functional psychoses are life-threatening illnesses, which need adequate care, particularly when patients go back to live in the community after hospital discharge.

Predicting the revolving door phenomenon among patients with schizophrenic, affective disorders and non-organic psychoses

OBJECTIVE: The aim of the study was to identify the variables that predict the revolving door phenomenon in psychiatric hospital at the moment of a second admission. METHODS: The sample consisted of 3,093 patients who have been followed during 5 to 24 years after their first hospital admission due to schizophrenia, and affective or psychotic disorders. Those who had had four or more admissions during the study period were considered as revolving door patients. Logistic regression analyses were used to assess the impact of gender, age, marital status, urban conditions, diagnosis, mean period of stay on the first admission, interval between the first and second admissions on the patterns of hospitalization. RESULTS: The variables with the highest predictive power for readmission were the interval between first and second admissions, and the length of stay in the first admission. CONCLUSIONS: These data may help public health planners in providing optimal care to a small group of patients with more effective utilization of the available services.

Quality of life, life satisfaction and happiness in shift- and non-shiftworkers

OBJECTIVE: To investigate the quality of life, life satisfaction, happiness and demands of work in workers with different work schedules. METHODS: The survey was carried out on professional workers in social care. Some were shiftworkers whose schedule included night shifts (N=311), some were shiftworkers without night shifts (N=207) and some were non-shiftworkers (N=1,210). Surveys were mailed and the response rate was 86%. For the purpose of this study several variables were selected from the Survey: The Quality of Life Profile, which measures importance, satisfaction, control and opportunities in nine domains of life plus measures of happiness, life satisfaction and demands of work. RESULTS: While both groups of shiftworkers, compared to non-shiftworkers, reported needing more physical effort to complete their work, and reported 'being' more physically tired, no differences were found in reports of overall happiness, life satisfaction or total quality of life. However, night-shiftworkers reported greater percentage of time unhappy than the other two groups of workers. In analyses of the quality of life, night-shiftworkers were less satisfied with domains of spiritual 'being' and physical and community 'belonging' than day-shiftworkers and non-shiftworkers. They also reported having fewer opportunities to improve their physical 'being', leisure, and personal growth than the other two groups. CONCLUSIONS: Quality of life in specific domains in night-shiftworkers was rated worse than in other groups of workers. Domain-based quality of life assessment gives more information regarding the particular needs of workers than overall or global measures of well-being.

Lead, hemoglobin, zinc protoporphyrin and ferritin concentrations in children

OBJECTIVE: To assess the relationship of blood lead and hemoglobin, zinc protoporphyrin, and ferritin concentrations in children. METHODS: A cross-sectional study was carried out in 136 anemic and non-anemic children from two rural villages near a lead smelter in Adrianópolis, Southern Brazil, from July to September 2001. Hemoglobin electrophoresis was performed to exclude children with hemoglobin variants and thalassemia syndromes associated with anemia. Lead was determined by atomic absorption spectrophotometry; hemoglobin by automated cell counting; zinc protoporphyrin by hematofluorometry; ferritin by chemiluminescence. Student's t-test, Mann-Whitney test, and the c² test were used to assess the significance of the differences between the variables investigated in anemic and non-anemic children. Stepwise multivariate linear regression analysis was performed using two models for anemic and non-anemic children respectively. RESULTS: Lead was negatively associated to hemoglobin (p<0.017) in the first model, and in the second model lead was positively associated to zinc protoporphyrin (p<0.004) after controlling for ferritin, age, sex, and per capita income. There was an inverse association between hemoglobin and blood lead in anemic children. It was not possible to confirm if anemic children had iron deficiency anemia or subclinical infection, considering that the majority (90.4%) had normal ferritin. CONCLUSIONS: The study detected a relationship between anemia and elevated blood lead concentrations. Further epidemiological studies are necessary to investigate the impact of iron nutritional interventions as an attempt to decrease blood lead in children.

Economic burden of expected epidemiological changes in diseases related to tobacco, Mexico

OBJECTIVE: To determine health care costs and economic burden of epidemiological changes in diseases related to tobacco consumption. METHODS: A time-series analysis in Mexico (1994-2005) was carried out on seven health interventions: chronic obstructive pulmonary diseases, lung cancer with and without surgical intervention, asthma in smokers and non-smokers, full treatment course with nicotine gum, and full treatment course with nicotine patch. According with Box-Jenkins methodology, probabilistic models were developed to forecast the expected changes in the epidemiologic profile and the expected changes in health care services required for selected interventions. Health care costs were estimated following the instrumentation methods and validated with consensus technique. RESULTS: A comparison of the economic impact in 2006 vs. 2008 showed 20-90% increase in expected cases depending on the disease (p<0.05), and 25-93% increase in financial requirements (p<0.01). The study data suggest that changes in the demand for health services for patients with respiratory diseases related to tobacco consumption will continue showing an increasing trend. CONCLUSIONS: In economic terms, the growing number of cases expected during the study period indicates a process of internal competition and adds an element of intrinsic competition in the management of preventive and curative interventions. The study results support the assumption that if preventive programs remain unchanged, the increasing demands for curative health care may cause great financial and management challenges to the health care system of middle-income countries like Mexico.

HIV testing among pregnant women in Brazil: rates and predictors

OBJECTIVE: To assess rates of offering and uptake of HIV testing and their predictors among women who attended prenatal care. METHODS: A population-based cross-sectional study was conducted among postpartum women (N=2,234) who attended at least one prenatal care visit in 12 cities. Independent and probabilistic samples were selected in the cities studied. Sociodemographic data, information about prenatal care and access to HIV prevention interventions during the current pregnancy were collected. Bivariate and multivariate analyses were carried out to assess independent effects of the covariates on offering and uptake of HIV testing. Data collection took place between November 1999 and April 2000. RESULTS: Overall, 77.5% of the women reported undergoing HIV testing during the current pregnancy. Offering of HIV testing was positively associated with: previous knowledge about prevention of mother-to-child transmission of HIV; higher number of prenatal care visits; higher level of education and being white. HIV testing acceptance rate was 92.5%. CONCLUSIONS: The study results indicate that dissemination of information about prevention of mother-to-child transmission among women may contribute to increasing HIV testing coverage during pregnancy. Non-white women with lower level of education should be prioritized. Strategies to increase attendance of vulnerable women to prenatal care and to raise awareness among health care workers are of utmost importance.