Effects of cyclooxygenase inhibitors on parasite burden, anemia and oxidative stress in murine Trypanosoma cruzi infection

Prostaglandins are known to be produced by macrophages when challenged with Trypanosoma cruzi, the etiological agent of Chagas` disease. It is not known whether these lipid mediators play a role in oxidative stress in host defenses against this important protozoan parasite. In this study, we demonstrated that inducible cyclooxygenase-mediated prostaglandin production is a key chemical mediator in the control of parasite burden and erythrocyte oxidative stress during T. cruzi infection in C57BL/6 and BALB/c mice, prototype hosts for the study of resistance and susceptibility in murine Chagas` disease. The results suggested the existence of at least two mechanisms of oxidative stress, dependent or independent with regard to the nitric oxide and cyclooxygenase pathway, where one or the other is more evident depending on the mouse strain.

5-Lipoxygenase plays a role in the control of parasite burden and contributes to oxidative damage of erythrocytes in murine Chagas` disease

Chagas` disease is accompanied by severe anemia and oxidative stress, which may contribute to mortality. In this study, we investigated the role of 5-lipoxygenase (5-LO) in the control of parasitism and anemia associated with oxidative damage of erythrocytes in experimental Trypanosoma cruzi infection. Wild-type C57BL/6, 129Sv mice treated or not with nordihydroguaiaretic acid (NDGA, 5-LO inhibitor), mice lacking the 5-LO enzyme gene (5-LO(-/-)) and inducible nitric oxide synthase gene (iNOS(-/-)) were infected with the Y strain of T cruzi. impairment of 5-LO resulted in increased numbers of trypomastigote forms in the blood and amastigote forms in the heart of infected mice. We assessed oxidative stress in erythrocytes by measuring oxygen uptake, induction time and chemiluminescence following treatment with tert-butyl hydroperoxide (TBH). Our results show that 5-LO metabolites increased lipid peroxidation levels in erythrocytes during the early phase of murine T cruzi infection. NDGA treatment reduced oxidative damage of erythrocytes in C57BL/6 T cruzi-infected mice but not in C57BL/6 iNOS-/- infected mice, showing that the action of NDGA is dependent on endogenous nitric oxide (NO). In addition, our results show that 5-LO metabolites do not participate directly in the development of anemia in infected mice. We conclude that 5-LO products may not only play a major role in controlling heart tissue parasitism, i.e., host resistance to acute infection with T cruzi in vivo, but in the event of an infection also play an important part in erythrocyte oxidative stress, an NO-dependent effect. (C) 2009 Elsevier B.V. All rights reserved.

Evaluation of Fungal Burden and Aflatoxin Presence in Packed Medicinal Plants Treated by Gamma Radiation

This study was developed to evaluate the fungal burden, toxigenic molds, and mycotoxin contamination and to verify the effects of gamma radiation in four kinds of medicinal plants stored before and after 30 days of irradiation treatment. Eighty samples of medicinal plants (Peumus boldus, Camellia sinensis, Maytenus ilicifolia. and Cassia angustifolia) purchased from drugstores, wholesale, and open-air markets in Sao Paulo city, Brazil, were analyzed. The samples were treated using a (60)Co gamma ray source (Gammacell) with doses of 5 and 10 kGy. Nonirradiated samples were used as controls of fungal isolates. For enumeration of fungi on medicinal plants, serial dilutions of the samples were plated in duplicate onto dichloran 18% glycerol agar. The control samples revealed a high burden of molds, including toxigenic fungi. The process of gamma radiation was effective in reducing the number of CFU per gram in all irradiated samples of medicinal plants after 30 days of storage, using a dose of 10 kGy and maintaining samples in a protective package. No aflatoxins were detected. Gamma radiation treatment can be used as an effective method for preventing fungal deterioration of medicinal plants subject to long-term storage.

Study of environmental burden of lead in children using teeth as bioindicator

The south region of Sao Paulo city hosts the Guarapiranga dam, responsible for water supply to 25% of the city population. Their surroundings have been subject to intense and irregular occupation by people from very low socioeconomics classes. Measurements undertaken on sediment and particulate materials in the dam revealed concentrations of lead. copper, zinc and cadmium above internationally accepted limits. Epidemiological and toxicological studies undertaken by the World Health Organization in individuals exhibiting lead concentrations in blood, near or below the maximum recommended (10 mu g dl(-1)), surprisingly revealed that toxic effects are more intense in individuals belonging to low socioeconomics classes. Motivated by these facts, we aimed at the investigation of chronic incorporation of lead. as well as the use of our BIOKINETICS code, which is based on an accepted ICRP biokinetics model for lead, in order to extrapolate the results from teeth to other organs. The focus of our data taking was children from poor families, living in a small, restrict and allegedly contaminated area in Sao Paulo city. Thus, a total of 74 human teeth were collected. The average concentration of lead in teeth of children 5 to 10 years old was determined by means of a high-resolution inductively coupled plasma mass spectrometer (ICP-MS). For standardization of the measurements, an animal bone certified material (H-Animal Bone), from the International Atomic Energy Agency, was analyzed. The amount of lead in children living in the surroundings of the dam, was approximately 40% higher than those from the control region, and the average lead concentration was equal to 1.3 mu g g(-1) approximately. Grouping the results in terms of gender, tooth type and condition, it was concluded that a carious molar of boys is a much more efficient contamination pathway for lead, resulting in concentrations 70% higher than in the control region. We also inferred the average concentrations of lead in other organs of these children, by making use of our BIOKINETIC code. (C) 2008 Elsevier Ltd. All rights reserved.

Microbiopsies of Surface Dental Enamel as a Tool to Measure Body Lead Burden

Lead (Pb) poisoning is preventable but continues to be a public health problem in several countries. Measuring Pb in the surface dental enamel (SDE) using microbiopsies is a rapid, safe, and painless procedure. There are different protocols to perform these microbiopsies, but the reliability of dental enamel lead levels (DELL) determination is dependent upon biopsy depth (BD). It is established that DELL decrease from the outermost superficial layer to the inner layer of dental enamel. The aim of this study was to determine DELL obtained by two different microbiopsy techniques on SDE termed protocol I and protocol II. Two consecutive enamel layers were removed from the same subject group (n = 138) for both protocols. Protocol I consisted of a biopsied site with a diameter of 4 mm after the application of 10 l HCl for 35 s. Protocol II involved a biopsied site of 1.6 mm diameter after application of 5 l HCl for 20 s. The results demonstrated that there were no significant differences for BD and DELL between homologous teeth using protocol I. However, there was a significant difference between DELL in the first and second layers using both protocols. Further, the BD in protocol II overestimated DELL values. In conclusion, SDE analyzed by microbiopsy is a reliable biomarker in protocol I, but the chemical method to calculate BD in protocol II appeared to be inadequate for measurement of DELL. Thus, DELL could not be compared among studies that used different methodologies for SDE microbiopsies.

Essays on growth and environment

This thesis consists of a summary and four self-contained papers. Paper [I] Following the 1987 report by The World Commission on Environment and Development, the genuine saving has come to play a key role in the context of sustainable development, and the World Bank regularly publishes numbers for genuine saving on a national basis. However, these numbers are typically calculated as if the tax system is non-distortionary. This paper presents an analogue to genuine saving in a second best economy, where the government raises revenue by means of distortionary taxation. We show how the social cost of public debt, which depends on the marginal excess burden, ought to be reflected in the genuine saving. We also illustrate by presenting calculations for Greece, Japan, Portugal, U.K., U.S. and OECD average, showing that the numbers published by the World Bank are likely to be biased and may even give incorrect information as to whether the economy is locally sustainable. Paper [II] This paper examines the relationships among per capita CO2 emissions, per capita GDP and international trade based on panel data spanning the period 1960-2008 for 150 countries. A distinction is also made between OECD and Non-OECD countries to capture the differences of this relationship between developed and developing economies. We apply panel unit root and cointegration tests, and estimate a panel error correction model. The results from the error correction model suggest that there are long-term relationships between the variables for the whole sample and for Non-OECD countries. Finally, Granger causality tests show that there is bi-directional short-term causality between per capita GDP and international trade for the whole sample and between per capita GDP and CO2 emissions for OECD countries. Paper [III] Fundamental questions in economics are why some regions are richer than others, why their growth rates differ, whether their growth rates tend to converge, and what key factors contribute to explain economic growth. This paper deals with the average income growth, net migration, and changes in unemployment rates at the municipal level in Sweden. The aim is to explore in depth the effects of possible underlying determinants with a particular focus on local policy variables. The analysis is based on a three-equation model. Our results show, among other things, that increases in the local public expenditure and income taxe rate have negative effects on subsequent income income growth. In addition, the results show conditional convergence, i.e. that the average income among the municipal residents tends to grow more rapidly in relatively poor local jurisdictions than in initially “richer” jurisdictions, conditional on the other explanatory variables. Paper [IV] This paper explores the relationship between income growth and income inequality using data at the municipal level in Sweden for the period 1992-2007. We estimate a fixed effects panel data growth model, where the within-municipality income inequality is one of the explanatory variables. Different inequality measures (Gini coefficient, top income shares, and measures of inequality in the lower and upper part of the income distribution) are examined. We find a positive and significant relationship between income growth and income inequality measured as the Gini coefficient and top income shares, respectively. In addition, while inequality in the upper part of the income distribution is positively associated with the income growth rate, inequality in the lower part of the income distribution seems to be negatively related to the income growth. Our findings also suggest that increased income inequality enhances growth more in municipalities with a high level of average income than in municipalities with a low level of average income.

Life situations and the care burden for stroke pa­tients and their informal caregivers in a prospective cohort study

Background. The purpose of this study was to analyse whether the parallel life situation between stroke patients and their informal caregivers (dyads) shown in cross-sectional studies prevails also in a longitudinal perspective. Methods. A total of 377 Swedish stroke patients, aged ‡65 years, and their 268 informal caregivers were followed from hospital admission and one year on. Analyses were based on patient interviews, functional ability (MMSE) score, Nottingham Health Profile (NHP) score, Hospital Anxiety and Depression (HAD) score, self-rated health score, and the Gothenburg Quality of Life (GQL) activity score. Similar information was obtained by postal questionnaires from informal caregivers, also including information on the nature and amount of assistance provided and on Caregiver Burden (CB) score. Results. Before index admission informal caregivers provided care on average 5 h per week and after discharge 11 h per week (P < 0.0001). Support volume was associated with patient sex (more for men), low patient’s functional ability, low received municipal social service support, closeness of patient–caregiver relation, and short distance to patient’s home. Significant positive associations within the dyads were found for HAD anxiety score (P < 0.0001), total NHP score (P < 0.0001), and GQL activity score (P < 0.0001) after adjustment for patient’s age, sex, functional ability, and patient–caregiver relationship. CB score increased with amount of informal caregiver support, patient’s age, and with low functional ability and low amount of municipal social service support. All these associations were constant across time. Conclusions. There was an association within the dyads regarding anxiety score, NHP score, and activity score. CB score was generally high.

February 2009: Tax Time

http://digitalcommons.winthrop.edu/dacusdocsnews/1035/thumbnail.jpg

Education, preferences for leisure, and the optimal income tax schedule

Recent advances in dynamic Mirrlees economies have incorporated the treatment of human capital investments as an important dimension of government policy. This paper adds to this literature by considering a two period economy where agents are di erentiated by their preferences for leisure and their productivity, both private information. The fact that productivity is only learnt later in an agent's life introduces uncertainty to agent's savings and human capital choices and makes optimal the use of multi-period tie-ins in the mechanism that characterizes the government policy. We show that optimal policies are often interim ine cient and that the introduction of these ine ciencies may take the form of marginal tax rates on labor income of varying sign and educational policies that include the discouragement of human capital acquisition. With regards to implementation, state-dependent linear taxes implement optimal savings, while human capital policies may require labor income taxes that depend directly on agents' schooling.

Yet another reason to tax goods

The optimal taxation of goods, labor and capital income is considered in a two period model where: i) private information changes through time; ii) savings are not observed, and; iii) savings a§ect preferences conditional on the realization of types. The simultaneous appearance of these three elements cause optimal commodity taxes to depend on o§-equilibrium savings. As a consequence, separability no longer su¢ ces for the uniform taxation prescription of Atkinson and Stiglitz (AS) to obtain. If preferences are homothetic AS is partially restored: taxes are uniform within periods, however, future consumption is taxed at a higher rate than current consumption.

The effects of tax incentives for small firms on employment levels

This paper will examine the effects of tax incentives for small businesses on employment level evaluating a program with this purpose implemented in Brazil in the 1990s. We first develop a theoretical framework which guides both the de nition of the parameters of interest and their identi cation. Selection problems both into the treatment group and into the data sample are tackled by combining fixed effects methods and regression discontinuity design on alternative sub-samples of a longitudinal database of manufacturing firms. The results show that on the one hand the size composition of the treated fi rms may be changed due to the survival of some smaller firms that would have exited had it not been eligible to the program. On the other hand, the treated firms who do not depend on the program to survive do employ more workers.

Sacrifice and efficiency of the income tax schedule

We investigate the efficiency of equal sacrifice tax schedules in an economy which primitives are exactly those in Mirrlees (1971): a continuum of individuals with identical preferences defined over consumption and leisure who differ with respect to their labor market productivity. Using a separable specification for preferences we derive the minimum equal sacrifice allocation and recover the tax schedule that implements it. The separable specification allows us to use the methodology developed by Werning (2007b) to check whether the schedule is efficient, that is, whether there is no alternative tax schedule that raises more revenue while delivering less utility to no one. We find that inefficiency does not arise for most parametrizations we use to approximate the US economy. For the few cases for which inefficiency does arise, it does so only for very high levels of income and marginal tax rates.

Tax filing choices for the household under separable spheres bargaining

If household choices can be rationalized by the maximization of a well defined utility function, allowing spouses to file individually or jointly is equivalent to offering the envelope of the two tax schedules. If, instead, household ’preferences’ are constantly being redefined through bargaining, the option to file separately may affect outcomes even if it is never chosen. We use Lundberg and Pollak’s (1993) separate spheres bargaining model to assess the impact of filing options on the outcomes of primary and secondary earners. Threat points of the household’s bargain are given for each spouse by the utility that he or she attains as a follower of a counter-factual off-equilibrium Stackelberg game played by the couple. For a benchmark tax system which treats a couple’s average taxable income as if it were that of a single individual, we prove that if choices are not at kinks, allowing couples to choose whether to file jointly or individually usually benefits the secondary earner. In our numeric exercises this is also the case when choices are at kinks as well. These findings are, however, quite sensitive to the details of the tax system, as made evident by the examination of an alternative tax system.