Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

The immune response is crucial for protection against disease; however, immunological imbalances can lead to heart and digestive tract lesions in chagasic patients. Several studies have evaluated the cellular and humoral immune responses in chagasic patients in an attempt to correlate immunological findings with clinical forms of Chagas disease. Moreover, immunoglobulins and cytokines are important for parasitic control and are involved in lesion genesis. Here, cytokine and IgG isotype production were studied, using total epimastigote antigen on sera of chagasic patients with indeterminate (IND, n = 27) and cardiac (CARD, n = 16) forms of the disease. Samples from normal, uninfected individuals (NI, n = 30) were use as controls. The results showed that sera from both IND and CARD patients contained higher levels of Trypanosoma cruzi-specific IgG1 (IgG1) antibodies than sera from NI. No difference in IgG2 production levels was observed between NI, IND and CARD patients, nor was a difference in IL-10 and IFN-³ production detected in the sera of IND, CARD and NI patients. However, IND patients displayed a positive correlation between IL-10 and IFN-³ levels in serum, while CARD patients showed no such correlation, indicating an uncontrolled inflammatory response in CARD patients. These findings support the hypothesis that a lack of efficient regulation between IFN-³ and IL-10 productions in CARD patients may lead to cardiac immunopathology.CNP

Characterising the KMP-11 and HSP-70 recombinant antigens' humoral immune response profile in chagasic patients

11 pages, 6 figures.-- The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-2334/9/186/pre pubBackground: Antigen specificity and IgG subclass could be significant in the natural history of Chagas' disease. The relationship between the different stages of human Chagas' disease and the profiles of total IgG and its subclasses were thus analysed here; they were directed against a crude T. cruzi extract and three recombinant antigens: the T. cruzi kinetoplastid membrane protein-11 (rKMP-11), an internal fragment of the T. cruzi HSP-70 protein192-433, and the entire Trypanosoma rangeli HSP-70 protein. Methods: Seventeen Brazilian acute chagasic patients, 50 Colombian chronic chagasic patients (21 indeterminate and 29 cardiopathic patients) and 30 healthy individuals were included. Total IgG and its subtypes directed against the above-mentioned recombinant antigens were determined by ELISA tests. Results: The T. cruzi KMP-11 and T. rangeli HSP-70 recombinant proteins were able to distinguish both acute from chronic chagasic patients and infected people from healthy individuals. Specific antibodies to T. cruzi crude antigen in acute patients came from IgG3 and IgG4 subclasses whereas IgG1 and IgG3 were the prevalent isotypes in indeterminate and chronic chagasic patients. By contrast, the specific prominent antibodies in all disease stages against T. cruzi KMP-11 and T. rangeli HSP-70 recombinant antigens were the IgG1 subclass.This work was supported by Colciencias Research project No. 1203-333- 18692. IDF was supported by Colciencias and the Universidad Javeriana's Young Researcher 2008 Programme (Bogotá, Colombia). MCT and MCL were supported by P06-CTS-02242 Grant from PAI (Junta de Andalucia) and RICET-RD06/0021-0014, Spain. MS received financial support from the Brazilian agency - CNPq.Peer reviewe

NR4A3 rearrangement reliably distinguishes between the clinicopathologically overlapping entities myoepithelial carcinoma of soft tissue and cellular extraskeletal myxoid chondrosarcoma

Myoepithelial carcinoma of soft tissue (MEC) and cellular extraskeletal myxoid chondrosarcoma (cEMC) share striking similarities. In this paper, we compare ten MECs with five cEMCs. MEC patients had an equal gender distribution. The age range was 15–76 years (mean, 42 years). Tumours were located on extremities, pelvic girdle, vulva and neck. Follow-up, available for nine patients, ranged from 4 to 85 months (mean, 35 months). Five patients were alive without evidence of disease, two were alive with disease and two died 8 months after the initial diagnosis. cEMCs were from three males and two females with an age range of 37–82 years (mean, 57 years); they presented in extremities, shoulder and paravertebral/cervical. Follow-up, available for four patients, ranged from 6 to 220 months (mean, 61 months). All patients were alive, two with recurrences and/or metastases and two without evidence of disease. Morphologically, the distinction between these two entities was difficult since all cases exhibited features typically seen in myoepithelial tumours. Immunohistochemically, MECs expressed pan-keratin (80 %), epithelial membrane antigen (EMA; 57 %), S100 (50 %), alpha-smooth muscle actin (ASMA; 75 %), calponin (67 %) and p63 (25 %). S100 and EMA were expressed in 40 % of cEMC cases respectively with additional immunoreactivity for p63, ASMA and glial fibrillary acidic protein in one case. Pan-keratin was negative in all neoplasms. NR4A3 rearrangement was present in four of four cEMCs and in none of the MECs. In contrast, three of nine (33 %) MECs and four of five (80 %) cEMCs showed an EWSR1 rearrangement. In summary, MECs and cEMCs share clinical, morphological, immunohistochemical and genetic characteristics. The pathognomic rearrangement of NR4A3 is a useful diagnostic feature in identifying cEMCs

Tegumentary leishmaniasis and coinfections other than HIV

<div><p>Background</p><p>Tegumentary leishmaniasis (TL) is a disease of skin and/or mucosal tissues caused by <i>Leishmania</i> parasites. TL patients may concurrently carry other pathogens, which may influence the clinical outcome of TL.</p><p>Methodology and principal findings</p><p>This review focuses on the frequency of TL coinfections in human populations, interactions between <i>Leishmania</i> and other pathogens in animal models and human subjects, and implications of TL coinfections for clinical practice. For the purpose of this review, TL is defined as all forms of cutaneous (localised, disseminated, or diffuse) and mucocutaneous leishmaniasis. Human immunodeficiency virus (HIV) coinfection, superinfection with skin bacteria, and skin manifestations of visceral leishmaniasis are not included. We searched MEDLINE and other databases and included 73 records: 21 experimental studies in animals and 52 studies about human subjects (mainly cross-sectional and case studies). Several reports describe the frequency of <i>Trypanosoma cruzi</i> coinfection in TL patients in Argentina (about 41%) and the frequency of helminthiasis in TL patients in Brazil (15% to 88%). Different hypotheses have been explored about mechanisms of interaction between different microorganisms, but no clear answers emerge. Such interactions may involve innate immunity coupled with regulatory networks that affect quality and quantity of acquired immune responses. Diagnostic problems may occur when concurrent infections cause similar lesions (e.g., TL and leprosy), when different pathogens are present in the same lesions (e.g., <i>Leishmania</i> and <i>Sporothrix schenckii</i>), or when similarities between phylogenetically close pathogens affect accuracy of diagnostic tests (e.g., serology for leishmaniasis and Chagas disease). Some coinfections (e.g., helminthiasis) appear to reduce the effectiveness of antileishmanial treatment, and drug combinations may cause cumulative adverse effects.</p><p>Conclusions and significance</p><p>In patients with TL, coinfection is frequent, it can lead to diagnostic errors and delays, and it can influence the effectiveness and safety of treatment. More research is needed to unravel how coinfections interfere with the pathogenesis of TL.</p></div

Prevalence of alcohol and tobacco use among Brazilian adolescents: a systematic review

OBJECTIVE: To analyze alcohol and tobacco use among Brazilian adolescents and identify higher-risk subgroups. METHODS: A systematic review of the literature was conducted. Searches were performed using four databases (LILACS, MEDLINE /PubMed, Web of Science, and Google Scholar), specialized websites and the references cited in retrieved articles. The search was done in English and Portuguese and there was no limit on the year of publication (up to June 2011). From the search, 59 studies met all the inclusion criteria: to involve Brazilian adolescents aged 10-19 years; to assess the prevalence of alcohol and/or tobacco use; to use questionnaires or structured interviews to measure the variables of interest; and to be a school or population-based study that used methodological procedures to ensure representativeness of the target population (i.e. random sampling). RESULTS: The prevalence of current alcohol use (at the time of the investigation or in the previous month) ranged from 23.0% to 67.7%. The mean prevalence was 34.9% (reflecting the central trend of the estimates found in the studies). The prevalence of current tobacco use ranged from 2.4% to 22.0%, and the mean prevalence was 9.3%. A large proportion of the studies estimated prevalences of frequent alcohol use (66.7%) and heavy alcohol use (36.8%) of more than 10%. However, most studies found prevalences of frequent and heavy tobacco use of less than 10%. The Brazilian literature has highlighted that environmental factors (religiosity, working conditions, and substance use among family and friends) and psychosocial factors (such as conflicts with parents and feelings of negativeness and loneliness) are associated with the tobacco and alcohol use among adolescents. CONCLUSIONS: The results suggest that consumption of alcohol and tobacco among adolescents has reached alarming prevalences in various localities in Brazil. Since unhealthy behavior tends to continue from adolescence into adulthood, public policies aimed towards reducing alcohol and tobacco use among Brazilians over the medium and long terms may direct young people and the subgroups at higher risk towards such behavior

Hybrid auctions

In this paper we analyze a hybrid auction that combines a first-price and a Vickrey auction. We show that this auction may generate more expected revenue than a standard first-price auction. (C) 2002 Elsevier Science B.V. All rights reserved

Acute and chronic effects of resistance exercise on blood pressure in elderly women and the possible influence of ACE I/D polymorphism

M&aacute;rcio Rabelo Mota,1,3 Ricardo Jac&oacute; Oliveira,2 Denize Faria Terra,3 Emerson Pardono,4 Maur&iacute;lio Tiradentes Dutra,2 Jeeser Alves de Almeida,3 Francisco Martins Silva3 1University Center of Bras&iacute;lia (UniCeub), Bras&iacute;lia, Brazil; 2University of Bras&iacute;lia (UnB), Bras&iacute;lia, Brazil; 3Catholic University of Bras&iacute;lia (UCB), Bras&iacute;lia, Brazil; 4Federal University of Sergipe (UFS), S&atilde;o Crist&oacute;v&atilde;o, Brazil Abstract: This study investigated the chronic effect of blood pressure (BP) and post-exercise hypotension (PEH) during resistance training (RT) and its relation with the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in hypertensive elderly women. Participants were divided into two groups: an experimental group (EG) with exercise and a control group (CG) without exercise. The EG performed one adaptation month and one repetition maximum load (1RM) test at the end of this period. After the first month, the EG conducted a three-month program of RT at 60%, 70%, and 80% of 1RM, respectively, for each month. The CG was evaluated at the end of each month. Systolic (SBP) and diastolic (DBP) blood pressure (Microlife BP 3AC1-1) were measured, with the subject in a seated position, during an acute session for both GE and CG as follows: every 5 minutes for 20 minutes at pre-exercise rest, immediately after the resistance exercise and control, and every 15 minutes during 1 hour of recovery after exercise and CG. Analysis of covariance showed reduction in SBP and DBP (P &le; 0.05) rest values after the RT program. PEH was observed only for the EG in acute sessions, for SBP after the second and third months (P &le; 0.05), and for DBP after the second and fourth months (P &le; 0.05). No significant differences in main effects and interaction effects between blood pressure and ACE I/D were observed. The occurrence of chronic reduction of blood pressure and PEH through EG may have a protective effect on the cardiovascular system with no ACE I/D polymorphism influence for this population. Keywords: post-exercise hypotension, resistance exercise, angiotensin-converting enzyme, genetics, polymorphis