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De Lima Barros M.B.,Institute Pesquisa Clinica Evandro Chagas IPEC | Schubach T.P.,Institute Pesquisa Clinica Evandro Chagas IPEC | Coll J.O.,Iguaçu University | Gremiao I.D.,Institute Pesquisa Clinica Evandro Chagas IPEC | And 2 more authors.
Revista Panamericana de Salud Publica/Pan American Journal of Public Health | Year: 2010

In the state of Rio de Janeiro, Brazil, sporotrichosis reached epidemic levels, involving humans and cats. Preliminary data indicate that approximately 2 200 human cases were diagnosed between 1998 and December of 2009, and 3 244 cats were treated. The geographic distribution of cases reveals a concentration in the City of Rio de Janeiro metropolitan area. The disease affects mostly women of a low socioeconomic status, aged 40 to 55 years, who work as housekeepers. Itraconazole has been the drug of choice for treatment. Although sporotrichosis does not usually affect organs other than the skin, mucosa, and subcutaneous tissue, it has an indirect social impact resulting from absenteeism, pain, and discomfort during the active disease stage, and the unpleasant appearance of the scars. In turn, systemic involvement is frequent in cats, leading to serious and difficult- to-treat forms of the disease and death. Considering that treatment time in animals is longer than in human beings, treating cats with sporotrichosis has been the greatest obstacle and the most important challenge for the control of this epidemic infection.


Chicaybam L.,Instituto Nacional Of Cancer | Chicaybam L.,Institute Pesquisa Clinica Evandro Chagas IPEC | Bonamino M.H.,Instituto Nacional Of Cancer
International Reviews of Immunology | Year: 2014

Adoptive cell transfer (ACT) is emerging as a powerful modality of cancer treatment. While ACT has proved able to induce massive clinical responses, genetic modification of T lymphocytes further improved clinical responses obtained. One of the major current limitations of ACT is the inability to discern healthy from malignant cells, leading to on target/off tumor responses that can limit its application. We here discuss some of the approaches currently under development and potential solutions to circumvent these limitations and extend this potentially curative therapy to different tumors by targeting a variety of antigens. © Informa Healthcare USA, Inc.


Rodrigues A.M.,Federal University of São Paulo | Rodrigues A.M.,Fungal Biodiversity Center | de Melo Teixeira M.,University of Brasilia | de Hoog G.S.,Fungal Biodiversity Center | And 7 more authors.
PLoS Neglected Tropical Diseases | Year: 2013

Sporothrix schenckii, previously assumed to be the sole agent of human and animal sporotrichosis, is in fact a species complex. Recently recognized taxa include S. brasiliensis, S. globosa, S. mexicana, and S. luriei, in addition to S. schenckii sensu stricto. Over the last decades, large epidemics of sporotrichosis occurred in Brazil due to zoonotic transmission, and cats were pointed out as key susceptible hosts. In order to understand the eco-epidemiology of feline sporotrichosis and its role in human sporotrichosis a survey was conducted among symptomatic cats. Prevalence and phylogenetic relationships among feline Sporothrix species were investigated by reconstructing their phylogenetic origin using the calmodulin (CAL) and the translation elongation factor-1 alpha (EF1α) loci in strains originated from Rio de Janeiro (RJ, n = 15), Rio Grande do Sul (RS, n = 10), Paraná (PR, n = 4), São Paulo (SP, n = 3) and Minas Gerais (MG, n = 1). Our results showed that S. brasiliensis is highly prevalent among cats (96.9%) with sporotrichosis, while S. schenckii was identified only once. The genotype of Sporothrix from cats was found identical to S. brasiliensis from human sources confirming that the disease is transmitted by cats. Sporothrix brasiliensis presented low genetic diversity compared to its sister taxon S. schenckii. No evidence of recombination in S. brasiliensis was found by split decomposition or PHI-test analysis, suggesting that S. brasiliensis is a clonal species. Strains recovered in states SP, MG and PR share the genotype of the RJ outbreak, different from the RS clone. The occurrence of separate genotypes among strains indicated that the Brazilian S. brasiliensis epidemic has at least two distinct sources. We suggest that cats represent a major host and the main source of cat and human S. brasiliensis infections in Brazil. © 2013 Rodrigues et al.


Santini-Oliveira M.,Institute Pesquisa Clinica Evandro Chagas IPEC | De Cassia Elias R.,Federal University of Rio de Janeiro | Veloso V.G.,Institute Pesquisa Clinica Evandro Chagas IPEC | Cattani V.B.,Institute Pesquisa Clinica Evandro Chagas IPEC | And 8 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2014

A lopinavir-ritonavir (LPV/r)-based regimen is recommended during pregnancy to reduce the risk of HIV mother-to-child transmission, but the appropriate dose is controversial. We compared the pharmacokinetics of standard and increased LPV/r doses during pregnancy. This randomized, open-label prospective study enrolled 60 pregnant women between gestational weeks 14 and 30. The participants received either the standard dose (400/100 mg twice a day [BID]) or increased dose (600/150 mg BID) of LPV/r tablets during pregnancy and the standard dose for 6 weeks after childbirth. Pharmacokinetics analysis was performed using a high-performance liquid chromatography-tandem mass spectrometry method. Adherent participants who received the standard dose presented minimum LPV concentrations of 4.4, 4.3, and 6.1 μg/ml in the second and third trimesters and postpartum, respectively. The increased-dose group exhibited values of 7.9, 6.9, and 9.2 μg/ml at the same three time points. Although LPV exposure was significantly higher in the increased-dose group, the standard dose produced therapeutic levels of LPV against wild-type virus in all adherent participants, except one patient in the third trimester; 50%, 37.5%, and 25%, and 0%, 15%, and 0% of the participants in the standard- and increased-dose groups failed to achieve therapeutic levels against resistant viruses during the second and third trimesters and after childbirth, respectively. After 12 weeks of treatment and after childbirth, all adherent participants achieved undetectable HIV viral loads, and their babies (49/54) were uninfected. No serious drug-related adverse events were observed. We conclude that the standard dose is appropriate for use during pregnancy and that an increased dose may be necessary for women harboring resistant HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT00605098.)© 2014, American Society for Microbiology.


Miranda L.H.M.,Institute Pesquisa Clinica Evandro Chagas IPEC | Conceicao-Silva F.,Instituto Oswaldo Cruz | Quintella L.P.,IPEC Inc | Kuraiem B.P.,Institute Pesquisa Clinica Evandro Chagas IPEC | And 2 more authors.
Comparative Immunology, Microbiology and Infectious Diseases | Year: 2013

Cutaneous lesions of feline sporotrichosis show high fungal load and are associated with severe disease and elevated zoonotic potential. The present study describes the histopathology and fungal load of the lesions in different clinical presentations of feline sporotrichosis. Cats with sporotrichosis were separated into groups L1, L2 and L3 (lesions in one, two and three or more locations, respectively) and subjected to skin biopsies for histopathology. Eighty-six cats were included in the study. Lesions were suppurative granulomatous in 84 cases and poorly formed granulomas were predominant. The well-formed granulomas were associated with group L1. The high fungal load was predominant in group L3 and in poorly formed granuloma cases and did not occur in well-formed granulomas cases. The good general condition was associated with low fungal load. These findings suggest that the fungal load control in animals with more localized lesions and well-organized response is linked with the improvement in the outcome of infected cats. © 2013 Elsevier Ltd.


Silva M.T.T.,Laboratorio Of Pesquisa Clinica Em Neuroinfecca O | Neves E.S.,Laboratorio Of Pesquisa Clinica Em Neuroinfecca O | Grinsztejn B.,Institute Pesquisa Clinica Evandro Chagas IPEC | De Melo Espindola O.,Institute Pesquisa Clinica Evandro Chagas IPEC | And 2 more authors.
AIDS | Year: 2012

HIV-individuals are at risk for human T-lymphotropic virus (HTLV) coinfection and neurological diseases. Little is known about the impact of HAART among coinfected patients. In this study, 47 out of 428 HIV individuals were coinfected with HTLV (10.9%). Coinfection was an independent variable associated with neurological outcome (odds ratio 8.73). Coinfection was associated with myelopathy [chi square (X) =93, P<0.001], peripheral neuropathy (X=6.5, P=0.01), and hepatitis C virus infection (X=36.5, P<0.001). HAART did not appear to protect against neurological diseases and had no impact on HTLV proviral load. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Silva D.A.D.,Institute Pesquisa Clinica Evandro Chagas IPEC | Silva D.A.D.,Laboratorio Of Pesquisa Clinica Em Dermatozoonoses Em Animais Domesticos | Madeira M.D.F.,Laboratorio Of Vigilancia Em Leishmanioses | Abrantes T.R.,Institute Pesquisa Clinica Evandro Chagas IPEC | And 3 more authors.
Veterinary Journal | Year: 2013

An immunoenzymatic assay (ELISA), an indirect immunofluorescence antibody test (IFAT) with different antigens (ELISA- Leishmania chagasi, ELISA-. L. major-like, IFAT-. L. chagasi and IFAT-. L. major-like), and an immunochromatographic test were assessed for the diagnosis of canine visceral leishmaniasis (CVL). Serum samples from 144 dogs from an endemic area for visceral leishmaniasis in the municipality of Rio de Janeiro were tested. The sensitivities of the serological tests were 93%, 100%, 73%, 60% and 93%, with specificities of 87%, 92%, 77%, 96% and 92% for the ELISA-. L. major-like, ELISA-. L. chagasi, IFAT-. L. major-like, IFAT-. L. chagasi and the immuno chromatographic test, respectively. ELISA-. L. chagasi was the best test for the diagnosis of CVL, but the immunochromatographic test could be a useful alternative as it offers simple and rapid diagnosis without the need for a specialized laboratory. © 2012 Elsevier Ltd.


Lapa J.S.,Institute Pesquisa Clinica Evandro Chagas IPEC
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology | Year: 2012

Most guidelines for Chagas disease recommend the performance of two serological tests in order to detect it. However, inconclusive results may arise from this strategy. The aim was to describe whether serological follow-up together with the patient's clinical characteristics could clarify the outcome of patients with initial inconclusive test results. In this retrospective case series, all results of Chagas disease serological tests and outpatient visits recorded from 2004 to 2008 were screened for inclusion. The inclusion criterion was clinical suspicion of chronic Chagas disease and the exclusion criteria were previous diagnosis of Chagas disease, suspicion of acute Chagas disease, and serological tests with no corresponding medical evaluation. A total of 1,732 patients were analyzed. Chronic Chagas disease prevalence was 21.1%. After the initial set of serological tests, 2.9% of patients had inconclusive test results. Most of these patients had definite diagnosis after clinical follow-up and the repetition of serological tests in a new blood sample. Loss to follow-up while partaking in the diagnostic investigation reached 17.7%. The prevalence of initial inconclusive serological tests for chronic Chagas disease is low. Clinical evaluations and follow-up clarify the definite diagnosis. Noncompliance to follow-up is a frequent problem. Strategies to reduce inconclusive results and noncompliance are discussed.


Ribeiro I.G.,Institute Pesquisa Clinica Evandro Chagas IPEC | Marin V.A.,Nucleo Of Inovacao Tecnologica Do Instituto Nacional Of Controle E Qualidade Em Saude
Ciencia e Saude Coletiva | Year: 2012

This article presents a review about the labeling of products that have Genetically Modified Organisms (GMO), also called transgenic elements in their composition. It addresses the conventions, laws and regulations relating to such products currently governing the market, the adequacy of these existing standards and their acceptance by society. It also examines the importance of the cautionary principle when assessing the application of new technologies or technologies where little is known or where there is no relevant scientific knowledge about the potential risks to the environment, human health and society.


Chicaybam L.,Instituto Nacional Of Cancer Inca | Chicaybam L.,Institute Pesquisa Clinica Evandro Chagas IPEC | Sodre A.L.,Instituto Nacional Of Cancer Inca | Curzio B.A.,Instituto Nacional Of Cancer Inca | Bonamino M.H.,Instituto Nacional Of Cancer Inca
PLoS ONE | Year: 2013

Gene transfer to T lymphocytes has historically relied on retro and lentivirus, but recently transposon-based gene transfer is rising as a simpler and straight forward approach to achieve stable transgene expression. Transfer of expression cassettes to T lymphocytes remains challenging, being based mainly on commercial kits. Aims: We herein report a convenient and affordable method based on in house made buffers, generic cuvettes and utilization of the widely available Lonza nucleofector II device to promote efficient gene transfer to T lymphocytes. Results: This approach renders high transgene expression levels in primary human T lymphocytes (mean 45%, 41-59%), the hard to transfect murine T cells (mean 38%, 36-42% for C57/BL6 strain) and human Jurkat T cell line. Cell viability levels after electroporation allowed further manipulations such as in vitro expansion and Chimeric Antigen Receptor (CAR) mediated gain of function for target cell lysis. Conclusions: We describe here an efficient general protocol for electroporation based modification of T lymphocytes. By opening access to this protocol, we expect that efficient gene transfer to T lymphocytes, for transient or stable expression, may be achieved by an increased number of laboratories at lower and affordable costs. © 2013 Chicaybam et al.

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