EFAR - Escola de Farmácia
URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/451
Notícias
O curso de Farmácia em Ouro Preto foi criado em 1839, sendo a mais antiga Escola de Farmácia da América Latina.
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23 resultados
Resultados da Pesquisa
Item Heart autonomic innervation during the acute phase of the experimental American trypanosomiasis in the dog.(1998) Machado, Conceição Ribeiro da Silva; Caliari, Marcelo Vidigal; Lana, Marta de; Tafuri, Washington LuizHeart autonomic innervation was studied in dogs during the acute phase of the experimental infection with the Berenice-78 strain of Trypanosoma cruzi. A glyoxylic acid–induced fluorescence method for catecholamines and a thiocholine method for demonstrating acetylcholinesterase activity showed the sympathetic and the parasympathetic nerve fibers, respectively. At day 34 of infection, moderate-to-intense rarefaction of both cholinergic and noradrenergic nerve fibers occurred in the atria of all animals coincident with moderate to intense myocarditis. In the ventricles, sympathetic denervation was clearly present only when the inflammatory processes were moderate to intense. Preliminary results on the chronic phase indicate that normal autonomic innervation coexists with an incipient chronic fibrosing myocarditis.Item Activity of the new triazole derivative albaconazole against Trypanosoma (Schizotrypanum) cruzi in dog hosts.(2004) Guedes, Paulo Marcos da Matta; Urbina, Julio Alberto; Lana, Marta de; Afonso, Luís Carlos Crocco; Veloso, Vanja Maria; Tafuri, Washington Luiz; Coelho, George Luiz Lins Machado; Chiari, Egler; Bahia, Maria TerezinhaAlbaconazole is an experimental triazole derivative with potent and broad-spectrum antifungal activity and a remarkably long half-life in dogs, monkeys, and humans. In the present work, we investigated the in vivo activity of this compound against two strains of the protozoan parasite Trypanosoma (Schizotrypanum) cruzi, the causative agent of Chagas’ disease, using dogs as hosts. The T. cruzi strains used in the study were previously characterized (murine model) as susceptible (strain Berenice-78) and partially resistant (strain Y) to the drugs currently in clinical use, nifurtimox and benznidazole. Our results demonstrated that albaconazole is very effective in suppressing the proliferation of the parasite and preventing the death of infected animals. Furthermore, the parasitological, PCR, serological, and proliferative assay results indicated parasitological cure indices of 25 and 100% among animals inoculated with T. cruzi strain Y when they were treated with albaconazole at 1.5 mg/kg of body weight/day for 60 and 90 days, respectively. On the other hand, although albaconazole given at 1.5 mg/kg/day was very effective in suppressing the proliferation of the parasite in animals infected with the Berenice-78 T. cruzi strain, no parasitological cure was observed among them, even when a longer treatment period (150 doses) was used. In conclusion, our results demonstrate that albaconazole has trypanocidal activity in vivo and is capable of inducing radical parasitological cure, although natural resistance to this compound was also indicated. Furthermore, the compound can be used in long-term treatment schemes (60 to 150 days) with minimal toxicity and thus represents a potentially useful candidate for the treatment of human Chagas’ disease.Item Variation in susceptibility to benznidazole in isolates derived from Trypanosoma cruzi parental strains.(2001) Veloso, Vanja Maria; Toledo, Max Jean de Ornelas; Lana, Marta de; Chiari, Egler; Tafuri, Washington Luiz; Bahia, Maria TerezinhaIn this work, the susceptibility to benznidazole of two parental Trypanosoma cruzi strains, Colombian and Berenice-78, was compared to isolates obtained from dogs infected with these strains for several years. In order to evaluate the susceptibility to benznidazole two groups of mice were infected with one of five distinct populations isolated from dogs as well as the two parental strains of T. cruzi. The first group was treated with benznidazole during the acute phase and the second remained untreated controls. The animals were considered cured when parasitological and serological tests remained persistently negative. Mice infected with the Colombian strain and its isolates Colombian (A and B) did not cure after treatment. On the other hand, all animals infected with Berenice-78 were cured by benznidazole treatment. However, 100%, 50% and 70% of cure rates were observed in animals infected with the isolates Berenice-78 B, C and D, respectively. No significant differences were observed in serological profile of infected control groups, with all animals presenting high antibody levels. However, the ELISA test showed differences in serological patterns between mice inoculated with the different T. cruzi isolates and treated with benznidazole. This variability was dependent on the T. cruzi population used and seemed to be associated with the level of resistance to benznidazole.Item Immunohistochemical studies in acute and chronic canine chagasic cardiomyopathy.(2002) Caliari, Marcelo Vidigal; Lana, Marta de; Cajá, Rosângela Aparecida França; Carneiro, Cláudia Martins; Bahia, Maria Terezinha; Santos, César Augusto Bueno dos; Magalhães, Gustavo Albergaria; Sampaio, Ivan Barbosa Machado; Tafuri, Washington LuizA major characteristic of Chagas’ disease is a myocarditis constituted primarily of mononuclear cells, both during the acute and chronic phases of the disease. Using monoclonal antibodies and image analyses we have quantified canine CD8+ T cells (caCD8+ T cells), canine CD4+ T cells (caCD4+ T cells) and neutrophils in canine chagasic myocardiopathy induced by two strains isolated from the first human clinical case of Chagas’ disease. We also evaluated the influence of tissue parasitism in the genesis of chronic myocarditis through immunohistochemistry. As in human myocarditis, there was a predominance of T lymphocytes in the inflammatory infiltrate in all animals studied. In the dogs inoculated with strain Berenice 78 (Be78) and necropsied during the acute phase of infection, we found 58% caCD8+ and 42% caCD4+ T cells. In chronically infected animals, 53% of T cells were represented by caCD8+ and 47% were caCD4+ T cells. Since normal canine lymphoid organs are constituted by 70–80% caCD4+ T cells and 20–30% caCD8+ T cells our results indicate a higher proliferation of caCD8+ T cells in dogs inoculated with the Be78 strain. In chronic myocarditis induced by the Berenice 62 (Be62) strain, caCD8+ cells constituted 33% of the T cells and 67% were caCD4+ T cells, a proportion similar to that found in normal canine lymphoid organs. Since the Be78 strain induces greater loss of myocardiocytes than strain Be62, we believe that the caCD8+ T cells, among other factors, can be important in the genesis of these lesions. Amastigote nests and immunohistochemically labelled Trypanosoma cruzi antigen were not found in dogs necropsied during the chronic phase. The absence of the parasite in the myocardium suggests the involvement of otherItem Chemotherapy with Benznidazole and Itraconazole for mice infected with different Trypanosoma cruzi clonal genotypes.(2003) Toledo, Max Jean de Ornelas; Bahia, Maria Terezinha; Carneiro, Cláudia Martins; Martins Filho, Olindo Assis; Tibayrenc, Michel; Barnabé, Christian; Tafuri, Washington Luiz; Lana, Marta deThe benznidazole (BZ) and itraconazole (ITC) susceptibilities of a standard set of Trypanosoma cruzi natural stocks were evaluated during the acute phase and the chronic phase of experimental chagasic infection in BALB/c mice. Twenty laboratory-cloned stocks representative of the total phylogenetic diversity of T. cruzi, including genotypes 20 and 19 (T. cruzi I) and genotypes 39 and 32 (T. cruzi II), were analyzed. Our results demonstrate important differences among stocks that could be pointed out as markers of biological behavior. Members of the T. cruzi I group were highly resistant to both BZ and ITC, whereas members of the T. cruzi II group were partially resistant to both drugs, despite their susceptibilities to ITC during the chronic phase of infection. The resistance to BZ observed for T. cruzi I was mainly triggered by genotype 20 isolates, whereas resistance to ITC was due to both genotype 20 and 19 isolates. Two polar patterns of response to BZ observed for genotype 39 isolates had a major impact on the partial resistance pattern observed for members of the T. cruzi II group. Genotype 32 isolates showed a typical profile of susceptibility. The correlation between the response to treatment and phylogenetic classification of T. cruzi stocks was clearer for ITC than for BZ. In conclusion, the data presented show a correlation between phylogenetic divergence among T. cruzi stocks and their susceptibilities to chemotherapeutic agents in vivo. Our results warn of the necessity to take into account the lesser genetic subdivisions of T. cruzi stocks since the upper subdivisions (T. cruzi I and II) show a great deal of heterogeneity for in vivo drug susceptibility.Item Effects of specific treatment on parasitological and histopathological parameters in mice infected with different Trypanosoma cruzi clonal genotypes.(2004) Toledo, Max Jean de Ornelas; Bahia, Maria Terezinha; Veloso, Vanja Maria; Carneiro, Cláudia Martins; Coelho, George Luiz Lins Machado; Alves, Cíntia Fontes; Martins, Helen Rodrigues; Cruz, Ruth Elizabeth; Tafuri, Washington Luiz; Lana, Marta deThe goal of this study was to verify the effect of specific treatment on parasitological and histopathological parameters in mice experimentally infected with different Trypanosoma cruzi clonal genotypes. Twenty cloned stocks were selected, representative of the whole phylogenetic diversity of the protozoan and belonging to the clonal genotypes 19 and 20 (T. cruzi I) and 39 and 32 (T. cruzi II). The stocks were inoculated in 40 BALB/c mice divided into four groups: (i) treated with benznidazole, (ii) treated with itraconazole and (iii and iv) untreated control groups (NT) for each drug, respectively. Seven parameters related to parasitaemia curves and histopathological lesions were analysed. Four during the acute phase (AP) and three during both the AP and chronic phase (CP) of infection. Statistical comparison between benznidazole-treated and NT groups for the biological parameters showed significant differences for all genotypes. Benznidazole treatment led to lower patent period, maximum of parasitaemia, day of maximum parasitaemia and area under the parasitaemia curve for all genotypes analysed. Percentage of positive haemoculture during AP and CP was lower for genotypes 19 and 32. Tissue parasitism (TP) and inflammatory process (IP) during AP were lower for genotypes 19 and 32, respectively. In general, itraconazole treatment induced a smaller reduction in these same parameters between treated and NT animals in relation to benznidazole treatment. Our results indicate that phylogenetic divergence among T. cruzi clonal genotypes must be taken in account in chemotherapy and studies dealing with all aspects of the parasite and the disease.Item Influence of the long-term Trypanosoma cruzi infection in vertebrate host on the genetic and biological diversity of the parasite.(2005) Veloso, Vanja Maria; Romanha, Alvaro José; Lana, Marta de; Murta, Silvane Maria Fonseca; Carneiro, Cláudia Martins; Alves, Cíntia Fontes; Borges, Erika Carime; Tafuri, Washington Luiz; Coelho, George Luiz Lins Machado; Chiari, Egler; Bahia, Maria TerezinhaThe influence of the long-term Trypanosoma cruzi infection in vertebrate host on the biological and genetic properties of the parasite was evaluated. Four T. cruzi isolates obtained from different chronic chagasic dogs infected with Berenice-78 T. cruzi strain during 2 and 7 years were comparatively analyzed. The long-term T. cruzi infection has led to alterations in parasitemia, virulence and pathogenicity of Be-78 strain for mice. These biological parameters varied from low to high in realation to the parental strain. Randomly amplified polymorphic DNA and isoenzyme profiles detected two distinct genetic groups of parasites. The first group included the parental strain and two T. cruzi isolates, and the second group the two other isolates. Interestingly, the isolates of the second group showed a reversibility of the genetic profile to the parental strain after 25 passages in mice. No correlation between the genetic groups and biological properties of the isolates was observed. Our findings confirmed the population heterogeneity of the Be-78 strain, and showed how differently it responds to the long-term infection in the same vertebrate hosts.Item Histopathological features, parasite density and cell phenotype of the popliteal lymph node in canine visceral leishmaniasis.(2008) Giunchetti, Rodolfo Cordeiro; Martins Filho, Olindo Assis; Carneiro, Cláudia Martins; Mayrink, Wilson; Marques, Marcos José; Tafuri, Washington Luiz; Oliveira, Rodrigo Corrêa de; Reis, Alexandre BarbosaWhile enlargement of popliteal lymph nodes (LN) is frequently described in canine visceral leishmaniasis (CVL), there are few histopathologic studies of lymph nodes during this chronic immunopathological condition.Besides a detailed histopathologic analysis, we have characterized the parasite load andmajor immunophenotypic features of theLNin Leishmania (Leishmania) chagasi-infected dogs. Our major histopathological findings highlight that hypertrophy/hyperplasia of LN cortical and medullary zones was the principal characteristic observed in asymptomatic dogs (AD), whereas atrophy of LN cortical zone was predominant in symptomatic animals (SD). The LN parasite density detected by anti-Leishmania immunohistochemical assay or expressed as Leishman Donovan Units was also highly correlated with the skin parasitism, the most reliable parameter to decode the clinical status of CVL. The major LN immunophenotypic changes during ongoing CVL were an increased frequency of T-lymphocytes, particularly CD8+ T-cells, upregulation of MHC-II expression by lymphocytes and decreased levels of CD21+ B-cells. Our findings further demonstrated that changes in the LNB-lymphocyte compartment exhibited a negative correlation with the skin parasite load. Conversely, we also showed evidence for a positive association between skin parasitismandLNT-cell-mediated immunity, suggesting thatT-cells, especiallyCD8+ lymphocytes, may have a Type-2 immunological profile in this lymphoid tissue in response to CVL.Item Host-parasite interactions in chagas disease : genetically unidentical isolates of a single Trypanosoma cruzi strain identified In vitro via LSSP-PCR.(2015) Paiva, Nívia Carolina Nogueira de; Vieira, Paula Melo de Abreu; Oliveri, Larissa Maris Rezende; Fonseca, Kátia da Silva; Lana, Gwenaelle Elza Nathalie Pound; Oliveira, Maykon Tavares de; Veloso, Vanja Maria; Reis, Alexandre Barbosa; Tafuri, Washington Luiz; Carneiro, Cláudia MartinsThe present study aims at establishing whether the diversity in pathogenesis within a genetically diverse host population infected with a single polyclonal strain of Trypanosoma cruzi is due to selection of specific subpopulations within the strain. For this purpose we infected Swiss mice, a genetically diverse population, with the polyclonal strain of Trypanosoma cruzi Berenice-78 and characterized via LSSP-PCR the kinetoplast DNA of subpopulations isolated from blood samples collected from the animals at various times after inoculation (3, 6 and 12 months after inoculation). We examined the biological behavior of the isolates in acellular medium and in vitro profiles of infectivity in Vero cell medium. We compared the characteristics of the isolates with the inoculating strain and with another strain, Berenice 62, isolated from the same patient 16 years earlier. We found that one of the isolates had intermediate behavior in comparison with Berenice-78 and Berenice-62 and a significantly different genetic profile by LSSP-PCR in comparison with the inoculating strain. We hereby demonstrate that genetically distinct Trypanosoma cruzi isolates may be obtained upon experimental murine infection with a single polyclonal Trypanosoma cruzi strain.Item Systemic and compartmentalized immune response in canine visceral leishmaniasis.(2009) Reis, Alexandre Barbosa; Martins Filho, Olindo Assis; Carvalho, Andréa Teixeira de; Giunchetti, Rodolfo Cordeiro; Carneiro, Cláudia Martins; Mayrink, Wilson; Tafuri, Washington Luiz; Oliveira, Rodrigo Corrêa deHuman visceral leishmaniasis (VL) and canine visceral leishmaniasis (CVL) are the most important emerging diseases with high prevalence in Latin American countries and are mainly caused by Leishmania (L.) chagasi (Syn = L. infantum). CVL has a great impact on Brazilian public health because domestic dogs are the most important VL peri-domicile reservoirs in both urban and peri-urban areas. Our findings highlight the complexity of cellular immunological events related to the natural infection from dogs by L. chagasi, additionally correlating major peripheral blood phenotypic markers with clinical status and tissues parasite density. Our main results demonstrated that lower frequency ofcirculating B cells and monocytes are important markers of severe CVL, whereas increased levels of CD8+ lymphocytes appear to be the major phenotypic feature of asymptomatic disease. Determination of the isotypes patterns during CVL demonstrated thatasymptomatic dogs and those with low parasitism are associated with an increase of IgG1, while the symptomatic dogs and those with high parasitism are associated with an increase of IgG, IgG2, IgM, IgA and IgE immunoglobulins. Pioneer findings obtained by our group showed a correlation between clinical status of CVL with degree of tissue parasite density. This data demonstrated that asymptomatic dogs presented low parasitism while symptomatic dogs are associated with high parasite load in various tissues such as skin, bone marrow and spleen. We have also investigated the association between tissue parasitism and CVL clinical forms. Regardless of clinical status, skin and spleen are the major sites of high parasite density during ongoing CVL. Furthermore, we demonstrated that bone marrow and spleen parasite density are the most reliable parasitological markers to decode the clinical status of CVL. In this article, we have reviewed some aspectsof the histopathological and immunological events occurring in natural and experimentalL. chagasi/L. infantum infection, pointing out the main L. chagasi-parasitized tissue. Wehave discussed the importance of the association between parasite density, immunological/ histopathological aspects and clinical status of the CVL, their current applications, challenges for the future and potential opportunities in CVL research.
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