Avaliaram-se três métodos de proliferação celular, índice mitótico/10 campos de grande aumento (10 CGA), quatro vezes 10 CGA (40 CGA) e índice de marcação por MIB-1, em uma série de tumores mamários caninos, e as possíveis correlações entre estes métodos. Foram estudados 56 tumores mamários caninos, 23 benignos e 33 malignos. Foi também avaliado o impacto prognóstico do índice mitótico (10 CGA) e o grau histológico maligno em 17 tumores malignos, sete carcinomas ductais e 10 carcinomas metaplásicos. A correlação entre os três métodos para avaliar a proliferação celular e o impacto prognóstico do índice mitótico por 10 CGA e o grau histológico maligno foi realizada. Os resultados mostraram que existe uma forte associação entre contagem de mitose e o índice de marcação por MIB-1(P<0,0001) e correlação entre contagem de mitoses em 40 CGA e índice de marcação por MIB-1 e entre índice mitótico em 10 CGA e 40 CGA (P<0,05). Observou-se correlação entre os três métodos de avaliação da proliferação celular e os fatores prognósticos semelhante aos estudos de câncer de mama humano.

Three methods for the analysis of cell proliferation, mitotic index/10 high-power fields (10 HPF), mitotic index/four sets of 10 HPF (40 HPF), and MIB-1 index were evaluated in a series of canine mammary gland tumors, as well as the possible correlation between them. Fifty-six canine mammary gland tumors, including 23 benign and 33 malignant, were studied. In addition, the prognostic impact of mitotic index/10 HPF, and histological malignancy grade were evaluated in 17 malignant tumors, being seven ductal and 10 metaplastic carcinomas. The three methods used to evaluate cell proliferation were correlated with the prognostic impact of mitotic index/10 HPF and histological malignancy grade. The results showed a strong association between mitotic figure counts and MIB-1 index (P<0.0001). A correlation was observed between mitotic count per 40 HPF and MIB-1, and between mitotic index per 10 HPF and 40 HPF (P<0.05). Moreover, histological malignancy grade and mitotic figure counts were excellent prognostic factors during three-year follow-up (P<0.05). There was a correlation between the three methods used for the evaluation of cell proliferation and prognostic factors as observed in human breast cancer studies.

Análise por citometria de fluxo de DNA foi realizada em 28 amostras de tumores mamários de cadela. Nove eram benignos e 19 malignos, sendo todos os benignos e 11 malignos (57,9%) diplóides (P<0,05). Dos tumores aneuploides, cinco (26,3%) eram hiperdiploides, um (5,3%) hipodiploide, um (5,3%) triploide e um (5,3%) multiploide. A análise dos marcadores de expressão PR e CD31 revelaram significativa diferença entre tumores diploides e aneuploides (P<0,05). A imunorreatividade do PR foi maior em tumores diplóides e a imunoreatividade do CD 31 maior em tumores aneuploides. Para os marcadores MIB-1, c-erbB-2, p53 e Ciclina D1 não foi observada diferença significativa (P>0,05). Pela citometria de fluxo e pela imunoistoquímica verificaram-se uma relação entre aneuploidia e características malignas das neoplasias, receptor de progesterona imunoreação negativa e alta densidade de microvascular. Não foi observada correlação entre conteúdo de DNA e a fase S ou imunorreatividade para os marcadores MIB-1, c-erbB-2, p53 e Ciclina D1.

Flow cytometric analysis of DNA content was performed on 28 samples of canine mammary tumors. Nine of them were benign and 19 were malignant. All benign tumors and 11 malignant tumors (57.9%) were diploid (P<0.05). Form the aneuploid tumors, five (26.3%) were hyperdiploid, one (5.3%) hypodiploid, one (5.3%) near triploid and one (5.3%) multiploid. The analysis of the expression of the markers PR and CD31 revealed a significant difference between diploid and aneuploid tumors (P<0.05). The immunoreactivity of PR was higher in diploid tumors, while the immunoreactivity of CD31 was stronger in aneuploid tumors. No difference between the markers MIB-1, c-erbB2, p53 and Cyclin D1 was observed (P>0.05). Using the flow cytometry analysis and immunohistochemistry, it was found a close relationship between aneuploidy and malignant character of neoplasias, progesterone receptor (PR) negative immunostaining and higher microvases density. No correlation between DNA content and S phase or immunoreactivity for the markers MIB-1, p53, c-erbB2 and Cyclin D1 was observed.

The objective of the present investigation was to study the expression of c-erbB-2 and MIB-1 and try to associate them with morphological features of the cell such as nuclear pleomorphism, mitotic count and histological grade in a series of 70 canine mammary gland tumors, 22 of them benign and 48 malignant. Tumors were collected at the Veterinary Hospital of UFMG (Brazil) and the Veterinary Faculty of Porto University (Portugal). c-erbB-2 expression was determined according to the guidelines provided by the manufacturer of the HercepTest system and nuclear pleomorphism, mitotic count and histological grade according the Elston and Ellis grading system. The HercepTest is the FDA-approved in vitro diagnostic test marketed by Dako. It is a semi-quantitative immunohistochemical assay used to determine overexpression of HER2 protein (human epidermal growth factor receptor) in breast cancer tissue. MIB-1 expression was also evaluated in 28 malignant tumors. Seventeen (35.4%) of the malignant tumors were positive for c-erbB-2 expression, which was positively associated with nuclear pleomorphism (P < 0.0001), histological grade (P = 0.0017) and mitotic count (P < 0.05). Nuclear pleomorphism also showed a positive association with MIB-1 index (P < 0.0001). These results suggest that some of the biological and morphological characteristics of the tumor are associated in canine mammary gland tumors, as also reported for human breast cancer. It was also possible to show that the immunoexpression of c-erbB-2 can be a factor in mammary carcinogenesis. This fact opens the possibility of using anti-c-erbB-2 antibodies in the treatment of canine mammary tumors.

Nosso estudo envolveu a análise de cepas de Plasmodium falciparum provenientes da Região Amazônica Brasileira, coletadas no Laboratório de Malária da SUCEN. Os estudos "in vitro" foram efetuados com a cloroquina (46 ensaios), quinino (42 ensaios) e mefloquina (51 ensaios). Os resultados mostraram resistência de 100% em relação à cloroquina, 2,4% ao quinino e 31,4% à mefloquina, na análise "in vitro". Sete pacientes foram tratados com quinino isolado e nove com a associação mefloquina + pirimetamina-sulfadoxina, não mostrando correlação com os testes "in vitro".

The present study is concerned with the analysis of Plasmodium falciparum strains from the Brazilian Amazon Region, collected at the Malaria Laboratory - SUCENT. "In vitro" sensitivity tests were performed using chloroquine (46 samples), quinine (42 samples) and mefloquine (51 samples). Results have shown "in vitro" resistance to chloroquine in 100% of the tested samples, to quinine in 2.4% and to mefloquine in 3L4%. Seven patients were treated with quinine and nine with the triple combination (mefloquine plus sulfadoxine plus pyrimethamine). No correlation was shown between the therapeutic response and the "in vitro" tests.

Cento e dez pacientes com malária falciparum não complicada, provenientes da Amazônia brasileira, foram tratados com cloridrato de tetraciclina, na dose de 250 mg a cada 6 horas por 7 dias, associado ao sulfato de quinino na dose de 1,5 a 2,0 gramas/dia nos 3 ou 4 dias iniciais de tratamento. Os pacientes tiveram acompanhamento clínico e parasitológico por pelo menos 7 dias e em todos observou-se a negativação da parasitemia após o tratamento. Setenta e cinco pacientes foram acompanhados por 28 dias ou mais e destes 71 tiveram resposta do tipo Se4do tipo RI. O cloridrato de tetraciclina associado ao sulfato de quinino mostrou-se altamente eficaz no tratamento de malária falciparum não complicada, sendo bem tolerado e portanto útil na terapêutica das infecções por P. falciparum multirresistentes contraídas na Amazônia.

110 patients with P. falciparum malaria and no complications from the Brazilian Amazon region were treated with the association tetracycline hydrocloride (1 g/d during 7 days) and quinine sulphate (1.5 or 2 g/d during 3 or 4 days) at the beginning of treatment. All patients were followed for at least 7 days and no blood parasites were detected ont the 7th day. Seventy- five patients could be followed for 28 days or longer and 4 of them (5.3%) showed parasitemia again. These results support the efficacy of the association quinineplus tetracycline in the treatment of P. falciparum malaria infections from the Amazon region.