Calcarea carbonica e associações (M8) como tratamento adjuvante de carcinoma inflamatório mamário em cão / Calcarea carbonica derivative complex (M8) as adjuvant treatment of inflammatory mammary carcinoma in a dog

Background: Inflammatory mammary carcinoma (IMC) is locally aggressive, fast growing, highly malignant tumor that affects humans and dogs. Affected dogs usually are presented with generalized edema, pain, erythema, and skin ulceration in mammary glands. Surgery is not recommended and an effective treatment has not been established [1]. Calcarea carbonica derivative complex (M8) has demonstrated anticancer properties in a murine model, by improving innate immune response against tumor cells [2,3]. M8 is a complex high diluted medication comprised of a 10%-20% concentration of Calcarea carbonica, Aconitum napellus, Arsenicum album, Asa foetida, Conium maculatum, Ipecacuanha, Phosphorus, Rhus tox, Silicea, Sulphur, and Thuya occidentalis, all in decimal dilutions of Hahnemann in distilled water and submitted to vigorous shaking. Aim: Describe an association of M8 and piroxicam (Non-steroidal anti-inflammatory drug) to treat a dog with IMC. Discussion: A 7 years old, mixed breed intact female dog was presented to the Federal University of Parana - Veterinary Hospital, Curitiba (HV-UFPR) for mammary glands examination. The owners related inflammation of mammary glands with clinical course of approximately 10 days, which was treated for mastitis (cephalexin and metergoline) without clinical improvement. Clinical examination revealed erythema, increased skin warmth, pain on palpation, and plaque involving the 4th and 5th right mammary glands. Abdominal ultrasound and serum biochemistry were unremarkable. Thoracic radiographs showed suspicious images of pulmonary metastasis. Fine needle biopsy was taken for cytologic examination. Cytological interpretation was a malignant epithelial neoplasm, probably a mammary carcinoma. Diagnosis of IMC was based on clinical signs and cytopathology. Dog was treated with oral (0.5 mL) and topical M8 twice a day for 15 days, and pyroxican, 0.3mg/kg, PO, q24h. Clinical improvement was observed 7 days after starting treatment. Until present date (70 treatment days with M8), dog has no clinical signs of IMC, and does not show signs of disease progression. Conclusion: The present report suggests that M8 associated with piroxicam contributes to improvement of IMC dog?s quality of life and survival rate. However, further clinical studies are needed to evaluate response to treatment in patients diagnosed with IMC.(AU)

Introdução: O carcinoma inflamatório mamário (CIM) é um tumor altamente maligno que acomete cães e pessoas, apresentando-se localmente invasivo e com crescimento rápido. Em cães, os sinais clínicos incluem edema e eritema generalizado das mamas acometidas, dor local e ulceração. A intervenção cirúrgica é contra-indicada e não há consenso sobre tratamento clínico eficaz [1]. Estudos em modelo murino demonstraram que Calcarea carbonica e associações (M8) possuem propriedades anticancerígenas através de estímulo da resposta imune inata [2,3]. O M8 é altamente diluído, composto de 10 a 20% de Calcarea carbonica, Aconitum napellus, Arsenicum album, Asa foetida, Conium maculatum, Ipecacuanha, Phosphorus, Rhus tox, Silicea, Sulphur, e Thuya occidentalis, todos na diluição decimal de Hahnemann em água destilada e submetido à agitação vigorosa. Objetivo: Descrever a associação de M8 e piroxicam (antiinflamatório não esteroidal) no tratamento de cão com CIM. Discussão: Uma cadela não castrada, sem raça definida, de 7 anos de idade foi trazida ao Hospital Veterinário da Universidade Federal do Paraná - Curitiba (HV-UFPR) com histórico de inflamação mamária com evolução de 10 dias e não responsiva ao tratamento para mastite (com cefalexina e metergolina). Ao exame físico, as mamas abdominais caudais e inguinais direita apresentavam-se em placa, com aumento de temperatura, edema e eritema localizados e presença de sensibilidade dolorosa ao toque. A ultrassonografia abdominal e bioquímica sérica não apresentaram alterações significativas, enquanto que a radiografia torácica evidenciou imagem sugestiva de metástase pulmonar. Realizou-se biópsia aspirativa por agulha fina para análise citológica, a qual foi compatível com neoplasia epitelial maligna, provavelmente carcinoma mamário. O diagnóstico de CIM baseou-se nos sinais clínicos e resultados citopatológicos. Instituiu-se tratamento com M8 oral (0,5mL a cada 12 horas) e tópico (nas mamas envolvidas), em associação com piroxicam (0,3mg/kg, PO, a cada 24 horas). Observou-se melhora clínica significativa após 7 dias de tratamento e até a presente data (70 dias de tratamento com M8) a paciente não apresenta sinais clínicos de CIM e de progressão da doença.Conclusão: O presente caso sugere que a associação de M8 e piroxicam contribui para melhora da qualidade de vida e aumento da taxa de sobrevida em cães com CIM. No entanto, mais estudos são necessários para avaliar a resposta clínica de pacientes com CIM tratados com M8.(AU)

Avaliação da produção de citocinas pelos macrófagos J774. G8 após o tratamento com bioterápicos / Evaluation of cytokine production by J774. G8 macrophages after treatment with biotherapics

Strains of macrophages, such as murine J774.G8 macrophages, are susceptible to influenza A infection [1]. One of the responses to viral infection involves the production of various types of immunostimulatory cytokines by infected cells [2].In all cases, there were no significant differences compared to control groups. However, the production of TNF-? detected in macrophages treated by intact and inactivated biotherapics presented a tendency to increase after infection. In fact, similar results were previously detected in other experiments conducted only with the intact biotherapic [3]. The release of the cytokine MCP1 in all experimental situations presented a tendency to decrease after the viral infection when compared to untreated macrophages. No statistically significant difference was detected in the production of IL 12 and IL 10. These experiments will be repeated to confirm the data obtained.(AU)

Tratamento in vivo com M8, uma solução complexa altamente diluída, reduziu a malignidade de um modelo de melanoma de camundongo / In vivo treatment with M8, a highly diluted tinctures complex, reduced the malignancy of a mouse melanoma model

Background: Cancer is a class of disease responsible for 13% of death cause worldwide. Among all types of cancers, one of the most aggressive and with the highest death rate is melanoma. It is highly metastatic and current treatments with chemotherapeutic drugs do not yield satisfactory results. Therefore, the interest on new therapeutics for cancer treatment has been increasing on research. Highly diluted tinctures (HDT) are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Previous results have demonstrated in vitro inhibition of invasion ability and in vivo anti-metastatic potential of B16F10 lung metastasis model after mice treatment with M8 inhalation.Conclusion: Even though further investigation are necessary to elucidate the mechanisms of action of M8 treatment there is an indication that these highly diluted tinctures could be a promising therapy to treat metastatic melanoma.(AU)

Introdução: O Câncer é uma classe de doenças responsáveis por 13% das causas de mortes no mundo todo. Entre todos os tipos de cânceres, um dos mais agressivos e com maior índice de mortalidade é o melanoma. Ele é altamente metastático, e os tratamentos atuais com drogas quimioterapeuticas não geram resultados satisfatórios. Portanto, o interesse em novos agentes terapeuticos para o tratamento do câncer tem aumentado na pesquisa. Soluções altamente diluídas (CAD) são destinadas à aumentar a resposta do sistema imunológico resultando em menores frequencias de várias doenças, e também não apresentam riscos de graves efeitos colaterais, devido à sua toxicidade reduzida. Resultados anteriores demostraram a inibição in vitro da habilidade de invasão e potencial antimetastático in vivo do modelo de metástase pulmonar da B16F10, após o tratamento dos camundongos pela inalação do M8.Conclusão: Mais pesquisas são necessárias para esclarecer os mecanismos de ação do tratamento com M8. Entretanto, há um indicativo de que soluções altamente diluídas podem ser terapias coadjuvantes para o tratamento do melanoma metastático.(AU)

Histological and immunohistochemical evaluation of sarcoma 180 in mice after treatment with and alfa-D-glucan from the lichen Ramalia celastri

The antitumoral activity of an alfa-D-glucan from the lichen Ramalia celastri was investigated using the tumor Sarcoma 180 (S-180). Mice were inoculated with the tumor and 24 h later received a single dose of alfa-D-glucan (200 mg/kg). Thirty-five days after inoculation the mice were sacrificed and the tumors were examined histopathologically. Morphological analyses showed that the tumor was invasive and that it produced typical and atypical mitoses, neovascularization and an infiltration of inflammatory cells. In treated mice, inflammatory cells were more frequent and the presence of nuclear fragments suggested tumor cell death by apoptosis. The tumors of control and alfa-D-glucan treated mice were negative for laminin but expressed fibronectin, the intensity and distribution of which varied in the connective tissue surrounding the tumor mass, in treated mice than in control mice, but in tumor cells, the expression was greater in control mice. The results indicate that alfa-D-glucan can inhibit tumor growth and affect host defense cell responses. The differences in fibronectin distribution between the control and alfa-D-glucan treated mice, suggest that this protein may play an important role in limiting the invasiveness of malignant cells.

Acid phosphatase activity in ungerminated conidia from Colletotrichum graminicola as determined by spectrophotometric and cytochemical methods

The acid phosphatase in ungerminated conidia from Colletotrichum graminicola, a corn pathogen, was investigated using spectrophotometric and cytochemical methods. Acid phosphatase activity was studied in a homogenate obtained by fragmentation of ungerminated conidia. With p-nitrophenylphosphate as substrate, the apparent Vmax and Km were 1.000 nmol p-nitrophenol/mg of protein/min and 0.631 mM, respectively. The pH and temperature optima were 5.5 and 60 graus Celsius, respectively. A cytochemical ultrastructural assay showed deposition of the reaction product inside vacuoles but not extracellularly on the cell surface. The permeabilization of conidia with Triton X-100 increased acid phosphatase activity eight fold. Compared to other procedures, our method was fast, easy to perform and gave consistent results.