Bioconjugate based on cisplatin and bacterial exopolysaccharide with reduced side effects: A novel proposal for cancer treatment.

BACKGROUND: In the search for alternatives that attenuate the toxicity associated to oncologic treatment with cisplatin (CDDP) and considering the potential health-beneficial properties of exopolysaccharides (EPS) produced by lactic acid bacteria, it was aimed on this study to evaluate the cytotoxic, toxicologic and antitumoral efficacy of a bioconjugate based on CDDP and EPS, on the experimental tumor of sarcoma 180. METHODS: After the synthesis of the cis-[Pt(NH3)2(Cl)2] complex and of the conjugate containing Lactobacillus fermentum exopolysaccharide was tested both in vitro and in vivo for evaluating the acute toxicity. RESULTS: The antitumoral study was performed using mice transplanted with sarcoma 180. The bioconjugate showed low to medium cytotoxicity for the cell lines tested, as well moderated acute toxicity. After determining the LD50, the following experimental groups were established for the antitumor assay: Control (NaCl 0,9%), CDDP (1 mg/kg), EPS and bioconjugate composition (200 mg/kg). The bioconjugate promoted a 38% regression in tumor mass when compared to the control, and a regression of 41% when compared to CDDP. Liver histopathological analysis revealed discrete alterations in animals treated with (CDDP + EPS) when compared to control. The bioconjugate also minimized changes in the renal parenchyma resulting from the tumor. CONCLUSION: Our results indicate that when CDDP is associated with EPS, this composition was more biocompatible, showing itself as a potent chemotherapeutic agent and lower tissue toxicity.

Role of synthetical amynoquinone ethyl 2-(1,4-dioxo-1,4-dihydronaphthalen-2-ylamino) acetate in inhibition of Ehrlich's tumor.

Quinones are naturally or synthetically occurring secondary metabolites that have various bio-dynamics, highlighting their antitumor potential. This has been explored through their selective cytotoxicity, and studies in medicinal chemistry about the relation between biological activity versus chemical structure may lead to the solution of the toxicity problems associated with quinones. In this context, the antitumor effect of a synthetic naphthoquinone, named Ethyl 2-(1,4-Dioxo-1,4-Dihydronaphthalen-2-Ylamino) Acetate, was tested using mice transplanted with Ehrlich ascitic tumor as an experimental model. The acute toxicity test was performed using 30 mice that received the aminoquinone at doses of 100, 200, 300, and 600 mg/kg. After evaluation of the clinical findings in the spontaneous activity tests, the LD50 calculation for the test substance showed low levels of toxicity at doses lower than 244.11 ± 23.29 mg/kg. Thus, three experimental groups were established, where animals transplanted with tumor cells received NaCl vehicle solution (control, n = 6), and the others were treated with 71.7 mg/kg of Methotrexate (n = 6) or 20 mg/kg of Aminoquinone (n = 6). All administrations were intraperitoneal, in a single dose. Three days after the implantation of the tumor cells the animals were weighed daily and evaluated for tumor biometry and development. The treatments occurred five days after the implantation of the tumor cells and were extended for 7 more days. At the end of the 12-day experimental period, all animals were euthanized for biochemical and histopathological analyses of the tumors and vital organs. The spontaneous activity test showed that the amount of responses associated with the nervous system tends to increase with the increase in dosage, highlighting the excitatory effect on the central nervous system in almost all dosages employed, followed by depressant activities on this system. There was a significant tumor reduction, both in animals treated with methotrexate (71.7 %) and in those treated with aminoquinone (91.6 %) in the control group. There was no significant difference in tumor volume between the animals treated with aminoquinone or methotrexate. The histopathological analysis revealed that in both treatments there were fewer mitoses in the tumor mass compared to the control group. However, there was apparent toxicity to the liver, heart, and left kidney in the treatment with methotrexate compared to aminoquinone. The significant capacity for tumor reduction presented by aminoquinone allows pointing it as a promising alternative for the development of a more efficient drug to control tumor development, being necessary for the development of new studies to deepen the knowledge about its mechanisms of action.

Spongy film of cellulosic polysaccharide as a dressing for aphthous stomatitis treatment in rabbits

To develop an experimental model of acute inflammation, like aphthous ulcers, in oral cavity of rabbits, and also, to evaluate the results of the application of a polysaccharide spongy film of molasses from sugar cane as assist treatment in the healing process. Twenty adult rabbits weighting between 2.5 kg and 3.9 kg were divided into two groups: experimental and control infected ulcers were induced on the jugal mucosa by surgical excision. They were treated at the experimental group by curettage and dressing with spongy film of cellulosic polysaccharide film, whereas saline solution was used in the control group. Temporal evolution of the healing area, histopathology and bacteriological analysis were used to evaluate the healing process on the 3rd (D3), 7th (D7) and 11th days (D11). The healing time and bacteriological study showed no statistical differences on the group means. Analyzing the histopathology of the experimental group we verified epithelial hyperplasia from D3 to D11, instead in the control group there was a greater clutter of the epithelial cells from the D3 to D11. The experimental model used caused aphthous ulcers and the polysaccharide sponge film can be used as an aid in the symptomatic treatment and healing of the ulcerative lesions of the oral mucosa.

Fatores de risco associados à infecção por Toxoplasma gondii em ovinos e caprinos no estado de Pernambuco / Risk factors for Toxoplasma gondii infection in sheep and goats in Pernambuco, Brazil

Objetivou-se com este estudo investigar a participação de Toxoplasma gondii em falhas reprodutivas em pequenos ruminantes de criatórios situados na Zona da Mata e no Agreste do Estado de Pernambuco e que apresentavam histórico de distúrbios reprodutivos. Foram selecionadas 12 propriedades das quais se coletaram amostras de 262 animais, sendo 167 caprinos e 95 ovinos. Realizou-se a pesquisa de anticorpos anti-Toxoplasma gondii, utilizando-se a técnica da Imunofluorescência Indireta (RIFI). Foram aplicados questionários investigativos nas propriedades visitadas para identificar os fatores de risco associados à infecção. Em 100% das propriedades foram encontrados animais soropositivos. Para T. gondii, das 167 amostras de soro caprino analisadas, 31,7% foram positivas, enquanto que na espécie ovina, das 95 amostras, 16,9% foram positivas. Para a espécie ovina, não foram observadas associações significativas. Para os caprinos, houve associação significativa (p<0,05) para as variáveis: manejo intensivo (OR=2,40), exploração leiteira (OR=2,10), animais procedentes de outros estados (OR=7,89) e monta natural (OR=5,69). Conclui-se que a infecção pelo T. gondii encontra-se disseminada nos rebanhos de caprinos e ovinos estudados e que medidas sanitárias devem ser adotadas para controlar os fatores de risco identificados neste estudo.

This study was conducted to investigate the participation of Toxoplasma gondii in reproductive failure in small ruminants raised in the Litoral/ Zona da Mata and Agreste of the State of Pernambuco, Brazil. Twelve flocks were selected from which 262 samples were collected, 167 from goats and 95 from sheep. Indirect Imunofluorescent Antibody Reaction (IFA) technique was used to detect antibodies anti-Toxoplasma gondii. A questionnaire was applied in flocks to identify risk factors associated with infection. Positive animals were found in 100% of the farms. Among 167 samples of goat serum analyzed, 31.7% were positive, whereas from 95 samples of sheep, 16.9% were positive. Results of brucellosis tests were negative for 100% of analyzed samples. For sheep, no significant association was found; however, for goats, there was a significant association (p<0.05) for intensive handling (OR=2.40), milk exploration (OR=2.10), animals originating from other states (OR=7.89) and natural breeding (OR=5.69). It was concluded that infection for T. gondii is spread in studied goat and sheep flocks and that sanitary measures must be adopted to control risk factors for infection.

Ocorrência e fatores de risco para Chlamydophilaabortus em ovinos e caprinos no estado de Pernambuco: [revisão] / Occurrence and risk factors for Chlamydophilaabortus infection in sheep and goats in Pernambuco: [revision]

Objetivou-se com este estudo identificar os fatores de risco associados à infecção por Chlamydophila abortus em caprinos e ovinos nas regiões do Litoral/ Zonada Mata e Agreste do Estado de Pernambuco. Foram colhidas 290 amostras de soros para pesquisa de anticorpos contra clamídia em 12 propriedades. Para identificar os fatores de risco foram aplicados questionários junto aos proprietários. A freqüência de animais soro-reagentes nos rebanhos estudados foi de 10,3%, sendo 12,0% para caprinos e 8,1% para ovinos, identificando-se 11/12 (91,6%) focos da infecção. Registra-se a primeira ocorrência de anticorpos anti-C. abortus em caprinos no estado de Pernambuco e em ovinos no Brasil. Os fatores derisco associados à infecção em caprinos foram a raça (OR=9,10) e o manejo intensivo (OR=6,41) e para ovinosnão foram encontradas associações significativas para nenhum fator analisado. Concluiu-se que a infecção porChlamydophila sp. encontra-se disseminada em criações de caprinos e ovinos da Zona da Mata e Agreste do Estado de Pernambuco. Medidas de controle devem ser implantadas nos criatórios estudados, enfocando principalmente os fatores de risco identificados neste estudo para reduzir a possibilidade de infecção por este agente.

The study aimed to identify risk factors associated with Chlamydophila abortus infection in sheep and goats from the Litoral/Zona da Mata and Agreste region of Pernambuco state, Brazil. Serum samples (n=290) were analyzed to detect Chlamydophila spp. antibodies in 12 farms. Questionnaires were applied to identify risk factors. Frequency ofserum-reactive animals were 10.3% (12.0% in ewes and 8.1% in goats) and 1/12 (91.6%) infection focuses were identified. This is the first report on anti-Chlamydophhila abortus antibodies in goats and sheep in Pernambuco and Brazil, respectively. Risk factorsassociated with goat infection were breed (OR=9.10) and management (OR=6.41). No significant associations in any of the analyzed factors were found for sheep. In summary, Chlamydophila sp. infection is disseminated in sheep and goat herds in the region. Control measures should be established, focusing primarily risk factor identified in this study, to reduce the possibility of infection by the agent.