No abstract

Piplartine {5,6-dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)pyridinone} and piperine {1-5-(1,3)-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]piperidine} are alkaloid amides isolated from Piper. Both have been reported to show cytotoxic activity towards several tumor cell lines. In the present study, the in vivo antitumor activity of these compounds was evaluated in 60 female Swiss mice (N = 10 per group) transplanted with Sarcoma 180. Histopathological and morphological analyses of the tumor and the organs, including liver, spleen, and kidney, were performed in order to evaluate the toxicological aspects of the treatment with these amides. Administration of piplartine or piperine (50 or 100 mg kg -1 day -1 intraperitoneally for 7 days starting 1 day after inoculation) inhibited solid tumor development in mice transplanted with Sarcoma 180 cells. The inhibition rates were 28.7 and 52.3% for piplartine and 55.1 and 56.8% for piperine, after 7 days of treatment, at the lower and higher doses, respectively. The antitumor activity of piplartine was related to inhibition of the tumor proliferation rate, as observed by reduction of Ki67 staining, a nuclear antigen associated with G1, S, G2, and M cell cycle phases, in tumors from treated animals. However, piperine did not inhibit cell proliferation as observed in Ki67 immunohistochemical analysis. Histopathological analysis of liver and kidney showed that both organs were reversibly affected by piplartine and piperine treatment, but in a different way. Piperine was more toxic to the liver, leading to ballooning degeneration of hepatocytes, accompanied by microvesicular steatosis in some areas, than piplartine which, in turn, was more toxic to the kidney, leading to discrete hydropic changes of the proximal tubular and glomerular epithelium and tubular hemorrhage in treated animals.

It has been reported that piplartine and piperine, alkaloid/amide compounds from Piper species, show antitumor activities. In the present paper, the effects of the combination of 5-fluorouracil (5-FU) with piplartine or piperine was determined using in vitro and in vivo experimental models. Hematological and biochemical analyses, as well as histopathological and morphological analyses of the tumor and the organs, including liver, spleen and kidney, were performed in order to evaluate the toxicological aspects associated with different treatments. The incubation of tumor cell lines with 5-FU in the presence of piplartine or piperine produced an increase in growth inhibition, as observed by lower IC50 values for 5-FU. These effects were also observed in vivo, where the combination with piplartine but not piperine with 5-FU led to a higher tumor growth inhibition. The results indicated that either piplartine- or 5-FU-treated animals showed a low inhibition rate when they were used individually at low doses of 28.67% and 47.71%, respectively, but when they were combined at the same dose, the inhibition rate increased significantly to 68.04%. The histopathological analysis showed that the livers and the kidneys of treated animals were only slightly and reversibly affected. Neither the enzymatic activity of transaminases nor the urea levels were significantly modified when compared with the control group. Hematological analysis showed leukopenia after 5-FU treatment, which was reversed by the combined use of piplartine and piperine. These findings indicate that piplartine may enhance the therapeutic effectiveness of chemotherapeutic drugs, and moreover, this combination could improve immunocompetence hampered by 5-FU.

In recent years, much attention has been focused on polysaccharides isolated from natural sources. The aim of this study was to investigate the in vitro and in vivo antitumor properties of a sulfated polysaccharide isolated from the seaweed C. feldmannii (Cf-PLS). Hematological, biochemical and histopathological analyses were performed in order to evaluate the toxicological aspects related to Cf-PLS treatment. Its effects on the immunological system were also investigated. The Cf-PLS did not show any significant in vitro cytotoxicity at the experimental exposure levels that were used, but showed in vivo antitumor effect. The inhibition rates of sarcoma 180 tumor development were 48.62 and 48.16% at the doses of 10 and 25 mg kg(-1), respectively. In addition, Cf-PLS was also able to increase the response elicited by 5-fluorouracil (5-FU) from 48.66 to 68.32%. The histopathological analysis of liver and kidney showed that both organs were moderately affected by Cf-PLS-treatment. Neither enzymatic activity of alanine aminotransferase nor urea or creatinine levels were significantly altered. In hematological analysis, leucopeny was observed after 5-FU treatment, but this effect was prevented when the treatment was associated with the Cf-PLS. It was also demonstrated that Cf-PLS acts as an immunomodulatory agent, raising the production of specific antibodies, and increasing the production of OVA-specific antibodies. It also induced a discreet hyperplasia of lymphoid folicules of the white pulp in the spleen of treated mice. In conclusion, Cf-PLS has some interesting anticancer activity that could be associated with its immunostimulating properties.

The mortality rate associated with oral cancer is estimated at approximately 12,300 deaths per year, and the survival rate is only 40% to 50% for diagnosed patients and is closely related to the duration of time between disease perception and its diagnosis and treatment. Socioeconomic risk factors are determinants of the incidence and mortality related to oral cancer. We conducted a retrospective, cross-sectional study of 573 records of patients with oral cancer at Haroldo Juaçaba Hospital – Cancer Institute of Ceará from 2000 to 2009 to evaluate the influence of socioeconomic factors on survival and epidemiological behavior of this neoplasia in a Brazilian population. In this study, patients with oral cancer were males greater than 60 years of age, presented squamous cell carcinoma in the floor of mouth and were characterized by low education levels. A total of 573 lesions were found in oral cavities. Cox proportional hazards regression model showed that the histological type, tumor stage, and low degree of education significantly influenced survival. A lower patient survival rate was correlated with a more advanced stage of disease and a worse prognosis. Squamous cell carcinoma is associated with a higher mortality when compared with other histological types of malign neoplasia.

Tissue bioengineering development is a global concern and different materials are studied and created to be safe, effective and with low cost. Nile Tilapia skin had shown its biological potential as covers for the burn wound. This study evaluates the tilapia skin histological, collagen properties and tensiometric resistance, after treatment by different sterilization methods. Tilapia skin samples were submitted to two sterilization processes: (1) chemical, which consisted in two 2% chlorhexidin baths, followed by sequential baths in increasing glycerol concentrations; and (2) radiation, when glycerolized skin samples were submitted to gamma radiation at 25, 30 and 50 kGy. Microscopic analyzes were performed through Haematoxylin-eosin and Picrosirius Red under polarized light. For tensiometric analysis, traction tests were performed. Glycerol treated skin presented a discrete collagen fibers disorganization within the deep dermis, while irradiated skin did not show any additional change. Throughout the steps of chemical sterilization, there was a higher proportion of collagen with red/yellow birefringence (type I) in the skin samples up to the first bath in chlorhexidin, when compared to samples after the first two glycerol baths (P < 0.005). However, there was no difference in relation to total collagen between groups. In irradiated skin, there was a larger total collagen preservation when using until 30 kGy (P < 0.005). Tensiometric evaluation did not show significant differences in relation to maximum load in the groups studied. We concluded that chemical and radiation (25 and 30 kGy) are efficient methods to sterilize Nile Tilapia skin without altering its microscopic or tensiometric characteristics.

Purpose:To establish an experimental model of traumatic ulcer in rat cheek mucosa for utilization in future alternative therapy studies. Methods: A total of 60 adult male rats (250 -300g) were used. Ulceration of the left cheek mucosa was provoked by abrasion using a nº 15 scalpel blade. The animals were observed for 10 days, during which they were weighed and their ulcers were measured. The histological characteristics were analyzed and scored according to the ulcer phase. In the statistical analysis, a value of p<0.01 was considered a statistically significant response in all cases. Results: During the five first days, the animals lost weight (Student t test, p<0.01). The ulcerated area receded linearly over time and was almost completely cicatrized after 10 days (ANOVA, Tendency posttest, p<0.0001). Groups on days 1, 2 and 3 days displayed similar results, but a decrease in scores were observed after the 4th day. Conclusion: The proposed cheek mucosa ulcer model in rats can be considered an efficient, low-cost, reliable, and reproducible method. Key words: Ulcer. Mouth Mucosa. Wound Heling. Rats. RESUMOObjetivo: Estabelecer um modelo experimental de úlcera traumática em mucosa jugal de ratos para utilização em futuros testes de terapias alternativas. Métodos: Foram utilizados 60 ratos, adultos, machos, pesando entre 250 a 300g. A ulceração na mucosa jugal esquerda foi provocada por meio da abrasão desta com uma lâmina de bisturi número 15. Os animais foram observados por um período de 10 dias, sendo estes pesados e suas escoriações mensuradas. As características histológicas foram analisadas e descritas adotando escores para comparação dos estágios da fase da úlcera. Na análise estatística um valor de p<0,01 foi considerado uma resposta estatisticamente significante em todos os casos. Resultados: Durante os cinco primeiros dias os animais perderam peso ("t" Student -p<0,01). A área da úlcera regrediu linearmente com o tempo, estando quase que completamente cicatrizada ao final de dez dias (ANOVA, pós-teste de Tendência -p<0,0001). Os grupos do 1º, 2º e 3º dias tiveram comportamento semelhante havendo uma diminuição dos escores a partir do 4º dia. Conclusão: O modelo de úlcera na mucosa jugal de ratos proposto pode ser considerado eficaz, apresentando reprodutibilidade confiável e baixo custo. Descritores: Úlcera. Mucosa Bucal. Cicatrização de Feridas. Ratos. -Acta Cirúrgica Brasileira -Vol. 26 (3) 2011Alves APNN et al.

Skin substitutes are considered a useful alternative for occlusive dressings in the treatment of superficial burns as they reduce the frequency of dressing replacement. This phase II randomized controlled trial aimed to evaluate the efficacy of Nile tilapia (Oreochromis niloticus) skin as an occlusive xenograft dressing for the treatment of burn wounds in humans. In order to assess the use of tilapia skin, the following variables were evaluated: number of days for wound healing, the number of times the occlusive dressing was changed, use of anesthetics or analgesics, pain assessment using the Visual Analogue Scale, and evaluation of burn improvement on the day of dressing removal. In total, 62 participants completed the study. It was found that in participants treated with tilapia skin, complete reepithelialization occurred in significantly fewer days; reported pain intensity was lower (study arms B and C), the amount of anesthetics/analgesics required was lower (study arms B and C), and the necessity of dressing changes was significantly reduced in comparison with volunteers treated with silver sulfadiazine. In our study, the tilapia skin xenograft showed good efficacy as an occlusive biological dressing for burn wound treatment in humans.