The potential antiangiogenic and antitumoral properties of SargA, a polysaccharide extracted from the brown marine alga Sargassum stenophyllum, were studied in assays carried out in chick embryos and mice. Gelfoam plugs containing SargA (2-1500 microg/plug) implanted in vivo into fertilized 6-day-old chicken eggs induced dose-related antiangiogenic activity in the chorioallantoic membrane (CAM). By day 8, the highest dose of SargA alone decreased the vessel number in the CAM by 64%, but coadministered with hydrocortisone (156 microg/plug, which alone caused 30% inhibition) failed to potentiate its antiangiogenic effect. Combined with basic fibroblast growth factor (50 ng/plug), SargA (1500 microg/plug) abolished angiogenesis stimulated by this factor in both chick embryo CAM and in subcutaneous (s.c.) Gelfoam plugs implanted in the dorsal skin of Swiss mice (measured as plug hemoglobin content). Repeated s.c. injections of SargA (1.5 or 150 microg per animal per day for 3 days) close to B16F10 melanoma cell tumors in the dorsal skin of mice markedly decreased tumor growth in a dose-related fashion (by 40% and 80% at 2 weeks after the first injection, respectively), without evident signs of toxicity. SargA caused graded inhibitions of migration and viability of cultured B16F10 cells and also displayed antithrombotic activity in human plasma (5 mg/ml increased thrombin time 2.5-fold relative to saline). Thus, SargA exhibits pronounced antiangiogenic as well as antitumoral properties. Although the latter action of SargA might be related to the inhibition of angiogenesis, the polysaccharide also exerts cytotoxic effects on tumor cells. Because of its chemical characteristics and polyanionic constituents, we postulate that the polysaccharide SargA might modulate the activity of heparin-binding angiogenic growth factors.
Glyphosate [N-(phosphonomethyl)-glycine] is a broad-spectrum, non-selective, postemergence herbicide that is extensively used in agriculture. Published data referring to the effects of this product on human health are contradictory. We showed previously that long-term treatment of rats with low doses of Glyphosate-Biocarb® may induce hepatic histological changes and bleeding without decreasing platelet counts. The aim of the current study was to investigate, in vitro, the effect of glyphosate on human blood platelet aggregation and coagulation. Materials and methods: Platelet aggregation was determined in the platelet-rich plasma using the agents: 6 µM-adenosine diphosphate, 6 µM-epinephrine and 4µg/mL-collagen. Pretreatment with 500 µg/mL glyphosate showed significant hypofunction of the three aggregating agents. The inhibitory effect was dose-dependent at concentrations from 50 to 500 µg/mL. The release of ATP was lower for glyphosate-treated platelets after stimulation by collagen. On the other hand, glyphosate did not promote any inhibitory effects on prothrombin time, thromboplastin time and thrombin time. In conclusion, the results demonstrate that glyphosate promotes changes in the platelet metabolism with an inhibitory effect on primary hemostasis. Rev. Bras. Hematol. Hemoter. 2010;32(4):291-294. Aceito após modificações: 08/06/2010 efeito inibitório na hemostasia primária. Rev. Bras. Hematol. Hemoter. 2010;32(4):291-294.Palavras-chave: Glifosato; agregação plaquetária; secreção plaquetária; coagulação sanguínea; resistência ao herbicida.
Chronic Myeloid Leukemia (CML) is a myeloproliferative disease characterized by the presence of the Philadelphia chromosome (translocation between chromosomes 9 and 22), resulting in the formation of the hybrid BCR-ABL protein. Currently, the treatment of CML patients is performed with imatinib mesylate (IM), which promotes the elimination of leukemic cells by inhibiting the kinase activity of BCR-ABL. This study evaluated the effectiveness of IM by monitoring 22 CML patients in a chronic phase treated at the CEPON/SC with IM for a minimum follow-up period of two years. Cytogenetic Response (CR) and bone marrow biopsies (BMB) were evaluated before and after IM treatment. BMB were evaluated by detection of reticulin degree and vascularization. The results were correlated to the CR. Mean time to achieve CR was 9 months and was attained by 77.27% of the patients. The results from the initial BMB analysis showed that 59.09% presented reticulin of between 2+ and 4+ whereas after treatment, only 27.17% presented this degree. With regard to vascularization of the initial sample, 90.91% were graded between II and IV, whereas after treatment, 40.91% had this degree. The results suggest a positive correlation of degree of reticulin and vascularization with CR.Uniterms: Chronic myeloid leukemia/treatment. Imatinib mesylate/effectiveness/leukemia treatment. Bone marrow/biopsies. Fibrosis. Vascularization.A Leucemia Mielóide Crônica (LMC) é uma doença mieloproliferativa caracterizada pela presença do cromossomo Filadélfia (translocação entre os cromossomos 9 e 22), que resulta na formação da proteína híbrida BCR-ABL. Atualmente o tratamento de pacientes com LMC é realizado com mesilato de imatinibe (MI), o qual promove a eliminação das células leucêmicas pela inibição da atividade quinase de BCR-ABL. O presente estudo avaliou a eficácia do MI por meio do acompanhamento de pacientes portadores de LMC em fase crônica, atendidos no CEPON/SC tratados com MI pelo tempo mínimo de dois anos. Foram avaliadas a Resposta Citogenética (RC) e as biópsias de medula óssea (BMO) antes e após o tratamento com MI. As BMO foram avaliadas quanto ao grau de reticulina e vascularização. Os resultados correlacionaram-se com a RC cujo tempo médio para obtenção da RC foi de 9 meses, sendo atingida por 77.27% dos pacientes. Na primeira BMO, 59.09% dos pacientes apresentaram grau de reticulina entre 2+ e 4+ e após o tratamento, apenas 27.17% apresentaram esta graduação. Quanto à vascularização da primeira amostra, 90.91% foram graduadas entre II e IV e após o tratamento, 40.91% apresentaram esta graduação. Os resultados sugerem uma correlação diretamente proporcional entre os graus de reticulina e vascularização com a RC.
We investigated the effects of Candida albicans, Cryptococcus neoformans and the respective culture supernatants on human platelet aggregation (PA). Both yeasts were unable to aggregate the platelets directly. On the other hand, cells of these yeasts significantly (P < 0.01) inhibited PA at concentrations equal to or higher than 1 x 10 6 cells/mL for C. albicans and equal to or higher than 1 x 10 5 cells/mL for C. neoformans. When the supernatants of one-week broth cultures were added to the activated platelets no inhibition in aggregation was observed. Apparently somatic components of these yeasts, but not their metabolic products, exert an antagonistic effect on the aggregation of human platelets, possibly aiding the fungi in their evasion of the microbicidal defense system during vascular dissemination.
Croton celtidifolius Baill is a tree found in the Atlantic
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