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31.
da Silva Júnior EN de Souza MC Pinto AV Pinto Mdo C Goulart MO Barros FW Pessoa C Costa-Lotufo LV Montenegro RC de Moraes MO Ferreira VF 《Bioorganic & medicinal chemistry》2007,15(22):7035-7041
Several arylamino derivatives of nor-beta-lapachone were synthesized in moderate to high yields and found to show very potent cytotoxicity against six neoplastic cancer cells: SF-295 (central nervous system), HCT-8 (colon), MDAMB-435 (breast), HL-60 (leukaemia), PC-3 (prostate), and B-16 (murine melanoma), with IC(50) below 1 microg/mL. Their cytotoxicities were compared to doxorubicin and with their synthetic precursors, beta-lapachone and nor-beta-lapachone. The activity against a normal murine fibroblast L-929 showed that some of the compounds were selective against cancer cells. The absence of hemolytic activity (EC(50)>200 microg/mL), performed with erythrocyte suspensions, suggests that the cytotoxicity of the compounds was not related to membrane damage of mouse erythrocytes. For comparison purposes, one isomeric compound based on nor-alpha-lapachone was also synthesized and showed lower activity than the related ortho-derivative. The modified arylamino quinones appear as interesting new lead compounds in anti-cancer drug development. 相似文献
32.
Marinho CC Voieta I Azeredo LM Nishi MP Batista TS Pereira AC Serufo JC Queiroz LC Ruiz-Guevara R Antunes CM Prata A Lambertucci JR 《Memórias do Instituto Oswaldo Cruz》2006,101(Z1):317-321
The best way to appraise the size of abdominal organs remains undefined. Herein we compare the size of liver and spleen in hepatosplenic schistosomiasis using clinical and ultrasound (US) examination, and the size of the organs measured by US with their visualization below the costal margin ("palpable by US"). For this study, 411 individuals from an endemic area for schistosomiasis mansoni in Brazil have been selected. We found that palpable spleens and left liver lobes are larger than non palpable ones. Also, 23% of normal spleens measured by US were palpable on clinical examination, and 22% of spleens increased in size on US were non palpable. A total of 21% of normal spleens were "palpable by US". We also found 54% of normal sized right liver lobes palpable on clinical examination, whilst 54% of the increased livers, measured by US, were non palpable. About 76% of normal right liver lobes were "palpable by US". We conclude that the association of clinical, ultrasound and magnetic resonance imaging (MRI) examinations, in the near future, should give the investigators the necessary tools to perform a more accurate clinical diagnosis of hepatosplenic schistosomiasis mansoni. 相似文献
33.
dos Santos AL Abreu CM Batista LM Alviano CS de Araújo Soares RM 《Current microbiology》2001,43(2):100-106
The proteinase profile of Blastocrithidia culicis was analyzed, as well as how different growth conditions influenced its expression by gelatin-SDS-PAGE and the use of specific
proteinase inhibitors. Multiple cell-associated proteinases with molecular masses corresponding to 33, 55, 60 kDa (cysteine
proteinases) and 77, 80, 90, and 108 kDa (metalloproteinases) were detected using these methods. All the metalloproteinases
identified were partitioned into the detergent phase after Triton X-114 extract, suggesting that they are membrane-bound,
while all cysteine proteinases were partitioned into the aqueous phase. The proteolytic zymograms were similar when three
different media were used for variable times of incubation. However, few quantitative and qualitative changes were observed.
The secreted proteinase profile showed an heterogeneous pattern of enzymatic activities whose expression was dependent on
time of growth and medium composition. However, the extracellular proteinase activities were abolished by 1,10-phenanthroline,
suggesting that all of them are zinc-metalloproteinases.
Received: 25 October 2000 / Accepted: 10 January 2001 相似文献
34.
Guilherme Rocha Melo Gondim Fabiana Baroni Alves Makdissi Ricardo Cesar Fogaroli Juan Bautista Donoso Collins Hirofumi Iyeyasu Douglas Guedes de Castro Maria Letícia Gobo Silva Michael Jenwei Chen Tharcisio Machado Coelho Henderson Ramos Antônio Cássio Assis Pellizzon 《Reports of Practical Oncology and Radiotherapy》2019,24(6):551-555
BackgroundWhole breast irradiation reduces loco-regional recurrence and risk of death in patients submitted to breast-conserving treatment. Data show that radiation to the index quadrant alone may be enough in selected patients.AimTo report the experience with intra-operative radiotherapy (IORT) with Electron-beam Cone in Linear Accelerator (ELIOT) and the results in overall survival, local control and late toxicity of patients submitted to this treatment.Materials and Methods147 patients treated with a median follow up of 6.9 years (0.1?11.5 years). The actuarial local control and overall survival probabilities were estimated using the Kaplan Meier method. All tests were two-sided and p ? 0.05 was considered statistically significant.ResultsOverall survival of the cohort in 5 years, in the median follow up and in 10 years was of 98.3%, 95.1% and 95.1%, respectively, whereas local control in 5 years, in the median follow up and in 10 years was of 96%, 94.9% and 89.5%, respectively. Two risk groups were identified for local recurrence depending on the estrogen or progesterone receptors, axillary or margin status and lymphovascular invasion (LVI) (p = 0.016).ConclusionsIORT is a safe and effective treatment. Rigorous selection is important to achieve excellent local control results. 相似文献
35.
36.
Alexandre Grangeiro Maria Mercedes Escuder Alex Jones Flores Cassanote Rosa Alencar Souza Artur O. Kalichman Valdiléa Veloso Maria Letícia Rodrigues Ikeda Nêmora Tregnago Barcellos Carlos Brites Unai Tupinanbás Noaldo O. Lucena Carlos Lima da Silva Heloisa Ramos Lacerda Beatriz Grinsztejn Euclides Ayres Castilho 《PloS one》2014,9(5)
Background
The HIV-Brazil Cohort Study was established to analyze the effectiveness of combination antiretroviral therapy (cART) and the impact of this treatment on morbidity, quality of life (QOL) and mortality. The study design, patients’ profiles and characteristics of cART initiation between 2003 and 2010 were described.Methodology/Principal Findings
Since 2003, the HIV-Brazil Cohort has been following HIV-infected adults receiving cART at 26 public health care facilities, using routine clinical care data and self-reported QOL questionnaires. When not otherwise available, data are obtained from national information systems. The main outcomes of interest are diseases related or unrelated to HIV; suppression of viral replication; adverse events; virological, clinical and immunological failures; changes in the cART; and mortality. For the 5,061 patients who started cART between 2003 and 2010, the median follow-up time was 4.1 years (IQR 2.2–5.9 years) with an 83.4% retention rate. Patient profiles were characterized by a predominance of men (male/female ratio 1.7∶1), with a mean age of 36.9 years (SD 9.9 years); 55.2% had been infected with HIV via heterosexual contact. The majority of patients (53.4%) initiated cART with a CD4+ T-cell count ≤200 cells/mm3. The medications most often used in the various treatment regimens were efavirenz (59.7%) and lopinavir/ritonavir (18.2%). The proportion of individuals achieving viral suppression within the first 12 months of cART use was 77.4% (95% CI 76.1–78.6). Nearly half (45.4%) of the patients presented HIV-related clinical manifestations after starting cART, and the AIDS mortality rate was 13.9 per 1,000 person-years.Conclusions/Significance
Results from cART use in the daily practice of health services remain relatively unknown in low- and middle-income countries, and studies with the characteristics of the HIV-Brazil Cohort contribute to minimizing these shortcomings, given its scope and patient profile, which is similar to that of the AIDS epidemic in the country. 相似文献37.
38.
Letícia B. Rocha Anna R. R. Santos Danielle D. Munhoz Lucas T. A. Cardoso Daniela E. Luz Fernanda B. Andrade Denise S. P. Q. Horton Waldir P. Elias Roxane M. F. Piazza 《PLoS neglected tropical diseases》2014,8(9)
Background
Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC/EHEC) are human intestinal pathogens responsible for diarrhea in both developing and industrialized countries. In research laboratories, EPEC and EHEC are defined on the basis of their pathogenic features; nevertheless, their identification in routine laboratories is expensive and laborious. Therefore, the aim of the present work was to develop a rapid and simple assay for EPEC/EHEC detection. Accordingly, the EPEC/EHEC-secreted proteins EspA and EspB were chosen as target antigens.Methodology
First, we investigated the ideal conditions for EspA/EspB production/secretion by ELISA in a collection of EPEC/EHEC strains after cultivating bacterial isolates in Dulbecco’s modified Eagle’s medium (DMEM) or DMEM containing 1% tryptone or HEp-2 cells-preconditioned DMEM, employing either anti-EspA/anti-EspB polyclonal or monoclonal antibodies developed and characterized herein. Subsequently, a rapid agglutination latex test (RALT) was developed and tested with the same collection of bacterial isolates.Principal findings
EspB was defined as a biomarker and its corresponding monoclonal antibody as the tool for EPEC/EHEC diagnosis; the production of EspB was better in DMEM medium. RALT assay has the sensitivity and specificity required for high-impact diagnosis of neglected diseases in the developing world.Conclusion
RALT assay described herein can be considered an alternative assay for diarrhea diagnosis in low-income countries since it achieved 97% sensitivity, 98% specificity and 97% efficiency. 相似文献39.
Matheus Balduíno Goncalves dos Reis Letícia Correa Manjolin Claudia do Carmo Maquiaveli Osvaldo Andrade Santos-Filho Edson Roberto da Silva 《PloS one》2013,8(11)
Epigallocatechin-3-gallate (EGCG), a dietary polyphenol (flavanol) from green tea, possesses leishmanicidal and antitrypanosomal activity. Mitochondrial damage was observed in Leishmania treated with EGCG, and it contributed to the lethal effect. However, the molecular target has not been defined. In this study, EGCG, (+)-catechin and (−)-epicatechin were tested against recombinant arginase from Leishmania amazonensis (ARG-L) and rat liver arginase (ARG-1). The compounds inhibit ARG-L and ARG-1 but are more active against the parasite enzyme. Enzyme kinetics reveal that EGCG is a mixed inhibitor of the ARG-L while (+)-catechin and (−)-epicatechin are competitive inhibitors. The most potent arginase inhibitor is (+)-catechin (IC50 = 0.8 µM) followed by (−)-epicatechin (IC50 = 1.8 µM), gallic acid (IC50 = 2.2 µM) and EGCG (IC50 = 3.8 µM). Docking analyses showed different modes of interaction of the compounds with the active sites of ARG-L and ARG-1. Due to the low IC50 values obtained for ARG-L, flavanols can be used as a supplement for leishmaniasis treatment. 相似文献
40.
Barros FW Bandeira PN Lima DJ Meira AS de Farias SS Albuquerque MR dos Santos HS Lemos TL de Morais MO Costa-Lotufo LV Pessoa Cdo Ó 《Bioorganic & medicinal chemistry》2011,19(3):1268-1276
Four derivatives of an α,β-amyrin mixture were synthesized by acylation with appropriate anhydrides. The structures of the compounds were confirmed by means of IR and (1)H and (13)C NMR. The compounds were screened for cytotoxic activity using four human tumor cell lines (HL-60, MDAMB-435, SF-295 and HCT-8) and normal peripheral blood mononuclear cells (PBMC). 3-O-Carboxymaleinate of α,β-amyrin (3a/3b) were found to be the only active compounds of the series (high cytotoxicity), showing IC(50) values ranging from 1.8 to 3μM. In PBMC, 3a/3b were not toxic, suggesting selectivity for tumor cells. To better understand the mechanism of action involved in the cytotoxicity of 3a/3b, HL-60 cells treated with 3a/3b were examined for morphological changes, DNA fragmentation, cell cycle perturbation, externalization of phosphatidylserine and activation of caspases 3/7, with doxorubicin serving as the positive control. The results indicate that the cytotoxicity of 3a/3b involves the induction of cell death by apoptosis. 相似文献