CLEUSA FUMICA HIRATA TAKAKURA

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Departamento de Patologia, Faculdade de Medicina

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  • article 7 Citação(ões) na Scopus
    Nitro-Heterocyclic compounds induce apoptosis-like effects in Leishmania (L). amazonensis promastigotes
    (2019) MENDONCA, Daiane Barros Dias; SILVA, Renata Ellen Costa; PALACE-BERL, Fanny; TAKAKURA, Cleusa F. H.; SOARES, Sandra Regina C.; BRAZ, Lucia Maria Almeida; TAVARES, Leoberto Costa; LINDOSO, Jose Angelo Lauletta
    Background: Three drugs - pentavalent antimonials, amphotericin B and pentamidine - are currently used for leishmaniasis treatment. They are administered for long periods, only parenterally, and have high cardiac, renal and hepatic toxicities. Therefore, the investigation of new compounds is required. Nitro-heterocyclic derivatives have been used as possible drug candidates to treat diseases caused by trypanosomatids. Methods: Leishmania (L.) amazonensis promastigotes (MHO/BR/73/M2269), maintained in the Laboratorio de Soroepidemiologia - Instituto de Medicina Tropical-USP, were exposed to five nitroheterocyclic derivatives, with differences at phenyl-ring position 4: BSF-C4H9, BSF-H, BSF-NO2, BSF-CH3 and BSF-Cl, for 48 hours. After analyzing viability (MTT assay), we evaluated cellular-morphology activity of compounds by transmission electron microscopy (TEM) and measurement of apoptosis (phosphatidylserine expression) by flow cytometry. Results: EC50 of amphotericin B and BSF-CH3 were 0.50 mu M and 0.39 mu M respective. Other nitro-heterocyclic compounds presented EC50 higher than amphotericin B. All compounds showed greater AV - and PI-positive expression than amphotericin B at 100 mu M, except BSF-NO2. TEM showed complete nuclear disfigurement with 100 mu M of BSF-NO2, 25 and 6.25 mu M of BSF-H, and 6.25 mu M BSF-Cl; presence of vesicles within the flagellar pocket with 25 mu M BSF-H; alteration of the kinetoplast with 25 mu M BSF-C4H9, 25 mu M of BSF-H, 6.25 mu M BSF-CH3 and 6.25 mu M of BSF-Cl. Conclusions: Nitro-heterocyclic compounds have shown activity against promastigotes of L. amazonensis, at lower concentrations. However, improvement of compound scaffolds are needed to assist the elucidation of the mechanism of action and to achieve greater activity.
  • article 28 Citação(ões) na Scopus
    Yellow fever and orthotopic liver transplantation: new insights from the autopsy room for an old but re-emerging disease
    (2019) DUARTE-NETO, Amaro N.; CUNHA, Marielton dos P.; MARCILIO, Izabel; SONG, Alice T. W.; MARTINO, Rodrigo B. de; HO, Yeh-Li; POUR, Shahab Z.; DOLHNIKOFF, Marisa; SALDIVA, Paulo H. N.; DUARTE, Maria I. S.; TAKAKURA, Cleusa F.; LIMA, Fabiana R.; TANIGAWA, Ryan Y.; IGLEZIAS, Silvia D'A; KANAMURA, Cristina T.; SANTOS, Angela B. G. dos; PERONDI, Beatriz; ZANOTTO, Paolo M. de A.; D'ALBUQUERQUE, Luiz A. C.; ALVES, Venancio A. F.
    Aims The clinical spectrum of yellow fever (YF) ranges from asymptomatic to fulminant hepatitis. During the sylvatic YF epidemic in the metropolitan area of Sao Paulo, Brazil in 2018, seven orthotopic liver transplantations (OLTs) were performed in our institution to treat fulminant YF hepatitis. Three patients recovered, while four patients died following OLT. The autopsy findings of all these cases are presented herein as the first description of YF in transplanted patients. Methods and results All patients were men, aged 16-40 years, without vaccination to YF virus (YFV). All organs were examined, with tissue sampling for histopathological analysis. Detection of YF virus antigens (YFV Ag) was performed with two primary antibodies (mouse polyclonal anti-YFV antibody directed to wild strain and a goat anti-YF virus antibody), and RT-PCR assays were utilised to detect YFV-RNA. All the cases depicted typical findings of YF hepatitis in the engrafted liver. The main extrahepatic findings were cerebral oedema, pulmonary haemorrhage, pneumonia, acute tubular necrosis and ischaemic/reperfusion pancreatitis. Of the four cases, the YVF Ag was detected in the heart in one case, liver and testis in three cases, and the kidney and spleen in all four cases. All four cases had YF virus RNA detected by RT-PCR in the liver and in other organs. Conclusions Infection of the engrafted liver and other organs by YFV, possibly combined with major ischaemic systemic lesions, may have led to the death of four of the seven patients undergoing OLT.