Medicinal Plants of Chile: Evaluation of their Anti-Trypanosoma cruzi Activity

San Martin, J (San Martin, Jose). Univ Talca, Inst Biol Vegetal & Biotecnol, Talca, ChileThe extracts of several plants of Central Chile exhibited anti-Trypanosoma cruzi trypomastigotes activity. Most active extracts were those obtained from Podanthus ovatifolius, Berberis microphylla, Kageneckia oblonga, and Drimys winteri. The active extract of Drimys winteri (IC50 51.2 mu g/mL) was purified and three drimane sesquiterpenes were obtained: polygodial, drimenol, and isodrimenin. Isodrimenin and drimenol were found to be active against the trypomastigote form of T cruzi with IC50 values of 27.9 and 25.1 mu M, respectivel

Target highlights in CASP13: experimental target structures through the eyes of their authors

The functional and biological significance of selected CASP13 targets are described by the authors of the structures. The structural biologists discuss the most interesting structural features of the target proteins and assess whether these features were correctly reproduced in the predictions submitted to the CASP13 experiment

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Participation of proteases in the infection of human Chorionic villi explants by Trypanosoma cruzi

Meeting Abstrac

Trypanasoma cruzi induces cellular proliferation in the trophoblastic cell line bewo

Droguett, D (Droguett, Daniel)[ 1,2 ]. [ 1 ] Univ Chile, Fac Med, Inst Biomed Sci, Santiago 7, Chile [ 2 ] Univ Talca, Fac Ciencias Salud, Talca, ChileChagas’ disease is caused by the haemophlagelated protozoan Trypanosoma cruzi (T. cruzi), which is able to cross the placental barrier and infect both the placenta and fetus. In ex vivo infected human chorionic villi, a low concentration of parasite induces activation of the Mitogen Activated Protein Kinase (MAPK) ERK1/2 signaling pathway, which plays an important role in cellular proliferation and differentiation. In order to determine whether the parasite is able to induce cellular proliferation in the trophoblast, BeWo cells were incubated in presence and absence of T. cruzi trypomastigotes (Y strain) (ratio parasite/BeWo cells 1:10) and in presence and absence of FBS for 2, 6, 12 and 24 hours. DNA synthesis was assayed by bromodeoxyuridine (BrdU) incorporation and determined by spectrometry and immunocytochemistry. Mitotic index was determined in DAPI stained samples and cell growth by detection of Nucleolar organizer regions (NORs) using silver staining (AgNORs). Parasites inside cells were identified by their nuclear and kinetoplast morphology. At least 500 cells were counted in each condition and analyzed using the MATLAB software; the statistical significance was analyzed by ANOVA followed by the Dunnetts post-test. The low concentration of T. cruzi used (mimicking women with chronic Chagas disease) induces a significant increase of BrdU incorporation into DNA and in the number of mitosis and of NORs in BeWo cells. We conclude that T. cruzi induces cell proliferation in the trophoblast; this process may form part of a “local placental antiparasite” defense mechanism. Financed by FONDECYT Projects Nº1120230 (UK), Nº 1130189 (JM), Nº1130113 (NG), 1120579 (SH). Support of CONICYT-PBCT Anillo ACT 112 and ICM (P09-015-F), Chile is also acknowledged

rypanosoma cruzi induces apoptosis in ex vivo infected human chorionic villi

Kemmerling, U (Kemmerling, U.). Univ Talca, Fac Ciencias Salud, Dept Estomatol, Talca, ChileChagas' disease, produced by the haemoflagellated protozoan Trypanosoma cruzi (T. cruzi), is one of the most frequent endemic diseases in Latin America. In spite that in the past few years T. cruzi congenital transmission has become of epidemiological importance, studies about this mechanism of infection are scarce. The placental tissue undergoes apoptosis throughout gestation, as part of its normal turnover. On the other hand, it is known that T cruzi induces, delays or inhibits apoptosis in other mammalian tissues. In order to determine the effect of parasite invasion on normal apoptosis in the placenta, explants of human chorionic villi were incubated with 105 trypomastigotes for 24 h. Effective infection was tested by visualizing T cruzi antigens in histological preparations and by PCR. Upon infection, apoptotic cell death was determined by light and transmission electron microscopy, TUNEL analysis, measurement of caspase-3 like activity and immunohistochemical detection of caspase 3 cleaved cytokeratin 18. Our results clearly show that T cruzi induces apoptosis in the chorionic villi and suggest that this is one of mechanisms used by the parasite to insure infection and invasion of human placenta and fetus. (C) 2011 Elsevier Ltd. All rights reserve