The anticancer drug tamoxifen is active against Trypanosoma cruzi in vitro but ineffective in the treatment of the acute phase of Chagas disease in mice

The activity of the antineoplastic drug tamoxifen was evaluated against Trypanosoma cruzi. In vitro activity was determined against epimastigote, trypomastigote and amastigote forms of CL14, Y and Y benznidazole resistant T. cruzi strains. Regardless of the strain used, the drug was active against all life-cycle stages of the parasite with a half maximal effective concentration ranging from 0.7-17.9 µM. Two experimental models of acute Chagas disease were used to evaluate the in vivo efficacy of treatment with tamoxifen. No differences in parasitemia and mortality were observed between control mock-treated and tamoxifen-treated mice.FAPESPFIOCRUZCNP

Tri-n-butyltin Hydride-Mediated Radical Reactions of ortho- and meta-Iodobenzamides to Synthesize Benzomacrolactams. Surprising Formation of Biphenyl Compounds from meta-Regioisomers

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Reactions of methyl 4-O-allyl-2,3-di-O-benzyl-6-deoxy-6-(3-iodobenzoylamino)-alpha-D-galactopyranoside, its gluco epimer, methyl 2,3-di-O-benzyl-6-deoxy-6-(3-iodobenzoylamino)4-O-(1-pentenyl)-alpha-D-glucopyranoside and its ortho-regioisomer with tri-n-butyltin hydride were performed in different conditions. Depending on reaction conditions the three meta-iodo isomers gave a surprising amount of biphenyl compounds. The 2-iodo isomer led only to the undesired but expected hydrogenolysis product. No cyclized products were isolated in all the reactions. The structures of the new biphenyl products were elucidated by (1)H and (13)C NMR spectroscopy, DEPT, COSY, HMQC and HMBC experiments and ESI-MS/MS. Mechanisms for the formation of these new biphenyl derivatives and hypotheses to explain the different outcomes for radical reactions of 3- or 2-iodobenzamides were presented.20815041514Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Age-specific salivary immunoglobulin A response to Streptococcus mutans GbpB

In a follow-up study of children infected with Streptococcus mutans at an early age (children previously shown to respond poorly to S. mutans GbpB), there was a delay in their immune response, rather than a complete inability to respond to this antigen. Epitopes in the N-terminal third of GbpB were identified as targets for naturally induced immunoglobulin A antibody in children at an early age.14680480

Combining remote sensing and household level data for regional scale analysis of land cover change in the Brazilian Amazon

Land cover change in the Brazilian Amazon depends on the spatial variability of political, socioeconomic and biophysical factors, as well as on the land use history and its actors. A regional scale analysis was made in Rondônia State to identify possible differences in land cover change connected to spatial policies of land occupation, size and year of establishment of properties, accessibility measures and soil fertility. The analysis was made based on remote sensing data and household level data gathered with a questionnaire. Both types of analyses indicate that the highest level of total deforestation is found inside agrarian projects, especially in those established more than 20 years ago. Even though deforestation rates are similar inside and outside official settlements, inside agrarian projects forest depletion can exceed 50% at the property level within 10–14 years after establishment. The data indicate that both small-scale and medium to large-scale farmers contribute to deforestation processes in Rondônia State encouraged by spatial policies of land occupation, which provide better accessibility to forest fringes where soil fertility and forest resources are important determinants of location choic

A new thiocyanoacetamide (2-cyano-2-p-nitrophenyl-N-benzylthioamide) reduces doxorubicin-induced in vitro toxicity in Sertoli cells by decreasing apoptosis and autophagy

Despite conflicting data on doxorubicin (DOX) reproductive toxicity, its chemotherapeutic potential sustains its use to treat different types of cancer. This work was designed to study the protective effect of a newly synthesized thiocyanoacetamide (TA), in comparison with selenium (Se), against doxorubicin-induced in vitro toxicity in rat Sertoli cells (SCs). DOX was administered alone or in combination with Se or TA. The possible protective role of increased concentrations of TA (0.25, 0.5 and 1 mM) or Se (12, 25 and 50 mu M) on SCs was tested against 1 mu M of DOX. From this screening, only the least toxic doses of TA and Se were used for further analysis. DOX cytotoxicity, as well as its impact on SCs viability, mitochondria) membrane potential (Delta Psi(m)), oxidative stress biomarkers, apoptosis and autophagy were assessed. Our results showed that DOX exerted its cytotoxic effect through a significant increase in cell death. DOX-mediated cell death was not related to autophagy nor to an overproduction of reactive oxygen species. It was rather due to apoptosis, as shown by the increased number of apoptotic cells and increased activity of caspase-3, or due to necrosis, as shown by the increase in lactate dehydrogenase (LDH) extracellular activity. Still, Bax and Bcl-2 protein expression levels, as well as Delta Psi(m) were not altered by the different treatments. Some individual doses of Se or TA induced a significant toxicity in SCs, however, when combined with DOX, there was a decrease in cell death, LDH extracellular activity, number of apoptotic cells and caspase-3 activity. Overall, our results indicate that DOX-mediated apoptosis in cultured SCs can possibly be averted through its association with specific doses of Se or TA. Nevertheless, TA showed a higher efficiency than Se in reducing DOX-induced toxicity in SCs by decreasing not only apoptosis, but also necrosis and autophagy. (C) 2019 Elsevier Inc. All rights reserved

Association between canine leishmaniosis and Ehrlichia canis co-infection: a prospective case-control study

Abstract Background In the Mediterranean basin, Leishmania infantum is a major cause of disease in dogs, which are frequently co-infected with other vector-borne pathogens (VBP). However, the associations between dogs with clinical leishmaniosis (ClinL) and VBP co-infections have not been studied. We assessed the risk of VBP infections in dogs with ClinL and healthy controls. Methods We conducted a prospective case-control study of dogs with ClinL (positive qPCR and ELISA antibody for L. infantum on peripheral blood) and clinically healthy, ideally breed-, sex- and age-matched, control dogs (negative qPCR and ELISA antibody for L. infantum on peripheral blood) from Paphos, Cyprus. We obtained demographic data and all dogs underwent PCR on EDTA-blood extracted DNA for haemoplasma species, Ehrlichia/Anaplasma spp., Babesia spp., and Hepatozoon spp., with DNA sequencing to identify infecting species. We used logistic regression analysis and structural equation modelling (SEM) to evaluate the risk of VBP infections between ClinL cases and controls. Results From the 50 enrolled dogs with ClinL, DNA was detected in 24 (48%) for Hepatozoon spp., 14 (28%) for Mycoplasma haemocanis, 6 (12%) for Ehrlichia canis and 2 (4%) for Anaplasma platys. In the 92 enrolled control dogs, DNA was detected in 41 (45%) for Hepatozoon spp., 18 (20%) for M. haemocanis, 1 (1%) for E. canis and 3 (3%) for A. platys. No Babesia spp. or “Candidatus Mycoplasma haematoparvum” DNA was detected in any dog. No statistical differences were found between the ClinL and controls regarding age, sex, breed, lifestyle and use of ectoparasitic prevention. A significant association between ClinL and E. canis infection (OR = 12.4, 95% CI: 1.5–106.0, P = 0.022) was found compared to controls by multivariate logistic regression. This association was confirmed using SEM, which further identified that younger dogs were more likely to be infected with each of Hepatozoon spp. and M. haemocanis, and dogs with Hepatozoon spp. were more likely to be co-infected with M. haemocanis. Conclusions Dogs with ClinL are at a higher risk of co-infection with E. canis than clinically healthy dogs. We recommend that dogs diagnosed with ClinL should be tested for E. canis co-infection using PCR

Submillimeter Studies of Prestellar Cores and Protostars: Probing the Initial Conditions for Protostellar Collapse

Improving our understanding of the initial conditions and earliest stages of protostellar collapse is crucial to gain insight into the origin of stellar masses, multiple systems, and protoplanetary disks. Observationally, there are two complementary approaches to this problem: (1) studying the structure and kinematics of prestellar cores observed prior to protostar formation, and (2) studying the structure of young (e.g. Class 0) accreting protostars observed soon after point mass formation. We discuss recent advances made in this area thanks to (sub)millimeter mapping observations with large single-dish telescopes and interferometers. In particular, we argue that the beginning of protostellar collapse is much more violent in cluster-forming clouds than in regions of distributed star formation. Major breakthroughs are expected in this field from future large submillimeter instruments such as Herschel and ALMA.Comment: 12 pages, 9 figures, to appear in the proceedings of the conference "Chemistry as a Diagnostic of Star Formation" (C.L. Curry & M. Fich eds.

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available