Metformin Treatment Modulates The Tumour-induced Wasting Effects In Muscle Protein Metabolism Minimising The Cachexia In Tumour-bearing Rats

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)Cancer-cachexia state frequently induces both fat and protein wasting, leading to death. In this way, the knowledge of the mechanism of drugs and their side effects can be a new feature to treat and to have success, contributing to a better life quality for these patients. Metformin is an oral drug used in type 2 diabetes mellitus, showing inhibitory effect on proliferation in some neoplastic cells. For this reason, we evaluated its modulatory effect on Walker-256 tumour evolution and also on protein metabolism in gastrocnemius muscle and body composition. Methods: Wistar rats received or not tumour implant and metformin treatment and were distributed into four groups, as followed: control (C), Walker 256 tumour-bearing (W), metformin-treated (M) and tumour-bearing treated with metformin (WM). Animals were weighed three times a week, and after cachexia state has been detected, the rats were euthanised and muscle and tumour excised and analysed by biochemical and molecular assays. Results: Tumour growth promoted some deleterious effects on chemical body composition, increasing water and decreasing fat percentage, and reducing lean body mass. In muscle tissue, tumour led to a decreased protein synthesis and an increased proteolysis, showing the higher activity of the ubiquitin-proteasome pathway. On the other hand, the metformin treatment likely minimised the tumour-induced wasting state; in this way, this treatment ameliorated chemical body composition, reduced the higher activities of proteolytic enzymes and decreased the protein waste. Conclusion: Metformin treatment not only decreases the tumour growth but also improves the protein metabolism in gastrocnemius muscle in tumour-bearing rats.16Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP [2010/00209-9, 2013/16115-1, 2014/13334-7]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - CNPq [304604/2010-0, 302863/2013-3]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP, Sao Paulo, Brazil [2008/07737-0]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

An End-to-End Approach for Recognition of Modern and Historical Handwritten Numeral Strings

An end-to-end solution for handwritten numeral string recognition is proposed, in which the numeral string is considered as composed of objects automatically detected and recognized by a YoLo-based model. The main contribution of this paper is to avoid heuristic-based methods for string preprocessing and segmentation, the need for task-oriented classifiers, and also the use of specific constraints related to the string length. A robust experimental protocol based on several numeral string datasets, including one composed of historical documents, has shown that the proposed method is a feasible end-to-end solution for numeral string recognition. Besides, it reduces the complexity of the string recognition task considerably since it drops out classical steps, in special preprocessing, segmentation, and a set of classifiers devoted to strings with a specific length

Oxygen Gas Phase Abundance Revisited

We present new measurements of the interstellar gas-phase oxygen abundance along the sight lines towards 19 early-type galactic stars at an average distance of 2.6 kpc. We derive O {\small I} column densities from {\it HST}/STIS observations of the weak 1355 \AA intersystem transition. We derive total hydrogen column densities [N(H {\small I})+2N(H$_2$)] using {\it HST}/STIS observations of \lya and {\it FUSE} observations of molecular hydrogen. The molecular hydrogen content of these sight lines ranges from f(H$_2$) = 2N(H$_2$)/[N(H {\small I})+2N(H$_2$)] = 0.03 to 0.47. The average $$ of 6.3$\times10^{21}$ cm$^{-2}$ mag$^{-1}$ with a standard deviation of 15% is consistent with previous surveys. The mean oxygen abundance along these sight lines, which probe a wide range of galactic environments in the distant ISM, is 10$^6$ \oh = $408 \pm 13$ (1 $\sigma$ in the mean). %$({\rm O/H})_{gas} = 408 \pm 14$(1 $\sigma$). We see no evidence for decreasing gas-phase oxygen abundance with increasing molecular hydrogen fraction and the relative constancy of \oh suggests that the component of dust containing the oxygen is not readily destroyed. We estimate that, if 60% of the dust grains are resilient against destruction by shocks, the distant interstellar total oxygen abundance can be reconciliated with the solar value derived from the most recent measurements %by Holweger and by Allende Prieto, Lambert & Asplund: of 10$^6$ \oh$_\odot$ = 517 $\pm$ 58 (1 $\sigma$). We note that the smaller oxygen abundances derived for the interstellar gas within 500 pc %by Meyer, Cardelli & Jura or from nearby B star surveys are consistent with a local elemental deficit.Comment: 9 figures, 37 page

Outcomes of Trypanosoma cruzi and Trypanosoma evansi infections on health of Southern coati (Nasua nasua), crab-eating fox (Cerdocyon thous), and ocelot (Leopardus pardalis) in the Brazilian Pantanal.

The occurrence of Trypanosoma spp. in wild carnivore populations has been intensively investigated during the last decades. However, the impact of these parasites on the health of free-living infected animals has been largely neglected. The Pantanal biome is the world's largest seasonal wetland, harboring a great diversity of species and habitats. This includes 174 species of mammals, of which 20 belong to the order Carnivora. The present study aimed to investigate the effect of Trypanosoma evansi and Trypanosoma cruzi infections and coinfections on the health of the most abundant carnivores in the Pantanal: coati (Nasua nasua), crab-eating fox (Cerdocyon thous), and ocelot (Leopardus pardalis). We captured 39 coatis, 48 crab-eating foxes, and 19 ocelots. Diagnostic tests showed T. cruzi infection in 7 crab-eating foxes and 5 coatis. Additionally, 7 crab-eating foxes, 10 coatis, and 12 ocelots were positive for T. evansi. We observed coinfections in 9 crab-eating foxes, 8 coatis, and 2 ocelots. This is the first report of T. evansi and T. cruzi infection on the health of free-living ocelots and crab-eating foxes. We showed that single T. evansi or T. cruzi infection, as well as coinfection, caused some degree of anemia in all animals, as well as an indirect negative effect on body condition in coatis and crab-eating foxes via anemia indicators and immune investment, respectively. Furthermore, the vigorous immune investment observed in sampled coatis, crab-eating foxes and ocelots infected by T. evansi, T. cruzi and coinfected can be highly harmful to their health. Overall, our results indicate that single and combined infection with T. evansi and T. cruzi represent a severe risk to the health of wild carnivores in the Pantanal region

Processo de transferência de tecnologia da universidade para a indústria: estudo de caso envolvendo a conversão de glicerol

Currently, public policy has encouraged innovation in universities and also transference of technology to the industry. Another important stage to be considered would be the registration or filing of a patent and the economical viability study. Government programs, such as the innovation incentive program, among others, should facilitate popularization and promote interest by industry. In this work we described the steps, from the conception of the idea to the scale up going through its interest by the industry. The case study is about the glycerol conversion utilizing modified niobia as catalysts

In vitro antileishmanial and antitrypanosomal activities of flavanones from Baccharis retusa DC. (Asteraceae)

Leishmaniasis and Chagas' are parasitic protozoan diseases that affect the poorest population in the world, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, novel, safe and more efficacious drugs are essential. in this work, the CH2Cl2 phase from MeOH extract from the leaves of Baccharis retusa DC. (Asteraceae) was fractioned to afford two flavonoids: naringenin (1) and sakuranetin (2). These compounds were in vitro tested against Leishmania spp. promastigotes and amastigotes and Ttypanosoma cruzi trypomastigotes and amastigotes. Compound 2 presented activity against Leishmania (L) amazonensis, Leishmania (V.) braziliensis, Leishmania (L) major, and Leishmania (L) chagasi with IC50 values in the range between 43 and 52 mu g/mL and against T. cruzi trypomastigotes (IC50= 20.17 mu g/mL). Despite of the chemical similarity, compound 1 did not show antiparasitic activity. Additionally, compound 2 was subjected to a methylation procedure to give sakuranetin-4'-methyl ether (3), which resulted in an inactive compound against both Leishmania spp. and T. cnizi. the obtained results indicated that the presence of one hydroxyl group at C-4' associated to one methoxyl group at C-7 is important to the antiparasitic activity. Further drug design studies aiming derivatives could be a promising tool for the development of new therapeutic agents for Leishmaniasis and Chagas' disease. (C) 2011 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Pesquisa e DesenvolvimentoUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP, BrazilInst Adolfo Lutz Registro, Dept Parasitol, São Paulo, BrazilUniv Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP, BrazilUniv Presbiteriana Mackenzie, Ctr Ciencias & Humanidades, São Paulo, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP, BrazilFAPESP: 06/57626-5FAPESP: 08/11496-9Conselho Nacional de Pesquisa e Desenvolvimento: 473405/2008-3Conselho Nacional de Pesquisa e Desenvolvimento: 477422/2009-8Web of Scienc

Velocity Dispersion of Excited H2

We present a study of the high rotational bands (J > 2) of H2 toward 4 early type galactic stars: HD 73882, HD 192639, HD 206267, and HD 207538. In each case, the velocity dispersion - characterized by the spectrum fitting parameter b - increases with the level of excitation, a phenomenon that has previously been detected by the Copernicus and IMAPS observatories. In particular, we show with 4 sigma confidence that for HD 192639 it is not possible to fit all J levels with a single b value, and that higher b values are needed for the higher levels. The amplitude of the line broadening, which can be as high as 10 km s^-1, makes explanations such as inhomogeneous spatial distribution unlikely. We investigate a mechanism in which the broadening is due to the molecules that are rotationally excited through the excess energy acquired after their formation on a grain (H2-formation pumping). We show that different dispersions would be a natural consequence of this mechanism. We note however that such process would require a formation rate 10 times higher then what was inferred from other observations. In view of the difficulty to account for the velocity dispersion as thermal broadening (T would be around 10,000 K), we conclude then that we are most certainly observing some highly turbulent warm layer associated with the cold diffuse cloud. Embedded in a magnetic field, it could be responsible for the high quantities of CH+ measured in the cold neutral medium.Comment: accepted in Ap

Antiparasitic Activity of Natural and Semi-Synthetic Tirucallane Triterpenoids from Schinus terebinthifolius (Anacardiaceae): Structure/Activity Relationships

Leishmaniasis and Chagas are diseases caused by parasitic protozoans that affect the poorest population in the World, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, the discovery of novel, safe and more efficacious drugs is essential. in this work, the in vitro antiparasitic activity and mammalian cytotoxicity of three natural tirucallane triterpenoids, isolated from leaves of Schinus terebinthifolius (Anacardiaceae), and nine semi-synthetic derivatives were investigated against Leishmania (L.) infantum and Trypanosoma cruzi. Trypomastigotes of T. cruzi were the most susceptible parasites and seven compounds demonstrated a trypanocidal activity with IC50 values in the range between 15 and 58 mu g/mL. Four compounds demonstrated selectivity towards the intracellular amastigotes of Leishmania, with IC50 values in the range between 28 and 97 mu g/mL. the complete characterization of triterpenoids was afforded after thorough analysis of nuclear magnetic resonance (NMR) data as well as electrospray ionization mass spectrometry (ESI-MS). Additionally, structure-activity relationships were performed using Decision Trees.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Universidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 Diadema, SP, BrazilAdolfo Lutz Inst, Ctr Parasitol, BR-01246902 São Paulo, BrazilUniv Fed Paraiba, Ctr Ciencias Aplicadas & Educ, BR-58297000 Rio Tinto, BrazilUniv Fed Uberlandia, Inst Quim, BR-38400902 Uberlandia, MG, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 Diadema, SP, BrazilCNPq: 300546/2012-2CNPq: 471458/2012-0FAPESP: 2011/51739-0FAPESP: 2012/18756-1FAPESP: 2013/16320-4Web of Scienc

Prediction of Early TBI Mortality Using a Machine Learning Approach in a LMIC Population.

Background: In a time when the incidence of severe traumatic brain injury (TBI) is increasing in low- to middle-income countries (LMICs), it is important to understand the behavior of predictive variables in an LMIC's population. There are few previous attempts to generate prediction models for TBI outcomes from local data in LMICs. Our study aim is to design and compare a series of predictive models for mortality on a new cohort in TBI patients in Brazil using Machine Learning. Methods: A prospective registry was set in São Paulo, Brazil, enrolling all patients with a diagnosis of TBI that require admission to the intensive care unit. We evaluated the following predictors: gender, age, pupil reactivity at admission, Glasgow Coma Scale (GCS), presence of hypoxia and hypotension, computed tomography findings, trauma severity score, and laboratory results. Results: Overall mortality at 14 days was 22.8%. Models had a high prediction performance, with the best prediction for overall mortality achieved through Naive Bayes (area under the curve = 0.906). The most significant predictors were the GCS at admission and prehospital GCS, age, and pupil reaction. When predicting the length of stay at the intensive care unit, the Conditional Inference Tree model had the best performance (root mean square error = 1.011), with the most important variable across all models being the GCS at scene. Conclusions: Models for early mortality and hospital length of stay using Machine Learning can achieve high performance when based on registry data even in LMICs. These models have the potential to inform treatment decisions and counsel family members. Level of evidence: This observational study provides a level IV evidence on prognosis after TBI