Predicting the bioconcentration factor in fish from molecular structures

The bioconcentration factor (BCF) is one of the metrics used to evaluate the potential of a substance to bioaccumulate into aquatic organisms. In this work, linear and non-linear regression QSARs were developed for the prediction of log BCF using different computational approaches, and starting from a large and structurally heterogeneous dataset. The new MLR-OLS and ANN regression models have good fitting with R-2 values of 0.62 and 0.70, respectively, and comparable external predictivity with R-ext(2) 0.64 and 0.65 (RMSEext of 0.78 and 0.76), respectively. Furthermore, linear and non-linear classification models were developed using the regulatory threshold BCF >2000. A class balanced subset was used to develop classification models which were applied to chemicals not used to create the QSARs. These classification models are characterized by external and internal accuracy up to 84% and 90%, respectively, and sensitivity and specificity up to 90% and 80%, respectively. QSARs presented in this work are validated according to regulatory requirements and their quality is in line with other tools available for the same endpoint and dataset, with the advantage of low complexity and easy application through the software QSAR-ME Profiler. These QSARs can be used as alternatives for, or in combination with, existing models to support bioaccumulation assessment procedures

Fuzzy formal concept analysis

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFormal Context Analysis is a mathematical theory that enables us to find concepts from a given set of objects, a set of attributes and a relation on them. There is a hierarchy of such concepts, from which a complete lattice can be made. In this paper we p831192205CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIOR306546/2017-5308524/2014-437th Conference of the North-American-Fuzzy-Information-Processing-Society (NAFIPS

Plasma kinetics of an LDL-like nanoemulsion and lipid transfer to HDL in subjects with glucose intolerance

OBJECTIVE: Glucose intolerance is frequently associated with an altered plasma lipid profile and increased cardiovascular disease risk. Nonetheless, lipid metabolism is scarcely studied in normolipidemic glucose-intolerant patients. The aim of this study was to investigate whether important lipid metabolic parameters, such as the kinetics of LDL free and esterified cholesterol and the transfer of lipids to HDL, are altered in glucose-intolerant patients with normal plasma lipids. METHODS: Fourteen glucose-intolerant patients and 15 control patients were studied; none of the patients had cardiovascular disease manifestations, and they were paired for age, sex, race and co-morbidities. A nanoemulsion resembling a LDL lipid composition (LDE) labeled with 14C-cholesteryl ester and ³H-free cholesterol was intravenously injected, and blood samples were collected over a 24-h period to determine the fractional clearance rate of the labels by compartmental analysis. The transfer of free and esterified cholesterol, triglycerides and phospholipids from the LDE to HDL was measured by the incubation of the LDE with plasma and radioactivity counting of the supernatant after chemical precipitation of non-HDL fractions. RESULTS: The levels of LDL, non-HDL and HDL cholesterol, triglycerides, apo A1 and apo B were equal in both groups. The 14C-esterified cholesterol fractional clearance rate was not different between glucose-intolerant and control patients, but the ³H-free-cholesterol fractional clearance rate was greater in glucose-intolerant patients than in control patients. The lipid transfer to HDL was equal in both groups. CONCLUSION: In these glucose-intolerant patients with normal plasma lipids, a faster removal of LDE free cholesterol was the only lipid metabolic alteration detected in our study. This finding suggests that the dissociation of free cholesterol from lipoprotein particles occurs in normolipidemic glucose intolerance and may participate in atherogenic signaling

Plasma kinetics of an LDL-like nanoemulsion and lipid transfer to HDL in subjects with glucose intolerance

OBJECTIVE: Glucose intolerance is frequently associated with an altered plasma lipid profile and increased cardiovascular disease risk. Nonetheless, lipid metabolism is scarcely studied in normolipidemic glucose-intolerant patients. The aim of this study was to investigate whether important lipid metabolic parameters, such as the kinetics of LDL free and esterified cholesterol and the transfer of lipids to HDL, are altered in glucose-intolerant patients with normal plasma lipids. METHODS: Fourteen glucose-intolerant patients and 15 control patients were studied; none of the patients had cardiovascular disease manifestations, and they were paired for age, sex, race and co-morbidities. A nanoemulsion resembling a LDL lipid composition (LDE) labeled with C-14-cholesteryl ester and H-3-free cholesterol was intravenously injected, and blood samples were collected over a 24-h period to determine the fractional clearance rate of the labels by compartmental analysis. The transfer of free and esterified cholesterol, triglycerides and phospholipids from the LDE to HDL was measured by the incubation of the LDE with plasma and radioactivity counting of the supernatant after chemical precipitation of non-HDL fractions. RESULTS: The levels of LDL, non-HDL and HDL cholesterol, triglycerides, apo A1 and apo B were equal in both groups. The 14 C-esterified cholesterol fractional clearance rate was not different between glucose-intolerant and control patients, but the H-3-free- cholesterol fractional clearance rate was greater in glucose-intolerant patients than in control patients. The lipid transfer to HDL was equal in both groups. CONCLUSION: In these glucose-intolerant patients with normal plasma lipids, a faster removal of LDE free cholesterol was the only lipid metabolic alteration detected in our study. This finding suggests that the dissociation of free cholesterol from lipoprotein particles occurs in normolipidemic glucose intolerance and may participate in atherogenic signaling.This study was supported by Fundação do Amparo à Pesquisa do Estado\ud de São Paulo (FAPESP), São Paulo, Brazil. Dr. Maranhão has a Research\ud Award from Conselho Nacional de Desenvolvimento Científico e\ud Tecnológico (CNPq) Brasília, Brazil. Dr. Bertato had a scholarship from\ud CNPq

Removal from the plasma of the free and esterified forms of cholesterol and transfer of lipids to HDL in type 2 diabetes mellitus patients

Background: The aim was to investigate new markers for type 2 diabetes (T2DM) dyslipidemia related with LDL and HDL metabolism. Removal from plasma of free and esterified cholesterol transported in LDL and the transfer of lipids to HDL are important aspects of the lipoprotein intravascular metabolism. The plasma kinetics (fractional clearance rate, FCR) and transfers of lipids to HDL were explored in T2DM patients and controls, using as tool a nanoemulsion that mimics LDL lipid structure (LDE). Results: C-14- cholesteryl ester FCR of the nanoemulsion was greater in T2DM than in controls (0.07 +/- 0.02 vs. 0.05 +/- 0.01 h(-1), p = 0.02) indicating that LDE was removed faster, but FCR H-3- cholesterol was equal in both groups. Esterification rates of LDE free-cholesterol were equal. Cholesteryl ester and triglyceride transfer from LDE to HDL was greater in T2DM (4.2 +/- 0.8 vs. 3.5 +/- 0.7%, p = 0.03 and 6.8 +/- 1.6% vs. 5.0 +/- 1.1, p = 0.03, respectively). Phospholipid and free cholesterol transfers were not different. Conclusions: The kinetics of free and esterified cholesterol tended to be independent in T2DM patients and the lipid transfers to HDL were also disturbed. These novel findings may be related with pathophysiological mechanisms of diabetic macrovascular disease.This study was supported by Fundação do Amparo à Pesquisa do Estado de\ud São Paulo (FAPESP), São Paulo, Brazil. Dr. Maranhão has a Research Award\ud from Conselho Nacional de Desenvolvimento Científico e Tecnológico\ud (CNPq) Brasília, Brazil

QSARINS-Chem standalone version: A new platform-independent software to profile chemicals for\ua0physico-chemical properties, fate, and toxicity

The new software QSARINS-Chem standalone version is a multiplatform tool, freely downloadable, for the in silico profiling of multiple properties and activities of organic chemicals. This software, which is based on the concept of the QSARINS-chem module embedded in the QSARINS software, has been fully redesigned and redeveloped in the Java\u2122 language. In addition to a selection of models included in the old module, the new software predicts biotransformation rates and aquatic toxicities of pharmaceuticals and personal care products in multiple organisms, and offers a suite of tools for the analysis of predictions. Furthermore, a comprehensive and transparent database of molecular structures is provided. The new QSARINS-Chem standalone version is an informative and solid tool, which is useful to support the assessment of the potential hazard and risks related to organic chemicals and is dedicated to users which are interested in the application of QSARs to generate reliable predictions

Removal from the plasma of the free and esterified forms of cholesterol and transfer of lipids to HDL in type 2 diabetes mellitus patients

Abstract Background The aim was to investigate new markers for type 2 diabetes (T2DM) dyslipidemia related with LDL and HDL metabolism. Removal from plasma of free and esterified cholesterol transported in LDL and the transfer of lipids to HDL are important aspects of the lipoprotein intravascular metabolism. The plasma kinetics (fractional clearance rate, FCR) and transfers of lipids to HDL were explored in T2DM patients and controls, using as tool a nanoemulsion that mimics LDL lipid structure (LDE). Results 14C- cholesteryl ester FCR of the nanoemulsion was greater in T2DM than in controls (0.07 ± 0.02 vs. 0.05 ± 0.01 h-1, p = 0.02) indicating that LDE was removed faster, but FCR 3 H- cholesterol was equal in both groups. Esterification rates of LDE free-cholesterol were equal. Cholesteryl ester and triglyceride transfer from LDE to HDL was greater in T2DM (4.2 ± 0.8 vs. 3.5 ± 0.7%, p = 0.03 and 6.8 ± 1.6% vs. 5.0 ± 1.1, p = 0.03, respectively). Phospholipid and free cholesterol transfers were not different. Conclusions The kinetics of free and esterified cholesterol tended to be independent in T2DM patients and the lipid transfers to HDL were also disturbed. These novel findings may be related with pathophysiological mechanisms of diabetic macrovascular disease