RESUMEN
The primary goal of this study was to describe and compare the criteria used to assess carcinogenic activity. The statistically-based predictive quantitative structure-activity relationship (QSAR) models based on the counter propagation artificial neural network (CPANN) algorithm, and knowledge-based expert systems based on a decision tree structural alert (SA) approach (Toxtree application), were considered. The integration of the QSAR (CPANN models) and SAR (Toxtree SA application) approach contributed to the mechanistic understanding of the QSAR model considered. The mapping technique inherent to CPANN Kohonen enables us to relate the similarities or dissimilarities within a congeneric set of chemicals with particular SAs for carcinogenicity. The focus of our investigations was the similarities and dissimilarities of the features used in the QSAR and SAR methods. Due to the complexity of the carcinogenic endpoint, the integration of different approaches allows the models to be improved and provides a valuable technique for evaluating the safety of chemicals.
Asunto(s)
Pruebas de Carcinogenicidad/métodos , Carcinógenos/química , Sistemas Especialistas , Redes Neurales de la Computación , Relación Estructura-Actividad Cuantitativa , Relación Estructura-Actividad , Animales , Carcinógenos/toxicidad , Modelos Químicos , Pruebas de Mutagenicidad , RatasRESUMEN
One of the main goals of the new chemical regulation REACH (Registration, Evaluation and Authorization of Chemicals) is to fill the gaps on the toxicological properties of chemicals that affect human health. Carcinogenicity is one of the endpoints under consideration. The information obtained from (quantitative) structure-activity relationship ((Q)SAR) models is accepted as an alternative solution to avoid expensive and time-consuming animal tests. The reported results were obtained within the framework of the European project 'Computer Assisted Evaluation of industrial chemical Substances According to Regulations (CAESAR)'. In this article, we demonstrate intermediate results for counter propagation artificial neural network (CP ANN) models for the prediction category of the carcinogenic potency using two-dimensional (2D) descriptors from different software programs. A total of 805 non-congeneric chemicals were extracted from the Carcinogenic Potency Database (CPDBAS). The resulting models had prediction accuracies for internal (training) and external (test) sets as high as 91-93% and 68-70%, respectively. The sensitivity and specificity of the test set were 69-73 and 63-72% correspondingly. High specificity is critical in models for regulatory use that are aimed at ensuring public safety. Thus, the errors that give rise to false negatives are much more relevant. We discuss how we can increase the number of correctly predicted carcinogens using the correlation between the threshold and the values of the sensitivity and specificity.
Asunto(s)
Pruebas de Carcinogenicidad/métodos , Modelos Químicos , Redes Neurales de la Computación , Relación Estructura-Actividad Cuantitativa , Toxicología/métodos , Estructura Molecular , Proyectos de Investigación , Sensibilidad y Especificidad , Programas InformáticosRESUMEN
The results of using of the new method analysis EMG in the evaluation of the influence of single pharmacological tests (PhT) for Parkinson's disease are described in this article. PhT applied for investigation of the group 41 patients diagnosed with Parkinson's disease of different etiologies, forms and stages. The study was carried out before taking the medicine and 40-60 minutes after taking the medicine. Patients were prescribed a single, habitual, individualized doses of anti-Parkinson's medicine. Analysis of the materials show that in the PhT, in 23% of the cases, for the group of muscles under study change in the tremor frequency in the direction of normality was observed. In 2% of the cases, reduction in the magnitude of tremor was observed. In 10% of the cases, both frequency and magnitude of tremors were registered. In 65% of the cases, no change what soever was indicated. For those patients for which the effectiveness of the medicine was manifested independently in certain groups of muscles, corrective medical therapy was recommended.