TOMOCOMD-CARDD, a novel approach for computer-aided 'rational' drug design: I. Theoretical and experimental assessment of a promising method for computational screening and in silico design of new anthelmintic compounds.

In this work, the TOMOCOMD-CARDD approach has been applied to estimate the anthelmintic activity. Total and local (both atom and atom-type) quadratic indices and linear discriminant analysis were used to obtain a quantitative model that discriminates between anthelmintic and non-anthelmintic drug-like compounds. The obtained model correctly classified 90.37% of compounds in the training set. External validation processes to assess the robustness and predictive power of the obtained model were carried out. The QSAR model correctly classified 88.18% of compounds in this external prediction set. A second model was performed to outline some conclusions about the possible modes of action of anthelmintic drugs. This model permits the correct classification of 94.52% of compounds in the training set, and 80.00% of good global classification in the external prediction set. After that, the developed model was used in virtual in silico screening and several compounds from the Merck Index, Negwer's handbook and Goodman and Gilman were identified by models as anthelmintic. Finally, the experimental assay of one organic chemical (G-1) by an in vivo test coincides fairly well (100%) with model predictions. These results suggest that the proposed method will be a good tool for studying the biological properties of drug candidates during the early state of the drug-development process.

Administraçäo de líquidos intraparto e ocorrência de taquipnéia transitória neonatal / Administration of intrapartum intusion and incidence of neonatal transient tachypnea

A Taquipnéia Transitória Neonatal (T.T.) é uma ocorrência freqüente nos berçarios. O seu quadro clínico já está bem estabelecido e o seu curso é benigno. A sua etiologia, no entanto, ainda é controversa. O excesso de líquido intersticial pulmonar é a hipótese mais aceita. O uso da venóclise intraparto poderia ocorrer para aumentar este escedente pulmonar. Foram estudados 145 RNs, sendo 57 no grupo teste (com uso de venóclise) e 88 no grupo contrôle (sem uso de venóclise). Os RNs foram incluídos ao acaso, sendo excluídos os portadores de outras patologias. Do total, 22 RNs apresentaram T.T. (15%), sendo 15 RNs diferença foi significante (P < 0,1). Näo foi possível vincular estadiferença ao volume infundado. Em números percentuais os partos cesáreos tiveram relevância nos casos de T.T., porém se significância estatística. Conclui-se que o uso da venóclise intraparto aumenta a freqüência da T.T.