Binding mode of conformations and structure-based pharmacophore development for farnesyltransferase inhibitors

Farnesyltransferase (FTase) is one of the prenyltransferase family enzymes that catalyse the transfer of 15-membered isoprenoid (farnesyl) moiety to the cysteine of CAAX motif-containing proteins including Rho and Ras family of G proteins. Inhibitors of FTase act as drugs for cancer, malaria, progeria and other diseases. In the present investigation, we have developed two structure-based pharmacophore models from protein–ligand complex (3E33 and 3E37) obtained from the protein data bank. Molecular dynamics (MD) simulations were performed on the complexes, and different conformers of the same complex were generated. These conformers were undergone protein–ligand interaction fingerprint (PLIF) analysis, and the fingerprint bits have been used for structure-based pharmacophore model development. The PLIF results showed that Lys164, Tyr166, TrpB106 and TyrB361 are the major interacting residues in both the complexes. The RMSD and RMSF analyses on the MD-simulated systems showed that the absence of FPP in the complex 3E37 has significant effect in the conformational changes of the ligands. During this conformational change, some interactions between the protein and the ligands are lost, but regained after some simulations (after 2 ns). The structure-based pharmacophore models showed that the hydrophobic and acceptor contours are predominantly present in the models. The pharmacophore models were validated using reference compounds, which significantly identified as HITs with smaller RMSD values. The developed structure-based pharmacophore models are significant, and the methodology used in this study is novel from the existing methods (the original X-ray crystallographic coordination of the ligands is used for the model building). In our study, along with the original coordination of the ligand, different conformers of the same complex (protein–ligand) are used. It concluded that the developed methodology is significant for the virtual screening of novel molecules on different targets.     

Short-Term Secondary Effects of a School-Based Drug Prevention Program: Cluster-Randomized Controlled Trial of the Brazilian Version of DARE’s Keepin’ it REAL

Prevention Science - This study aimed to evaluate the effectiveness of the drug and violence resistance educational program (PROERD) on short-term secondary outcomes, such as intentions to use...     

Trans-Pacific tele-ultrasound image transmission of fetal central nervous system structures

Objective: To assess the quality of images and video clips of fetal central nervous (CNS) structures obtained by ultrasound and transmitted via tele-ultrasound from Brazil to Australia.

Methods: In this cross-sectional study, 15 normal singleton pregnant women between 20 and 26 weeks were selected. Fetal CNS structures were obtained by images and video clips. The exams were transmitted in real-time using a broadband internet and an inexpensive video streaming device. Four blinded examiners evaluated the quality of the exams using the Likert scale. We calculated the mean, standard deviation, mean difference, and p values were obtained from paired t tests.

Results: The quality of the original video clips was slightly better than that observed by the transmitted video clips; mean difference considering all observers = 0.23 points. In 47/60 comparisons (78.3%; 95% CI?=?66.4–86.9%) the quality of the video clips were judged to be the same. In 182/240 still images (75.8%; 95% CI?=?70.0–80.8%) the scores of transmitted image were considered the same as the original.

Conclusion: We demonstrated that long distance tele-ultrasound transmission of fetal CNS structures using an inexpensive video streaming device provided images of subjective good quality.     

Reconstruction of parietal bone defects with adiposederived mesenchymal stem cells. Experimental study

Purpose:This study assessed the regeneration potential of mesenchymal stem cells (MSC) from adipose tissue associated with platelet-rich plasma (PRP) in bone regeneration.Methods:Thirty Wistar rats (Rattus norvegicus albinos) were divided into five groups (according to the grafting material and time to euthanasia): (1) autograft - 14 days (control), (2) autograft - 28 days (control), (3) MSC + PRP - 14 days, (4) MSC + PRP + papaverine - 14 days and (5) MSC + PRP + papaverine - 28 days. After euthanasia, the graft was removed and histological slides were prepared. They were assessed by a blinded pathologist using a previously published histological scale as parameter.Results:There was some degree of neoformed bone trabeculae (NBT) in 93.3% of the samples, as well as osteoblastic activity (OA). The autograft groups (14 and 28 days) had higher levels in the formation of bone trabeculae. Nonparametric data were analyzed using the Wilcoxon-Mann-Whitney test and proved not to be statistically significant at p < 0.05.Conclusions:Experimental parietal bone reconstruction, combining MSC, PRP and papaverine presented regeneration in all groups with no significant difference among them.Key words: Bone Regeneration, Platelet-Rich Plasma, Tissue Engineering, Rats     

Phenotypic and genetic features of enteropathogenic Escherichia coli isolates from diarrheal children in the Ribeirão Preto metropolitan area,São Paulo State,Brazil

This study was designed to characterize a collection of 60 enteropathogenic Escherichia coli (EPEC) isolates from diarrheic feces of patients in the Ribeirão Preto metropolitan area regarding different phenotypic and molecular features. We examined antibiotic resistance profiles, occurrence of virulence factors‐encoding genes, intimin subtypes and the correlation of serotypes among typical (tEPEC) and atypical (aEPEC) EPEC isolates. The results demonstrated that atypical EPEC was more heterogeneous than typical EPEC concerning the characteristics investigated and 45.2% do not belong to classical EPEC serogroups. Intimin subtype β was the most frequent among the EPEC isolates (46.7%), being detected in both tEPEC and aEPEC. The majority of aEPEC isolates presented localized adherence‐like (LAL) pattern to HEp‐2 cells, although aEPEC isolates displaying diffuse adherence (DA) or non‐adherent were also detected. High prevalence of antimicrobial resistance was found for ampicillin, cephalothin, sulfonamide and tetracycline. In general, tEPEC isolates were more resistant to the antimicrobials tested than aEPEC isolates.