Pharmacophore Model of Cruzain Inhibitors

Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the most serious amongst the so-called neglected diseases in Latin America, specially in Brazil. So far there has been no effective treatment for the chronic phase of this disease. Cruzain is a major cysteine protease of T cruzi and it is recognized as a valid target for Chagas disease chemotherapy. The mechanism of cruzain action is associated with the nucleophilic attack of an activated sulfur atom towards electrophilic groups. In this report, features of a putative pharmacophore model of the enzyme, developed as a virtual screening tool for the selection of potential cruzain inhibitors, are described. The final proposed model was applied to the ZINC v.7 database and afterwards experimentally validated by an enzymatic inhibition assay. One of the compounds selected by the model showed cruzain inhibition in the low micromolar range.

Trojan Horse Method: a useful tool for electron screening effect investigation

Direct measurements in the last decades have highlighted a new problem related to the lowering of the Coulomb barrier between the interacting nuclei due to the presence of the ""electron screening"" in the laboratory measurements. It was systematically observed that the presence of the electronic cloud around the interacting ions in measurements of nuclear reactions cross sections at astrophysical energies gives rise to an enhancement of the astrophysical S(E)-factor as lower and lower energies are explored [1]. Moreover, at present Such an effect is not well understood as the value of the potential for screening extracted from these measurements is higher than the tipper limit of theoretical predictions (adiabatic limit). On the other hand, the electron screening potential in laboratory measurement is different from that occurring in stellar plasmas thus the quantity of interest in astrophysics is the so-called ""bare nucleus cross section"". This quantity can only be extrapolated in direct measurements. These are the reasons that led to a considerable growth on interest in indirect measurement techniques and in particular the Trojan Horse Method (THM) [2,3]. Results concerning the bare nucleus cross sections measurements will be shown in several cases of astrophysical interest. In those cases the screening potential evaluated by means of the THM will be compared with the adiabatic limit and results arising from extrapolation in direct measurements.

Complementarity of Subjective Global Assessment (SGA) and Nutritional Risk Screening 2002 (NRS 2002) for predicting poor clinical outcomes in hospitalized patients

Background & aims: We evaluated the ability of Nutritional Risk Screening 2002 (NRS 2002) and Subjective Global Assessment (SGA) to predict malnutrition related to poor clinical outcomes. Methods: We assessed 705 patients at a public university hospital within 48 h of admission. Logistic regression and number needed to screen (NNS) were calculated to test the complementarity between the tools and their ability to predict very long length of hospital stay (VLLOS), complications, and death. Results: Of the patients screened, 27.9% were at nutritional risk (NRS+) and 38.9% were malnourished (SGA B or C). Compared to those patients not at nutritional risk, NRS+, SGA B or C patients were at increased risk for complications (p = 0.03, 0.02, and 0.003, respectively). NRS+ patients had an increased risk of death (p = 0.03), and SGA B and C patients had an increased likelihood of VLLOS (p = 0.008 and p < 0.0001, respectively). Patients who were both NRS+ and SGA C had lower estimates of NNS than patients who were NRS+ or SGA C only, though their confidence intervals did overlap. Conclusions: The concurrent application of SGA in NRS+ patients might enhance the ability to predict poor clinical outcomes in hospitalized patients in Brazil. (C) 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Use of the mini nutritional assessment tool in elderly people from long-term institutions of southeast of Brazil

Background: the Mini Nutritional Assessment (MNA) is a multidimensional method of nutritional evaluation that allows the diagnosis of malnutrition and risk of malnutrition in elderly people, it is important to mention that this method has not been well studied in Brazil. Objective: to verify the use of the MNA in elderly people that has been living in long term institutions for elderly people. Design: transversal study. Participants: 89 people (>= 60 years), being 64.0% men. The average of age for both genders was 73.7 +/- 9.1 years old, being 72.8 +/- 8.9 years old for men, and 75.3 +/- 9.3 years old for women. Setting: long-term institutions for elderly people located in the Southeast of Brazil. Methods: it was calculated the sensibility, specificity, and positive and negative predictive values. It was data to set up a ROC curve to verify the accuracy of the MNA. The variable used as a ""standard"" for the nutritional diagnosis of the elderly people was the corrected arm muscle area because it is able to provide information or an estimative of the muscle reserve of a person being considered a good indicator of malnutrition in elderly people. Results: the sensibility was 84.0%, the specificity was 36.0%, the positive predictive value was 77.0%, and the negative predictive value was 47.0%; the area of the ROC curve was 0.71 (71.0%). Conclusion: the MNA method has showed accuracy, and sensibility when dealing with the diagnosis of malnutrition and risk of malnutrition in institutionalized elderly groups of the Southeastern region of Brazil, however, it presented a low specificity.