Discovery of a Class of Diketopiperazines as Antiprion Compounds

Prion diseases are fatal neurodegenerative and infectious disorders for which effective pharmacological tools are not yet available. This unmet challenge and the recently proposed interplay between prion diseases and Alzheimer's have led to a more urgent demand for new antiprion agents. Herein, we report the identification of a novel bifunctional diketopiperazine (DKP) derivative 1 d , which exhibits activity in the low micromolar range against prion replication in ScGT1 cells, while showing low cytotoxicity. Supported by properly addressed molecular modeling studies, we hypothesized that a planar conformation is the major determinant for activity in this class of compounds. Moreover, studies aimed at assessing the mechanism‐of‐action at the molecular level showed that 1 d might interact directly with recombinant prion protein (recPrP) to prevent its conversion to the pathogenic misfolded prion protein (PrP^Sc)‐like form. This investigation suggests that DKP based antiprion compounds can serve as a promising lead scaffold in developing new drugs to combat prion diseases.     

Folate and iron in fertile age women from a Venezuelan community affected by incidence of neural tube defects

The objective of this transversal study was to determine folate and iron nutritional status of women in fertile age from Municipio Jiménez, Lara State, Venezuela. The sampling was probabilistic by conglomerates from the urban and rural areas, selecting 15 conglomerates from which women between 12 and 45 years (269), were studied. After signing informed consent, participating were interviewed for personal data, antecedents related to folate and iron, socioeconomic data (Graffar-Mendez Castellano method and unsatisfied basic needs). In blood sample was determined Hemoglobin, and Erythrocytic Folate (FE). Serum was obtained to determine Ferritin and Serum Folate (FS). 53.53% of the sample presented low FS levels, 10.78% were FS deficient. Severe FE deficiency was present in 80.7% of the cases, moderate deficiency affected 5.9%. For both tests, median was higher for women in treatment with Acido Fólico or pregnant (p = 0.000), median for FE was higher for adults (p = 0.001) and in non poor women (p = 0.011). There were no significant differences for coffee, alcohol, anticonceptive consumption, urban or rural resident or socioeconomic strata. The prevalence of anemia was 11.2% being significantly more frequent in adults than in adolescents (p = 0.029) and in urban women (p = 0.042). Low ferritin were found in 37.3% of the sample, the effect of different variables was not statistically significant. In conclusion, there is a high prevalence of iron and folate deficiencies in women of fertile age from Municipio Jiménez, which could constitute a conditioning factor for the appearance of neural tube defects.     

Impact of fortification of flours with iron to reduce the prevalence of anemia and iron deficiency among schoolchildren in Caracas, Venezuela: a follow-up

In Venezuela, a severe economic crisis starting in 1983 provoked a progressive reduction in the quantity and quality of food consumed by people from the low socioeconomic strata of the population. This situation resulted in a continuous increase in the prevalence of iron deficiency in the 1980s and 1990s. In 1993, an iron-fortification program was started, in which precooked corn and white wheat flours were enriched with iron, vitamin A, thiamine, niacin, and riboflavin. White wheat flour was enriched with the same nutrients, except for vitamin A. In 1996 we published the results of the impact of fortification of precooked corn and white wheat flours on the prevalence of anemia and iron deficiency in the population. A survey carried out in Caracas in 307 children aged 7, 11, and 15 years showed that the prevalence of iron deficiency measured by serum ferritin concentration dropped from 37% in 1992 to 16% in 1994, only one year after the iron-fortification program began. The prevalence of anemia, as measured by the hemoglobin concentration, diminished from 19% to 10% during the same period. This article reports the results of three other surveys carried out in 1997, 1998, and 1999 on children of the same age and socioeconomic groups that were evaluated in 1990, 1992, and 1994. There were no significant differences in anemia or iron deficiency among the last three surveys. The prevalence results from the last seven years seem to indicate that, after a dramatic reduction in 1994, iron deficiency tended to stabilize, while the prevalence of anemia increased to the same level found in 1992, before the fortification program started.     

A comparative study of parallel software SURF implementations

Nowadays, it is common to find problems that require recognizing objects in an image, tracking them along time, or recognizing a complete real‐world scene. One of the most known and used algorithms to solve these problems is the Speeded Up Robust Features (SURF) algorithm. SURF is a fast and robust local, scale and rotation invariant, features detector. This means that it can be used for detecting and describing a set of points of interest (keypoints) from an image. Because of the importance of this algorithm and the rise of the parallelism‐based technologies, in the last years, diverse parallel implementations of SURF have been proposed. These parallel implementations are based on very different techniques: Compute Unified Device Architecture, OpenMp, OpenCL, and so on. In conclusion, we think valuable a comparative study of all of them highlighting the advantages and disadvantages of each parallel implementation. To our best knowledge, this article is the first attempt to do this comparative study. In order to make this study, we have used the standard metrics and image collection in this field, as well as other important metrics in parallelism as speedup and efficiency. Copyright © 2013 John Wiley & Sons, Ltd.     

Surface modification of carbon-supported iron catalyst during the wet air oxidation of phenol: Influence on activity, selectivity and stability

Catalytic wet air oxidation (CWAO) of phenol with iron/activated carbon catalysts (Fe/AC) at temperature of 400 K and 8 atm of total pressure is an efficient treatment to oxidize a resistant pollutant such as phenol into biodegradable species, mainly short chain acids. Extended studies employing activated carbon catalysts point out significant changes in the carbon as a consequence of the CWAO process. After the long-term experiments carried out in this work it was concluded that these modifications consist of loss of microporosity, temporary decrease of the mesoporosity, decrease of the carbon/oxygen ratio on the catalyst surface, more acidic pH_slurry values, and aggregation of the -Fe₂O₃ crystallites. The causes that provoke these changes and the reasons why they do not alter significantly the CWAO efficiency were analyzed. The way of exposition of Fe/AC catalyst to the reactants plays an important role in its activity and selectivity towards complete mineralization, namely oxidation to CO₂ and H₂O.     

Characterization of plasmids which mediate resistance to multiple antibiotics in gram-negative bacteria of nosocomial origin

BACKGROUND: The genetic and molecular mechanisms involved in antimicrobial resistance of 10 strains of gramnegative bacilli (1 Serratia marcescens; 2 Escherichia coli; 1 Proteus mirabilis; 4 Klebsiella pneumoniae; 1 Enterobacter cloacae y 1 Alcaligenes faecalis), isolated from adult patients with nosocomial pulmonary infection at the in-patient facilities of the University Hospital of Los Andes, Mérida, Venezuela, have been studied. METHODS: The antimicrobial susceptibility was determined by minimum inhibitory concentrations using the dilution method in agar. The study of extrachromosomal genes was carried out by conjugation, bacterial infection with the bacteriophage M13 and curing of plasmid by acridine orange. The plasmids were isolated by alkaline lysis and analysis of restriction endonuclease digestion was carried out separately using the enzymes EcoRI and HindIII. A DNA probe, derived from the region which encodes the TEM-1 beta-lactamase of the plasmid pBR322 was used for dot-blot hybridization tests. RESULTS: All of the gramnegative bacilli showed resistance to ampicillin, carbenicillin and cephalothin (> 128 micrograms/ml) and 3 strains also showed resistance to gentamicin (> 64 micrograms/ml). Genetic and molecular procedures showed the presence of conjugative plasmids of approximately 54 kb in all the 10 strains. The restriction patterns obtained by using EcoRI and HindIII indicated common DNA fragments in most of the plasmids studied. The dot-blot hybridization tests confirmed homology between the plasmids and the DNA probe used (TEM-1 beta-lactamase). CONCLUSIONS: In this study, the gramnegative bacteria of nosocomial origin harbored self-transferable plasmids of approximately 54 kb, which mediate resistance to gentamicin and encode a beta-lactamase of the TEM group.