Identification of cisapride as new inhibitor of putrescine uptake in Trypanosoma cruzi by combined ligand- and structure-based virtual screening.

Nowadays, the pharmacological therapy for the treatment of Chagas disease is based on two old drugs, benznidazole and nifurtimox, which have restricted efficacy against the chronic phase of the illness. To overcome the lack of efficacy of the traditional drugs (and their considerable toxicity), new molecular targets have been studied as starting points to the discovery of new antichagasic compounds. Among them, polyamine transporter TcPAT12 (also known as TcPOT1.1) represents an interesting macromolecule, since polyamines are essential for Trypanosoma cruzi, the parasite that causes the illness, but it cannot synthesize them de novo. In this investigation we report the results of a combined ligand- and structure-based virtual screening for the discovery of new inhibitors of TcPAT12. Initially we filtered out ZINC and Drugbank databases with similarity and QSAR models and then we submitted the candidates to a validated docking based screening. Four structures were selected and tested in T. cruzi epimastigotes proliferation and two of them, Cisapride and [2-(cyclopentyloxy)phenyl]methanamine showed inhibitory effects. Additionally, we performed transport assays which demonstrated that Cisapride interferes with putrescine uptake in a specific mode.

Trace metals and oxidative status in soft tissues of caged mussels (Aulacomya atra) on the North Patagonian coastline.

This study investigated metal accumulation and oxidative effects in mantle, gill and digestive gland of the ribbed mussel Aulacomya atra from the Argentinean North Patagonian coastline. Mussels were transplanted over an 18-month period from a site with low anthropogenic impact to a harbor site with higher seawater concentration of aluminum, chromium, copper, manganese, nickel and zinc. Total trace metal concentration in seawater did not change throughout the 18-month transplant in either site. A. atra bioaccumulated metals in digestive gland, gills and mantle at different levels. Digestive gland had the highest concentration of metals, especially towards the end of the transplant experiment in the harbor area. Mussels transplanted to the harbor site experienced an upregulation in their antioxidant system, which likely explains the lack of oxidative damage to lipids despite higher metal accumulation. These results demonstrate that A. atra selectively accumulates metals from the water column and their prooxidant effects depend on the tissue antioxidant defenses and the exposure time.

[Wikipedia and wikinutrition: key tools for the global promotion of nutrition]. / Wikipedia y Wikinutrición: herramientas clave para la promoción global de la nutrición.

Wikipedia is an encyclopedia collaboratively edited by volunteers from around the world built on the Web since 2003. Today is the sixth most visited site on the Internet, making it the biggest hit of participatory democracy in the field of information dissemination. The English edition, with more than 3 million items, has become an indispensable part of the Internet and the largest and most popular reference work. In this context, it could be argued that Wikipedia is a valuable tool for the general knowledge of the nutritional sciences terminology. At the same time, it does not only facilitate access to knowledge but also can generate it. It also permits to socialize these spaces for collaboration and development, contributing therefore to disclose science to the society. Consequently, in this article we present and discuss the main features of Wikipedia, emphasizing above all its role in food science and nutrition.

[Usefulness of Clinical Risk Index for Babies based on birth weight in predicting hospital death and severe intraventicular hemorrhage in the SEN 1500 Spanish neonatal network]. / Análisis de la utilidad del Clinical Risk Index for Babies por estratos de peso como predictor de muerte hospitalaria y de hemorragia intraventricular grave en la Red Neonatal Española SEN 1500.

OBJECTIVE: To evaluate the usefulness of the Clinical Risk Index for Babies (CRIB) in predicting hospital mortality and severe intraventricular hemorrhage (IVH) in very low birth weight infants stratified by weight groups, in the Spanish neonatal network SEN 1500. PATIENTS AND METHODS: A prospective cohort study was made. Morbidity-mortality data and CRIB were collected in newborns weighing below 1500 g and admitted to 68 neonatal intensive care units between January 2002 and December 2006. Data were analyzed globally and stratified by weight groups (< 501 g, 500-750 g, 751-1000 g, 1001-1250 g, 1251-1500 g). Multivariate models were generated and ROC curves were plotted for estimating predictive values. RESULTS: A total of 10,608 patients were analyzed. The mean weight was 1116 g (SD 267), and gestational age 29.5 weeks (SD 2.9). Low birth weight for gestational age was 34.3% and the multiple birth rate 36%. Prenatal corticoids were given in 78.2%. Severe intraventricular hemorrhage was diagnosed in 8.5%. Gender, prenatal corticoids, birth weight, gestational age and CRIB proved significant for the outcomes. CRIB showed the highest predictive accuracy in all strata (P < 0.001) except in the 501-750 g group, where it was similar to gestational age. Body weight showed the lowest AUC in all groups, except in the 1251-1500 g group, where it was no different to gestational age. Gestational age and CRIB yielded greater AUC values than weight (P < 0.001) in all groups. No significant differences were found between CRIB and gestational age, except in the 751-1000 g group, where gestational age was greater (P = 0.029). CONCLUSIONS: The CRIB is the best predictor among newborns below 1500 g, except in the 501-750 g group, where CRIB is similar to gestational age. Body weight is the worst predictor, except in the group 1251-1500 g, where it is similar to gestational age. The accuracies of CRIB and gestational age in the prediction of IVH are similar, and both superior to body weight. This similarity persists in all the groups, except in the 751-1000 g interval, where gestational age is a better predictor.

[The genetics of child temperament]. / Genética del temperamento en niños.

INTRODUCTION: In spite of the high initial expectancy in preliminary results concerning the genetics of personality, these studies have not provided satisfactory results. The failure could be related to the lack of biological validity of personality concept and the important influence of environmental factors on personality. A possible way to solve this problem is to look at the temperament of preschool children. It is expected that variability in infants' behaviour can be better defined and with less environmental influence. DEVELOPMENT: Firstly, twin and adoption studies of child temperament in comparison with the studies of personality in adults are reviewed. Secondly, the molecular association studies carried out concerning child temperament are analyzed. The serotonin transporter gene (5-HTT), D4 receptor gene (DRD4) and mono amino oxidade-A gene (MAOA) have been considered candidates to explain variability in child temperament because these genes have been related with specific personality dimensions and mental diseases. Finally, the methodological problems and the future direction of research in this field are considered. CONCLUSIONS: Heritability shows higher values in infant temperament than in adult personality. Different gene polymorphisms on 5-HTT, DRD4 and MAOA could explain some individual variability in children's behavior, although replication studies are needed to confirm the role of these genes. Longitudinal studies in large samples that include gene and environmental interactions are one of the best ways to improve our knowledge about the genetics of child temperament.

Transfusion of post-operative shed blood: laboratory characteristics and clinical utility.

Increased awareness of the potential hazards of allogenic blood transfusion, such as incompatibility reactions, metabolic and immunologic disorders, or transmission of viral diseases, has led to an emphasis on allogeneic blood alternatives. For orthopaedic surgery, several autologous transfusion modalities have emerged as alternatives to allogeneic blood transfusion, avoiding its immunomodulatory effects. Among them, transfusion or return of post-operative salvaged shed blood has become popular in major orthopaedic procedures. However, although the effectiveness of this blood-saving method is well documented, several authors have questioned its safety and recommended the use of washed blood. Therefore, this review analyses the haematologic characteristics of unwashed filtered shed blood, including metabolic status and survival of red blood cells, the components of the haemostatic system, the content of fat particles, bacterial and tumour cells and the possibility of their removal, the content of inflammatory mediators, and the effects on the patient's immune system. From data reviewed in this paper, it can be concluded that post-operative salvage of blood seems to be an excellent source of functional and viable red cells without many of the transfusion-related risks and with some immuno-stimulatory effects. In addition, from our experience, post-operative re-infusion of unwashed shed blood after major spine procedures has proved to reduce post-operative homologous transfusion requirements and to complement pre-operative autologous blood donation, without any clinically relevant complication.

[Prevalence of anti-smoking counseling in a primary care clinic: comparison of patient charts with patient reports]. / Prevalencia del consejo antitabaco en un centro de atención primaria: comparación del registro en la historia clínica con lo referido por el usuario.

OBJECTIVE: To estimate the prevalence of anti-tobacco counseling of smokers. DESIGN: Cross-sectional, descriptive study. SETTING: Primary care center. SUBJECTS: Random sample of 1,228 patients over 14 years of age who visited a doctor or nurse over the year prior to the study. MEASURES: 1) Telephone interview: age, sex, medical history, education, smoking status, number of cigarettes daily, frequency of visits to the doctor, receipt of anti-smoking advice, reason for seeking medical care, the type of professional who saw the patient and the patient's attitude toward the advice. 2) Patient chart: record of advice given. RESULTS: Five hundred sixty-three questionnaires were valid. Smokers made up 37% (95% CI 33%-41%) of the population, with a mean age of 33.37 (18.14 years; 39.1% of men and 36.1% of the women smoked. The prevalence of anti-smoking counseling according to the patient was 62.3% (95% CI: 56-69%). There was little agreement between counseling as reported by the patients and as recorded in the patient's chart (kappa index 0.149, p = 0.01). The mean age of patients advised to quit (34.8 + 10.89 years) was higher than that of those who did not receive advice to quit. Seventy percent of patients who came to the clinic more than 3 times per year reported having been advised to quit, whereas 50% of those who came fewer than 3 times per year were so advised. Among patients who were advised to quit, 78.3% said the advice came when they had come to the clinic about matters related to smoking. According to patients, advice was usually given by a doctor (76.7%). After being advised to quit, 32.55% of the smokers did so, 6.2% of them for longer than 6 months. CONCLUSIONS: The percentage of smokers at our clinic is similar to that in the general population. The prevalence of anti-smoking counseling reported by the user is greater than that reported in other studies, but can clearly be improved. Anti-smoking advice is underreported in our patient charts in comparison with patient reports. The patients who receive advice most often are those who come to the clinic frequently and those who come for smoking-related problems. Physicians are the professionals who most often advise patients on smoking.

Complications and functional outcome following artificial anal sphincter implantation.

BACKGROUND: The postoperative complications and functional outcome following 24 consecutive implantations of an artificial anal sphincter were assessed prospectively. METHODS: A total of 24 artificial anal sphincters (Acticon Neosphincter) were implanted in 22 patients (mean age 47 years). The mean follow-up period was 28 (range 6-48) months. Results were assessed prospectively by two independent observers at 4-month intervals. The cumulative probability of artificial anal sphincter removal was analysed by the Kaplan-Meier method. RESULTS: Five patients were free of complications. During the postoperative period, complications occurred in nine patients, two of whom required reoperation. During follow-up, complications developed in ten patients, nine of whom were reoperated. Definitive device explantation was necessary in seven patients. The cumulative probability of device explantation was 44 per cent at 48 months. The 15 patients with functioning implants were followed up for a mean of 26 (range 7-48) months. Continence grading improved from a mean of 18 (range 14-20) in the preoperative period to 4 (range 0-14) after operation (P < 0.001). Resting anal canal pressure in patients with a functioning implant increased from a mean of 35 (range 8-87) mmHg before operation to 54 (range 34-70) mmHg after implantation (P < 0.01). CONCLUSION: An artificial anal sphincter is a useful alternative for refractory faecal incontinence but the incidence of late postoperative complications is high.

Ascorbic acid in diet supplements: loss in the manufacturing process and storage.

The ascorbic acid content was determined in 25 different diet supplements commercially available to the consumer in two pharmaceutical forms (pills and ampoules). These products are widely consumed by several population groups (elderly people, sportsmen, adolescents, children, etc.). High-performance liquid chromatography was used as the analytical technique. The proposed method has been validated with good linearity, reproducibility, recovery and accuracy, and can be used in routine analyses and in quality control. The ascorbic acid content in pills ranged from 15.62 to 50.16 mg/g, and in that ampoules from 2.12 to 8.83 mg/ml. Depending on the dosage rates, these levels would represent approximately 20-50% of the daily dietary intake recommended by the National Research Council. Possible losses in the manufacturing process and stability during storage for 30 days at 40 +/- 2 degrees C without light, were tested. In relation to the ascorbic acid concentrations stated on the labels, a loss of 12.0-21.9% in pills and of 11.7-18.0% in ampoules was detected. In relation to the stability conditions, the losses are of 1.8-24.8% in pills and of 10.4-19.3% in ampoules. The pasteurisation and sterilisation processes produced a mean loss of ascorbic acid in ampoules of 2.1 and 1.4%, respectively. A statistically significant direct correlation was observed between ascorbic acid loss and content in proteins, humidity, ash, and fructose. The influence of the pharmaceutical form was also tested. Data revealed that the control of losses during the manufacturing and commercialisation process of these products is necessary to ensure the intake of vitamin C from these products by the consumer.

The development of multiple domains of child and adolescent self-concept: a cohort sequential longitudinal design.

The development of child and adolescent self-concept was examined as a function of the self-concept domain, social/developmental/educational transitions, and gender. In two overlapping age cohorts of public school students (Ns = 936 and 984), five dimensions of self-concept were evaluated every 6 months in a manner that spanned grades 3 through 11 (representing the elementary, middle, and high school years). Domains of self-concept included academic competence, physical appearance, behavioral conduct, social acceptance, and sports competence. Structural equation modeling addressed questions about the stability of individual differences over time. Multilevel modeling addressed questions about mean-level changes in self-concept over time. Significant effects emerged with regard to gender, age, dimension of self-concept, and educational transition.

Livedo reticularis and thrombotic purpura related to the use of diphenhydramine associated with pyrithyldione.

We describe the case of a young woman who habitually took large doses of a combination of diphenhydramine and pyrithyldione. She complained of arthralgia, painful recurring plaques and nodules, together with persistent reticular purpuric mottling and areas of necrosis on her legs. There were positive antinuclear antibodies and rheumatoid factor and histologically massive thrombosis of the dermal vessels without signs of vasculitis. Other cases of similar adverse reactions attributed to this drug combination used as a hypnotic have been described.

Positivity of patch tests in cutaneous reaction to aminocaproic acid: two case reports.

We observed two cases of maculopapular eruption occurring 12-72 h after the administration of aminocaproic acid (ACA). Patch tests performed with ACA were positive. Clinical and allergologic patterns suggest the type IV mechanism of hypersensitivity. We present what we believe are the first two cases described of hypersensitivity to this drug.

Unliganded T3R, but not its oncogenic variant, v-erbA, suppresses RAR-dependent transactivation by titrating out RXR.

V-erbA is thought to be an antagonist of thyroid hormone receptor (T3R) function. Here we show that unliganded T3R, but not v-erbA, suppresses retinoic acid (RA)-dependent induction of the RAR-beta 2 promoter by competing for the common dimerization partner, the retinoid X receptor (RXR). Firstly, T3R suppression can be alleviated by co-transfection of RXR. Secondly, T3R, but not v-erbA, competes with RAR for RXR and causes the dissociation of a preformed RAR/RXR-RARE ternary complex in vitro. A single point mutation located in the dimerization interface of v-erbA (Pro349 to Ser) abolishes the transdominant phenotype when introduced at the respective position in T3R. The hypertransforming v-erbA variant r12, in which this mutation is reversed (Ser349 to Pro) suppresses RA-induced differentiation in chicken erythroid progenitors, while v-erbA does not. Our data thus suggest that unliganded T3R and v-erbA act as dominant suppressors through mechanistically distinct pathways.