Synthesis, biological activity, and four-dimensional quantitative structure-activity analysis of 2-arylidene indan-1,3-dione derivatives tested against Daphnia magna.

A series of 18 2-arylidene indan-1,3-dione derivatives was synthesized and tested against Daphnia magna to assess the environmental toxicity of these compounds. Aiming to investigate the toxicity mechanism for this series of compounds, a four-dimensional quantitative structure-activity analysis (4D-QSAR) was performed through the partial least square regression (PLS). The best PLS model was built with two factors and the selected field descriptors, of Coulomb (C) and Lennard-Jones (L) nature, describing 77.43% of variance and presenting the following statistics: r 2 = 0.89; SEC = 0.30; Q 2 = 0.81; SEV = 0.36. According to the literature, the bioactivity of α,ß-unsaturated ketones, a functionality present in the series of compounds under investigation, is related to the conjugated double bond with the carbonyl group. The presence of a positive Coulomb descriptor nearby the carbonyl moieties, obtained as a result of the regression model, indicates that these polar groups are also related to the toxicity on D. magna. From the PLS regression model, the toxicity EC50-48 h values increases with the positive Coulomb descriptor and diminishes with the negative Lennard-Jones descriptors. It could be concluded that the presence of small polar groups in the aromatic ring of the arylidene moiety tends to increase the toxicity, while bulkier apolar substituents lead to a decrease of the toxicity.

Salivary nitric oxide and alpha-amylase as indexes of training intensity and load.

This study examined the variation in salivary nitric oxide (NO), alpha-amylase (sAA) and serum markers of muscle injury during 21 weeks of training in elite swimmers. Samples of saliva and blood were collected once a month during 5 months from 11 male professional athletes during their regular training season. The variation in each marker throughout the 21 weeks was compared with the dynamics of training volume, intensity and load. Unstimulated whole saliva was assessed for NO and sAA whereas venous blood was assessed for lactate dehydrogenase, creatine kinase, and γ-glutamyltransferase. Nitric oxide and sAA showed a proportional response to the intensity of training. However, whereas the concentration of NO increased across the 21 weeks, the activity of sAA decreased. Similar variations in the concentration of NO and the markers of muscle injury were also observed. The higher concentration of NO might be attributed to changes in haemodynamics and muscle regenerative processes. On the other hand, autonomic regulation towards parasympathetic predominance might have been responsible for the decrease in sAA activity. These findings provide appealing evidence for the utilization of salivary constituents in sports medicine to monitor training programmes.

A critical view on antimalarial endoperoxide QSAR studies.

Malaria is one of the most dangerous diseases in developing countries. The chemotherapy of malaria has been based on drugs developed more than half a century ago. These drugs are continuously losing their efficacy, mainly due to multi-drug resistance developed by the malaria-causing parasite. In the last three decades, artemisinin and artemisinin-like compounds have proven to be efficient alternatives to the chemotherapeutic control of malaria. These facts have led to an increasing interest in the development of Quantitative Structure Activity Relantioship (QSAR) models for these compounds. This work presents a critical view on some QSAR models, and shows that, due to lack of a rigorous selection of the descriptors entering the models, most of them are unable to accurately indicate the molecular cause of biological activity. Some reasons for the weakness of the published models are discussed.

Response of salivary markers of autonomic activity to elite competition.

We investigated the response of salivary total protein (TP), alpha-amylase (sAA) and chromogranin A (CgA) to sporting competition and their relation with positive and negative affect. 11 professional swimmers were examined during the first day of a national contest and on a recreated event that matched time-of-the-day and day-of-the-week assessments 2 weeks later. Total protein was determined by the Bradford method and sAA and CgA by Western blotting upon awakening, 30 and 60 min post awakening, immediately before warming up for competition and 5, 20 and 60 min after competition. Psychometric instruments included the Positive Affect and Negative Affect Schedule-X. The concentrations of TP, sAA and CgA differed from controls only prior to and 5 min after the event. We observed positive correlations between higher negative affect scores with higher levels of TP, sAA and CgA prior to the event on the competition day. All 3 markers showed a similar reactivity to sporting competition, which may be attributed to the mechanisms responsible for protein secretion into saliva when collection is performed with no exogenous stimulation. TP is an attractive marker in sports psychology since its determination is faster and cheaper than traditional kinetic or immune assays.

[Process assessment in the care for patients with chronic degenerative disease in a basic health unit]. / Avaliação do processo de atendimento a pacientes portadores de doença crônico-degenerativa em uma unidade básica de saúde.

The efficacy of health actions, related to arterial hypertension and used as a strategy to decrease morbimortality due to cardiovascular diseases, in accordance with the "risk approach" and carried out in a Primary Health Care Clinic is assessed. These actions are based on the detection of arterial hypertension in the adult population attended at the Clinic and on the control of blood pressure levels in hypertensive individuals in which other known risk factors continue to be controlled, as well as on further treatment of eventual complications. Data relating to the 3,793 patients who were attended at least once by doctors of the adult sector of a training health-center located in S. Paulo county (Brazil) during the period from June 1990 to May 1991, inclusive, were evaluated. This evaluation was made according to each diagnosis undertaken as well as to the concentration of each type of consultation whether occasional, or follow-up. Of these 3,793 patients analysed, 839 presented arterial hypertension and/or diabetes, and were grouped into four categories: the exclusively hypertensive, the hypertensive with other associated chronic diseases (except diabetes), the diabetic and the diabetic with arterial hypertension. The results of this study brought the following aspects to light: 1) The low coverage of hypertensive individuals and diabetics being attended by the health service when only the population attended by the health service is taken into consideration. 2) The incidence of patients diagnosed as hypertensive in occasional consultations who did not return to the health service for medical follow-up indicates the difficulties involved in attracting such individuals permanently.(ABSTRACT TRUNCATED AT 250 WORDS)