NMR investigation and theoretical calculations of the effect of solvent on the conformational analysis of 4',7-di-hydroxy-8-prenylflavan

The NMR conformational study of 4',7-di-hydroxy-8-prenylflavan 1 was carried out in acetone-d6, DMSO-d6 and CDCl3 which enabled the proposition of three conformations, namely 1a, 1b and 1c, differing in the position of the prenyl group. Geometry optimizations performed using AM1 method showed that 1a (deltaHf = -86.2 kcal/mol) is as stable as 1b (deltaHf = -85.1 kcal/mol) and 1c (deltaHf = -85.4 kcal/mol). When the solvent was included, the calculations showed that the solute-solvent interactions could be explained either in the light of the electronic intermolecular delocalization or the electrostatic character between solute and solvent. Theoretical calculations (HF/6-31G*, deltaFT/BLYP/6-31G*, and deltaFT/B3LYP/6-31G*) showed that the combination of these types of interactions present in each solute-solvent system, dependent on the chemical properties of the solvent, lead to different spatial arrangements of the prenyl group, which in turn determined the conformation of 1.

Structural and reactivity analyses of 2-benzylamino-1,4-naphthoquinone by X-ray characterization, electrochemical measurements, and dft single-molecule calculations

This study represents an integrated approach towards understanding the electronic and structural aspects of 2-benzylamino-1,4-naphthalenedione, a representative 2-amino-napfthoquinone. To this end, theoretical calculations performed at the B3PW91/6-31+G(d) level of density functional theory, electrochemical and X-ray structural investigation were employed. Two intramolecular H-bonds and other two intermolecular H-bonds were observed, including non-classical interactions. Cyclic voltammogram (CV) and differential pulse voltammetry (DPV) show two pairs of peaks, being each one a monoelectronic process.

Application of GA-PLS and GA-KPLS calculations for the prediction of the retention indices of essential oils

Genetic algorithm and partial least square (GA-PLS) and kernel PLS (GA-KPLS) techniques were used to investigate the correlation between retention indices (RI) and descriptors for 117 diverse compounds in essential oils from 5 Pimpinella species gathered from central Turkey which were obtained by gas chromatography and gas chromatography-mass spectrometry. The square correlation coefficient leave-group-out cross validation (LGO-CV) (Q²) between experimental and predicted RI for training set by GA-PLS and GA-KPLS was 0.940 and 0.963, respectively. This indicates that GA-KPLS can be used as an alternative modeling tool for quantitative structure-retention relationship (QSRR) studies.

Comparative analysis of the trypanocidal activity and chemical properties of E-lychnophoric acid and its derivatives using theoretical calculations

E-Lychnophoric acid 1, its derivative ester 2 and alcohol 3 killed 100% of trypomastigote blood forms of Trypanosoma cruzi at the concentrations of 13.86, 5.68, and 6.48 µg/mL, respectively. Conformational distribution calculations (AM1) of 1, 2 and 3 gave minimum energies for the conformers a, b, c, and d, which differ from each other only in the cyclononene ring geometry. Calculations (DFT/BLYP/6-31G*) of geometry optimization and chemical properties were performed for conformers of 1, 2, and 3. The theoretical results were numerically compared to the trypanocidal activity. Calculated values of atomic charge, orbital population, and vibrational frequencies showed that the C-4-C-5 pi-endocyclic bond does not affect the trypanocidal activity of the studied compounds. Nevertheless, the structure of the group at C-4 strongly influences the activity. However, the theoretical results indicated that the intra-ring (C-1 and C-9) and pi-exocycle (C-8 and C-14) carbons of caryophyllene-type structures promote the trypanocidal activity of these compounds.

Nitrogen fertilizer (15N) leaching in a central pivot fertigated coffee crop

Nitrogen has a complex dynamics in the soil-plant-atmosphere system. N fertilizers are subject to chemical and microbial transformations in soils that can result in significant losses. Considering the cost of fertilizers, the adoption of good management practices like fertigation could improve the N use efficiency by crops. Water balances (WB) were applied to evaluate fertilizer N leaching using 15N labeled urea in west Bahia, Brazil. Three scenarios (2008/2009) were established: i) rainfall + irrigation the full year, ii) rainfall only; and iii) rainfall + irrigation only in the dry season. The water excess was considered equal to the deep drainage for the very flat area (runoff = 0) with a water table located several meters below soil surface (capillary rise = 0). The control volume for water balance calculations was the 0 - 1 m soil layer, considering that it involves the active root system. The water drained below 1 m was used to estimate fertilizer N leaching losses. WB calculations used the mathematic model of Penman-Monteith for evapotranspiration, considering the crop coefficient equal to unity. The high N application rate associated to the high rainfall plus irrigation was found to be the main cause for leaching, which values were 14.7 and 104.5 kg ha-1 for the rates 400 and 800 kg ha-1 of N, corresponding to 3.7 and 13.1 % of the applied fertilizer, respectively.

Geographical patterns of proportionate mortality for the most common causes of death in Brazil

Mortality due to chronic diseases has been increasing in all regions of Brazil with corresponding decreases in mortality from infectious diseases. The geographical variation in proportionate mortality for chronic diseases for 17 Brazilian state capitals for the year 1985 and their association with socio-economic variables and infectious disease was studied. Calculations were made of correlation coefficients of proportionate mortality for adults of 30 years or above due to ischaemic heart disease, stroke and cancer of the lung, the breast and stomach with 3 socio-economic variables, race, and mortality due to infectious disease. Linear regression analysis included as independent variables the % of illiteracy, % of whites, % of houses with piped water, mean income, age group, sex, and % of deaths caused by infectious disease. The dependent variables were the % of deaths due to each one of the chronic diseases studied by age-sex group. Chronic diseases were an important cause of death in all regions of Brazil. Ischaemic heart diseases, stroke and malignant neoplasms accounted for more than 34% of the mortality in each of the 17 capitals studied. Proportionate cause-specific mortality varied markedly among state capitals. Ranges were 6.3-19.5% for ischaemic heart diseases, 8.3-25.4% for stroke, 2.3-10.4% for infections and 12.2-21.5% for malignant neoplasm. Infectious disease mortality had the highest (p < 0.001) correlation with all the four socio-economic variables studied and ischaemic heart disease showed the second highest correlation (p < 0.05). Higher socio-economic level was related to a lower % of infectious diseases and a higher % of ischaemic heart diseases. Mortality due to breast cancer and stroke was not associated with socio-economic variables. Multivariate linear regression models explained 59% of the variance among state capitals for mortality due to ischaemic heart disease, 50% for stroke, 28% for lung cancer, 24% for breast cancer and 40% for stomach cancer. There were major differences in the proportionate mortality due to chronic diseases among the capitals which could not be accounted for by the social and environmental factors and by the mortality due to infectious disease.

The AIDS epidemic in the Amazon region: a spatial case-control study in Rondonia, Brazil

OBJECTIVE To analyze spatial changes in the risk of AIDS and the relationship between AIDS incidence and socioeconomic variables in the state of Rondonia, Amazon region. METHODS A spatial, population case-control study in Rondonia, Brazil, based on 1,780 cases reported to the Epidemiological Surveillance System and controls based on demographic data from 1987 to 2006. The cases were grouped into five consecutive four-year periods. A generalized additive model was adjusted to the data; the dependent variable was the status of the individuals (case or control), and the independent variables were a bi-dimensional spline of the geographic coordinates and some municipality-level socioeconomic variables. The observed values of the Moran’s I test were compared to a reference distribution of values generated under conditions of spatial randomness. RESULTS AIDS risk shows a marked spatial and temporal pattern. The disease incidence is related to socioeconomic variables at the municipal level in Rondônia, such as urbanization and human capital. The highest incidence rates of AIDS are in municipalities along the BR-364 highway and calculations of the Moran’s I test show positive spatial correlation associated with proximity of the municipality to the highway in the third and fourth periods (p = 0.05). CONCLUSIONS Incidence of the disease is higher in municipalities of greater economic wealth and urbanization, and in those municipalities bisected by Rondônia’s main roads. The rapid development associated with the opening up of once remote regions may be accompanied by an increase in these risks to health.

Assessing usual dietary intake in complex sample design surveys: the National Dietary Survey

The National Cancer Institute (NCI) method allows the distributions of usual intake of nutrients and foods to be estimated. This method can be used in complex surveys. However, the user must perform additional calculations, such as balanced repeated replication (BRR), in order to obtain standard errors and confidence intervals for the percentiles and mean from the distribution of usual intake. The objective is to highlight adaptations of the NCI method using data from the National Dietary Survey. The application of the NCI method was exemplified analyzing the total energy (kcal) and fruit (g) intake, comparing estimations of mean and standard deviation that were based on the complex design of the Brazilian survey with those assuming simple random sample. Although means point estimates were similar, estimates of standard error using the complex design increased by up to 60% compared to simple random sample. Thus, for valid estimates of food and energy intake for the population, all of the sampling characteristics of the surveys should be taken into account because when these characteristics are neglected, statistical analysis may produce underestimated standard errors that would compromise the results and the conclusions of the survey.

Functional disability of adults in Brazil: prevalence and associated factors

ABSTRACT OBJECTIVE To estimate the prevalence and factors associated with functional disability in adults in Brazil. METHODS We used information from the health supplement of the National Household Sample Survey in 2008. The dependent variable was the functional disability among adults of 18 to 65 years, measured by the difficulty of walking about 100 meters; independent variables were: health plan membership, region of residence, state of domicile, education level, household income, economic activity, self-perception of health, hospitalization, chronic diseases, age group, sex, and color. We calculated the gross odds ratios (OR), and their respective confidence intervals (95%), and adjusted them for variables of study by ordinal logistic regression, following hierarchical model. Sample weights were considered in all calculations. RESULTS We included 18,745 subjects, 74.0% of whom were women. More than a third of adults reported having functional disability. The disability was significantly higher among men (OR = 1.17; 95%CI 1.09;1.27), people from 35 to 49 years (OR = 1.30; 95%CI 1.17;1.45) and 50 to 65 years (OR = 1.38; 95%CI 1.24;1.54); economically inactive individuals (OR = 2.21; 95%CI 1.65;2.96); adults who reported heart disease (OR = 1.13; 95%CI 1.03;1.24), diabetes mellitus (OR = 1.16; 95%CI 1.05;1.29), arterial systemic hypertension (OR = 1.10; 95%CI 1.02;1.18), and arthritis/rheumatism (OR = 1.24; 95%CI 1.15;1.34); and participants who were admitted in the last 12 months (OR = 2.35; 95%CI 1.73;3.2). CONCLUSIONS Functional disability is common among Brazilian adults. Hospitalization is the most strongly associated factor, followed by economic activity, and chronic diseases. Sex, age, education, and income are also associated. Results indicate specific targets for actions that address the main factors associated with functional disabilities and contribute to the projection of interventions for the improvement of the well-being and promotion of adults' quality of life.

Peroxidase antibody test for mucocutaneous leishmaniasis serology performance indexes and comparison with a fluorescent antibody test: Comparação com o desempenho da reação de imunofluorescência

Performance indexes of the peroxidase antibody test were compared to that of the fluorescent antibody test. The peroxidase antibody test had a statistically higher sensitivity and negative predictive value and a higher efficiency than the fluorescent antibody test but its specificity and positive predictive value were within the 95% confidence limits for the values found for the fluorescent antibody test. Such differences did not change when Chagas' disease and visceral leishmaniasis sera were included in index calculations. Statistical analysis showed that the two tests have a substantial degree of agreement but the immunofluorescent test had a specificity index and a positive predictive value equal to 100.0% when Chagas' disease and visceral leishmaniasis sera were not included in the calculations of the performance index; in this instance, a positive test result equals a disclosure of the disease attribute due to the inexistence of false positive results. The enzyme/ protein ratio of the peroxidase conjugate, resulting in heavy or light-labeled conjugates may pose technical problems to its use in serology tests.

COLONIZATION AND LABORATORY MAINTENANCE OFAnopheles albimanus WIEDEMANN IN VENEZUELA

Anopheles albimanus is one of the main vectors of malaria in Central America and the Caribbean, based on its importance, there are previous reports of the successful colonization of this species in Latin America countries. Mosquitoes were collected in the Aragua State of Venezuela colonized in the laboratory, using a simple and efficient maintenance method. Based on life table calculations under well established laboratory conditions, the Survival Rate Probability was constant and always close to 1 in immature stages, the Reproductive Net Rate (Ro) was 3.83, the generation time (Tc) was 24.5 days and the Intrinsic Growth Rate (rm) was 0.0558. This is the first report of the colonization of A. albimanus in Venezuela.

Febrifugine derivative antimalarial activity: quantum mechanical predictors

Plasmodium falciparum resistant strain development has encouraged the search for new antimalarial drugs. Febrifugine is a natural substance with high activity against P. falciparum presenting strong emetic property and liver toxicity, which prevent it from being used as a clinical drug. The search for analogues that could have a better clinical performance is a current topic. We aim to investigate the theoretical electronic structure by means of febrifugine derivative family semi-empirical molecular orbital calculations, seeking the electronic indexes that could help the design of new efficient derivatives. The theoretical results show there is a clustering in well-defined ranges of several electronic indexes of the most selective molecules. The model proposed for achieving high selectivity was tested with success.

Cost of drugs manufactured by the University Hospital - role of the Central Pharmacy

The hospital pharmacy in large and advanced institutions has evolved from a simple storage and distribution unit into a highly specialized manipulation and dispensation center, responsible for the handling of hundreds of clinical requests, many of them unique and not obtainable from commercial companies. It was therefore quite natural that in many environments, a manufacturing service was gradually established, to cater to both conventional and extraordinary demands of the medical staff. That was the case of Hospital das Clinicas, where multiple categories of drugs are routinely produced inside the pharmacy. However, cost-containment imperatives dictate that such activities be reassessed in the light of their efficiency and essentiality. METHODS: In a prospective study, the output of the Manufacturing Service of the Central Pharmacy during a 12-month period was documented and classified into three types. Group I comprised drugs similar to commercially distributed products, Group II included exclusive formulations for routine consumption, and Group III dealt with special demands related to clinical investigations. RESULTS: Findings for the three categories indicated that these groups represented 34.4%, 45.3%, and 20.3% of total manufacture orders, respectively. Costs of production were assessed and compared with market prices for Group 1 preparations, indicating savings of 63.5%. When applied to the other groups, for which direct equivalent in market value did not exist, these results would suggest total yearly savings of over 5 100 000 US dollars. Even considering that these calculations leave out many components of cost, notably those concerning marketing and distribution, it might still be concluded that at least part of the savings achieved were real. CONCLUSIONS: The observed savings, allied with the convenience and reliability with which the Central Pharmacy performed its obligations, support the contention that internal manufacture of pharmaceutical formulations was a cost-effective alternative in the described setting.

Análise estatística da distribuição de Poisson

The general properties of POISSON distributions and their relations to the binomial distribuitions are discussed. Two methods of statistical analysis are dealt with in detail: X2-test. In order to carry out the X2-test, the mean frequency and the theoretical frequencies for all classes are calculated. Than the observed and the calculated frequencies are compared, using the well nown formula: f(obs) - f(esp) 2; i(esp). When the expected frequencies are small, one must not forget that the value of X2 may only be calculated, if the expected frequencies are biger than 5. If smaller values should occur, the frequencies of neighboroughing classes must ge pooled. As a second test reintroduced by BRIEGER, consists in comparing the observed and expected error standard of the series. The observed error is calculated by the general formula: δ + Σ f . VK n-1 where n represents the number of cases. The theoretical error of a POISSON series with mean frequency m is always ± Vm. These two values may be compared either by dividing the observed by the theoretical error and using BRIEGER's tables for # or by dividing the respective variances and using SNEDECOR's tables for F. The degree of freedom for the observed error is one less the number of cases studied, and that of the theoretical error is always infinite. In carrying out these tests, one important point must never be overlloked. The values for the first class, even if no concrete cases of the type were observed, must always be zero, an dthe value of the subsequent classes must be 1, 2, 3, etc.. This is easily seen in some of the classical experiments. For instance in BORKEWITZ example of accidents in Prussian armee corps, the classes are: no, one, two, etc., accidents. When counting the frequency of bacteria, these values are: no, one, two, etc., bacteria or cultures of bacteria. Ins studies of plant diseases equally the frequencies are : no, one, two, etc., plants deseased. Howewer more complicated cases may occur. For instance, when analising the degree of polyembriony, frequently the case of "no polyembryony" corresponds to the occurrence of one embryo per each seed. Thus the classes are not: no, one, etc., embryo per seed, but they are: no additional embryo, one additional embryo, etc., per seed with at least one embryo. Another interestin case was found by BRIEGER in genetic studies on the number os rows in maize. Here the minimum number is of course not: no rows, but: no additional beyond eight rows. The next class is not: nine rows, but: 10 rows, since the row number varies always in pairs of rows. Thus the value of successive classes are: no additional pair of rows beyond 8, one additional pair (or 10 rows), two additional pairs (or 12 rows) etc.. The application of the methods is finally shown on the hand of three examples : the number of seeds per fruit in the oranges M Natal" and "Coco" and in "Calamondin". As shown in the text and the tables, the agreement with a POISSON series is very satisfactory in the first two cases. In the third case BRIEGER's error test indicated a significant reduction of variability, and the X2 test showed that there were two many fruits with 4 or 5 seeds and too few with more or with less seeds. Howewer the fact that no fruit was found without seed, may be taken to indicate that in Calamondin fruits are not fully parthenocarpic and may develop only with one seed at the least. Thus a new analysis was carried out, on another class basis. As value for the first class the following value was accepted: no additional seed beyond the indispensable minimum number of one seed, and for the later classes the values were: one, two, etc., additional seeds. Using this new basis for all calculations, a complete agreement of the observed and expected frequencies, of the correspondig POISSON series was obtained, thus proving that our hypothesis of the impossibility of obtaining fruits without any seed was correct for Calamondin while the other two oranges were completely parthenocarpic and fruits without seeds did occur.

Congenital toxoplasmosis and DALYs in the Netherlands

The calculation of disability-adjusted life years (DALYs) enables public health policy makers to compare the burden of disease of a specific disease with that of other (infectious) diseases. The incidence of a disease is important for the calculation of DALYs. To estimate the incidence of congenital toxoplasmosis (CT), a random sample of 10,008 dried blood spot filter paper cards from babies born in 2006 in the Netherlands were tested for Toxoplasma gondii-specific IgM antibodies. Eighteen samples were confirmed as positive for IgM, resulting in an observed birth incidence of CT of 1.8 cases per 1,000 live-born children in 2006 and an adjusted incidence of 2.0 cases per 1,000. This means that 388 infected children were born in 2006. The most likely burden of disease is estimated to be 2,300 DALYs (range 820-6,710 DALYs). In the previous calculations, using data from a regional study from 1987, this estimate was 620 DALYs (range 220-1,900 DALYs). The incidence of CT in the Netherlands is much higher than previously reported; it is 10 times higher than in Denmark and 20 times higher than in Ireland, based on estimates obtained using the same methods. There is no screening program in the Netherlands; most children will be born asymptomatic and therefore will not be detected or treated.