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.

Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.