Development and biological evaluation of API-ILs based on anti-bacterial and anti-fungal drugs

In recent years Ionic Liquids (ILs) are being applied in life sciences. ILs are being produce with active pharmaceutical drugs (API) as they can reduce polymorphism and drug solubility problems [1] Also ILs are being applied as a drug delivery device in innovative therapies What is appealing in ILs is the ILs building up platform, the counter-ion can be carefully chosen in order to avoid undesirable side effects or to give innovative therapies in which two active ions are paired. This work shows ILs based on ampicillin (an anti-bacterial agent) and ILs based on Amphotericin B. Also we show studies that indicate that ILs based on Ampicillin could reverse resistance in some bacteria. The ILs produced in this work were synthetized by the neutralization method described in Ferraz et. al. [2] Ampicillin anion was combined with the following organic cations 1-ethyl-3-methylimidazolium, [EMIM]; 1-hydroxy-ethyl-3-methylimidazolium, [C2OHMIM]; choline, [cholin]; tetraethylammonium, [TEA]; cetylpyridinium, [C16pyr] and trihexyltetradecylphosphonium, [P6,6,6,14]. Amphotericin B was combined with [C16pyr], [cholin] and 1-metohyethyl-3-methylimidazolium, [C3OMIM]. The ILs-APIs based on ampicillin[2] were tested against sensitive Gram-negative bacteria Escherichia coli ATCC 25922 and Klebsiella pneumonia (clinical isolated), as well as on Gram positive Staphylococcus Aureus ATCC 25923, Staphylococcus epidermidis and Enterococcus faecalis. The arising resistance developed by bacteria to antibiotics is a serious public health threat and needs new and urgent measures. We study the bacterial activity of these compounds against a panel of resistant bacteria (clinical isolated strains): E. coli CTX M9, E. coli TEM CTX M9, E. coli TEM1, E. coli CTX M2, E. coli AmpC Mox2. In this work we demonstrate that is possible to produce ILs from anti-bacterial and anti-fungal compounds. We show here that the new ILs can reverse the bacteria resistance. With the careful choice of the organic cation, it is possible to create important biological and physic-chemical properties. This work also shows that the ion-pair is fundamental in ampicillin mechanism of action.

Cellular uptake of BCG-loaded chitosan microparticles and in vivo evaluation of immune response following intranasal immunisation

Attenuated Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only currently available vaccine against tuberculosis. It is highly effective in pre-exposure immunisation against TB in children when administered by subcutaneous route to newborns. However, it does not provide permanent protection in adults. In this work, polymeric chitosan-alginate microparticles have been evaluated as potential nasal delivery systems and mucosal adjuvants for live attenuated BCG. Chitosan (CS) has been employed as adjuvant and mucosal permeation-enhancer, and, together with alginate (ALG), as additive to enhance BCG-loaded microparticles (MPs) cellular uptake in a human monocyte cell line, by particle surface modification. The most suitable particles were used for vaccine formulation and evaluation of immune response following intranasal immunisation of BALB/c mice.

Re-evaluation of a reported increased micronucleus frequency in lymphocytes of workers occupationally exposed to formaldehyde

A replicate evaluation of increased micronucleus (MN) frequencies in peripheral lymphocytes of workers occupationally exposed to formaldehyde (FA) was undertaken to verify the observed effect and to determine scoring variability. May–Grünwald–Giemsa-stained slides were obtained from a previously performed cytokinesis-block micronucleus test (CBMNT) with 56 workers in anatomy and pathology laboratories and 85 controls. The first evaluation by one scorer (scorer 1) had led to a highly significant difference between workers and controls (3.96 vs 0.81 MN per 1000 cells). The slides were coded before re-evaluation and the code was broken after the complete re-evaluation of the study. A total of 1000 binucleated cells (BNC) were analysed per subject and the frequency of MN (in ‰) was determined. Slides were distributed equally and randomly between two scorers, so that the scorers had no knowledge of the exposure status. Scorer 2 (32 exposed, 36 controls) measured increased MN frequencies in exposed workers (9.88 vs 6.81). Statistical analysis with the two-sample Wilcoxon test indicated that this difference was not significant (p = 0.17). Scorer 3 (20 exposed, 46 controls) obtained a similar result, but slightly higher values for the comparison of exposed and controls (19.0 vs 12.89; p = 0.089). Combining the results of the two scorers (13.38 vs 10.22), a significant difference between exposed and controls (p = 0.028) was obtained when the stratified Wilcoxon test with the scorers as strata was applied. Interestingly, the re-evaluation of the slides led to clearly higher MN frequencies for exposed and controls compared with the first evaluation. Bland–Altman plots indicated that the agreement between the measurements of the different scorers was very poor, as shown by mean differences of 5.9 between scorer 1 and scorer 2 and 13.0 between scorer 1 and scorer 3. Calculation of the intra-class correlation coefficient (ICC) revealed that all scorer comparisons in this study were far from acceptable for the reliability of this assay. Possible implications for the use of the CBMNT in human biomonitoring studies are discussed.

New xanthenodione: synthesis and antioxidant activity evaluation

6th Spanish-Portuguese-Japanese Organic Chemistry Symposium, Lisboa, de 18 a 20 de Julho de 2012 (Poster Communication).

Avaliação e promoção da qualidade dos cuidados prestados em creche familiar: primeiros resultados de um estudo de investigação/acção

Neste artigo apresentam-se os resultados do projecto de investigação/acção Promoção da qualidade dos cuidados prestados em amas e creche familiar (resposta enquadrada pelo Decreto-Lei n.º158/84). É um estudo exploratório, de carácter longitudinal, que teve como principais objectivos: (1) avaliar a qualidade da resposta creche familiar em duas instituições do Distrito de Lisboa; (2) analisar se variáveis como a idade, nível de escolaridade e tempo de experiência das amas, o rácio TE/ama e a idade das crianças estavam associadas à qualidade de cuidados prestada; (3) sistematizar os passos de um programa de promoção da qualidade baseado numa metodologia de consultoria; e (4) determinar os efeitos do programa de consultoria na promoção da qualidade. Participaram neste projecto 10 amas enquadradas na creche familiar de um centro infantil do Centro Distrital de Segurança Social de Lisboa, 21 amas de centros infantis da Santa Casa da Misericórdia de Lisboa e os Técnicos de Enquadramento responsáveis pelo apoio técnico. A Family Child Care Environment Rating Scale, Revised Edition (FCCERS-R) de Harms, Cryer e Clifford (2007), traduzida pela equipa de investigação, foi o principal instrumento utilizado. A recolha de dados decorreu em três momentos: (1) avaliação inicial; (2) reunião de consultoria; e (3) avaliação final.Os resultados encontrados mostram que a qualidade dos cuidados prestados pelas amas é adequada/mínima, com excepção dos itens relacionados com a interacção ama-criança onde a qualidade é boa, sendo a subescala actividades aquela onde foram encontrados valores mais baixos. Não foram encontradas associações significativas entre a qualidade e o tempo experiência das amas. Relativamente às restantes variáveis – idade das amas, rácio TE/ama e idade das crianças – encontraram-se algumas associações com a qualidade global e em algumas das subescalas da FCCERS-R. Foram encontradas diferenças entre os dados da 1ª e da 2ª observação que parecem poder associar-se ao processo de consultoria implementado.

Shell variation in Patellid limpets: scales of spatial variability

World Congress of Malacology, Universidade dos Açores, Ponta Delgada, 21-28 de julho.

Electrochemical evaluation of total antioxidant capacity of beverages using a purine-biosensor

In this paper, it was evaluated the total antioxidant capacity (TAC) of beverages using an electrochemical biosensor. The biosensor consisted on the purine base (guanine or adenine) electro-immobilization on a glassy carbon electrode surface (GCE). Purine base damage was induced by the hydroxyl radical generated by Fenton-type reaction. Five antioxidants were applied to counteract the deleterious effects of the hydroxyl radical. The antioxidants used were ascorbic acid, gallic acid, caffeic acid, coumaric acid and resveratrol. These antioxidants have the ability to scavenger the hydroxyl radical and protect the guanine and adenine immobilized on the GCE surface. The interaction carried out between the purinebase immobilized and the free radical in the absence and presence of antioxidants was evaluated by means of changes in the guanine and adenine anodic peak obtained by square wave voltammetry (SWV). The results demonstrated that the purine-biosensors are suitable for rapid assessment of TAC in beverages.

Exposição profissional a nanopartículas na indústria farmacêutica: estudo exploratório

Mestrado em Segurança e Higiene no Trabalho

A model for heterogeneous networks management and Performance evaluation

In general, modern networks are analysed by taking several Key Performance Indicators (KPIs) into account, their proper balance being required in order to guarantee a desired Quality of Service (QoS), particularly, cellular wireless heterogeneous networks. A model to integrate a set of KPIs into a single one is presented, by using a Cost Function that includes these KPIs, providing for each network node a single evaluation parameter as output, and reflecting network conditions and common radio resource management strategies performance. The proposed model enables the implementation of different network management policies, by manipulating KPIs according to users' or operators' perspectives, allowing for a better QoS. Results show that different policies can in fact be established, with a different impact on the network, e.g., with median values ranging by a factor higher than two.

Evaluation of coumarins effect in saccharomyces cerevisiae

Coumarin and derivates (coumarins) are phenolic compounds widely distributed in the plant kingdom, as for example in tonka beam and cassia cinnamon. These compounds are involved in various processes such as the defense against phytopathogens, the response to abiotic stress and the regulation of oxidative stress. Coumarins can be produced synthetically and are broadly used as additives in the food, perfumes and cosmetics and pharmaceutical industry due th their vast array of biological activities, including anticoagulant, analgesic, anti-inflammatory and anti-microbial.

Evaluation of 99mTc-Sestamibi as a potential tool to investigate PgP activity in inflammation

Introduction: In the XXI Century ’s Society the scientific investigation process has been growing steadily , and the field of the pharmaceutical research is one of the most enthusiastic and relevant . Here, it is very important to correlate observed functional alterations with possibly modified drug bio distribution patterns . Cancer, inflammation and inf ection are processes that induce many molecular intermediates like cytokines, chemokines and other chemical complexes that can alter the pharmacokinetics of many drugs. One cause of such changes is thought to be the modulator action of these complexes in t he P - Glyco p rotein activity, because they can act like inducers/inhibitors of MDR - 1 expression. This protein results from the expression of MDR - 1 gene, and acts as an ATP energy - dependent efflux pump, with their substrates including many drugs , like antiretrovirals, anticancers, anti - infectives, immunosuppressants, steroids or opioids . Objectives: Because of the lack of methods to provide helpful information in the investigation of in vivo molecular changes in Pgp activity during infection/infl ammation processes, and its value in the explanation of the altered drug pharmacokinetic, this paper want to evaluate the potential utility of 99m Tc - Sestamibi scintigraphy during this kind of health sciences investigation. Although the a im is indeed to create a technique to the in vivo study of Pgp activity, this preliminary Project only reaches the in vitro study phase, assumed as the first step in a n evaluation period for a new tool development. Materials and Methods: For that reason , we are performing in vitro studies of influx and efflux of 99m Tc - Sestamibi ( that is a substrate of Pgp) in hepatocytes cell line (HepG2). We are interested in clarify the cellular behavior of this radiopharmaceutical in Lipopolysaccharide(LPS) stimulated cells ( well known in vitro model of inflammation) to possibly approve this methodology. To validate the results, the Pgp expression will be finally evaluated using Western Blot technique. Results: Up to this moment , we still don’t have the final results, but we have already enough data to let us believe that LPS stimulation induce a downregulation of MDR - 1, and consequently Pgp, which could conduce to a prolonged retention of 99m Tc - Sestamibi in the inflamed cells . Conclusions: If and when this methodology demonstrate the promising results we expect, one will be able to con clude that Nuclear Medicine is an important tool to help evidence based research also on this specific field .

Anthropometric evaluation and micronutrients intake in patients submitted to laparoscopic Roux-en-Y gastric bypass with a postoperative period of ≥1 year

Backgroung - Bariatric surgery is indicated as the most effective treatment for morbid obesity; the Roux-en-Y gastric bypass (RYGB) is considered the procedure of choice. However, nutritional deficiency may occur in the postoperative period as a result of reduced gastric capacity and change in nutrients absorption in the gastrointestinal tract. The prescription of vitamin and mineral supplementation is a common practice after RYGB; however, it may not be sufficient to prevent micronutrient deficiencies. The aim of this study was to quantify the micronutrient intake in patients undergoing RYGB and verify if the intake of supplementation would be enough to prevent nutritional deficiencies. Methods - The study was conducted on 60 patients submitted to RYGB. Anthropometric, analytical, and nutritional intake data were assessed preoperatively and 1 and 2 years postoperatively. The dietary intake was assessed using 24-h food recall; the values of micronutrients evaluated (vitamin B12, folic acid, iron, and calcium) were compared to the dietary reference intakes (DRI). Results - There were significant differences (p < 0.05) between excess weight loss at the first and second year (69.9 ± 15.3 vs 9.6 ± 62.9 %). In the first and second year after surgery, 93.3 and 94.1 % of the patients, respectively, took the supplements as prescribed. Micronutrient deficiencies were detected in the three evaluation periods. At the first year, there was a significant reduction (p < 0.05) of B12, folic acid, and iron intake. Conclusions - Despite taking vitamin and mineral supplementation, micronutrient deficiencies are common after RYGB. In the second year after surgery, micronutrient intake remains below the DRI.

Violência contra a mulher, coesão familiar e drogas

OBJETIVO: Avaliar a associação entre coesão, adaptabilidade e risco mental familiar com violência física contra a mulher e uso de drogas. MÉTODOS: Estudo tipo caso-controle pareado realizado entre 2004 e 2005 na cidade de João Pessoa, Paraíba. A amostra foi constituída por 260 mulheres, divididas em 130 agredidas e 130 não agredidas. O grupo caso foi constituído de mulheres que prestaram queixa por agressão física doméstica na Delegacia Especializada da Mulher. O grupo controle foi pareado com mulheres vizinhas de bairro das vítimas queixosas na Delegacia. A coesão, a adaptabilidade e o risco mental foram avaliados pela escala Family Adaptability and Cohesion Evaluation Scales. Na análise estatística, foram utilizados os testes qui-quadrado e Exato de Fisher, com nível de significância de 5%. RESULTADOS: Os dois grupos se comportaram de forma diferente em relação ao risco mental e coesão, mas semelhantes quanto à adaptabilidade familiar (p=0,0917). As mulheres agredidas apresentaram risco mental alto (43,1%) e médio (39,2%), diferentemente das não agredidas (p=0,0016), que apresentaram médio risco (55,4%). Houve diferença significativa entre os dois grupos para o uso de drogas, com consumo maior nas famílias das mulheres agredidas (90,8%) do que das não agredidas (56,9%). A droga mais utilizada foi o álcool, sendo o mais alto fator de risco para a agressão, quando consumido diariamente (OR=37,33) ou associado a outra droga (OR=29,56). CONCLUSÕES: O desequilíbrio pela falta de união entre a família e o uso de drogas altera decisivamente no funcionamento familiar, podendo gerar conflitos e agressões domésticas.