Micro- and mesoporous structures as drug delivery carriers for salicylic acid

The potential of salicylic acid (SA) encapsulated in porous materials as drug delivery carriers for cancer treatment was studied. Different porous structures, the microporous zeolite NaY, and the mesoporous SBA-15 and MCM-41 were used as hosts for the anti-inflammatory drug. Characterization with different techniques (FTIR, UV/vis, TGA, 1H NMR, and 13C CPMAS NMR) demonstrated the successful loading of SA into the porous hosts. The mesoporous structures showed to be very efficient to encapsulate the SA molecule. The obtained drug delivery systems (DDS) accommodated 0.74 mmol (341 mg/gZEO) in NaY and 1.07 mmol (493 mg/gZEO) to 1.23 mmol (566 mg/gZEO) for SBA-15 and MCM-41, respectively. Interactions between SA molecules and pore structures were identified. A fast and unrestricted liberation of SA at 10 min of the dissolution assay was achieved with 29.3, 46.6, and 50.1 µg/mL of SA from NaY, SBA-15, and MCM-41, respectively, in the in vitro drug release studies (PBS buffer pH 7.4, 37 °C). Kinetic modeling was used to determine the release patterns of the DDS. The porous structures and DDS were evaluated on Hs578T and MDA-MB-468 breast cancer cell lines viability. The porous structures are nontoxic to cancer cells. Cell viability reduction was only observed after the release of SA from MCM- 41 followed by SBA-15 in both breast cancer cell lines.

Propolis: A complex natural product with a plethora of biological activities that can be explored for drug development

The health industry has always used natural products as a rich, promising, and alternative source of drugs that are used in the health system. Propolis, a natural resinous product known for centuries, is a complex product obtained by honey bees from substances collected from parts of different plants, buds, and exudates in different geographic areas. Propolis has been attracting scientific attention since it has many biological and pharmacological properties, which are related to its chemical composition. Several in vitro and in vivo studies have been performed to characterize and understand the diverse bioactivities of propolis and its isolated compounds, as well as to evaluate and validate its potential. Yet, there is a lack of information concerning clinical effectiveness. The goal of this review is to discuss the potential of propolis for the development of new drugs by presenting published data concerning the chemical composition and the biological properties of this natural compound from different geographic origins.

Validation of the Portuguese Version of EHP-30 (The Endometriosis Health Profile-30)

Introduction: Endometriosis Health Profile Questionnaire-30 is currently the most used questionnaire for quality of life measurement in women with endometriosis. The aim of this study is to evaluate the psychometric properties and to validate the Portuguese Endometriosis Health Profile Questionnaire-30 version. MATERIAL AND METHODS A sequential sample of 152 patients with endometriosis, followed in a Portugal reference center, were asked to complete a questionnaire on social and demographic features, the Portuguese version of the Endometriosis Health Profile Questionnaire-30 and of the Short Form Health Survey 36 Item â version 2. Appropriate statistical analysis was performed using descriptive statistics, factor analysis, internal consistency, item-total correlation and convergent validity. RESULTS Factorial analysis confirmed the validity of the five-dimension structure of the Endometriosis Health Profile Questionnaire-30 core questionnaire, which explained 83.2% of the total variance. All item-total correlations presented acceptable results and high internal consistency, with Cronbach's alpha ranging between 0.876 and 0.981 for the core questionnaire and between 0.863 and 0.951 for the modular questionnaire. Significant negative associations between similar scales of Endometriosis Health Profile Questionnaire-30 and Short Form Health Survey 36 Item â version 2 were demonstrated. Data completeness achieved was high for all dimensions. The emotional well-being scale in the core questionnaire and the infertility scale in the modular section had the highest median scores, and therefore the most negative impact on the quality of life of participating women. DISCUSSION The test-retest reliability and responsiveness of the questionnaire should be evaluated in future studies. CONCLUSION The present study demonstrates that the Portuguese version of the Endometriosis Health Profile Questionnaire-30 is a valid, reliable and acceptable tool for evaluating the health-related quality of life of Portuguese women with endometriosis.

A novel hanging spherical drop system for the generation of cellular spheroids and high throughput combinatorial drug screening

We propose a novel hanging spherical drop system for anchoring arrays of droplets of cell suspension based on the use of biomimetic superhydrophobic flat substrates, with controlled positional adhesion and minimum contact with a solid substrate. By facing down the platform, it was possible to generate independent spheroid bodies in a high throughput manner, in order to mimic in vivo tumour models on the lab-on-chip scale. To validate this system for drug screening purposes, the toxicity of the anti-cancer drug doxorubicin in cell spheroids was tested and compared to cells in 2D culture. The advantages presented by this platform, such as feasibility of the system and the ability to control the size uniformity of the spheroid, emphasize its potential to be used as a new low cost toolbox for high-throughput drug screening and in cell or tissue engineering.

Marine origin polysaccharides in drug delivery systems

Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine.

Can the dopaminergic-related effects of general anesthetics be linked to mechanisms involved in drug abuse and addiction?

BACKGROUND: General anesthetics (GA) are well known for the ability to induce a state of reversible loss of consciousness and unresponsiveness to painful stimuli. However, evidence from animal models and clinical studies show that GA exposure may induce behavioral changes beyond acute effects. Most research and concerns are focused on changes in cognition and memory. METHODS: We will look at effects of GA on behavior that is mediated by the dopaminergic system. RESULTS: Pharmacological resemblance of GA with drugs of abuse, and the complexity and importance of dopaminergic systems in both reward seeking and addictive illnesses make us believe that it deserves an overview about what is already known and what matters to us as healthcare workers and specifically as anesthesiologists. CONCLUSION: A review of available evidence strongly suggests that there may be a link between the effects of GA on the brain and substance abuse, partly explained by their influence on the dopaminergic system.

Biodegradable drug-eluting stents: Targeting urothelial tumors of upper urinary tract

INTRODUCTION & OBJECTIVES: Urothelial tumors of upper urinary tract are ranked among the most common types of cancers worldwide. The current standard therapy to prevent recurrence is intravesical Bacillus Calmetteâ Guerin (BCG) immunotherapy, but it presents several disadvantages such as BCG failure and intolerance. Another way is to use chemotherapy, which is generally better tolerated that BCG. In this case, drugs such as epirubicin, doxorubicin, paclitaxel and gemcitabine are used. Nevertheless, intravesical chemotherapy only prevents recurrence in the short-term. These failings can be partially attributed to the short residence time and low bioavailability of the drug within the upper urinary tract and the cancer cells, resulting in a need for frequent drug instillation. To avoid these problems, biodegradable ureteral stents impregnated by supercritical fluid CO2 (SCF) with each of the four anti-cancer drugs were produced. MATERIAL & METHODS: Four formulations with different concentrations of gelatin and alginate and crosslink agent were tested and bismuth was added to confer radiopaque properties to the stent. The preliminary in vivo validation studies in female domestic pigs was conducted at the University of Minho, Braga, after formal approval by the institutionâ s review board and in accordance with its internal ethical protocol for animal experiments. Paclitaxel, epirubicin, doxorubicin and gemcitabine were impregnated in the stents and the release kinetics was measured in artificial urine solution (AUS) for 9 days by UV spectroscopy in a microplate reader. The anti-tumoral effect of the developed stents in transitional cell carcinoma (TCC) and HUVEC primary cells, used as control, was evaluated. RESULTS: The in vivo validation of this second-generation of ureteral stents performed was herein demonstrated. Biodegradable ureteral stents were placed in the ureters of a female pigs, following the normal surgical procedure. The animals remained asymptomatic, with normal urine flow. The in vitro release study in AUS of the stent impregnated showed a higher release in the first 72h for the four anti-cancer drugs impregnated after this time the plateau was achieved and the stent degraded after 9 days. The direct and indirect contact of the anti-cancer biodegradable stents with the TCC and HUVEC cell lines confirm the anti-tumor effect of the stents impregnated with the four anti-cancer drugs, reducing around 75% of the viability of the TCC cell line after 72h and no killing effect in the HUVEC cells. CONCLUSIONS: The use of biodegradable ureteral stent in urology clinical practice not only reduce the stent-related symptoms but also open new treatment therapyâ s, like in urothelial tumors of upper urinary tract. Furthermore, we have demonstrated the clinical validation in vivo pig model. This study has thus shown the killing efficacy of the anti-cancer drug eluting biodegradable stents in vitro for the TCC cell line, with no toxicity observed in the control, non-cancerous cells.The direct and indirect contact of the anti-cancer biodegradable stents with the TCC and HUVEC cell lines confirm the anti-tumor effect of the stents impregnated with the four anti-cancer drugs, reducing around 75% of the viability of the TCC cell line after 72h and no killing effect in the HUVEC cells. This study has thus shown the killing efficacy of the anti-cancer drug eluting biodegradable stents in vitro for the TCC cell line, with no toxicity observed in the control, non-cancerous cells.

Development of a poly(L-Lactic acid) based drug release system

Dissertação de mestrado em Biofísica e Bionanossistemas

Infants’ behavioral and physiological profile and mother–infant interaction

This study aims to (a) identify and profile groups of infants according to their behavioral and physiological characteristics, considering their neurobehavioral organization, social withdrawal behavior, and endocrine reactivity to stress, and to (b) analyze group differences in the quality of mother–infant interaction. Ninety seven 8-week-old infants were examined using the Neonatal Behavioral Assessment Scale and the Alarm Distress Baby Scale. Cortisol levels were measured both before and after routine inoculation between 8 and 12 weeks. At 12 to 16 weeks mother–infant interaction was assessed using the Global Rating Scales of Mother–Infant Interaction. Three groups of infants were identified: (a) ‘‘withdrawn’’; (b) ‘‘extroverted’’; (c) ‘‘underaroused.’’ Differences between them were found regarding both infant and mother behaviors in the interaction and the overall quality of mother–infant interaction. The identification of behavioral and physiological profiles in infants is an important step in the study of developmental pathways.

Infant’s psychophysiological profile and temperament at 3 and 12 months

This study is intended to analyze (1) differences in infant temperament at 3 and 12 months according to infants' psychophysiological profiles: "withdrawn" "extroverted", and "underaroused" and (2) changes in infant temperament from 3 to 12 months, namely according to the infant psychophysiological profile and the quality of mother-infant interaction. Ninety-four 8-week-old infants were assessed using the Neonatal Behavioral Assessment Scale (NBAS, Brazelton & Nugent, 1995) and the Alarm Distress Baby Scale (ADBB, Guedeney & Fermanian, 2001). Saliva samples were collected at 8-12 weeks old, both before and after a routine inoculation for cortisol reactivity measurement. Mother-infant interaction was evaluated at 12-16 weeks, using the Global Rating Scales (GRS, Murray, Fiori-Cowley, Hooper, & Cooper, 1996). Mothers' reports on infant temperament at 3 and 12 months were collected using the Infant Behavior Questionnaire (IBQ, Rothbart, 1981). Significant differences in mothers' perception of infant temperament were found at both 3 and 12 months in infants with distinct psychophysiological profiles. Stability was observed in most of the temperament's dimensions from 3 to 12 months old; still, there were changes in mothers' perception of infant temperament in terms of level of distress, cuddliness, sadness and approach. Infant psychophysiological profile and mother-infant interaction both influence with the pattern of those changes. The results corroborate that infant's characteristics early in life as well as contextual factors influence with mothers' perception of infant temperament and with changes across the 1st year of life.

Factores de risco de abuso no relacionamento íntimo: Estudo de validação da versão portuguesa do questionário “Personal and Relationships Profile”

O presente artigo trata do estudo das características psicométricas da versão portuguesa do questionário “Personal and Relationships Profile" (PRP, Straus, Hamby, Boney-McCoy, & Sugarman, 1999). Este instrumento destina-se a avaliar os principais factores relacionados com a ocorrência de abuso no relacionamento com o companheiro; integra 21 sub-escalas substantivas e uma sub-escala de desejabilidade social. Foram participantes 551 estudantes universitários (60.3% do sexo feminino), na sua maioria com idades compreendidas entre os 19 e os 25 anos e com uma relação do tipo namoro. O questionário apresenta elevada consistência interna (α=.90), e as sub-escalas têm valores de alpha de Cronbach compreendidos entre .50 e .84. Confirma-se também a validade externa dado que um elevado número de sub-escalas do PRP, se encontra significativamente correlacionado com a escala de abuso físico sem sequelas (CT52). Os resultados obtidos confirmam a validade da versão portuguesa do questionário PRP, possibilitando a investigadores e práticos no âmbito das relações maritais um instrumento de screening para sinalização, aprofundamento e orientação das linhas de acção específicas no tratamento e/ou investigação dos principais factores associados à violência conjugal.

New integrative computational approaches unveil the Saccharomyces cerevisiae pheno-metabolomic fermentative profile and allow strain selection for winemaking

During must fermentation by Saccharomyces cerevisiae strains thousands of volatile aroma compounds are formed. The objective of the present work was to adapt computational approaches to analyze pheno-metabolomic diversity of a S. cerevisiae strain collection with different origins. Phenotypic and genetic characterization together with individual must fermentations were performed, and metabolites relevant to aromatic profiles were determined. Experimental results were projected onto a common coordinates system, revealing 17 statistical-relevant multi-dimensional modules, combining sets of most-correlated features of noteworthy biological importance. The present method allowed, as a breakthrough, to combine genetic, phenotypic and metabolomic data, which has not been possible so far due to difficulties in comparing different types of data. Therefore, the proposed computational approach revealed as successful to shed light into the holistic characterization of S. cerevisiae pheno-metabolome in must fermentative conditions. This will allow the identification of combined relevant features with application in selection of good winemaking strains.