Os comportamentos espectroeletroquímicos do ácido acetilsalicílico (AAS) e seu produto de hidrólise, o ácido salicílico (AS), foram estudados em soluções aquosas nas regiões de pH ácido, neutro e alcalino. Resultados para experimentos de voltametria cíclica sugeriram possíveis processos de eletro-oxidação e eletro-redução dos fármacos. O monitoramento do espectro de absorbância na região do UV-vis, simultâneo à medida de carga envolvida na eletrólise, permitiu a identificação de processos redox e o cálculo do número de elétrons envolvidos, aplicando a Lei de Faraday. O fármaco mostrou-se estável em pH ácido, reduziu em pH neutro e oxidou em pH alcalino. Tanto no processo de eletro-redução como na eletro-oxidação, os mecanismos propostos estabelecem o envolvimento de 1 elétron para a identificação de mudanças no nível molecular. Estas foram observadas pelas alterações de espectros de absorbância na região do UV-vis. Técnicas complementares, ressonância paramagnética eletrônica (RPE) e espectroscopia de transmitância FT-IR, foram usadas para a caracterização dos produtos obtidos em experimentos de eletrólise. As respostas espectrofotométricas associadas à processos eletroquímicos permitiram o desenvolvimento de método espectroeletroquímico para a detecção do fármaco em amostras reais contidas em soluções com pH neutro, utilizando a técnica de voltabsormetria derivada linear (DLVA). A interação entre os fármacos e íons de ferro no ambiente do estômago, foi simulada em experimentos in vitro, empregando eletroquímica e espectrofotometria. Na presença do AAS ocorreram interações fracas sem a interferência para a absorção de ferro pelo organismo. Em contrapartida, o AS interagiu formando um complexo estável com o Fe3+, podendo ser apontado como um potencial interferente para a absorção de ferro provocando anemia em indivíduos vegetarianos que fazem uso contínuo deste fármaco. / The spectroelectrochemical behavior of acetylsalicylic acid (ASA) and its spin off hydrolysis, salicylic acid (SA), were studied in aqueous solutions in the acid, neutral and alkaline pH regions. Results for cyclic voltammetry experiments suggested a possible electro-oxidation and electro-reduction of the drugs. The monitoring of the absorbance spectra in the region of the UV-vis, simultaneously with the measurement of the charge involved in the electrolysis, allowed the identification of redox processes and the calculation of the number of electrons involved applying Faraday\'s Law. The drug was stable in acid solutions, reduced in neutral and oxidized in alkaline ones. In electro-reduction and electro-oxidation processes, the proposed mechanisms establish the involvement of 1 electron to identify changes at the molecular level. These were observed by changes in absorbance spectra in the UV-vis region. Complementary techniques, electronic paramagnetic resonance (EPR) and FT-IR transmittance spectroscopy were used to characterize the products obtained in electrolysis experiments. The spectrophotometric responses associated to the electrochemical processes allowed the development of a spectroelectrochemical method for the detection of the drug in real samples contained in solutions with neutral pH, using the technique of derivative linear voltabsorptometry (DLVA). The interaction between drugs and iron ions in the stomach environment was simulated in in vitro experiments using electrochemistry and spectrophotometry. In the presence of ASA, weak interactions occurred without interference for the absorption of iron by the organism. On the other hand, AS interacted to form a stable complex with Fe3+ and could be considered as a potential interfering agent for the iron absorption, causing anemia in vegetarian individuals who make continuous use of this drug.

A inflamação e o estresse oxidativo são condições frequentes em indivíduos com doença renal crônica (DRC) em hemodiálise (HD) e influenciam o seu estado clínico e nutricional. O objetivo do trabalho foi analisar os efeitos do uso de ácido acetilsalicílico (AAS) nos marcadores inflamatórios e de estresse oxidativo de indivíduos em HD e investigar possíveis associações entre estes marcadores e as características pessoais, clínicas e nutricionais da população estudada. A amostra inicial foi composta por 42 pacientes em HD, dos quais 36 concluíram o estudo. Houve predomínio de indivíduos do sexo masculino (57,1%) e o diabetes mellitus (DM) foi a principal causa de perda da função renal. A média de idade dos participantes foi de 51,3 ± 15,5 anos e o tempo médio de tratamento hemodialítico correspondeu a 41,1 ± 38,6 meses. O Índice de Massa Corporal (IMC) médio foi de 24,9 ± 6,1 kg/m² e o Malnutrition Inflammation Score (MIS) indicou 66,7% de adequação do estado nutricional. As coletas de sangue ocorreram antes da intervenção medicamentosa e aos 30 e 60 dias de uso da dose não considerada anti-inflamatória (300mg) do AAS. As variáveis bioquímicas avaliadas foram: proteína C-reativa ultrassensível (PCR-us), albumina, total de hidroperóxidos (FOX), glutationa reduzida (GSH), malondialdeído (MDA) e vitaminas A e E. O uso do AAS promoveu redução da PCR-us somente aos 60 dias de uso do medicamento (8,30 ± 9,09 vs 6,37 ± 8,90, p=0,01). As concentrações séricas de albumina diminuíram aos 30 (5,21 ± 0,59 vs 4,85 ± 0,81, p<0,01) e 60 dias de intervenção (4,85 ± 0,81 vs 3,70 ± 0,40, p<0,01). Houve aumento de FOX (0,20 ± 0,08 vs 0,38 ± 0,18, p<0,01) e da GSH (3,86 ± 1,02 vs 4,41 ± 1,14, p<0,01) aos 30 dias de intervenção. Aos 60 dias de uso do AAS houve diminuição das concentrações de FOX (0,38±0,18 vs 0,17 ± 0,06, p<0,01) e GSH (4,41 ± 1,14 vs 1,25 ± 0,51, p<0,01), quando comparadas com as concentrações dos 30 dias de intervenção. Os valores séricos de MDA não se alteraram durante o estudo. Houve redução da vitamina A aos 30 dias de uso do AAS (3,20 ± 1,2 vs 2,78 ± 0,86, p<0,01) e aumento das concentrações séricas de vitamina E aos 60 dias de intervenção (20,80 ± 6,44 vs 22,93 ± 7,86, p<0,05). No final da intervenção, o uso do AAS promoveu diminuição da inflamação, mesmo com a redução das concentrações séricas de albumina, e aumento da peroxidação lipídica. As variáveis pessoais, clínicas e nutricionais dos participantes apresentaram associações com os marcadores bioquímicos avaliados, mas estas associações não foram influenciadas pelo uso do AAS. / Inflammation and oxidative stress are frequent conditions in individuals with chronic kidney disease (CKD) on hemodialysis (HD) and influence its clinical and nutritional status. The aim of this study was to analyze the effects of acetylsalicylic acid (ASA) in inflammatory markers and oxidative stress in HD individuals, investigating possible associations between these markers and the personal, clinical, and nutrition characteristics of the population studied. The initial sample was composed of 42 HD patients, of which 36 completed the study. There was a predominance of males, 57.1%, and the main cause of loss of renal function was diabetes mellitus (DM). The average age of participants was 51.3 ± 15.5 years and mean duration of hemodialysis treatment corresponded to 41.1 ± 38.6 months. The mean Body Mass Index (BMI) was 24.9 ± 6.1 kg / m² and the Malnutrition Inflammation Score (MIS) showed that 66.7% of patients had appropriate nutritional status. Blood samples were collected before drug intervention at 30 and 60 days of use of ASA (300mg), this dose is not considered anti-inflammatory. Biochemical variables evaluated were: high-sensitivity C-reactive protein (hs-CRP), albumin, total hydroperoxides (FOX), reduced glutathione (GSH), malondialdehyde (MDA) and vitamins A and E. The use of ASA produced a decreased of hs-CRP only after 60 days of the drug use (8.30 ± 9.09 vs. 6.37 ± 8.90, p=0.01). Serum albumin decreased at 30 (5.21 ± 0.59 vs. 4.85 ± 0.81, p<0.01) and 60 (4.85 ± 0.81 vs. 3.70 ± 0.40, p<0.01) days of intervention. There was an increase of FOX (0.20 ± 0.08 vs. 0.38 ± 0.18, p<0.01) and GSH (3.86 ± 1.02 vs. 4.41 ± 1.14, p<0.01) after 30 days of intervention. After 60 days of use of ASA occurred a decrease the concentrations of FOX (0.38 ± 0.18 vs. 0.17 ± 0.06, p<0.01) and GSH (4.41 ± 1.14 vs. 1.25 ± 0.51, p<0.01) when compared with the concentrations of the 30 days of intervention. Serum levels of MDA did not change during the study. There was a reduction of vitamin A after 30 days of use of ASA (3.20 ± 1.2 vs. 2.78 ± 0.86, p<0.01) and increased serum concentrations of vitamin E at 60 days of intervention (20.80 ± 6.44 vs. 22.93 ± 7.86, p<0.05). At the end of intervention the ASA usage caused a reduction of inflammation, despite the serum albumin reduction, and increased lipid peroxidation. Personal variables, clinical and nutritional of participants presented associations with the biochemical markers evaluated, but these associations were not influenced by the use of ASA.

Orientador: Lauro Tatsuo Kubota / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-04T14:04:43Z (GMT). No. of bitstreams: 1 Moreira_AltairBenedito_D.pdf: 839003 bytes, checksum: df3c721cb44a6846a7d2abd555ad8847 (MD5) Previous issue date: 2005 / Resumo: Neste trabalho são descritos o desenvolvimento dos métodos analíticos para a determinação de ácido acetilsalicílico (AAS), paracetamol (PA) e cafeína (CF) em fase sólida por espectroscopia de fluorescência. A fluorescência nativa do PA no estado sólido foi demonstrada pela primeira vez. Todos os estudos realizados neste trabalho foram desenvolvidos visando principalmente a aplicação no controle de qualidade em indústrias químicas e farmacêuticas. Os estudos foram direcionados ao desenvolvimento de métodos analíticos para a determinação de AAS e PA, individualmente. Também foram desenvolvidos métodos para a determinação simultânea das misturas (CF e AAS) e (CF e PA) usando como ferramenta estatística a calibração multivariada para a construção dos modelos, empregando o algoritmo de regressão por mínimos quadrados parciais (PLSR-1). Foram otimizadas a quantidade de amostra colocada no porta amostra e a distância desta da fibra óptica para todos os métodos analíticos desenvolvidos neste trabalho, e as melhores condições foram de 25 mg e 0,9 cm, respectivamente. Os métodos desenvolvidos para a determinação individual de AAS e PA em amostras sólidas apresentaram boa precisão, exatidão e alta freqüência analítica, podendo chegar a 300 determinações por hora. A exatidão foi checada comparando os valores obtidos pelo método desenvolvido com os procedimentos adotados pela farmacopéia britânica e os resultados foram estatisticamente o mesmo a nível de 95% de confiança. Para a determinação simultânea das misturas, os modelos construídos apresentaram excelente desempenho de previsão. Os resíduos foram inferiores a 10% para a maior parte das amostras usadas nos conjuntos de validação externa. A qualidade dos modelos foi avaliada através do coeficiente de variabilidade (CV), o qual variou entre 4 e 7% para todos os modelos. Desta maneira, os métodos desenvolvidos neste trabalho são uma boa alternativa aos métodos tradicionais descritos na literatura, devido suas características favoráveis como elevada freqüência analítica, possibilidade de monitoramento on line em linha de produção e principalmente por serem não destrutivos, não gerarem resíduos e serem de baixo custo. / Abstract: In this work are described the development of analytical method for acetylsalicylic acid (AAS), paracetamol (PA) and caffeine (CF) determinations in solid phase by fluorescence spectroscopy. The native fluorescence of PA was demonstrated in the solid state for the first time. All studies performed here were developed seeking mainly the application in the quality control in chemical and pharmaceutical industries. The studies were addressed to the development of analytical methods for the AAS and PA determination, individually. Methods for the simultaneous determination (CF and AAS) and (CF and PA) using as statistical tool the multivariate calibration for the models construction, employing the partial least squares regression (PLSR-1) algorithm were also developed. The amount of sample placed in the sample compartment and the distance between the fiber optic and sample were optimized for all analytical methods developed in this work and the better conditions were 25 mg and 0.9 cm, respectively. The developed methods for single determination of AAS and PA in samples gave good performance. A high analytical frequency, being able to reach 300 determinations per hour. The accuracy checked comparing the obtained values by the developed methods with the procedures adopted by the British Pharmacopoeia and the results were statistically the same at 95% confidence level. For the simultaneous determination of the mixtures, the built models presented excellent performance of prediction. The residuals were lower than 10% for most used samples in the external validation set. The quality of the models was evaluated through the coefficient of variability (CV), which changed between 4 and 7% for the models. Looking for innovative methods that generate no residue, quick, non-destructive, on line monitoration in production line and low cost is a good option to the traditional methods. / Doutorado / Quimica Analitica / Doutor em Quimica

No description available.

Acetylsalicylic acid (ASA), aspirin, is a renowned NSAID that its role in the process of bone metabolism has recently come to light. However, the influence of ASA on the odontogenesis of human dental pulp cells (HDPCs) remains elusive. In search of materials that would synergize the healing potential of the dental pulp, this study aimed to investigate the role of ASA on the odontogenesis of HDPCs in vitro and the influence of ASA on TGF-ß1 liberation from dentin. HDPCs were cultured in a culture medium with different concentrations of ASA: 25, 50, 75, 100, 200 μg/mL and 0 μg/mL as a control. The mitochondria activity of HDPCs was assessed using an MTT assay. Crystal violet staining and triton were used to evaluate cell proliferation rates. ALP activity was measured with the fluorometric assay. Expressions of DSP and RUNX2 were determined with ELISA. DSP and RUNX2 mRNA levels were measured with RT‐qPCR. Alizarin red staining was conducted to evaluate the mineralized nodule formation. Dentin slices were submerged in PBS (negative control), 17% EDTA (positive control), and ASA before collecting the solution for TGF-ß1quantification by ELISA. The data were analyzed by t tests and ANOVA followed by the Tukey post hoc tests. P values < 0.05 were considered statistically significant. The results showed that 25-50 μg/mL ASA promoted mitochondria activity of HDPCs at 72h (P<0.05) and yielded significantly higher proliferation rates of HDPCs than the control at 14d and 21d (P<0.001). All concentrations of ASA promoted odontogenic differentiation of HDPCs by enhancing the mineralization and the levels of DSP, RUNX2, and their mRNA expression in a dose-dependent manner (P<0.05). Also, ASA yielded significantly higher TGF-ß1 liberation after conditioning dentin for 5min (P<0.001) and 10min (P<0.05). In conclusion, the data suggest that ASA promotes the odontogenic potential of HDPCs and TGF-ß1 liberation from dentin in vitro and might be incorporated into the novel pulp capping materials for dental tissue regeneration.

No / Aspirin, formally known as acetylsalicylic (ASA), is most widely used and cheapest over-the counter drugs. It is used not only for the common fevers, headaches and inflammation, but also for reducing the risk of heart attacks. In recent years, it is also linked to anti-cancer potential. Recently the US Preventive Services Working Group (UPSTF) release aspirin as a guide for cardiovascular disease and primary prevention of colorectal cancer. Platelets have been shown to play a crucial role in cancer metastasis for many years and are proposed to have an intimate reciprocal crosstalk with cancer cells. They may alter the properties of each other and have reciprocal effects. But the exact role of platelets in modifying the tumor cell properties has not been established. In clinical, cancer patients may receive platelets from outside to treat thrombocytopenia and bleeding induced by intensive chemotherapy. Therefore understanding the exact role of platelets in carcinogenesis always is a research interest, especially when evaluating anti-cancer drugs. In this study we exam the effect of platelets on viability, proliferation and adhesion of lung cancer cells A549 in culture conditions, using different concentrations of platelet rich plasma (PRP) with and without the presence of antiplatelet drug aspirin. The tumor cell EMT transformation was also investigated under different combination of PRP and aspirin in vitro. Our data showed that low-dose of aspirin can promote cell proliferation and high-dose of aspirin could inhibit cell proliferation. High concentrations of platelet-rich plasma can inhibit cell proliferation but low concentrations of platelet-rich plasma had no significant effect on cell proliferation. Platelet-rich plasma can gather around the cell to form a gelatinous film, and this lead us to a promoted tumor cell distant metastasis model. We further found out that the combination of aspirin and PRP could increase cell viability compared to single use of PRP and Aspirin can affect cell proliferation by inhibiting platelet effects. Platelet-rich plasma reduces the adhesion of A549 cell can be attenuated by aspirin. Further works will focus on combination of different doses of aspirin and PRP to confirm the above results. Other format of aspirin (nano-form) and other NSAID inflammatory drugs like Ibuprofen will also be tested. / Abstract of conference paper.

A homocisteína é um aminoácido sulfurado derivado do metabolismo da metionina. Quando os níveis plasmáticos de homocisteína ultrapassam 10-15 μM, tem-se uma condição conhecida como hiperhomocisteinemia, a qual pode ser classificada em leve (>10 μM), moderada (>30 μM) ou severa (>100 μM). A hiperhomocisteinemia leve não tem origem genética, sendo considerada um fator de risco para o desenvolvimento de doenças neurodegenerativas e vasculares, incluindo isquemia cerebral e cardíaca. Nosso grupo de pesquisa desenvolveu um modelo químico induzido de hiperhomocisteinemia leve crônica em ratos adultos jovens e, usando esse modelo foi mostrado que existe associação entre essa condição e alterações em parâmetros de inflamação e estresse oxidativo/nitrativo em tecido cerebral. O objetivo do presente estudo foi avaliar se o ácido acetilsalicílico tem papel neuroprotetor no efeito da homocisteína sobre os níveis de interleucinas IL-1β e IL-6, atividade e imunoconteúdo da acetilcolinesterase, biodisponibilidade de óxido nítrico, atividade e imunoconteúdo das enzimas antioxidantes superóxido dismutase e catalase, conteúdo de sulfidrilas e índice de dano ao DNA. Também realizamos análise morfológica por microscopia eletrônica de transmissão em córtex cerebral de ratos submetidos ao modelo. Ratos Wistar receberam homocisteína (0,03 μmol/g de peso corporal) por injeções subcutâneas duas vezes ao dia e ácido acetilsalicílico (25 mg/Kg de peso corporal) por injeções intraperitoneais uma vez ao dia, do dia 30 ao 60º dia pós-parto Ratos controles receberam o mesmo volume da solução veículo. Doze horas após a última injeção, alguns animais foram decapitados para posteriores análises bioquímicas, e outros animais foram perfundidos para posterior análise morfológica. Os resultados mostraram que os ratos submetidos à hiperhomocisteinemia leve apresentaram aumento significativo dos níveis de IL-1β, IL-6 e da atividade da acetilcolinesterase, bem como níveis reduzidos de nitritos. A homocisteína também diminuiu as atividades da superóxido dismutase e catalase, bem como o imunoconteúdo da catalase. Danos às proteínas e DNA, assim como alterações ultraestruturais também foram observadas no córtex cerebral dos animais hiperhomocisteinêmicos. O ácido acetilsalicílico preveniu totalmente o efeito da homocisteína sobre a atividade da acetilcolinesterase, atividade e imunoconteúdo da catalase, e alterações ultraestruturais. As alterações nos níveis de IL-1β, atividade de superóxido dismutase, conteúdo de sulfidrilas e dano ao DNA foram parcialmente prevenidas pelo ácido acetilsalicílico. Nossos achados mostraram que o modelo induzido quimicamente de hiperhomocisteinemia leve alterou alguns parâmetros inflamatórios, oxidativos/nitrativos e morfológicos. Nossos resultados também sugerem que o ácido acetilsalicílico desempenha um papel neuroprotetor nas condições apresentadas, pois preveniu a maior parte dessas alterações. Porém, a administração crônica do ácido acetilsalícico também apresentou efeito per se significativo de dano ao DNA, o qual deve ser melhor elucidado em estudos posteriores. / Homocysteine is a sulfur amino acid derived from methionine metabolism. When plasma homocysteine levels exceed 10-15 μM, there is a condition known as hyperhomocysteinemia, which can be classified as mild (>10 μM), moderate (>30 μM), or severe (>100 μM). Mild hyperhomocysteinemia does not have genetic origin and it is considered a risk factor for the development of neurodegenerative and vascular diseases, including cerebral and cardiac ischemia. Our research group has developed an induced chemical model of chronic mild hyperhomocysteinemia in young adult rats and using this model, it has been shown an association between this condition and changes in parameters of inflammation and oxidative/nitrative stress in brain tissue. The objective of the present study was to evaluate if acetylsalicylic acid has a neuroprotective role in the effect of homocysteine on IL-1β and IL-6 interleukin levels, acetylcholinesterase activity and immunocontent, nitric oxide bioavailability, activity and immunocontent of antioxidant enzymes superoxide dismutase and catalase, sulfhydryl content and DNA damage index. We also performed morphological analysis by transmission electron microscopy in the cerebral cortex of rats submitted to the model. Wistar male rats received homocysteine (0.03 μmol/g of body weight) by subcutaneous injections twice a day and acetylsalicylic acid (25 mg/Kg of body weight) by intraperitoneal injections once a day from the 30th to the 60th postpartum day Control rats received the same volume of vehicle solution. Twelve hours after the last injection, some animals were decapitated for subsequent biochemical analyzes, and other animals were perfused for subsequent morphological analysis. The results showed that rats submitted to mild hyperhomocysteinemia significantly increased levels of IL-1β, IL-6, acetylcholinesterase activity and reduced nitrite levels. Homocysteine also decreased the activities of superoxide dismutase and catalase, as well as catalase's immunocontent. Damage to proteins and DNA as well as ultrastructural changes were also observed in the cerebral cortex of hyperhomocysteinemic animals. Acetylsalicylic acid totally prevented the effect of homocysteine on acetylcholinesterase activity, catalase activity and immunocontent, and ultrastructural changes. Alterations in IL-1β levels, superoxide dismutase activity, sulfhydryl content and DNA damage were partially prevented by acetylsalicylic acid. Our findings showed that the chemically induced model of mild hyperhomocysteinemia altered some inflammatory, oxidative/nitrative and morphological parameters. Our results also suggest that acetylsalicylic acid plays a neuroprotective role in the conditions presented, as it prevented most of these changes. However, chronic administration of acetylsalicylic acid also had a significant effect of DNA damage, which should be better elucidated in later studies.

As doenças cardiovasculares são as principais causas de morte no Brasil e no mundo e constituem problema de saúde médico-social, de grande impacto econômico. As alterações no perfil lipídico e hematológico são fundamentais na formação da aterosclerose, considerando que o LDL (do inglês Low-Density Lipoprotein) e a agregação plaquetária estão envolvidos na formação dos trombos e, consequentemente, em eventos vaso-oclusivos. Entre os fármacos utilizados, encontram-se as estatinas. A rosuvastatina, um dos fármacos utilizados, é inibidora da hidroximetilglutaril coenzima A (HMG CoA) redutase e possui melhor perfil farmacodinâmico entre as estatinas, com maior potência e seletividade. O ácido acetilsalicílico, anti-inflamatório não-esteroide com atividade antiplaquetária mais difundido na terapia, é utilizado, por esse efeito, em associação com estatinas. Fatores limitantes para o uso da rosuvastatina e o ácido acetilsalicílico são: a baixa permeabilidade da rosuvastatina cálcica, e consequente baixa biodisponibilidade (biodisponibilidade absoluta 20%), e tempo de meia-vida do ácido acetilsalicílico de 6-7 h, o que leva à necessidade de elevadas doses e maior frequência de administração de ambos os fármacos. Visto que a associação das estatinas e do ácido acetilsalicílico promove melhor eficácia na prevenção e tratamento de doenças cardiovasculares, o objetivo foi aumentar a solubilidade da estatina e, consequentemente, a sua biodisponibilidade, e a meia-vida do ácido acetilsalicílico, juntamente com a diminuição da toxicidade desse último.. Por outro lado, considerando-se a importância dos dendrímeros como transportadores de fármacos na latenciação, propôs-se o planejamento e a síntese de pró-fármacos dendriméricos, potencialmente cardiovasculares, derivados da associação de rosuvastatina e ácido acetilsalicílico, utilizando etilenoglicol e pentaeritritol como núcleos e ácido L(-)-málico, ácido 2,2-bis(hidroximetil)propiônico e etilenoglicol, como espaçantes.. Obtiveram-se dois pró-fármacos, que se constituem em dendrons como parte dos dendrímeros planejados. O primeiro foi sintetizado pelo método convergente em duplo estágio e faz parte do bloco da camada externa do dendrímero I e o segundo, pela abordagem convergente clássica, sendo este o dendron do dendrímero II. Parte limitante na obtenção desses dendrímeros, além das etapas de purificação, são as etapas de desproteção. / Cardiovascular diseases have been the main causes of death in Brazil and in the world and are medical-social health problem with great economic impact. Alterations in the lipid hematological profiles are essentials in atherosclerosis, as LDL (Low-Density Lipoprotein) and the platelet aggregation are involved in the thrombus formation and, consequently, in occlusive vessel events. Among the drugs used to overcome those alterations are the statins. Rosuvastatin, one of the drugs used, is a hydroxymethylglutaryl coenzine A (HMG CoA) reductase inhibitor and it has the best pharmacodynamics profile among the statins, with higher potency and selectivity. Acetylsalicylic acid, a non-steroid anti-inflammatory agent with antiplatelet activity most disseminated in therapeutics, has been used in combination with statins due to this effect. Limited factors for the use of rosuvastatin and acetylsalycilic acid are the low permeability of the former, and consequently a low bioavailability (20% absolute bioavailability), and a 6 to 7 h half-life time of acetylsalycilic acid. Those factors lead to the need of high doses and higher frequency of administration of both drugs. Considering the combination of statins and acetylsalycilic acid promotes a better efficacy in either prevention or in the treatment of cardiovascular diseases, the objective of this work was to increase the rosuvastatin solubility and, consequently, its bioavailability, and the half-life time of acetylsalicylic acid, together with the decrease of its toxicity. On the other hand, considering the importance of dendrimers as drug carriers in prodrug approach, the design and synthesis of potentially cardiovascular dendrimer prodrugs derived from de combination of rosuvastatin and acetylsalicylic acid was proposed. With this goal, ethylene glycol and pentaerytritol were used as core and L(-)malic acid, 2,2-bis(hydroxymethyl)propionic acid and ethylene glycol were used as spacer groups. Two prodrug dendrons were obtained as part of the designed dendrimers. The first one was synthesized by two-step convergent method and it is part of the external layer block of dendrimer I. The second was obtained through classical convergent synthesis as the dendron of dendrimer II. The purification and deprotection steps showed to be the greatest obstacles for obtaining the proposed compounds.

The purpose of this research was to investigate the effects that aspirin (ASA) and its metabolites, salicylic acid (SA) and acetic acid (AA), have on the delivery of drugs across biological barriers when used in conjunction with electroporation. Electroporation is a technique used to enhance drug delivery across bio-membranes in which a transmembrane potential is induced into cellular membranes, resulting in the creation of aqueous pores that allow molecules to pass through the otherwise impermeable barrier. Aspirin is a widely used drug that has been used for over a century and has been proven relatively safe at normal doses as indicated by the low number of reports of poisoning cases it has been involved in. Components of aspirin are known to soften the cellular membranes by solubilizing the cell's surface proteins. B16F10 murine melanoma cancer cells were used in this investigation and treated with a 120µM buffered solution of calcein, a fluorescent indicator, in which the amount of delivered tracer molecules was measured using fluorescence. Identical concentrations of ASA and SA were investigated (1mM, 5mM, and 10mM) separately, focusing the effects concentration has electroporation delivery. Diluted acetic acid was also investigated at pH values of 6.42, 5.36, and 4.40. The concentration of acetic acid that had the lowest pH and ASA with the highest concentration had the greatest impacts on the augmentation of calcein delivery. Therefore, this demonstrates that aspirin and acetic acid have the potential to improve targeted molecular delivery in combination with electroporation.

Puncturevine (Tribulus terrestris L.) is an annual plant of the Zygophyllaceae family. Its medicinal properties have long been used in traditional Chinese and Indian medicine to treat various diseases. It has been shown that active substances, among which we count steroid saponins, glycosides, flavonoids, phytosterols and alkaloids, have effects on reproduction, effects aphrodisiac, antibacterial, anti-carcinogenic, anti-oxidant, diuretic, antidiabetic, cardiovascular and many other. The aim of this work was to verify the effect of elicitors on the content of selected active ingredients in Puncturevine. The elicitor in this work was acetylsalicylic acid of three different concentrations (10-3 mol.l-1, 10-4 mol.l-1, 10-5 mol.l-1) applied by spraying. Using high performance liquid chromatography and mass spectrometry were in fruits and stems determined the content of diosgenin, protodioscin, ruscogenin. For all three compounds was observed positive effect of the elicitor on their content.