Role on serine protease inhibitors in the pathogenisis of Steinernema carpocapsae

Tese de Doutoramento, Biologia (Biologia Celular e Molecular), 18 de Novembro de 2013, Universidade dos Açores.

Evaluation of atmospheric deposition and patterns of polycyclic aromatic hydrocarbons in façades of historic monuments of Oporto (Portugal)

Atmospheric pollution by motor vehicles is considered a relevant source of damage to architectural heritage. Thus the aim of this work was to assess the atmospheric depositions and patterns of polycyclic aromatic hydrocarbons (PAHs) in façades of historical monuments. Eighteen PAHs (16 PAHs considered by US EPA as priority pollutants, dibenzo[a,l]pyrene and benzo[j]fluoranthene) were determined in thin black layers collected from façades of two historical monuments: Hospital Santo António and Lapa Church (Oporto, Portugal). Scanning electron microscopy (SEM) was used for morphological and elemental characterisation of thin black layers; PAHs were quantified by microwave-assisted extraction combined with liquid chromatography (MAE-LC). The thickness of thin black layers were 80–110 μm and they contained significant levels of iron, sulfur, calcium and phosphorus. Total concentrations of 18 PAHs ranged from 7.74 to 147.92 ng/g (mean of 45.52 ng/g) in thin black layers of Hospital Santo António, giving a range three times lower than at Lapa Church (5.44– 429.26 ng/g; mean of 110.25 ng/g); four to six rings compounds accounted at both monuments approximately for 80–85% of ΣPAHs. The diagnostic ratios showed that traffic emissions were significant source of PAHs in thin black layers. Composition profiles of PAHs in thin black layers of both monuments were similar to those of ambient air, thus showing that air pollution has a significant impact on the conditions and stone decay of historical building façades. The obtained results confirm that historical monuments in urban areas act as passive repositories for air pollutants present in the surrounding atmosphere.

Antiretroviral activity of protease inhibitors against Toxoplasma gondii

The introduction of highly active antiretroviral therapy (HAART) has caused a marked reduction in the occurrence and severity of parasitic infections, including the toxoplasmic encephalitis (TE). These changes have been attributed to the restoration of cell-mediated immunity. This study was developed to examine the activity of six antiretroviral protease inhibitors (API) on Toxoplasma gondii tachyzoites. The six API showed anti-Toxoplasma activity, with IC50 value between 1.4 and 6.6 µg/mL. Further studies at the molecular level should be performed to clarify if the use of API could be beneficial or not for AIDS patients with TE.

Prophylaxis in Hemophilia A Patients with Inhibitors

The development of antibodies to factor VIII is one of the most serious complications of haemophilia treatment. Approximately 30% of patients with severe haemophilia develop neutralizing inhibitors to replacement FVIII. Although most patients with inhibitors do not bleed more frequently than patients without inhibitors, bleeding is more difficult to control and this patients suffer more severe bleeding and have greater morbidity and mortality. Patients with persistent high-titer inhibitor who are not candidates or fail ITI, pose a great challenge to haemophilia management. The efficacy and safety of prophylaxis with bypassing agents in reducing bleeding tendency, has been described in numerous studies. Patients and methods: We report tree adult severe haemophilia A patients, two with persistent high-titre inhibitors and one who failed ITI, on prophylactic treatment after several significant musculoskeletal and life-threatening haemorrhagic episodes (intrabdominal/intramuscular) and pseudotumor haemorrhage. Treatment regimens consisted of APCC (Feiba®) in doses of 60-70UKg-1, 2-3 times per week, according underlying bleeding phenotype. Breakthrough bleeds were treated with either APCC (Feiba®) or rFVIIa (NovoSeven®). Results and Conclusion: There was reduction in total bleeding episodes in two patients (43% to 80%) and one patient remained stable, while receiving prophylaxis. Absence of severe and life threatening bleeding episodes, as well as inpatient stays, contributing to a better quality of life in those patients, was observed. APCC (Feiba®) was well tolerated and no thrombotic events were observed.

Baseline Susceptibility of Primary HIV-2 to Entry Inhibitors

BACKGROUND: The baseline susceptibility of primary HIV-2 to maraviroc (MVC) and other entry inhibitors is currently unknown. METHODS: The susceptibility of 19 HIV-2 isolates obtained from asymptomatic and AIDS patients and seven HIV-1 clinical isolates to the fusion inhibitors enfuvirtide (ENF) and T-1249, and to the coreceptor antagonists AMD3100, TAK-779 and MVC, was measured using a TZM-bl cell-based assay. The 50% inhibitory concentration (IC(50)), 90% inhibitory concentration (IC(90)) and dose-response curve slopes were determined for each drug. RESULTS: ENF and T-1249 were significantly less active on HIV-2 than on HIV-1 (211- and 2-fold, respectively). AMD3100 and TAK-779 inhibited HIV-2 and HIV-1 CXCR4 tropic (X4) and CCR5 tropic (R5) variants with similar IC(50) and IC(90) values. MVC, however, inhibited the replication of R5 HIV-2 variants with significantly higher IC(90) values (42.7 versus 9.7 nM; P<0.0001) and lower slope values (0.7 versus 1.3; P<0.0001) than HIV-1. HIV-2 R5 variants derived from AIDS patients were significantly less sensitive to MVC than variants from asymptomatic patients, this being inversely correlated with the absolute number of CD4(+) T-cells. CONCLUSIONS: T-1249 is a potent inhibitor of HIV-2 replication indicating that new fusion inhibitors might be useful to treat HIV-2 infection. Coreceptor antagonists TAK-779 and AMD3100 are also potent inhibitors of HIV-2 replication. The reduced sensitivity of R5 variants to MVC, especially in severely immunodeficient patients, indicates that the treatment of HIV-2-infected patients with MVC might require higher dosages than those used in HIV-1 patients, and should be adjusted to the disease stage.

Earth mortars from pre-historic habitat settlements in south Portugal. Case studies

J. Iberian Archaeology 13 (2010), 51-67

Earth building materials in pre-historic domestic architectures on the south of Portugal

HERITAGE 2008 - World Heritage and Sustainable Development. Barcelos: Green Lines Institute for Sustainable Development, Vol. 2, p. 571-579

Historic timber roof structures

Dissertação para obtenção do Grau de Mestre em Engenharia Civil – Estruturas e Geotecnia

Applications of the indole scaffold in medicinal chemistry: development of new antioxidants, COX inhibitors and antitubercular agents

Dissertação para obtenção do Grau de Doutor em Química, especialidade Química Orgânica

Development of novel benzimidazole- based COX Inhibitors new synthetic strategies and screening of heterocyclic structures

Dissertação para obtenção do Grau de Doutor em Química, especialidade Química Orgânica

Archaeometallurgical study of the Proto-historic collection of Moinhos de Golas (North Portugal): a forecast for technological changes?

This work presents the archaeometallurgical study of a group of metallic artefacts found in Moinhos de Golas site, Vila Real (North of Portugal), that can generically be attributed to Proto-history (1st millennium BC, Late Bronze Age and Iron Age). The collection is composed by 35 objects: weapons, ornaments and tools, and others of difficult classification, as rings, bars and one small thin bent sheet. Some of the objects can typologically be attributed to Late Bronze Age, others are of more difficult specific attribution. The archaeometallurgical study involved x-ray digital radiography, elemental analysis by micro-energy dispersive X-ray fluorescence spectrometry and scanning electron microscopy with energy dispersive spectroscopy, microstructural observations by optical microscopy and scanning electron microscopy. The radiographic images revealed structural heterogeneities frequently related with the degradation of some artefacts and the elemental analysis showed that the majority of the artefacts was produced in a binary bronze alloy (Cu-Sn) (73%), being others produced in copper (15%) and three artefacts in brass (Cu-Zn(-Sn-Pb)). Among each type of alloy there’s certain variability in the composition and in the type of inclusions. The microstructural observations revealed that the majority of the artefacts suffered cycles of thermo-mechanical processing after casting. The diversity of metals/alloys identified was a discovery of great interest, specifically due to the presence of brasses. Their presence can be interpreted as importations related to the circulation of exogenous products during the Proto-history and/or to the deposition of materials during different moments at the site, from the transition of Late Bronze Age/Early Iron Age (Orientalizing period) onwards, as during the Roman period.