Eruca sativa: Benefits as antioxidants source versus risks of already banned pesticides

Eruca sativa (rocket salad) has been intensely consumed all over the world, insomuch as, this work was undertaken to evaluate the antioxidant status and the environmental contamination (positive and negative nutritional contribution) of leaves and stems from this vegetable. Antioxidant capacity of rocket salad was assessed by mean of optical methods, such as the total phenolic content (TPC), reducing power assay and DPPH radical scavenging activity. The extent of the environmental contamination was reached through the quantification of thirteen organochlorine pesticides (OCP) by using gas chromatography coupled with electron-capture detector (GC-ECD) and compound confirmations employing gas chromatography tandem mass-spectrometry (GC-MS/MS). The OCP residues were extracted by using Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) methodology.The extent of the environmental contamination was reached through the quantification of thirteen OCP by using gas chromatography coupled with electron-capture detector (GC-ECD) and compound confirmations employing GC-MS/MS. The OCP residues were extracted by using Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) methodology. This demonstrated that leaves presented more antioxidant activity than stems, emphasizing that leaves contained six times more polyphenolic compounds than stems. In what concerns the OCP occurrence, the average recoveries obtained at the three levels tested (40, 60 and 80 µg kg−1) ranged from 55% to 149% with a relative standard deviation of 11%, (except hexachrorobenzene). Three vegetables samples were collected from supermarkets and analysed following this study. According to data, only one sample achieved 16.21 of β-hexachlorocyclohexane, confirmed by GC-MS/MS. About OCP quantification, the data indicated that only one sample achieved 16.21 µg kg−1 of β-hexachlorocyclohexane, confirmed by GC-MS/MS, being the QuEChERS a good choice for the of OCPs extraction. Furthermore, the leaves consumption guaranty higher levels of antioxidants than stems.

Exploring cinnamic acid scaffold: development of promising neuroprotective lipophilic antioxidants

New lipophilic hydroxycinnamic acid based derivatives were designed and synthesized and their antioxidant and neuroprotective activities evaluated. The chemical modification introduced in the cinnamic acid scaffold leads to compounds with amplified lipophilicity and in general with increased antioxidant activity when compared to natural models (caffeic and ferulic acids). The compounds did not display cytotoxicity and present a significant neuroprotective effect against 6-OH-DA induced damage to SH-SY5Y cells. Compound 6 stands out as an efficient radical scavenger and iron(II) chelator that ensures drug-like properties. Moreover, neuroprotection against oxidative damage was observed even at low concentration (1 μM). Therefore, compound 6 developed by a biology-oriented approach displays a combination of important features for a further optimization process that will generate a new effective antioxidant with therapeutic application for oxidative-stress-related events, namely neurodegenerative diseases.

The Risks of Self - Medication: Case Report of Familial Misuse of AM3 (Immunoferon®)

Over the last decades extended medical knowledge has been an important health care benefit in terms of disease prevention and management. However, probably with no exception, most pharmaceutical products are not devoid of adverse consequences. Immunomodulators are commonly considered a “benign” drug whose advantages bypass consequences. The immunomodulator AM3 (Immunoferon®) is a clinically used, orally administered compound whose active principle is stabilised in an inorganic matrix of calcium. We report the misuse of AM3 in three members of a family; father and two children. The drug was prescribed to the father who subsequently administered it to the children without seeking medical advice. Two months later, all subjects developed abdominal and/or flank colicky pain. Hypercalciuria was diagnosed in the children with different degrees of severity. It is likely that the calcium content of the inorganic matrix played an important role in the onset of symptoms. No adverse side effects related to the inorganic matrix of calcium of immunoferon® have been documented so far. This family case report calls attention to the risks of self -medication in a susceptible family. Paediatric patients are vulnerable as they rely on adults for the supply of medications. Concerning the use of drugs in family, especially nonprescription drugs, the quality of health care provided to the children depends on the health literacy of their parents.

Using gold nanoparticles in protein crystallography: studies in crystal growth and derivatization

Dissertation for the Master Degree in Structural and Functional Biochemistry

High-Content Analysis of Breast Cancer Using Single-Cell Deep Transfer Learning

High-content analysis has revolutionized cancer drug discovery by identifying substances that alter the phenotype of a cell, which prevents tumor growth and metastasis. The high-resolution biofluorescence images from assays allow precise quantitative measures enabling the distinction of small molecules of a host cell from a tumor. In this work, we are particularly interested in the application of deep neural networks (DNNs), a cutting-edge machine learning method, to the classification of compounds in chemical mechanisms of action (MOAs). Compound classification has been performed using image-based profiling methods sometimes combined with feature reduction methods such as principal component analysis or factor analysis. In this article, we map the input features of each cell to a particular MOA class without using any treatment-level profiles or feature reduction methods. To the best of our knowledge, this is the first application of DNN in this domain, leveraging single-cell information. Furthermore, we use deep transfer learning (DTL) to alleviate the intensive and computational demanding effort of searching the huge parameter's space of a DNN. Results show that using this approach, we obtain a 30% speedup and a 2% accuracy improvement.

Novel approaches for culturing hepatocytes for drug testing applications

Dissertation presented to obtain the Ph.D degree in Biochemisry, Biotechnology

Sarcoplasmic reticulum calcium ATPase is inhibited by organic vanadium coordination compounds: pyridine-2,6-dicarboxylatodioxovanadium(V), BMOV, and an amavadine analogue

Inorg Chem. 2008 Jul 7;47(13):5677-84. doi: 10.1021/ic702405d

Bone Histomorphometry Revisited

Bone histomorphometry is defined as a quantitative evaluation of bone micro architecture, remodelling and metabolism. Bone metabolic assessment is based on a dynamic process, which provides data on bone matrix formation rate by incorporating a tetracycline compound. In the static evaluation, samples are stained and a semi-automatic technique is applied in order to obtain bone microarchitectural parameters such as trabecular area, perimeter and width. These parameters are in 2D, but they can be extrapolated into 3D, applying a stereological formula. Histomorphometry can be applied to different areas; however, in recent decades it has been a relevant tool in monitoring the effect of drug administration in bone. The main challenge for the future will be the development of noninvasive methods that can give similar information. In the herein review paper we will discuss the general principles and main applications of bone histomorphometry.

Effect of C282Y Genotype on Self-Reported Musculoskeletal Complications in Hereditary Hemochromatosis

OBJECTIVE: Arthropathy that mimics osteoarthritis (OA) and osteoporosis (OP) is considered a complication of hereditary hemochromatosis (HH). We have limited data comparing OA and OP prevalence among HH patients with different hemochromatosis type 1 (HFE) genotypes. We investigated the prevalence of OA and OP in patients with HH by C282Y homozygosity and compound heterozygosity (C282Y/H63D) genotype. METHODS: A total of 306 patients with HH completed a questionnaire. Clinical and demographic characteristics and presence of OA, OP and related complications were compared by genotype, adjusting for age, sex, body mass index (BMI), current smoking and menopausal status. RESULTS: In total, 266 of the 306 patients (87%) were homozygous for C282Y, and 40 (13%) were compound heterozygous. The 2 groups did not differ by median age [60 (interquartile range [IQR] 53 to 68) vs. 61 (55 to 67) years, P=0.8], sex (female: 48.8% vs. 37.5%, P=0.18) or current smoking habits (12.4% vs. 10%, P=0.3). As compared with compound heterozygous patients, C282Y homozygous patients had higher median serum ferritin concentration at diagnosis [1090 (IQR 610 to 2210) vs. 603 (362 to 950) µg/L, P<0.001], higher median transferrin saturation [80% (IQR 66 to 91%) vs. 63% (55 to 72%), P<0.001]) and lower median BMI [24.8 (22.1 to 26.9) vs. 26.2 (23.5 to 30.3) kg/m2, P<0.003]. The overall prevalence of self-reported OA was significantly higher with C282Y homozygosity than compound heterozygosity (53.4% vs. 32.5%; adjusted odds ratio [aOR] 2.4 [95% confidence interval 1.2-5.0]), as was self-reported OP (25.6% vs. 7.5%; aOR 3.5 [1.1-12.1]). CONCLUSION: Patients with C282Y homozygosity may be at increased risk of musculoskeletal complications of HH.

Recent droughts and the impact of North Atlantic Oscillation in Iberia; a spatiotemporal analysis based on vegetation temperature condition Index (VTCI)

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

Hemocromatose Hereditária do Tipo 1 e Porfíria Cutânea Tarda - Relato de Caso de um Doente Heterozigoto Composto para as Mutações C282Y e H63D

A porfíria cutânea tarda (PCT) é uma doença do metabolismo das porfirinas caracterizada por fotossensibilidade intensa, associada a lesões bolhosas cobertas por crosta de difícil cicatrização, cicatrizes atróficas e hipertricose em áreas fotoexpostas assim como alterações da função hepática. A hemocromatose hereditária (HH) é a doença genética autossómica recessiva mais frequente na população. Apresentamos o caso de um doente saudável de 38 anos, referenciado por vesículas na face, superfícies extensoras dos braços e dorso das mãos, associadas com hipertricose na região zigomática e quistos de mília no dorso das mãos. Análises laboratoriais mostraram um aumento dos níveis séricos e urinários das porfirinas, do ferro sérico e ferritina elevada. Um diagnóstico de porfíria cutânea tarda foi inferido com base na apresentação clínica, exame histopatológico e resultados laboratoriais. O estudo genético para as mutações do gene da hemocromatose hereditária revelou um doente heterozigoto composto para as mutações mais comuns: C282Y, H63D. A porfíria cutânea tarda pode ser um importante marcador cutâneo para pacientes com mutações do gene HH. A hemocromatose hereditária, se não tratada pode levar à cirrose hepática e carcinoma hepatocelular. Os sinais cutâneos podem ter um papel fundamental no diagnóstico precoce, evitando complicações futuras e possibilitando o aconselhamento genético e teste genético aos filhos dos doentes afectados.

Analysis of benefits of the process of certification on international standars: ISO 9001-2008 for Mapfre Assistencia Portugal

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Finance from the NOVA – School of Business and Economics

Clinical and Molecular Characterization of Diastrophic Dysplasia in the Portuguese Population

SLC26A2-related dysplasias encompass a spectrum of diseases: from lethal achondrogenesis type 1B (ACG1B; MIM #600972) and atelosteogenesis type 2 (AO2; MIM #256050) to classical diastrophic dysplasia (cDTD; MIM #222600) and recessive multiple epiphyseal dysplasia (rMED; MIM #226900). This study aimed at characterizing clinically, radiologically and molecularly 14 patients affected by non-lethal SLC26A2-related dysplasias and at evaluating genotype-phenotype correlation. Phenotypically, eight patients were classified as cDTD, four patients as rMED and two patients had an intermediate phenotype (mild DTD - mDTD, previously 'DTD variant'). The Arg279Trp mutation was present in all patients, either in homozygosity (resulting in rMED) or in compound heterozygosity with the known severe alleles Arg178Ter or Asn425Asp (resulting in DTD) or with the mutation c.727-1G>C (causing mDTD). The 'Finnish mutation', c.-26+2T>C, and the p.Cys653Ser, both frequent mutations in non-Portuguese populations, were not identified in any of the patients of our cohort and are probably very rare in the Portuguese population. A targeted mutation analysis for p.Arg279Trp and p.Arg178Ter in the Portuguese population allows the identification of approximately 90% of the pathogenic alleles.

Dominant and Recessive RYR1 Mutations in Adults with Core Lesions and Mild Muscle Symptoms

INTRODUCTION: Ryanodine receptor gene (RYR1) mutations have been associated with central core disease (CCD), multiminicore/minicore/multicore disease (MmD), and susceptibility to malignant hyperthermia (MH). METHODS: Patients with muscle symptoms in adulthood, who had features compatible with CCD/MmD, underwent clinical, histological, and genetic (RYR1 and SEPN1 genes) evaluations. Published cases of CCD and MmD with adult onset were also reviewed. RESULTS: Eight patients fulfilled the criteria for further analysis. Five RYR1 mutations, 4 of them unreported, were detected in 3 patients. Compound heterozygosity was proven in 1 case. CONCLUSIONS: To our knowledge, this is the only report of adult onset associated with recessive RYR1 mutations and central core/multiminicores on muscle biopsy. Although adult patients with CCD, MmD, and minimally symptomatic MH with abnormal muscle biopsy findings usually have a mild clinical course, differential diagnosis and carrier screening is crucial for prevention of potentially life-threatening reactions to general anesthesia.

Kinetics of the cercaria-schistosomul um transformation in vivo: 2. The effect of oxamniquine

To study the cercaria-schistosomulum transformation in vivo, underthe influence of an antischistosomal compound (oxamniquine), a model using cercarial infections into the abdominal cavity of mice was chosen. This procedure provided easy and reproducible recoveries of larvae from peritoneal washings with appropriate solutions for a long time (30 to 180 min) after inoculation. The results show that high doses of oxamniquine (given intramuscularly one hour before the infection) produce a marked delay in the kinetics of the cercaria-schistosomulum transformation. Cercariae, tail-less cercarial bodies and schistosomula were recovered from the peritoneal cavity ofdrug treated mice in numbers significantly different from those recovered from untreated mice.