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Efflux Pumps Modulation in Colorectal Adenocarcinoma Cell Lines: The Role of Nuclear Medicine

Journal of Cancer Therapy 2011年第3期2卷 408-417页

作者： Joao Casalta-Lopes Ana Margarida Abrantes Mafalda Laranjo joana rio Ana Cristina Goncalves Barbara Oliveiros Ana Bela Sarmento-Ribeiro Maria Filomena Botelho Biophysics Unit IBILIFaculty of MedicineUniversity of CoimbraCoimbraPortugal Centre of Investigation on Cancer Envi-ronmentGenetics and OncobiologyFaculty of MedicineUniversity of CoimbraCoimbraPortugal Institute of Nuclear Sciences Applied to Health University of CoimbraCoimbraPortugal Applied Molecular Biology Unit Faculty of MedicineUniversity of CoimbraCoimbraPortugal.

Introduction: Multidrug resistance (MDR) is one of the major problems of chemotherapy. Overexpression of efflux pumps, such as P-glycoprotein (Pgp), multiple resistance-related protein 1 (MRP-1) and lung resistance protein (LRP) can lead to MDR. Verapamil and L-buthionine-sulfoximine (BSO) are two modulators of these proteins. This study aims to compare 99mTc-Sestamibi transport kinetics in human colorectal adenocarcinoma cell lines, in the presence and absence of the MDR modulators verapamil and BSO. Material and Methods: MDR proteins expression was evaluated in sensitive (WiDr) and resistant (LS1034) human colorectal adenocarcinoma cell lines. Intracellular and plasma membrane Pgp and MRP1, and LRP expression was analyzed by flow-cytometry and western blot. Cellular transport kinetics was assessed using 99mTc-Sestamibi. MDR modulation was evaluated though retention studies in resistant cells after incubation with the modulators. Results: Pgp expression was significantly higher (p≤0.001) in resistant cells. These results were confirmed by western blot analysis. 99mTc-Sestamibi uptake and retention percentage were significantly higher (p99mTc-Sestamibi, there were differences among the MDR modulators used (p99mTc-Sestamibi could indicate MDR phenotype in colorectal adenocarcinoma cells. As the modulators used showed a reversion of the retention profile only for the first minutes, their administration should occur immediately before the administration of cytotoxic drugs.

关键词： Multidrug Resistance P-Glycoprotein Multidrug Resistance-Associated Protein 1 Major Vault Protein

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Novel synthetic opioids-toxicological aspects and analysis

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Forensic Sciences Research 2019年第2期4卷 111-140页

作者： Inês Tabarra Sofia Soares Tiago Rosado joana Gonçalves Àngelo Luís Sara Malaca Mário Barroso Thomas Keller José Restolho Eugenia Gallardo Centro de Investigação em Ciências da Saude(CICS-UBI) Universidade da Beira InteriorCovilhãPortugal Laboratorio de Fármaco-Toxicologia-UBIMedical Universidade da Beira InteriorCovilhãPortugal Serviço de Química e Toxicologia Forenses Instituto Nacional de Medicina Legal e Ciências ForensesDelegac¸ão do SulLisboaPortugal Departament of Toxicology Institute of Forensic MedicineSalzburgAustria nal von minden GmbH RegensburgGermany

Over the past few years,there has been an emerging number of new psychoactive *** drugs are frequently mentioned as“legal highs”,“herbal highs”,“bath salts”and“research chemicals”.They are mostly sold and advertised on online forums and on the dark *** emerging new psychoactive substances are designed to mimic the effects of psychoactive groups,which are often abused *** synthetic opioids are a new trend in this context and represent an alarming threat to public *** the wide number of fatalities related to these compounds reported within the last few years,it is an important task to accurately identify these compounds in biologic matrices in order to administer an effective treatment and reverse the respiratory depression caused by opioid related *** dealing with fentanyl intoxication cases should consider that it could,in fact,be a fentanyl *** this reason,it is a helpful recommendation to include synthetic opioids in the routine toxicological screening procedures,including analysis in alternative matrices,if available,to investigate poly-drug use and possible tolerance to *** address this public health problem,better international collaboration,effective legislation,effective investigation,control of suspicious“research chemicals”online forums and continuous community alertness are *** article aims to review diverse reported fatalities associated with new synthetic opioids describing them in terms of pharmacology,metabolism,posology,available forms,as well as their toxic effects,highlighting the sample procedures and analytical techniques available for their detection and quantification in biological matrices.

关键词： Forensic sciences forensic toxicology new synthetic opioids biological specimens toxicity analysis

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Trophic niche changes associated with the eradication of invasive mammals in an insular lizard: an assessment using isotopes

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Current Zoology 2022年第2期68卷 211-219页

作者： Sara F.NUNES Mario MOTA-FERREIRA Marta SAMPAIO joana ANDRADE Nuno OLIVEIRA Rui REBELO Ricardo ROCHA Faculty of Sciences Centre for EcologyEvolution and Environmental ChangesUniversity of LisbonLisbon1749-016Portugal CIBI0-lnBI0 Research Center in Biodiversity and Genetic ResourcesUniversity of PortoVairao4485-661Portugal CIBI0-lnBI0 Research Center in Biodiversity and Genetic ResourcesInstitute of AgronomyUniversity of LisbonLisbon1349-017Portugal Sociedade Portuguesa Para o Estudo das Aves Av.Columbano Bordalo Pinheiro873°AndarLisboa1070-062Portugal

Invasive species are a major threat to island biodiversity,and their eradications have substantially contributed to the conservation of island ***,the consequences of eradications on the trophic ecology of native taxa are largely ***,we used the eradication of invasive black rats Rattus rattus and European rabbits Oryctolagus cuniculus from the Berlenga Island,in the western coast of Portugal,as a whole-ecosystem experiment to investigate the effects of the eradication of invasive mammals on the trophic niche and body dimensions of the island-restricted Berlenga wall lizard Podarcis carbonelli berlengensis over a 2-year *** results suggest an expansion of the isotopic niche and an intensification of the sexual dimorphism of the lizard following mammal ***,we found considerable variability in isotopic niche across the island and detected evidence of sex-specific and season-modulated nutritional requirements of this threatened *** findings support that the eradication of 2 of the planets most problematic invasive vertebrates led to changes in the lizard trophic niche and sexual dimorphism in just 2 *** suggests that the ecological pressuresfor example,prey availability and habitat structureto which lizards are exposed have substantially changed *** study emphasizes the scientific value of island eradications as experiments to address a wide range of ecological questions and adds to the increasing body of evidence supporting substantial conservation gains associated with these restoration interventions.

关键词： food-webs invasive species eradication Oryctolagus cuniculus Podarcis carbonelli berlengensis Rattus rattus

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A biophysical perspective on the unexplored mechanisms driving Parkinson’s disease by amphetamine-like stimulants

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Neural Regeneration Research 2021年第11期16卷 2213-2214页

作者： Carla Ferreira joana Couceiro Sandra Tenreiro Alexandre Quintas Molecular Pathology and Forensic Biochemistry Laboratory Centro de Investigação Interdisciplinar Egas MonizP-2825-084 CaparicaPortugal Laboratório de Ciências Forenses e Psicológicas Egas Moniz Campus Universitário–Quinta da GranjaMonte de CaparicaP-2825-084 CaparicaPortugal Faculty of Medicine of Porto University Al.Prof.Hernâni MonteiroP-4200–319 PortoPortugal iNOVA4Health CEDOCNOVA Medical SchoolNMSUniversidade Nova de Lisboa1169-056 LisboaPortugal

Epidemiological studies have reported an increased risk of Parkinson’s disease(PD)development in amphetamine-type stimulant users during their lifetime(Garwood et al.,2006;Rumpf et al.,2017).Protein inclusions mainly composed of misfolded and aggregatedα-synuclein are the pathological hallmark of PD and other disorders known as *** studies present evidence that amphetamine upregulatesα-synuclein synthesis in substantia *** increment ofα-synuclein levels promotes its aggregation and amyloid fibril formation,increasing reactive oxygen species(ROS),and consequently dopamine oxidation(Wang and Witt,2014),known to be toxic for dopaminergic neurons involved in motor function and limbicmotor *** the years,these damaged cells lose their functionality and may die precociously,depleting the reserve of neural cells necessary for the normal neurological function which contributes to the onset of PD,when a critical number of cells are lost(Garwood et al.,2006).Therefore,the use of amphetamine-type stimulants may be a trigger event in the development of PD and parkinsonism,in conjugation to other risk factors that a given individual may *** the evidence,a previous study suggests that there is not enough data to corroborate the loss of dopamine neurons due to human amphetamine-type stimulant exposure,and consequently its implication in the PD development(Kish et al.,2017).

关键词： driving increment lifetime

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Pseudoathletic Appearance:A Case Report in a Male

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Case Reports in Clinical Medicine 2015年第12期4卷 361-363页

作者： joana Moreira Goncalo Gomes Pereira Mário Santos Vaz de Macedo General Practice Department USF CoveloPortoPortugal General Practice Department USF Sem FronteirasSanta Maria da FeiraPortugal

Multiple Symmetric Lipomatosis (MSL) is a rare condition characterized by a symmetrical pattern of massive fatty deposits. This condition predominates in males, between 30 and 60 years. In this article, the authors present a case report of a 47-year-old man that resorted to consultation to perform routine medical exams, without any complaint associated. Physical examination shows multiple bilateral swellings in the proximal region of the upper limbs and analytically presents hyperuricemia, hypertriglyceridemia, hypercholesterolemia and changes in hepatic tests. CT revealed the presence of non-encapsulated homogeneous masses of adipose tissue in the proximal region of the limbs. Currently the patient is asymptomatic, being monitoring in consultation.

关键词： Symmetric Multiple Lipomatosis Hyperuricemia Hypertriglyceridemia Hypercholesterolemia

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Milroy Disease:A Case Report

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Case Reports in Clinical Medicine 2015年第11期4卷 349-351页

作者： Goncalo Gomes Pereira joana Moreira Vaz de Macedo Mário Santos General Practice Departement USF Sem FronteirasSanta Maria da FeiraPortugal General Practice Departement USF CoveloPortoPortugal

Hereditary lymphoedema type I is a congenital onset primary lymphoedema with autosomal dominant inheritance, which is characterized by the swelling of the lower body. In this article, the authors report a case of a 32-year-old woman with repeating episodes of swollen limbs. Imaging studies and genetic study were carried out and a Milroy’s syndrome diagnosis was established. The patient started sintomatic treatment of the edema, with fitting stockings and descompressive massage, with symptomatic benefit.

关键词： Milroy Disease Lower Limbs Edema FLT4 Gene VEGFR-3

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The spindle assembly checkpoint:perspectives in tumorigenesis and cancer therapy

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Frontiers in Biology 2011年第2期6卷 147-155页

作者： joana BARBOSA Ana Vanessa NASCIMENTO Juliana FARIA Patrícia SILVA Hassan BOUSBAA Centro de Investigação em Ciências da Saúde(CICS) Instituto Superior de Ciências da Saúde-NorteCESPURua Central de Gandra13174585-116 Gandra PRDPortugal

Loss or gain of chromosomes,a condition known as aneuploidy,is a common feature of tumor cells and has therefore been proposed as the driving force for *** chromosomal instability can arise during mitosis as a result of mis-segregation of the duplicated sister chromatids to the two daughter *** normal cells,missegregation is usually prevented by the spindle assembly checkpoint(SAC),a sophisticated surveillance mechanism that inhibits mitotic exit until all chromosomes have successfully achieved bipolar attachment to spindle *** abrogation of SAC activity is lethal to normal as well as to tumor cells,as a consequence of massive chromosome ***,many human aneuploid tumor cells exhibit a weakened SAC activity that allows them to tolerate gains or losses of a small number of chromosomes;and interfering with this SAC residual activity may constitute a suitable strategy to kill cancer *** review focuses on the potential link between SAC and tumorigenesis,and the therapeutic strategy to target the SAC for cancer treatment.

关键词： spindle assembly checkpoint mitosis chromosome instability tumor cancer therapy

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Property mapping of polycrystalline diamond coatings over large area

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Journal of Advanced Ceramics 2014年第1期3卷 56-70页

作者： Awadesh Kumar MALLIK Sandip BYSAKH Monjoy SREEMANY Sudakshina ROY Jiten GHOSH Soumyendu ROY joana Catarina MENDES Jose GRACIO Someswar DATTA CSIR-Central Glass&Ceramic Research Institute Kolkata 700032West BengalIndia Department of Physics Indian Institute of Technology BombayPowaiMumbai 400076MaharashtraIndia Instituto de Telecomunicações Campus Universitário de Santiago3810-193Portugal Nanotechnology Research Division Centre for Mechanical Technology and AutomationUniversity of Aveiro3810-193Portugal

Large-area polycrystalline diamond(PCD)coatings are important for fields such as thermal management,optical windows,tribological moving mechanical assemblies,harsh chemical environments,biological sensors,*** plasma chemical vapor deposition(MPCVD)is a standard technique to grow high-quality PCD films over large area due to the absence of contact between the reactive species and the filament or the chamber ***,the existence of temperature gradients during growth may compromise the desired uniformity of the final diamond *** the present work,a thick PCD coating was deposited on a 100-mm silicon substrate inside a 915-MHz reactor;the temperature gradient resulted in a non-uniform diamond *** attempt was made to relate the local temperature variation during deposition and the different properties of the final *** was found that there was large instability inside the system,in terms of substrate temperature(as high asΔT=212℃),that resulted in a large dispersion of the diamond coating’s final properties:residual stress(-15.8 GPa to+6.2 GPa),surface morphology(octahedral pyramids with(111)planes to cubo-octahedrals with(100)flat top surfaces),thickness(190μm to 245μm),columnar growth of diamond(with appearance of variety of nanostructures),nucleation side hardness(17 GPa to 48 GPa),quality(Raman peak FWHM varying from 5.1 cm^(-1) to 12.4 cm^(-1) with occasional splitting).This random variation in properties over large-area PCD coating may hamper reproducible diamond growth for any meaningful technological application.

关键词： plasma-enhanced chemical vapor deposition(CVD) diamond film mechanical properties nanostructures

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Hyperbaric oxygen therapy as a complementary treatment for radiation proctitis:Useless or useful?-A literature review

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World Journal of Gastroenterology 2021年第27期27卷 4413-4428页

作者： Diogo Alpuim Costa Carla Espiney Amaro Ana Nunes joana Santos Cardoso Pedro Modas Daniel Isabel Rosa João Vieira Branco Department of Haematology and Oncology CUF OncologiaLisboa 1998-018Portugal Centro de Medicina Subaquática e Hiperbárica(CMSH) Portuguese NavyLisboa 1649-020Portugal Centro de Investigação Naval(CINAV) Portuguese NavyBase Naval do AlfeiteAlmada 2810-001Portugal OVA Medical School Faculdade de Ciências MédicasLisboa 1169-056Portugal Department of Otorhinolaryngology Hospital das Forças Armadas(HFAR)Lisboa 1649-020Portugal Department of Gastroenterology Hospital das Forças Armadas(HFAR)Lisboa 1649-020Portugal Department of Vascular Surgery Centro Hospitalar Universitário de Lisboa CentralHospital de Santa MartaLisboa 1169-024Portugal Department of Intensive Care Unit Hospital das Forças Armadas(HFAR)Lisboa 1649-020Portugal Department of General Surgery Hospital das Forças Armadas(HFAR)Lisboa 1649-020Portugal

Radiotherapy(RT)is the backbone of multimodality treatment of more than half of cancer *** new modern RT techniques,late complications may occur such as radiation proctitis(RP).The natural history of RP is *** symptoms may resolve spontaneously or require conservative *** the other hand,for similar and uncomplicated clinical contexts,symptoms may persist and can even be refractory to the progressive increase in treatment *** the last decades,an enormous therapeutic armamentarium has been considered in RP,including hyperbaric oxygen therapy(HBOT).Currently,the evidence regarding the impact of HBOT on RP and its benefits is *** prospective and randomised studies are necessary to validate HBOT’s effectiveness in the‘real world’clinical *** article reviewed the relevant literature on pathophysiology,clinical presentation,different classifications and discuss RP management including a proposal for a therapeutic algorithm with a focus on HBOT.

关键词： Radiation proctitis Radiation proctopathy Radiotherapy Radio-induced lesion Late radiation tissue injury Delayed radiation injury Late sequelae Hyperbaric oxygen therapy Hyperbaric oxygen Review

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^(99m)Tc in the evaluation of microleakage of composite resin restorations with SonicFill^(TM).An in vitro experimental model

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Open Journal of Stomatology 2012年第4期2卷 340-347页

作者： Carrilho Eunice Abrantes Margarida Casalta-Lopes Joao Botelho Filomena Paula Anabela Ambrósio Pedro Marto Carlos Miguel Rebelo Diana Marques joana Polido Mário Ferreira Manuel Marques Faculty of Medicine University of CoimbraCoimbraPortugal

Introduction: The composite SonicFillTM (Kerr/Kavo) is indicated for posterior restorations, with a single increment up to 5 mm due to reduced polymerization shrinkage, thus reducing working time. Aim: Evaluation of marginal microleakage with SonicFillTM. Method and Materials: There were sectioned sixty noncarious human molars in the occluso-cervical direction. Class V cavities were prepared on each tooth with gingival margin walls in a standardized way. The specimens were divided into 4 groups: group 1—restored with SonicFillTM (Kerr/Kavo), group 2—restored with FiltekTM SupremeXTE (3M ESPE), group 3—the cavities were not restored;group 4—restored with SonicFillTM (Kerr/Kavo). In groups 1, 2 and 4 the enamel was conditioned with 37% orthophosphoric acid and applied the self-etch adhesive system Clear- fillTM SE BOND (Kuraray). The specimens were stored in distilled water at 37?C for 7 days. After, the specimens, were immersed in a solution of 99mTc-Pertechnetate and the radioactivity was assessed with a gamma camera. The nonparametric Kruskal-Wallis and Mann-Whitney test with Bonferroni correction at a significance level of 5% were used for the statistical analyses. Results: There are significant differences between the positive and negative control groups and between these and experimental groups (p TM and FiltekTM SupremeXTE. Conclusion: The new composite SonicFillTM and FiltekTM SupremeXTE showed no difference concerning dye penetration. The Sonic- FillTM restorative system showed no influence in concerning microleakage.

关键词： Posterior resin Composites Composite Restorations Polymerization Stress Polymerization Shrinkage Microleakage Thermocycling

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