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Novel synthetic opioids-toxicological aspects and analysis

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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Thiopurine-methyltransferase variants in inflammatory bowel disease:Prevalence and toxicity in Brazilian patients

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World Journal of Gastroenterology 2014年第12期20卷 3327-3334页

作者： Ana Teresa P Carvalho Barbara C esberard Renata S B Fróes Davy C M Rapozo Ana B Grinman Tatiana A Simo Juliana C V C Santos Antonio José V Carneiro Luis Felipe Ribeiro-Pinto Heitor S P de Souza Disciplina de Gastroenterologia e endoscopia Digestiva Universidade do Estado do Rio de Janeiro Programa de Carcinogênese Molecular Instituto Nacional de Cancer Laboratório de toxicologia e Biologia Molecular Universidade do Estado do Rio de Janeiro servi?o de Gastroenterologia Departamento de Clínica MédicaUniversidade Federal do Rio de Janeiro

AIM: To analyze the prevalence of thiopurine-methyltransferase (TPMT) genotypes and their association with drug toxicity in inflammatory bowel disease (IBD) patients from southeastern Brazil.

关键词： Inflammatory bowel disease Thiopurine-methyl-transferase Azathioprine Drug toxicity Pancreatitis

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Comprehensive analysis of HFe gene in hereditary hemochromatosis and in diseases associated with acquired iron overload

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World Journal of Hepatology 2019年第2期11卷 186-198页

作者： Wagner Narciso de Campos Juliana Doblas Massaro eduardo Luiz Rachid Can?ado Cláudia emília Vieira Wiezel Aguinaldo Luiz Sim?es Andreza Correa Teixeira Fernanda Fernandes de Souza Celso Teixeira Mendes-Junior Ana de Lourdes Candolo Martinelli eduardo Ant?nio Donadi Division of Clinical Immunology Department of MedicineRibeir?o Preto Medical SchoolUniversity of S?o Paulo department of Gastroenterology Clinical Gastroenterology and Clinical Hepatology of Clinical HospitalUniversity of S?o Paulo School of Medicine department of Genetics Ribeir?o Preto Medical SchoolUniversity of S?o Paulo Division of Gastroenterology Department of MedicineRibeir?o Preto Medical SchoolUniversity of S?o Paulo departamento de química Laboratório de Pesquisas Forenses e Gen?micasFaculdade de FilosofiaCiências e Letras de Ribeir?o PretoUniversidade de S?o Paulo

BACKGRoUND Patients with hepatitis C virus(HCV) and hepatocellular carcinoma(HCC) may or not develop iron overload(Io),which is associated with worst prognosis,because can cause serious damage to *** gene controls the iron uptake from gut,particularly in patients with hereditary hemochromatosis(HH).AIM To identify associations between HFe coding region in patients exhibiting hereditary hemochromatosis and in diseases associated with acquired *** We sequenced exons 2 to 5 and boundary introns of HFe gene,evaluating all polymorphic sites in patients presenting hereditary(hemochromatosis) or acquired iron overload HCV and HCC) and in healthy controls,using Sanger *** also determined the ensemble of extended haplotype in healthy control individuals,including several major histocompatibility complex loci,using sequence specific *** reconstruction was performed using the Arlequin and Phase softwares,and linkage disequilibrium(LD) between histocompatibility loci and HFe gene was performed using the Haploview *** The HFe*003 allele was overrepresented(f = 71%) and HFe*001 allele was underrepresented(f = 14%) in HH patients compared to all groups.A strong linkage disequilibrium was observed among the H63 D-G,IVS2(+4)-C and C282 YG gene variants,particularly in HH;however,the mutation IVS2(+4)T>C was not directly associated with HH *** HFe*001/HFe*002 genotype conferred susceptibility to HCC in HCV patients exhibiting Io(P = 0.02,oR =14.14).Although HFe is telomeric to other histocompatibility genes,the H63 DG/IVS2(+4)-C(P ≤ 0.00001/P ≤ 0.0057) combination was in LD with HLA-B*44 allele group in healthy *** LD was observed between HFe alleles and other major histocompatibility *** A differential HFe association was observed for HH and for diseases associated with acquired Io(HCV,HCC).Since HFe is very distant from other histocompatibility loci,only weak associations were observed with these a

关键词： HFe gene Hepatocellular carcinoma Hepatitis C Hemochromatosis hereditary Alleles Haplotypes

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Mitochondrial DNA as a Risk Factor for False Positives in Case-Control Association Studies

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Journal of Genetics and Genomics 2015年第4期42卷 169-172页

作者： Antonio Salas Joanna L.elson Unidade de Xenética Instituto de Medicina Legaland Departamento de Anatomía Patolóxica e Ciencias ForensesFacultad de MedicinaUniversidad de Santiago de CompostelaGalicia 15782Spain Mitochondrial Research Group Institute of Genetic MedicineCentre for LifeNewcastle University Centre for Human Metabolomics North-West University

During the last decade, hundreds of studies have been pub- lished examining whether significant associations exist be- tween mitochondrial DNA （mtDNA） variants and/or haplogroups （clades） and particular diseases （generally com- mon/complex diseases）（Fig. 1）. However, several authors have gathered evidence indicating a high incidence of false positive findings in mtDNA case-control association studies. Raule et al. （2007） and Herrnstadt and Howell （2004） showed various problems affecting mtDNA case-control association studies. Salas et al.

关键词： DNA Mitochondrial DNA as a Risk Factor for False Positives in Case-Control Association Studies

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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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Social Isolation in Male Rats During Adolescence Inhibits the Wnt/β-Catenin Pathway in the Prefrontal Cortex and enhances Anxiety and Cocaine-Induced Plasticity in Adulthood

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Neuroscience Bulletin 2020年第6期36卷 611-624页

作者： Santiago Cuesta Alejandrina Funes Alejandra M.Pacchioni Area toxicologia Departamento de Ciencias de los Alimentos y del MedioambienteFacultad de Ciencias Bioquimicas y FarmaceuticasUniversidad Nacional de RosarioSuipacha 5312000 RosarioSanta FeArgentina Consejo Nacional de Investigaciones Cientificas y Tecnicas RosarioArgentina Present Address:department of Microbiology University of Texas Southwestern Medical CenterDallasTX 75390USA

In adult animals,it is well established that stress has a proactive effect on psychostimulant ***,whether only a short period of stress during adolescence can also affect cocaine responses later in life and what mechanisms are involved are ***,we showed that 5 days of social isolation during rat adolescence had a long-term impact on anxiety-like behaviors,cocaine-induced conditioned place preference,and the expression of sensitization during *** the molecular level,social isolation decreased the activity of the Wnt/β-catenin pathway in the prefrontal cortex(PFC).Furthermore,after the expression of cocaine sensitization,isolated rats showed an increase in this pathway in the nucleus ***,these findings suggest that,adolescent social isolation by altering the Wnt/β-catenin pathway in the developing PFC might increase the cocaine responses during adulthood,introducing this pathway as a novel neuroadaptation in the cortical-accumbens connection that may mediate a stress-induced increase in vulnerability to drugs.

关键词： Social isolation Adolescence Cocaine vulnerability Wnt/(i-catenin pathway

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Diagnosis of Laron syndrome using monoplex-polymerase chain reaction technology with a whole-genome amplification template: A case report

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World Journal of Clinical Cases 2019年第23期7卷 4029-4035页

作者： Adina Neumann Miguel Angel Alcantara-ortigoza Ariadna Gonzalez-del Angel Felipe Camargo-Diaz esther Lopez-Bayghen Laboratorio de Investigacion y Diagnostico Molecular Instituto de Infertilidad y Genetica Mexico SCINGENESMexico City 05320Mexico Instituto Nacional de Pediatria Torre de InvestigacionMexico City 04530Mexico Laboratorio de Biologia Molecular Departamento de Genetica HumanaInstituto Nacional de PediatriaMexico City 04530Mexico departamento de toxicologia Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional(CINVESTAV-IPN)Mexico City 07360Mexico

BACKGRoUND Laron syndrome(LS)is an autosomal recessive hereditary condition affecting only 1/1000000 *** cause is associated with mutations in the growth hormone(GH)receptor(GHR),leading to GH *** patients typically present with severe growth retardation,obesity,and abnormal sexual ***,LS diagnosis is performed ***,we assessed the efficiency of Pre-implantation Genetic Testing(PGT)coupled with monoplex-polymerase chain reaction(PCR)technology for detecting this monogenic disease in embryos from a couple confirmed as LS heterozygous carriers CASe SUMMARY The couple LS-carriers were confirmed by the presence of a first child born with *** couple underwent a standard in vitro fertilization(IVF)*** was collected from trophectoderm cells from day 5 *** genome amplification(WGA)was performed using a Sureplex DNA Amplification System and analyzed by PCR,targeting the deletion of the exons 5 and 6 in the GHR gene as well as PGT by Next-generation Sequencing(Illumina).eleven embryos were collected and analyzed.27.3%were the wild type for GHR,45.5%were heterozygotes,and 18.2%homozygous *** embryo yielded no *** 2-embryos transfers were performed;2 normal homozygous and four heterozygous carriers were selected for *** first two transfers were unsuccessful,whereas the final transfer with two heterozygous embryos resulted in clinical *** genomic composition of the fetus was verified,applying the same techniques using amniocytes,extracted after 21 wk of the ongoing *** fetus was confirmed as GHR deletion in exon 5-6,carrier.A non-affected baby was *** Here,we present a case demonstrating that using WGA as a template in addition to PCR targeting specific gene regions,exons 5 and 6 on the GHR gene,could identify LS carrier *** provides evidence that WGA and PCR serve as an excellent tool to detect this specific monogenic disease in IVF e

关键词： Growth hormone insensitivity Growth hormone receptor mutations Intragenic deletions Molecular diagnosis embryo diagnosis Laron syndrome Case report

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Lime and orange essential oils and D-limonene as a potential CoVID-19 inhibitor:Computational,in chemico,and cytotoxicity analysis

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Food Bioscience 2023年第1期51卷 1151-1158页

作者： Aldrey Nathalia Ribeiro Correa Patrícia Weimer Rochele Cassanta Rossi Jessica Fernanda Hoffmann Letícia Scherer Koester edna Sayuri Suyenaga Cristiano Dietrich Ferreira Instituto Tecnologico em Alimentos para Saúde Universidade do Vale do Rio dos Sinos93022-750Sao LeopoldoRSBrazil Programa de Pos-Graduaçao em Ciencias Farmacˆeuticas Universidade Federal do Rio Grande do Sul90610-000Porto AlegreRSBrazil Programa de Pos-Graduaçao em toxicologia e Analises Toxicologicas Universidade Feevale93352-000Novo HamburgoRSBrazil

The CoVID-19 pandemic has substantially impacted the world health systems,causing public health concerns,and the search for new compounds with antiviral activity is of extreme *** molecules with bioactive potential are a trend,with essential oils(eos)being the focus of recent ***,this study evaluates in chemico the D-limonene inhibitory activities in the viral genome of SARS-CoV-2 and analyzes the cytotoxic potential and safety profile of D-limonene and lime and orange eos with a high content of *** eos were extracted and characterized,and the in chemico computational analysis for the determination as a potential anti-SARS-CoV-2 was performed with D-limonene,the major compound in *** cytotoxicity analysis of eos and Dlimonene was carried out with MRC-5 and HaCaT,and the preliminary safety profile was also evaluated by the HeT-CAM assay.D-limonene was suggested as a promising compound for anti-SARS-CoV-2 research,since the molecule does not provide mutagenic and cytotoxic fragments,and does not have irritating potential when diluted,in addition to having favorable pharmacokinetic characteristics,through in chemico ***,the results reveal the antiviral potential of lime and orange eos,as well as their major *** this sense,further studies should be conducted to understand the antiviral mechanisms.

关键词： essential oils D-limonene anti-Sars-CoV-2 CoVID-19

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Pitfalls of barcodes in the study of worldwide SARSCoV-2 variation and phylodynamics

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Zoological Research 2021年第1期42卷 87-93页

作者： Jacobo Pardo-Seco Alberto Gómez-Carballa Xabier Bello Federico Martinón-Torres Antonio Salas Unidade de Xenética Instituto de Ciencias Forenses(INCIFOR)Facultade de MedicinaUniversidade de Santiago de Compostelaand GenPoB Research GroupInstituto de Investigación Sanitaria(IDIS)Hospital Clínico Universitario de Santiago(SERGAS)Galicia 15706Spain Genetics Vaccines and Pediatric Infectious Diseases Research Group(GENVIP)Instituto de Investigación Sanitaria de Santiago(IDIS)and Universidad de Santiago de Compostela(USC)Galicia 15706Spain Translational Pediatrics and Infectious Diseases Department of PediatricsHospital Clínico Universitario de Santiago de Compostela(SERGAS)Galicia 15706Spain

deAR eDIToR,Analysis of SARS-CoV-2 genome variation using a minimal number of selected informative sites conforming a genetic barcode presents several *** show that purely mathematical procedures for site selection should be supervised by known phylogeny(i)to ensure that solid tree branches are represented instead of mutational hotspots with poor phylogeographic proprieties,and(ii)to avoid phylogenetic *** propose a procedure that prevents information redundancy in site selection by considering the cumulative informativeness of previously selected sites(as a proxy for phylogenetic-based criteria).This procedure demonstrates that,for short barcodes(e.g.,11 sites),there are thousands of informative site combinations that improve previous *** also show that barcodes based on worldwide databases inevitably prioritize variants located at the basal nodes of the phylogeny,such that most representative genomes in these ancestral nodes are no longer in ***,coronavirus phylodynamics cannot be properly captured by universal genomic barcodes because most SARS-CoV-2 variation is generated in geographically restricted areas by the continuous introduction of domestic variants.

关键词： dynamics properly purely

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Comprehensive Analysis of Pan-African Mitochondrial DNA Variation Provides New Insights into Continental Variation and demography

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Journal of Genetics and Genomics 2016年第3期43卷 133-143页

作者： Maria Cerezo Leonor Gusmao Viktor Cerny Nabeel Uddin denise Syndercombe-Court Alberto Gdmez-Carballa Tanja Gobel Peter M. Schneider Antonio Salas Unidade de Xenetica Departamento de Anatomia Patoloxica e Ciencias Forenses Instituto de Medicina Legal Facultade de Medicina Universidade de Santiago de Compostela Galicia 15782 Spain The Wellcome Trust Sanger Institute Hinxton CBIO 1SA UK DNA Diagnostic Laboratory Institute of Biology State University of Rio de Janeiro Rio de Janeiro 20550-900 Brazil IPATIMUP Institute of Molecular Pathology and Immunology of the University of Porto Porto 4200-465 Portugal Archaeogenetics Laboratory Institute of Archaeology of the Academy of Sciences of the Czech Republic Prague 118-01 Czech Republic Faculty of Life Sciences and Medicine King's College London London SE1 9NH UK Barts and The London School of Medicine and dentistry Blizard Institute London E1 2AT UK Institute of Legal Medicine Medical Faculty University of Cologne Cologne D-50823 Germany

Africa is the cradle of all human beings, and although it has been the focus of a number of genetic studies, there are many questions that remain unresolved. We have performed one of the largest and most comprehensive meta-analyses of mitochondrial DNA （mtDNA） lineages carried out in the African continent to date. We generated high-throughput mtDNA single nucleotide polymorphism （SNP） data （230 SNPs） from 2024 Africans, where more than 500 of them were additionally genotyped for the control region. These data were analyzed together with over 12,700 control region profiles collected from the literature, representing more than 300 population samples from Africa. Insights into the African homeland of humans are discussed. Phylogeographic patterns for the African continent are shown at a high phylogeographic resolution as well as at the population and regional levels. The deepest branch of the mtDNA tree, haplogroup L0, shows the highest sub-haplogroup diversity in Southeast and east Africa, suggesting this region as the homeland for modem humans. Several demographic estimates point to the coast as a facilitator of human migration in Africa, but the data indicate complex patterns, perhaps mirroring the effect of recent continental-scaled demographic events in re-shaping African mtDNA variability.

关键词： mtDNA Haplotype Haplogroup SNP MALDI-ToF

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