Tesis sobre el tema "TTrx"
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Gregory, Mary Sarah-Jane y n/a. "Thioredoxin and Oxidative Stress". Griffith University. School of Health Science, 2004. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20040301.082639.
Texto completoGregory, Mary Sarah-Jane. "Thioredoxin and Oxidative Stress". Thesis, Griffith University, 2004. http://hdl.handle.net/10072/367183.
Texto completoThesis (Masters)
Master of Philosophy (MPhil)
School of Health Sciences
Full Text
Kerkmann, Heiko. "Differentielle Interaktionen hochpotenter Lokalanästhetika mit TTX-sensitiven und TTX-resistenten Natriumströmen an Spinalganglienzellen der erwachsenen Ratte". Wettenberg : VVB Laufersweiler, 2005. http://deposit.d-nb.de/cgi-bin/dokserv?idn=978034708.
Texto completoIakovleva, Irina. "Selection of transthyretin amyloid inhibitors". Doctoral thesis, Umeå universitet, Institutionen för medicinsk kemi och biofysik, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-123939.
Texto completoKerkmann, Heiko [Verfasser]. "Differentielle Interaktionen hochpotenter Lokalanästhetika mit TTX-sensitiven und TTX-resistenten Natriumströmen an Spinalganglienzellen der erwachsenen Ratte / Heiko Kerkmann". Gießen : Universitätsbibliothek, 2015. http://d-nb.info/1069740705/34.
Texto completoPullmann, Martin. "Dynamische Blockierung TTX-resistenter Natriumkanäle durch Lokalanästhetika". [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=969813872.
Texto completoPanenic, Robert. "TTX-induced disuse of mammalian skeletal muscle". Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=59523.
Texto completoKerkmann, Heiko [Verfasser]. "Differentielle Interaktionen hochpotenter Lokalanästhetika mit TTX-sensitiven und TTX-resistenten Natriumströmen an Spinalganglienzellen der erwachsenen Ratte / vorgelegt von Heiko Kerkmann". Wettenberg : VVB Laufersweiler, 2005. http://d-nb.info/978034708/34.
Texto completoAzevedo, Ana do Carmo Ramalho Moreira. "Familial amyloid polyneuropathy: TTR sequencing and "in silico" analysis". Master's thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/15608.
Texto completoFamilial amyloid polyneuropathy (FAP) or paramiloidosis is an autosomal dominant neurodegenerative disease with onset on adult age that is characterized by mutated protein deposition in the form of amyloid substance. FAP is due to a point alteration in the transthyretin (TTR) gene and until now more than 100 amyloidogenic mutations have been described in TTR gene. FAP shows a wide variation in age-at-onset (AO) (19-82 years, in Portuguese cases) and the V30M mutation often runs through several generation of asymptomatic carriers, before expressing in a proband, but the protective effect disappear in a single generation, with offspring of late-onset cases having early onset. V30M mutation does not explain alone the symptoms and AO variability of the disease observed in the same family. Our aim in this study was to identify genetic factors associated with AO variability and reduced penetrance which can have important clinical implications. To accomplish this we genotyped 230 individuals, using a directautomated sequencing approach in order to identify possible genetic modifiers within the TTR locus. After genotyping, we assessed a putative association of the SNPs found with AO and an intensive in silico analysis was performed in order to understand a possible regulation of gene expression. Although we did not find any significant association between SNPs and AO, we found very interesting and unreported results in the in silico analysis since we observed some alterations in the mechanism of splicing, transcription factors binding and miRNAs binding. All of these mechanisms when altered can lead to dysregulation of gene expression, which can have an impact in AO and phenotypic variability. These putative mechanisms of regulation of gene expression within the TTR gene could be used in the future as potential therapeutical targets, and could improve genetic counselling and follow-up of mutation carriers.
A Polineuropatia amiloidótica familiar (FAP) ou paramiloidose é uma doença neurodegenerativa autossómica dominante com início na vida adulta sendo caracterizada pela deposição da proteína mutada na forma de substância amilóide. A FAP é devida a uma mutação pontual no gene transtirretina (TTR) e até agora mais de 100 mutações amiloidogénicas foram descritas neste gene. A FAP apresenta uma grande variação na idade de início (AO) (19-82 anos, nos casos portugueses) e a mutação V30M pode segregar através de várias gerações de portadores assintomáticos, antes de se expressar num probando. No entanto, este efeito protetor pode desaparecer numa única geração, com os filhos de casos tardios a apresentarem um início precoce. A mutação V30M não explica por si só os sintomas e a variabilidade da AO observada dentro de uma mesma família. O nosso objetivo neste trabalho foi identificar fatores genéticos associados com a variabilidade da AO e a penetrância reduzida. De modo a cumprir este objetivo genotipámos 230 doentes, por sequenciação automática, para identificar possíveis modificadores genéticos dentro do locus da TTR. Após a genotipagem, investigamos uma possível associação dos SNPs encontrados com a AO e realizamos uma intensiva análise in silico de modo a perceber uma possível regulação da expressão génica. Apesar de não termos encontrado nenhuma associação entre os SNPs e a AO, encontrámos resultados não descritos e muito interessantes na análise in silico dado termos observado algumas alterações a nível do mecanismo de splicing, ligação de fatores de transcrição e ligação de miRNAs. Todos estes mecanismos quando alterados podem levar à desregulação da expressão do gene, o que pode ter um impacto na AO e variabilidade fenotípica. Estes mecanismos hipotéticos da regulação da expressão génica no gene da TTR podem ser úteis para no futuro serem aplicados como potenciais alvos terapêuticos, beneficiando o aconselhamento genético e o follow-up dos portadores da mutação.
Lobato, Luísa Maria Correia Lopes. "A nefropatia na Polineuropatia Amiloidótica Familiar de Tipo Português (TTR V30M)". Doctoral thesis, Instituto de Ciências Biomédicas Abel Salazar, 2003. http://hdl.handle.net/10216/63699.
Texto completoLobato, Luísa Maria Correia Lopes. "A nefropatia na Polineuropatia Amiloidótica Familiar de Tipo Português (TTR V30M)". Tese, Instituto de Ciências Biomédicas Abel Salazar, 2003. http://hdl.handle.net/10216/63699.
Texto completoHäfner, Sibylle. "Strukturelle und physikochemische Determinanten von Substanzen für die Blockade TTX-resistenter Natriumkanäle". [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=969261888.
Texto completoDreimann, Marc. "Therapeutika des neuropathischen Schmerzes blockieren den TTX-resistenten Natriumkanal des peripheren nozizeptiven Systems". [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=963032496.
Texto completoDonato, Micheline Freire. "Purificação, caracterização bioquímica e eletrofisiológica da toxina Mic6c7NTX da Peçonha da Serpente Micrurus ibiboboca (Merrem, 1820)". Universidade Federal da Paraíba, 2008. http://tede.biblioteca.ufpb.br:8080/handle/tede/6863.
Texto completoCoordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Snake venoms contain a complex arsenal of protein bio-active components, many of these being neurotoxins (NTXs). These snakes have high neurotoxic activity venom, corresponding to the Elapidae family, which includes coral snakes (Micrurus) whose venom contains circa 90-95% of low molecular mass protein components. Among these, several are postsynaptic neurotoxins or α- NTXs (MM = 6-9 kDa). The Micrurus ibiboboca (Merren, 1820) is a snake of the Elapidae family witch is quite common in the Northeast of Brazil. In spite of the great diversity of species of Micrurus, scarce works involving the nervous system with isolated and pure toxins of those serpents has been developed in level biochemical, pharmacological and electrophysiological. The aim of this study was to purify the toxin Mic6c7NTX of the Micrurus ibiboboca venom, characterize to biochemically and electrophysiologically the toxin Mic6c7NTX in the peripheral nervous system (PNS) of rats, evaluating alterations in the record of the Compound Action Potential (CAP) of the isolate nerve and the toxin activity on the voltage-dependent sodium channels (Nav) in the neurons of the dorsal root ganglion (DRG). The venom was extracted from the Micrurus ibiboboca collected in Paraiba State (Brazil). Initially, electrophysiological tests (current clamp method) using the single sucrose gap technique were accomplished with crude venom (100μg/mL). It was observed that in this concentration the crude venom caused reduction in the CAP amplitude (25%). This neurotoxity led into an intriguing question: what components of the venom would promote to reduction in the excitability of the nerve? Based upon this question, I decided to purify the venom throughout the Liquid Chromatography of the High Performance (HPLC) of the Cation Exchange Chromatography (CIEX) and the Reverse Phase Chromatography (RPC). The molecular mass (MM) of the raw toxin was determined by mass-spectrometry (MALDI-QTOF/ MS) and N-terminal sequence by means of Edman s Degradation. The search for similarity with other toxins was accomplished against proteomic data bank. The CIEX profile showed 19 fractions and the highest peak fraction was used for the second dimension. The toxin Mic6c7NTX obtained by RPC showed elution in 26.7%of the acetonitrile (ACN) and MM 7.047.56Da. The obtained partial N-terminal sequence showed 31 aminoacid residues. The search for similarity of structure and function showed great similarity (65%) with other short chain α-NTXs Australian elapids snakes. The electrophysiological studies (single sucrose gap technique) showed that the toxin Mic6c7NTX (1 μM) reduced the excitability of the isolate nerve similarly to the reduction observed in the crude venom about 21%. Other CAP parameters such as despolarization speed (DSCAP), repolarization time (τCAP) and peak of time (PTCAP) did not show alterations. This suggests that the toxin may be affecting the Nav channels. For the confirmation of that hypothesis experiments were accomplished with whole cell patch-clamp technique in DRG neurons. This results showed that the toxin Mic6c7NTX (1 WM) abolished completely the current of Nav channels sensitive the tetrodotoxin (TTX-S). Also the Nav channels TTX resistant (TTX-R) were investigated in the presence of the Mic6c7NTX toxin previously using TTX (100 nM). This results showed that the toxin Mic6c7NTX (100 nM) abolished completely the current of Nav channels TTX-R and IC50 = 30nM. However, reversion of this blocking was not observed. The present study biochemically and electrophysiologically characterized an α-NTX of the Micrurus ibiboboca elapid snake. Furthermore, it showed a potent toxin with affinity Nav channels TTX-S and TTX-R of the PNS. This is the first α-NTX isolated and identified of the venom from the Micrurus ibiboboca (Merrem, 1820) snake.
As serpentes da família Elapidae possuem uma peçonha com alta atividade neurotóxica e capacidade de letalidade. Fazem parte dessa família as serpentes corais americanas (gênero Micrurus) com suas peçonhas contendo cerca de 90-95% de componentes protéicos, sendo na sua maior parte neurotoxinas com baixa massa molecular (6-8 kDa), podendo ser destacadas as neurotoxinas com ação pós-sinápticas ou α-Neurotoxinas (α-NTX). A Micrurus ibiboboca (Merrem, 1820) é uma serpente da família Elapidae, comum na região Nordeste. Apesar da grande diversidade de espécies do gênero Micrurus sp., escassos trabalhos envolvendo atividade de toxinas isoladas e puras destas peçonhas e sistema nervoso têm sido desenvolvidos em nível bioquímico, farmacológico ou eletrofisiológico. O objetivo desse estudo foi purificar a toxina Mic6c7NTX da peçonha de M. ibiboboca, caracterizar bioquímicamente e investigar com ferramentas eletrofisiológicas a ação da toxina no Sistema Nervoso Periférico (SNP) de ratos avaliando alterações no Potencial de Ação Composto (PAC) do nervo isquiático isolado e a atividade da toxina nos canais para sódio dependentes de voltagem (Nav) em neurônios do gânglio da raiz dorsal (DRG). A peçonha da M. ibiboboca foi extraída de serpentes coletadas no Estado da Paraíba (Brasil). Inicialmente, ensaios eletrofisiológicos com o método de current clamp utilizando a técnica de single sucrose gap foram realizados com a peçonha bruta (100 Wg/mL). Os resultados mostraram que a peçonha bruta nessa concentração promoveu redução na amplitude do PAC (25%). Esse efeito da toxina na excitabilidade do nervo levantou o questionamento: Que componentes da peçonha estariam causando essa diminuição da excitabilidade? A peçonha foi purificada por meio de Cromatografia Líquida de Alta Performance (HPLC), de troca catiônica (CIEX) e fase reversa (RPC). Na sequência, os picos da CIEX foram submetidos à RPC e posteriormente analisados por espectrometria de massas (MALDI-TOF/MS) que detectou a massa molecular da toxina Mic6c7NTX de 7.047,56 Da. Em seguida, foi determinado o seu N-terminal por Degradação de Edman que apresentou 31 resíduos de aminoácidos e serviu de estudo para a bioinformática na busca por similaridade em banco de dados proteômicos com outras toxinas protéicas, demonstrando que a toxina Mic6c7NTX apresentou similaridade (65%) com α-NTXs de cadeia curta de serpentes elapídicas australianas. Posteriormente, foi investigado o efeito da toxina isolada no SNP. Os estudos eletrofisiológicos em single sucrose gap demonstraram que a toxina Mic6c7NTX (1 WM) reduziu a excitabilidade do nervo isolado de forma similar à observada pela peçonha bruta. Não foram observadas alterações significantes em outros parâmetros do PAC, como velocidade de despolarização (VDPAC), tempo de repolarização (τPAC) e tempo de pico (PTPAC), sugerindo que a toxina atuasse num sítio de ligação específico dos [Escreva uma citação do documento ou o 11 canais Nav no SNP. Para a confirmação dessa hipótese foram realizados experimentos de voltage clamp com a técnica de whole cell patch-clamp em cultura primária de neurônios DRG da medula espinhal de ratos. Os resultados mostraram que a toxina Mic6c7NTX (1 WM) aboliu completamente as correntes dos canais Nav sensíveis à tetrodotoxina (TTX-S). Também foi investigado o efeito da toxina sobre a população de canais Nav resistentes à TTX (TTX-R), utilizando previamente TTX (100 nM) para bloquear os canais Nav TTX-S. Os registros com a toxina Mic6c7NTX (100 nM) demonstraram um bloqueio total da corrente nos canais Nav TTX-R dos DRGs e uma IC50 da toxina em torno de 30 nM. Também foi observado que essa toxina se liga aos canais Nav de forma lenta e irreversível. O presente estudo caracterizou bioquímica e eletrofisiologicamente uma α-NTX da serpente elapídica Micrurus ibiboboca. Farmacologicamente, trata-se de uma potente toxina com afinidade aos canais Nav TTX-S e TTX-R do SNP. Essa é a primeira α-NTX isolada e caracterizada da peçonha da serpente Micrurus ibiboboca (Merrem, 1820).
Andersson, Karin, M. Pokrzywa, Ingrid Dacklin y Erik Lundgren. "Inhibition of TTR aggregation-induced cell death : a new role for serum amyloid P component". Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten), 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-65622.
Texto completoEpub 2013 Feb 4.
Jampala, Raghavendra. "Synthesis of AG10 analogs and optimization of TTR ligands for Half-life enhancement (TLHE) of Peptides". Scholarly Commons, 2017. https://scholarlycommons.pacific.edu/uop_etds/2975.
Texto completoFeldman, Chris R. "Evolutionary Genetics of Tetrodotoxin (TTX) Resistance in Snakes: Tracking a Feeding Adaptation from Populations Through Clades". DigitalCommons@USU, 2008. https://digitalcommons.usu.edu/etd/159.
Texto completoBelous, Gregg R. "Novel Machine Learning Techniques for Left Ventricular Analysis in Echocardiography". Thesis, Griffith University, 2020. http://hdl.handle.net/10072/400568.
Texto completoThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Eng & Built Env
Science, Environment, Engineering and Technology
Full Text
Kerkmann, Heiko [Verfasser]. "Modell und Berechnung von Konzentrations-Inhibitionskurven hoch- und niedrigpotenter Substanzen am TTX-resistenten Natriumkanal der erwachsenen Ratte / Heiko Kerkmann". Gießen : Universitätsbibliothek, 2013. http://d-nb.info/1065394853/34.
Texto completoGrzymala-Lubanski, Bartosz. "Anticoagulation treatment in patients with a mechanical heart valve". Doctoral thesis, Umeå universitet, Institutionen för folkhälsa och klinisk medicin, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-128355.
Texto completoLobato, Maria Inês Rodrigues. "Estudo de marcadores moleculares relacionados a cadeia dos retinóides (TTR e RXR[beta] e suas relações com endofenótipos clínicos e dismórficos em esquizofrenia)". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2004. http://hdl.handle.net/10183/5554.
Texto completoDuong, Sun. "Evaluation of novel fluorescent probes for in vivo Transthyretin amyloid using fibrils generated in vitro under varying conditions". Thesis, Linköpings universitet, Institutionen för fysik, kemi och biologi, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-154611.
Texto completoCosta, Luiz Augusto de Oliveira. "Estudo de viabilidade técnica, econômica e ambiental preliminar da aplicação da tecnologia de Tratamento Térmico de Resíduos e Materiais Multifásicos-TTRM a resíduos de terra diatomácea de usina genérica de produção de biodiesel". Universidade do Estado do Rio de Janeiro, 2014. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=8130.
Texto completoRenewable energy has played an ever increasing role in the global energy matrix. In Brazil, the public administration has shown efforts to increase the share of renewable fuels and the biodiesel production. The Brazilian National Waste Policy has among its goals non-generation, minimization, reuse, recycling and hazard reduction of waste, considering the alternative of landfill disposal only where waste treatment is not viable. However, the final filtering process in biodiesel production can generate a great amount of waste, including diatomaceous earth waste with significant inflammable characteristic. This work conducts a feasibility study of Multiphase Waste and Materials Thermal Treatment technology applied to diatomaceous earth waste generated from a generic biodiesel production plant. The present study has been based on: the results of diatomaceous earth waste thermal treatment tests performed by PETROBRAS and ALBRECHT both on laboratory and pilot scales; Technical and operational assumptions; and economic reference data. Specific scenarios were established to study the applicability and sensitivity analysis where performed for key factors of costs composition. The study concluded that thermal treatment is technically applicable to diatomaceous earth waste. In the economic dimension all indicators were be positive even where variations of 25% were introduced into the main input parameters. In the environmental dimension the Multiphase Waste Thermal Treatment of diatomaceous earth waste proved to be aligned with the Brazilian National Waste Policy, with regard to hazard reduction and minimization of waste generation as well as improving the potential for waste reuse.
Björnfot, Therese y Pia Kujala. "Engelsk språkinlärning och läromedel : En kvalitativ läromedelsanalys av Happy – Textbook year 3". Thesis, Mälardalens högskola, Akademin för utbildning, kultur och kommunikation, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-37448.
Texto completoBranco, Bárbara da Costa. "Metodologia para deteção e diferenciação entre a estirpe vacinal e estirpes selvagens de Salmonella spp. por RT-PCR". Master's thesis, Universidade de Aveiro, 2017. http://hdl.handle.net/10773/21528.
Texto completoA realização deste trabalho teve como principais objetivos o acompanhamento da rotina laboratorial do Instituto Nacional de Investigação Agrária e Veterinária (INIAV, I.P.) e o desenvolvimento e implementação de nova uma metodologia por PCR em tempo real (RT-PCR) que permita a confirmação de Salmonella após execução da norma ISO 6579:1-2017, e a distinção entre a estirpe vacinal e as estirpes selvagens de Salmonella presentes em amostras provenientes de produção primária. A rotina laboratorial consistia a análise de amostras alimentares, ambientais e de produção primária, inseridas em diferentes atividades (e.g. Plano de Inspeção de Géneros Alimentícios, Plano Nacional de Controlo de Salmonella, Postos de Inspeção Fronteriços e Ensaios Interlaboratoriais). Todas as amostras foram analisadas tendo em conta os parâmetros microbiológicos estabelecidos para a pesquisa de Campylobacter spp., pesquisa de enterotoxinas estafilocóccicas, pesquisa de Escherichia coli STEC/VTEC, pesquisa e contagem de Listeria monocytogenes, contagem de Enterobacteriaceae e de microrganismos a 30°C e pesquisa de Salmonella spp. A vacinação contra Salmonella é uma medida importante no controlo de bandos de frangos, perus, galinhas poedeiras e reprodutoras. Por isso, é essencial detetar no menor tempo possível a presença desta bactéria e consequentemente o seu serotipo, permitindo saber qual a estirpe de Salmonella que está a infetar os bandos. Então, procedeu-se ao desenvolvimento de uma nova metodologia relativamente rápida (i.e., após duas horas), qualitativa (i.e., presença/ausência) para deteção e diferenciação de estirpes de Salmonella através de uma técnica por RT-PCR baseada na utilização de três sondas do tipo TaqMan, contendo uma delas bases de LNA, tornando-a mais específica para deteção do serotipo vacinal. As amostras alimentares são testadas diretamente da purificação de uma colónia em NA do meio XLD que irá para serotipificação. Caso haja fluorescência no canal HEX, significa que foi detetada a sequência do gene ttr, utilizado para testar a presença de Salmonella. No caso de amostras de produção primária, são retiradas cerca de 10 colónias do XLD para NA (i.e., se através do aspeto macroscópico se suspeitar que existem diferentes serotipos) e da placa de XLD que é analisada em Lisboa, para serotipificação, e é retirada uma colónia (já purificada) de modo a confirmar os resultados obtidos, na medida em que os testes de confirmação serológicos e biológicos são realizados a partir desta mesma colónia isolada. Aqui, espera-se que haja fluorescência no canal Cy5 (nhaA-V) que deteta o gene nhaA no caso de a estirpe ser vacinal. Se a estirpe for selvagem, não haverá curva de amplificação na corrida de RT-PCR visto existir uma sequência para estirpes selvagens que compete com os locais de ligação da sonda nhaA-V. Desta forma, e associando ao seguimento das primeiras fases da norma ISO 6579 é possível garantir o isolamento de Salmonella e a eliminação dos falsos positivos. A existência de um controlo interno de amplificação (IAC) que deteta a sequência do plasmídeo pUC19, através do canal ROX, fornece uma ferramenta importante para a indicação de falsos negativos, que possam ser causados por inibição da reação de PCR, provocada pelas diferentes matrizes, ou até por algum erro no funcionamento do termociclador. Assim, foi possível concluir que a nova metodologia permite detetar Salmonella spp., após isolamento em meio XLD através da ISO 6579, e diferenciar a estirpe vacinal das selvagens, uma vez que o aspeto macroscópico obtido apresenta diferenças (i.e., aspeto côncavo no caso da estirpe vacinal e aspeto convexo no caso de estirpes selvagens). Foi ainda possível verificar que o caldo MKTTn favorecia o crescimento da estirpe vacinal e permitia com maior facilidade a sua deteção.
This project’s main goals were to follow the Instituto Nacional de Investigação Agrária e Veterinária (National Institute for Agrarian and Veterinary Research - INIAV, I.P.) laboratory daily routine and the development and implementation of a new methodology in real-time PCR (RT-PCR) that allowed the confirmation of Salmonella after the execution of normative ISO 6579:1-2017, and the distinction between vaccine and wildtype strains of Salmonella present in primary production’s samples. Laboratory daily routine consisted in the analysis of food, environmental and primary production samples, inserted in different activities (e.g., Food Inspection Plan, Airport and Seaport frontier analytical Support, Salmonella National Surveillance Plan and samples of interlaboratory assays. Every sample was analyzed taking into account the microbiological parameters established for the detection of Campylobacter spp., detection of staphylococcal enterotoxins, detection of Escherichia.coli STEC/VTEC, detection and enumeration of Listeria monocytogenes, enumeration of Enterobacteriaceae and plate count technique of microorganisms at 30°C and detection of Salmonella spp.. The vaccination in poultry is an important measure in control of Salmonella in the broilers, turkeys, laying and breeding hens. That is why it is essential to detect as fast as possible the presence of this bacteria and consequently its serotype, allowing us to know which Salmonella’s strain is infecting the flocks. Then, we proceeded to the development of a relatively fast (i.e., after two hours of the PCR run) and qualitative (i.e., presence/absence) new methodology for the Salmonella strains detection and differentiation through RT-PCR technique based on the utilization of three TaqMan probes, one of them containing LNA bases, making it more specific for vaccine serotype detection. The food samples are directly tested from the purification of a colony in NA plate of the XLD medium which will go to the serotyping. In case of a fluorescence detection in the HEX channel, a sequence of the ttr gene was detected, which is used to detect the presence of Salmonella spp.. In case of primary production samples, 10 colonies from XLD medium are inoculated into NA plate (i.e., if there is a suspicion of the existence of different serotypes through the macroscopic appearance) and from the XLD plates which go to Lisbon, for serotyping a colony is purified so it can confirm the obtained results, in so far as the serological and biological confirmation tests are performed from this isolated colony. Here is expected to exist fluorescence in channel Cy5 (nhaA-V) which detects the nhaA gene in case of the vaccine serotype. There will be no amplification curve in the RT-PCR assay in case of wildtype strain since there is a sequence for wildtype strains that compete with specific probes of vaccine strain for similar binding sites during RT-PCR. Therefore, and associating to the follow-up of the ISO 6579 first stages it is possible to assure the Salmonella isolation and the detection of false positive results. The existence of an internal amplification control (IAC) that detects the pUC19 plasmid’s sequence, through the ROX channel, provides an important tool for the indication of false-negative results, that may be caused by the PCR reaction inhibition, caused by the different matrices, or even by an error in the thermocycle operation. Therefore, it was possible to conclude that the new methodology allows to detect Salmonella spp., after isolation in the XLD medium, following ISO 6579, and differentiate the vaccinal strains from the wildtype once since the obtained macroscopic appearance reveals differences, i.e., concave appearance in the vaccinal strain’s case and convex appearance in the wildtype strains. It was also possible to see that the MKTTn broth was the medium which favoured the vaccine strain growth and allowed a easier detection.
Froder, Hans. "Desenvolvimento de métodos para a quantificação direta de Salmonella sp. por PCR-tempo real e por transcriptase reversa-PCR-tempo real". Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/9/9131/tde-25012011-175156/.
Texto completoIn order to get fast and trustworthy results that allow monitoring the microbiological food safety either by industries or governmental agencies, diverse alternative methods have been developed for Salmonella detection and quantification. The purposes of this study were to evaluate the viability of the use of QIAamp® DNA Stool Mini Kit for Salmonella DNA extraction and purification; to validate assays based on real time-PCR (PCR-RT) to quantify Salmonella DNA by using ttr or tuf, and to develop an assay to quantify Salmonella based on reverse transcriptase- PCR-real time (RT-PCR-RT). For QIAamp® DNA Stool Mini Kit evaluation feces taken directly from the rectum of infected or health animals were used, with the former being artificially contaminated. Samples were submitted to DNA extraction, according to manufacturers protocol. The isolated DNA were quantified using a Salmonella-specific PCR-RT targeting the ttr locus. The same assay was used for Salmonella cells originated from culture medium. The PCR-RT assay with tuf as target was first validated employing different Salmonella serovars and other Enterobacteriaceae strains. After, its efficiency was evaluated on food-models (chicken and swine) spiked with high (≈ 6 log CFU/mL) and low (≈ 2 log CFU/mL) Salmonella Typhimurium DT 104 populations. The validation of the quantitative RT-PCR-RT method was first conducted with cells grown in culture medium, and then in the same food-model used for PCR-RT. For both methods aliquots of foodmodels were maintained at 20 ºC and 8 ºC being evaluated at different incubation times. Enumeration of total mesophilic microorganisms and Salmonella based on conventional methods were used as controls. The DNA recovery rate in swine feces artificially inoculated, after QIAamp® DNA Stool Mini Kit treatment, was between 25% to 50% depending the initial amount of cells. Using the extracted DNA and submitting it to PCR-RT for ttr a detection level of 2,8 CFU eq/g of feces was obtained. This method showed lower sensitivity than the conventional. Salmonella quantification by PCR-RT employing tuf showed a detection level lower than 1 log CFU eq. The results obtained with this method and cells suspended in culture medium or in food-model systems were, in general slightly lower that those obtained with the conventional method. The efficiency of amplification for PCR-RT tuf was 94%. Detection limit of RT-PCR-RT was similar to that of ttr (2 log CFU eq) and efficiency of amplification was 100%. tuf was expressed in logarithmic phase of bacteria growth curve showing that it is a good viability indicator for Salmonella.
Scafà, Martina. "Un esempio di Economia Circolare: il riciclo e il riuso dei dispositivi Tessili per Sala Operatoria". Master's thesis, Alma Mater Studiorum - Università di Bologna, 2016.
Buscar texto completoBlasi, Pérez Daniel. "Drug Discovery Targeted to Transthyretin Related Amyloidosis". Doctoral thesis, Universitat de Barcelona, 2013. http://hdl.handle.net/10803/108283.
Texto completoBoldbaatar, Batbold. "The role of non-coding genetic variants on transthyretin gene transcription in transthyretin amyloidosis". Thesis, 2021. https://hdl.handle.net/2144/42221.
Texto completoMacedo, Nídia Sampaio. "TTR-induced cytoskeleton remodelling: a double-edged sword". Master's thesis, 2018. https://hdl.handle.net/10216/117140.
Texto completoMacedo, Nídia Sampaio. "TTR-induced cytoskeleton remodelling: a double-edged sword". Dissertação, 2018. https://repositorio-aberto.up.pt/handle/10216/117140.
Texto completoMartins, César Fernando de Bessa. "Estudo da expressão da transtirretina (TTR) no cérebro de ratinho". Master's thesis, 2008. http://hdl.handle.net/10400.6/2781.
Texto completoTransthyretin (TTR) is a tetrameric protein which exists in the serum and cerebrospinal fluid (CSF) of vertebrates. It’s main biological known functions comprise the transport of tyroxine (T4) and retinol (vitamin A) through the formation of a complex with the retinol binding protein (RBP). Additionally, it has been shown that TTR is capable to bind and sequester beta amyloid peptide (A-Beta), weakening it’s deposition in nervous tissues, a key feature of Alzheimer’s disease (AD). Consequently, it has been suggested a protective role for this protein against the development of AD, supported by reports that indicate a negative correlation between the levels of TTR in the CSF and the severity degree of this neurodegenerative disease. The liver and the brain choroid plexus (CP) are well documented as the major sites of TTR synthesis, however recently, evidence has emerged that aim to an expression of this protein in others regions of the brain, prompting some controversy. In an attempt to contribute to the resolution of this controversy, in situ hybridization (ISH) and imunohistochemical (IHC) investigations were performed in wild-type mice brain, previously serialized, in order to characterize the cellular distribution of TTR in this organ. The acquired data indicates that besides an intense staining in the PC epithelial cells, as expected, the mRNA of TTR is also present in specific regions of the cerebral parenchyma, such as the cerebellum and rachidian bulb, with possible implications on the properties of this protein in the brain.
Pullmann, Martin [Verfasser]. "Dynamische Blockierung TTX-resistenter Natriumkanäle durch Lokalanästhetika / vorgelegt von Martin Pullmann". 2003. http://d-nb.info/969813872/34.
Texto completoSilva, Joana Patrícia Abreu. "Modulators of phenotypic variability in Familial Amyloid Polyneuropathy (TTR-FAP Val30Met)". Master's thesis, 2017. https://repositorio-aberto.up.pt/handle/10216/109157.
Texto completoSilva, Joana Patrícia Abreu. "Modulators of phenotypic variability in Familial Amyloid Polyneuropathy (TTR-FAP Val30Met)". Dissertação, 2017. https://repositorio-aberto.up.pt/handle/10216/109157.
Texto completoPen-wen-sen y 沈姵妏. "To examine the conjugal functions of two ttrA homologs in SCP1 and S. coelicolor chromosome". Thesis, 2009. http://ndltd.ncl.edu.tw/handle/p394u7.
Texto completo國立臺北科技大學
生物科技研究所
97
Streptomyces has linear chromosomes and linear plasmids, and terminal proteins are covalently linked at 5’ ends of these DNA. Part of Streptomyces linear plasmids own conjugal ability, they can transfer themselves and chromosomes into recipients. One of related gene of conjugal transfer of Streptomyces linear replicons is ttrA, and previously study showed that ttrA of S. lividans chromosome and SLP2 linear plasmid worked in cis for DNA transfer during conjugation. ttrA homologs are commonly located in the end of linear replicons of Streptomyces, but the linear plasmid SCP1 carries two ttrA homologous, with lower identity, located on the central region. This study was analyzed the function of ttrA homologs of Streptomyces in conjugation by gene replacement. The ttrA of S. coelicolor chromosome showed the different effects on two strains, M145 without plasmids and 3456 with integrated SCP1. M145-
Chang, Hsiang-Yu y 張翔喻. "Studies on quantitative gene probe development for pufferfish and genotoxicity of TTX". Thesis, 2011. http://ndltd.ncl.edu.tw/handle/17638139549831038336.
Texto completo亞洲大學
保健營養生技學系碩士班
99
The majority 30 species of Taiwan pufferfish species are born with tetrodotoxin (TTX) and non-economic value due to small quantity of production. Due to fraud or incorrect manufacturing processes, different proportions of unexpected or pufferfish muscle may be incorporated. The volatility of these factors may lead to counterfeit and concerned issue for public food safety. To solve these problems, a rapid qualitative and quantitative method which can accurately and quantitatively authenticate the source fish species under different of production processing should be established as soon as possible. The first study was focused on the gene map analysis of cytochrome b (cyt b) and cytochrome c oxidase I (COI) for Lagocephalus genus and Takifugu genus. The results show the strong genus-specificity and sensitivity on cyt b gene of L. genus and COI gene of T. genus. The further designed genus specific primers and genus Taqman probes are LF-cytb74163 / LR-cytb86890 and T. genus: TF-COI31332 / TR-COI41233, L- probe cytb and T- probe COI of L. genus and T. genus respectively. The amplified length of fragments was 150 base pairs for L. genus and 121 base pairs for T. genus. Specificity and sensitivity of specific primers and genus Taqman probes were also tested. These results demonstrated the primers and Taqman probes were able to discriminate efficiently of L. and T. genus individually and did not have reaction with other species. The detection limit of DNA concentration is 10-2 ng/μL of L. genus and T. genus. Furthermore, apply the above method to identify the commercially products is successfully identify the dry-dressed fish fillets collected before which were all made from pufferfish. The recent collection of these two years from Taiwan’s northern, central, southern and eastern the samples were all not made from pufferfish. It was shown the primers and Taqman probes were able to identificate the processed products and coupled with Real-time PCR is an accurate qualitative analysis technique. Once the TTX was ingested into the body, the toxicity mechanism is blocking the sodium channels entry of sodium ion on neuronal membranes. Suppose low dose-TTX has been ingested that forms a number of different mononucleotide and dinucleotide adducts in DNA, TTX-derived DNA adducts may cause liver cell toxicity. This study actually provided a very important reference on TTX toxicogenomics analysis. In our study, the in vitro test of TTX interacted with a single nucleotide dGMP via the HPLC analysis was done. It was shown that TTX did not have reaction with dGMP. Our data can be used as the basic information of TTX toxicogenomics. To summarize our study actually provided a very important reference on quantitative analysis of sensitive and reliable analyzing method for food safety and especially for adulterated pufferfish products. In addition, the TTX of genotoxicity also provide the basis toxicogenomics information for future related research purposes, and this is also the first study. Our study actually proved groundbreaking and practicability on science research.
Magalhães, Marisa Monteiro. "Estudo da estabilidade da TTR após o transplante hepático em doentes PAF". Master's thesis, 2016. http://hdl.handle.net/10451/25517.
Texto completoA Polineuropatia Amiloidótica Familiar (PAF) é uma doença autossómica dominante progressiva caraterizada pela deposição de fibras amilóides formadas pela proteína Transtirretina (TTR). É uma patologia severa e que constitui um paradigma, uma vez que existem observações fenotípicas que sugerem um modelo de patogénese mais complexo do que a simples presença de mutações na cadeia polipeptídica da TTR. De modo a tentar compreender de que forma outros fatores não genéticos podem alterar a progressão desta doença, o presente trabalho apostou na análise de vários estados de progressão da PAF, para o qual se utilizou amostras de plasma de indivíduos portadores heterozigóticos da mutação V30M sintomáticos e indivíduos que sofreram um transplante de fígado cadáver. Foram avaliados os interactuantes da TTR e os níveis de glicação. O trabalho desenvolvido mostrou inequivocamente que o tempo de meia vida da TTR ronda os 3 dias, sendo que ao fim do sexto dia a variante mutada já foi totalmente substituída pela variante WT em indivíduos transplantados com fígado cadáver. Já os interactuantes da TTR identificados neste trabalho em pacientes PAF não transplantados foram a albumina, o retinol-binding protein, urocortino-3 e IgG1, sendo que a albumina e o retinol-binding protein já tinham sido descritos na literatura. Contudo, nos pacientes transplantados e monitorizados estavam apenas presentes a albumina, a IgG1 e o urocortino-3. A execução deste trabalho permite reforçar o envolvimento de fatores não genéticos no modelo de patogénese da PAF, nomeadamente um modelo multifatorial.
Familial Amyloid Polyneuropathy (FAP) is a progressive autosomal dominant disease characterized by the deposition of amyloid fibrils formed by the protein transthyretin (TTR). It is a severe disease and it is a paradigm, since there are phenotypic observations which suggest a more complex model of pathogenesis, with more than the presence of mutations in the polypeptide chain of TTR. In order to try to understand how other non-genetic factors can alter the progression of this disease, this study bet on the analysis of various progression states of PAF, for which was used plasma samples from heterozygous carries of V30M mutation with symptoms and individuals who have undergone a liver transplant. We evaluated the moleculs that interact with TTR and glycation levels. The work clearly showed that the half-life of TTR was around 3 days, and at the end of the sixth day the mutated variant has been completely replaced by the WT variant. The interacting molecules of TTR identified in this study in non-transplanted PAF patients were albumin, retinol-binding protein, urocortino-3 and IgG1, wherein the albumin and retinol-binding protein were already described in the literature. However, in transplanted patients were present only albumin, IgG1 and urocortino-3. The execution of this work reinforces the involvement of non-genetic factor in the pathogenesis modelo f FAP.
Santos, Luís Miguel Cardoso dos. "Search for early TTR-related biomarkers in a transgenic AD mouse model". Master's thesis, 2013. https://repositorio-aberto.up.pt/handle/10216/71161.
Texto completoAbdullahi, Hassan. "Studies of an unusual transthyretin protein (TTR GLU51_SER52DUP) associated with familial amyloidosis". Thesis, 2017. https://hdl.handle.net/2144/23758.
Texto completoSantos, Luís Miguel Cardoso dos. "Search for early TTR-related biomarkers in a transgenic AD mouse model". Dissertação, 2013. https://repositorio-aberto.up.pt/handle/10216/71161.
Texto completoHe, Chih-Wen y 何志文. "To examine the conjugal functions of ttrA homologs in S. coelicolor chromosome and linear plasmid SCP1". Thesis, 2011. http://ndltd.ncl.edu.tw/handle/j8pm69.
Texto completo國立臺北科技大學
生物科技研究所
99
Streptomyces processes linear chromosomes and linear plasmids, and most of the linear plasmids can be transferred by conjugation. The mechanism of conjugal transfer for E. coli circular plasmids is not applied to the conjugal system of Streptomyces. Previous research in Streptomyces conjugation had shown that the terminally located ttrA genes on the S. lividans chromosome and SLP2 were involved in conjugation probably acting in cis. Homologs of ttrA exist in the terminal regions of most Streptomyces chromosomes and some linear plasmids. However two ttrA homologs are located in the central region on the linear plasmid SCP1. This study was to understand whether ttrA gene on the S. coelicolor chromosomes and SCP1 were also involved in conjugal transfer. The ttrA gene (SCO0002) of S. coelicolor 3456 (containing integrated SCP1) was deleted and the mutant was mated with S. coelicolor M130 and S. lividans TK54. In mating with M130, the recombinant frequency was decreased by 60 to 176 folds. In mating with S. lividans TK54, the recombinant frequency was decreased by about 1,000 folds. The results indicated that ttrA on the S. coelicolor chromosome was more conjugatant influenced in inter-specifical transfer than intra-specifical transfer. In addition, two the ttrA homologs on SCP1 (SCP1.136 and SCP1.216Ac) were knockout individually. When these mutants were mated with S. coelicolor or S. lividans, the recombinant frequencies were decreased by about 10 folds. Double knockout mutant was also created, and the mutant was mated with S. coelicolor M145, the recombinant frequency was deceased by about 800 times. These results showed that the both ttrA homologs on SCP1 were involved in conjugal transfer.
Gaiteiro, Cristiana Milhazes. "Role of TTR in A β peptide brain efflux - Impact in Alzheimer's disease". Master's thesis, 2014. https://repositorio-aberto.up.pt/handle/10216/80517.
Texto completoGaiteiro, Cristiana Milhazes. "Role of TTR in A β peptide brain efflux - Impact in Alzheimer's disease". Dissertação, 2014. https://repositorio-aberto.up.pt/handle/10216/80517.
Texto completoGilberto, Samuel Filipe da Graça. "Efeito do fibrinogénio na formação de fibras de TTR em doentes com amiloidose familiar". Master's thesis, 2011. http://hdl.handle.net/10451/8778.
Texto completoA Polineuropatia Amiloidótica Familiar (PAF) é uma doença neurodegenerativa hereditária caracterizada pela deposição de transtirretina (TTR) no sistema nervoso periférico. Como consequência, verifica-se perda de sensibilidade nos membros dos pacientes, seguida de atrofia muscular, fraqueza e morte 10 a 20 anos após o início dos sintomas. O desenvolvimento desta doença requer a presença de TTR mutada, conhecendo-se mais de 80 mutações que levam à formação de fibras amilóides. Como mecanismo para a formação destes agregados, estudos in vitro apontam para uma destabilização dos tetrâmeros que contêm variantes da TTR, resultando na formação de monómeros amiloidogénicos. No entanto, existem diversas observações que sugerem um mecanismo mais complexo in vivo, envolvendo factores não genéticos. Por exemplo, indivíduos que possuem a mesma mutação no gene da TTR, incluindo gémeos monozigóticos, não mostram o início da sintomatologia com a mesma idade. Existem ainda diferenças geográficas no que toca à idade de desenvolvimento dos sintomas e na própria morfologia dos agregados. Ao contrário do expectável, indivíduos homozigóticos para genes de TTR mutada não apresentam uma forma mais agressiva da doença. Com um papel central nestas diferenças fenotípicas poderão constar mecanismos de defesa, como é o caso do conjunto de proteínas denominadas chaperones moleculares. Seguindo esta hipótese, observou-se recentemente uma interacção da TTR com o chaperone extracelular fibrinogénio. Curiosamente, o fibrinogénio encontra-se selectivamente modificado em pacientes PAF. Esta modificação pós-traducional, denominada glicação, foi descrita como estando envolvida noutras doenças de natureza semelhante à PAF, como é o caso da doença de Alzheimer ou de Parkinson. Neste trabalho, investigou-se o efeito do fibrinogénio e da glicação na amiloidogénese da TTR. Verificou-se que o fibrinogénio tem a capacidade de prevenir a sua agregação, atingindo-se a actividade máxima numa proporção molar fibrinogénio:TTR de 1:20, sugerindo uma relevância desta interacção in vivo, já que neste caso esta proporção é aproximadamente 1:2. Adicionalmente, observou-se que a glicação do fibrinogénio leva a uma abolição da referida função. Paralelamente, foi realizado um mapeamento dos locais modificados do fibrinogénio com vista a estabelecer a correlação entre os locais modificados e a perda de função deste. Desta forma, foi estabelecido um método optimizado para realizar este mapeamento por espectrometria de massa, tendo-se identificado um total de 60 locais modificados nas três cadeias do fibrinogénio, α, β e γ, com uma cobertura de sequência média de 82%.
Familial Amyloidotic Polyneuropathy (FAP) is an hereditary neurodegenerative disease characterized by the deposition of transthyretin (TTR) in the peripheral nervous system. As a consequence, sensibility loss in the patients’ arms and legs takes place, followed by muscle atrophy and death after 10 to 20 years of the disease onset. The development of this disease requires the presence of a mutated variant of TTR, being described more than 80 mutations that result in amyloid fiber formation. As a mechanism for TTR aggregation, in vitro studies suggest that in these patients TTR tetramer (its native form) is destabilized, resulting in the formation of amyloidogenic monomers. However, several observations suggest a more complex mechanism in vivo, with the implication of non-genetic factors. For instance, patients that share the same mutation in the TTR gene, including monozygous twins, do not show the same disease onset age. There are also geographical differences when it comes to the aggregates’ morphology and also the disease onset age. Opposite from the expected, homozygous individuals to mutated TTR genes do not show a more aggressive form of the disease. With a central role in these phenotypic differences may be defense mechanisms, such as molecular chaperones. Following this hypothesis, recently an interaction between TTR and the extracellular chaperone fibrinogen was described. Surprisingly, fibrinogen is selectively modified in FAP patients. This post-translational modification, termed glycation, was previously described as being involved in other conformational diseases, such as Alzheimer’s and Parkinson’s diseases. In this work, the effect of fibrinogen and glycation in TTR amyloidogenesis was studied by monitoring the aggregation process using spectroscopic methods. It was observed that fibrinogen has the ability to prevent its aggregation, achieving its maximum activity in a molar ratio of 1:20 (fibrinogen:TTR), suggesting a relevance of this interaction in vivo, as in this case the ratio fibrinogen:TTR is approximately 1:2. Moreover, it was observed that fibrinogen glycation abolishes its chaperone function. Additionally, the glycation sites in fibrinogen were mapped, in order to correlate those sites with the loss of fibrinogen’s chaperone function. Therefore, here is also established an optimized method to perform such mapping using mass spectrometry, having been identified a total of 60 modified sites in the three fibrinogen chains, α, β e γ, with an average sequence coverage of 82%.
Silva, Marina Isabel Oliveira da. "Dissecting the role of cytoskeleton remodelling in a Drosophila model of TTR-induced neurodegeneration". Master's thesis, 2015. https://repositorio-aberto.up.pt/handle/10216/82245.
Texto completoFerreira, Miguel Fernando Alves. "Phenotypic variability in familial amyloid polyneuropathy: TTR modifiers in Caenorhabditis elegans and human models". Doctoral thesis, 2019. https://hdl.handle.net/10216/121022.
Texto completoFerreira, Miguel Fernando Alves. "Phenotypic variability in familial amyloid polyneuropathy: TTR modifiers in Caenorhabditis elegans and human models". Tese, 2019. https://hdl.handle.net/10216/121022.
Texto completoSilva, Marina Isabel Oliveira da. "Dissecting the role of cytoskeleton remodelling in a Drosophila model of TTR-induced neurodegeneration". Dissertação, 2015. https://repositorio-aberto.up.pt/handle/10216/82245.
Texto completoYu, Chen Wan y 陳婉瑜. "Blockade of the TTX-resistant Na+ channel by multivalent cations in dorsal root ganglion neurons". Thesis, 2002. http://ndltd.ncl.edu.tw/handle/66738233537446350819.
Texto completo國立臺灣大學
生理學研究所
90
TTX(tetrodotoxin)is a common animal toxin to block the Na+ channel. According to the sensitivity to the TTX, Na+ channel can be divided into two groups, the TTX-sensitive Na+ channels and the TTX-resistant Na+ channels. TTX-resistant Na+ channels have been found in peripheral nervous systems, and may play an important in the transmission of slow pain. The TTX-resistant Na+ channels have lower affinity to TTX, much slower activation and inactivation rate, and more sensitive to inorganic Ca2+ channel blockers(Cd2+、Co2+、Mn2+、Zn2+、Ni2+、La3+) than TTX-sensitive ones. However, the mechanism underlying the block of the TTX-resistant Na+ channels by the inorganic cations remains unknown. We found that the blocking effect of these cations on the TTX-resistant Na+ channels in dorsal root ganglion neurons are both concentration dependent and flow dependent. The blocking effect is much more manifest in the presence of inward Na+ current than outward Na+ current, with the blocking potency La3+> Zn2+> Ni2+> Co2+>Mn2+. On the other hand, the voltage dependence is Mn2+>Co2+>Ni2+ >Zn2+>La3+. These findings suggest that these cations and Na+ ion can bind to a single-file multi-ion region in TTX-resistant Na+ channels, and these region may contain ion binding sites consisting of carboxyl groups, sulfhydryl groups, and/or oxygen-containing groups.