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1.
Artigo em Inglês | MEDLINE | ID: mdl-36901636

RESUMO

Over the last few decades, the number of lumbar interbody fusion surgeries performed has been constantly increasing, with transforaminal lumbar interbody fusion (TLIF) being one of the most common surgical techniques. Due to easy accessibility, patients frequently use YouTube to obtain information on health-related issues. Consequently, online video platforms may be a valuable tool for patient education. The aim of this study was to assess the quality, reliability, and comprehensiveness of online videos on TLIF. We screened 180 videos on YouTube, yielding a total of 30 videos that met the inclusion criteria. These videos were evaluated using Global Quality Scale, DISCERN reliability tool, and JAMA Benchmark Score, and assessed in regard to their comprehensiveness and coverage of relevant aspects. At the time of rating, the videos had between 9188 and 1,530,408 views and between 0 and 3344 likes. The median rater assessment for all videos was "moderate quality". GQS and subjective grades showed a moderate to strong statistically significant association with views and likes. Considering this association of GQS and subjective grade with views and likes, these criteria could be used by laypersons to identify good-quality content. Nevertheless, there is an urgent need for peer-reviewed content that covers all of the relevant aspects.


Assuntos
Mídias Sociais , Fusão Vertebral , Humanos , Vértebras Lombares , Reprodutibilidade dos Testes , Educação de Pacientes como Assunto , Escolaridade , Gravação em Vídeo , Disseminação de Informação
2.
Mol Pharmacol ; 85(3): 451-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24378333

RESUMO

Triapine (3-AP; 3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a ribonucleotide reductase inhibitor, has been extensively evaluated in clinical trials in the last decade. This study addresses the role of endoplasmic reticulum (ER) stress in the anticancer activity of 3-AP and the derivative N(4),N(4)-dimethyl-triapine (3-AP-Me), differing from 3-AP only by dimethylation of the terminal nitrogen. Treatment of colon cancer cells with 3-AP or 3-AP-Me activated all three ER stress pathways (PERK, IRE1a, ATF6) by phosphorylation of eIF2α and upregulation of gene expression of activating transcription factors ATF4 and ATF6. In particular, 3-AP-Me led to an upregulation of the alternatively spliced mRNA variant XBP1 (16-fold). Moreover, 3-AP and 3-AP-Me activated the cellular stress kinases c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases, and inhibition of JNK activity antagonized the cytotoxic effect of both compounds. Subsequent to induction of the unfolded protein response, a significant upregulation of proapoptotic proteins was detected, including the transcription factor CHOP and Bim, an essential factor for ER stress-related apoptosis. In correlation with the higher degree of ER stress after 3-AP-Me treatment, also a more potent depolarization of mitochondrial membranes was found. These data suggest that 3-AP and 3-AP-Me induce apoptosis via ER stress. This was further corroborated by showing that inhibition of protein biosynthesis with cycloheximide prior to 3-AP and 3-AP-Me treatment leads to a significant reduction of the antiproliferative properties of both compounds. Taken together, this study demonstrates that induction of ER stress contributes to the mode of action of 3-AP and that terminal dimethylation leads to an even more pronounced manifestation of this effect.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Piridinas/farmacologia , Tiossemicarbazonas/farmacologia , Fator 4 Ativador da Transcrição/genética , Fator 6 Ativador da Transcrição/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Proteínas de Ligação a DNA/genética , Retículo Endoplasmático/genética , Estresse do Retículo Endoplasmático/genética , Fator de Iniciação 2 em Eucariotos/genética , Células HCT116 , Células HL-60 , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Membranas Mitocondriais/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Fosforilação/genética , Fatores de Transcrição de Fator Regulador X , Fator de Transcrição CHOP , Fatores de Transcrição/genética , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Resposta a Proteínas não Dobradas/genética , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Proteína 1 de Ligação a X-Box , Proteínas Quinases p38 Ativadas por Mitógeno/genética
3.
Oncol Rep ; 31(3): 1147-56, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24378831

RESUMO

Osteosarcoma is a rare but aggressive bone neoplasm in humans, which is commonly treated with surgery, classical chemotherapy and radiation. Sorafenib, an inhibitor of a number of kinases targeting the Raf/MEK/ERK pathway, is a promising new chemotherapeutic agent in human medicine that has been approved since 2006 for the therapy of renal cell carcinoma and since 2007 for the treatment of hepatocellular carcinoma. Here, we studied the antimetastatic potential of 4 µM of this multikinase inhibitor in a human osteosarcoma cell line. DNA microarray-based gene expression profiling detected 297 and 232 genes upregulated or downregulated at a threshold of >2-fold expression alteration (P<0.05) in the sorafenib-treated cells. Three genes (CXCR4, FOS and S100A4) that are involved in tumor progression were chosen for validation by quantitative PCR (qPCR) and protein expression analysis. The decrease in RNA expression detected by microarray profiling was confirmed by qPCR for all three genes (P<0.01). On the protein level, sorafenib-induced reduction of S100A4 was verified both by western blotting and immunohistochemistry. For CXCR4 and c-Fos, a reduced protein expression was shown by immunohistochemistry, for c-Fos also by immunoblotting. We conclude that sorafenib could serve as a potent chemotherapeutical agent by which to inhibit the metastatic progression of osteosarcomas.


Assuntos
Antineoplásicos/farmacologia , Niacinamida/análogos & derivados , Proteínas Oncogênicas v-fos/metabolismo , Compostos de Fenilureia/farmacologia , Receptores CXCR4/metabolismo , Proteínas S100/metabolismo , Neoplasias Ósseas , Linhagem Celular Tumoral , Regulação para Baixo , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Niacinamida/farmacologia , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Oncogênicas v-fos/genética , Osteossarcoma , Receptores CXCR4/genética , Proteína A4 de Ligação a Cálcio da Família S100 , Proteínas S100/genética , Sorafenibe , Transcriptoma/efeitos dos fármacos
4.
Planta Med ; 79(16): 1489-94, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24146062

RESUMO

After oral administration of 100 mg/kg b. w. (235.8 µmol/kg) salicortin to Wistar rats, peak serum concentrations of 1.43 mg/L (13.0 µM) catechol were detected after 0.5 h in addition to salicylic acid by HPLC-DAD after serum processing with ß-glucuronidase and sulphatase. Both metabolites could also be detected in the serum of healthy volunteers following oral administration of a willow bark extract (Salicis cortex, Salix spec., Salicaceae) corresponding to 240 mg of salicin after processing with both enzymes. In humans, the cmax (1.46 mg/L, 13.3 µM) of catechol was reached after 1.2 h. The predominant phase-II metabolite in humans and rats was catechol sulphate, determined by HPLC analysis of serum samples processed with only one kind of enzyme. Without serum processing with glucuronidase and sulphatase, no unconjugated catechol could be detected in human and animal serum samples. As catechol is described as an anti-inflammatory compound, these results may contribute to the elucidation of the mechanism of the action of willow bark extract.


Assuntos
Catecóis/sangue , Glucosídeos/farmacocinética , Salix/química , Administração Oral , Animais , Catecóis/química , Cromatografia Líquida de Alta Pressão , Glucosídeos/administração & dosagem , Glucosídeos/química , Humanos , Ratos , Ratos Wistar
5.
BMC Vet Res ; 9: 108, 2013 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-23710975

RESUMO

BACKGROUND: Contagious Bovine Pleuropneumonia (CBPP) is the most important chronic pulmonary disease of cattle on the African continent causing severe economic losses. The disease, caused by infection with Mycoplasma mycoides subsp. mycoides is transmitted by animal contact and develops slowly into a chronic form preventing an early clinical diagnosis. Because available vaccines confer a low protection rate and short-lived immunity, the rapid diagnosis of infected animals combined with traditional curbing measures is seen as the best way to control the disease. While traditional labour-intensive bacteriological methods for the detection of M. mycoides subsp. mycoides have been replaced by molecular genetic techniques in the last two decades, these latter approaches require well-equipped laboratories and specialized personnel for the diagnosis. This is a handicap in areas where CBPP is endemic and early diagnosis is essential. RESULTS: We present a rapid, sensitive and specific diagnostic tool for M. mycoides subsp. mycoides detection based on isothermal loop-mediated amplification (LAMP) that is applicable to field conditions. The primer set developed is highly specific and sensitive enough to diagnose clinical cases without prior cultivation of the organism. The LAMP assay detects M. mycoides subsp. mycoides DNA directly from crude samples of pulmonary/pleural fluids and serum/plasma within an hour using a simple dilution protocol. A photometric detection of LAMP products allows the real-time visualisation of the amplification curve and the application of a melting curve/re-association analysis presents a means of quality assurance based on the predetermined strand-inherent temperature profile supporting the diagnosis. CONCLUSION: The CBPP LAMP developed in a robust kit format can be run on a battery-driven mobile device to rapidly detect M. mycoides subsp. mycoides infections from clinical or post mortem samples. The stringent innate quality control allows a conclusive on-site diagnosis of CBPP such as during farm or slaughter house inspections.


Assuntos
Doenças dos Bovinos/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/veterinária , Pleuropneumonia Contagiosa/diagnóstico , Animais , Sequência de Bases , Líquido da Lavagem Broncoalveolar/microbiologia , Bovinos , Doenças dos Bovinos/microbiologia , DNA Bacteriano/genética , Dados de Sequência Molecular , Mycoplasma mycoides/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Pleuropneumonia Contagiosa/microbiologia , Kit de Reagentes para Diagnóstico/veterinária , Sensibilidade e Especificidade
6.
PLoS One ; 8(5): e63125, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23671661

RESUMO

Reference genes (RGs) with uniform expression are used for normalization of reverse transcription quantitative PCR (RT-qPCR) data. Their optimization for a specific biological context, e.g. a specific tissue, has been increasingly considered. In this article, we compare RGs identified by expression data meta-analysis restricted to the context tissue, the jejunum of Mus musculus domesticus, i) to traditional RGs, ii) to expressed interspersed repeated DNA elements, and iii) to RGs identified by meta-analysis of expression data from diverse tissues and conditions. To select the set of candidate RGs, we developed a novel protocol for the cross-platform meta-analysis of microarray data. The expression stability of twenty-four putative RGs was analysed by RT-qPCR in at least 14 jejunum samples of the mouse strains C57Bl/6N, CD1, and OF1. Across strains, the levels of expression of the novel RGs Plekha7, Zfx, and Ube2v1 as well as of Oaz1 varied less than two-fold irrespective of genotype, sex or their combination. The gene set consisting of Plekha7 and Oaz1 showed superior expression stability analysed with the tool RefFinder. The novel RGs are functionally diverse. This facilitates expression studies over a wide range of conditions. The highly uniform expression of the optimized RGs in the jejunum points towards their involvement in tightly regulated pathways in this tissue. We also applied our novel protocol of cross-microarray platform meta-analysis to the identification of RGs in the duodenum, the ileum and the entire small intestine. The selection of RGs with improved expression stability in a specific biological context can reduce the number of RGs for the normalization step of RT-qPCR expression analysis, thus reducing the number of samples and experimental costs.


Assuntos
Perfilação da Expressão Gênica/métodos , Jejuno/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Algoritmos , Animais , Feminino , Perfilação da Expressão Gênica/normas , Perfilação da Expressão Gênica/estatística & dados numéricos , Redes Reguladoras de Genes , Fatores de Transcrição Kruppel-Like/genética , Masculino , Metanálise como Assunto , Camundongos , Camundongos Endogâmicos C57BL , Modelos Genéticos , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos/normas , Análise de Sequência com Séries de Oligonucleotídeos/estatística & dados numéricos , Proteínas/genética , Padrões de Referência , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Reação em Cadeia da Polimerase Via Transcriptase Reversa/estatística & dados numéricos , Análise de Sequência de DNA , Enzimas de Conjugação de Ubiquitina/genética
7.
Cell Rep ; 1(5): 506-15, 2012 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-22701816

RESUMO

The timing and mechanisms of mitochondrial DNA (mtDNA) segregation and transmission in mammals are poorly understood. Genetic bottleneck in female germ cells has been proposed as the main phenomenon responsible for rapid intergenerational segregation of heteroplasmic mtDNA. We demonstrate here that mtDNA segregation occurs during primate preimplantation embryogenesis resulting in partitioning of mtDNA variants between daughter blastomeres. A substantial shift toward homoplasmy occurred in fetuses and embryonic stem cells (ESCs) derived from these heteroplasmic embryos. We also observed a wide range of heteroplasmic mtDNA variants distributed in individual oocytes recovered from these fetuses. Thus, we present here evidence for a previously unknown mtDNA segregation and bottleneck during preimplantation embryo development, suggesting that return to the homoplasmic condition can occur during development of an individual organism from the zygote to birth, without a passage through the germline.


Assuntos
Blastocisto/citologia , Divisão Celular/genética , DNA Mitocondrial/genética , Desenvolvimento Embrionário/genética , Haplótipos/genética , Macaca mulatta/embriologia , Oócitos/citologia , Animais , Blastocisto/metabolismo , Blastômeros/citologia , Blastômeros/metabolismo , DNA Mitocondrial/metabolismo , Embrião de Mamíferos/citologia , Embrião de Mamíferos/embriologia , Embrião de Mamíferos/metabolismo , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Feminino , Feto/citologia , Feto/embriologia , Feto/metabolismo , Dosagem de Genes/genética , Macaca mulatta/genética , Macaca mulatta/metabolismo , Oócitos/metabolismo , Gravidez
8.
Arzneimittelforschung ; 53(2): 87-92, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12642963

RESUMO

Opipramol (4-[3-(5H-dibenz[b,f]-azepine-5-yl)-propyl]-1-piperazine-ethanol dihydrochloride, CAS 315-72-0) is regarded as an anxiolytic compound with antidepressant properties, and it is one of the most frequently prescribed psychotropic drugs in Germany. In two open, randomized cross-over studies in 20 (study 1) and 18 (study II) healthy volunteers, the relative bioavailability of 50 mg opipramol-2HCl from a sugar-coated tablet was compared with an aqueous solution, and of 100 mg opipramol-2HCl from a newly developed film-coated tablet was compared with the sugar-coated tablet. The concentrations of opipramol were determined in plasma by high-performance liquid chromatography (HPLC) with photometric detection. The mean dose corrected kinetic parameters of opipramol were similar after administration of all formulations. The peak concentrations of opipramol were 13-15 ng ml-1 (study I) and 28 ng ml-1 (study II). They were achieved after 3 h. The area under the plasma concentration-time curve was about 170 ng ml-1 h (study I) and about 320 ng ml-1 h (study II). The terminal plasma half-life was 11 h. Bioequivalence was proven between sugar-coated tablet and aqueous solution, and between film-coated tablet and sugar-coated tablet, respectively. In addition, in study II the plasma concentrations and pharmacokinetic parameters of the metabolites opipramol N-oxide and deshydroxyethyl opipramol were determined.


Assuntos
Antidepressivos Tricíclicos/farmacocinética , Opipramol/farmacocinética , Adulto , Antidepressivos Tricíclicos/administração & dosagem , Antidepressivos Tricíclicos/efeitos adversos , Área Sob a Curva , Disponibilidade Biológica , Biotransformação , Estudos Cross-Over , Feminino , Humanos , Masculino , Opipramol/administração & dosagem , Opipramol/efeitos adversos , Soluções Farmacêuticas , Comprimidos com Revestimento Entérico
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