RESUMO
OBJECTIVES: The objective of this study was to develop and validate 6 checklists for evaluating abdominal pain in clinical simulation scenarios; to assess student competencies in managing 6 clinical cases using OSCE, based on faculty evaluations; and to analyze discrepancies between faculty and student evaluations. DESIGN: A practical workshop was designed to address 6 clinical scenarios of abdominal surgical conditions. Four scenarios employed medium fidelity simulators, while 2 scenarios employed standardized patient methodology. Prior to the workshop, students received theoretical audiovisual material. At the conclusion of the workshop, students were evaluated using checklists that assessed communication, privacy, anamnesis, and technical skills. Ten workshops were conducted over 3 years, using the OSCE (Objective Structured Clinical Examination) format for evaluation. SETTING: In the statistical analysis, t-Student tests or ANOVA were employed to ascertain whether there were any significant differences between the groups. In the process of validating checklists for clinical scenarios, 6 experts were asked to evaluate each item on a scale of 1 to 9. To assess the degree of agreement among experts, the intraclass correlation coefficient (ICC) was employed. PARTICIPANTS: The study involved a total of 670 third-year medical students from the University of Murcia (UMU), Spain, who participated in the subject "Medical-Surgical Skills." RESULTS: High levels of appropriateness were observed for the checklist items, with mean scores above 7.5 points, as well as high levels of inter-expert agreement. Students obtained a mean score of 8 points in the evaluation of each clinical scenario. No significant differences were found between faculty and student scores (p < 0.05). CONCLUSIONS: The learning method focused on clinical scenarios of abdominal surgical diseases effectively enhanced the clinical skills of third-year medical students. It used pre-existing audiovisual materials, hands-on workshops with medium-fidelity simulators, and standardized patients. Consistent evaluations from students and faculty confirmed the efficacy of these strategies.
Assuntos
Dor Abdominal , Lista de Checagem , Estágio Clínico , Competência Clínica , Humanos , Dor Abdominal/diagnóstico , Cirurgia Geral/educação , Educação de Graduação em Medicina/métodos , Treinamento por Simulação/métodos , Feminino , Avaliação Educacional/métodos , Masculino , Estudantes de Medicina/estatística & dados numéricos , Simulação de PacienteRESUMO
Safinamide is a new add-on drug to levodopa for the treatment of Parkinson's disease (PD) with motor fluctuations. Due to the recent incorporation of safinamide into routine clinical practice, no post-authorisation phase IV studies on the safety of safinamide have been conducted to date. This study provides clinical management guidelines for safinamide based on the opinion of a group of experts in movement disorders. This project was developed in 2 phases: 16 local meetings in phase 1 and a national meeting in phase 2. The meetings followed a pre-established agenda. The present clinical practice guidelines are based on the main conclusions reached during the national meeting. The group concluded that safinamide is effective in reducing motor and non-motor fluctuations. PD patients with mild-to-moderate fluctuations benefit most from treatment, although the drug may also improve the clinical status of patients with advanced PD. The dose of other dopaminergic drugs may be reduced after introducing safinamide, which would contribute to reducing such adverse reactions as impulse control disorder. At doses higher than those usually prescribed, safinamide may also improve dyskinesia. The experts agreed that safinamide is well tolerated and causes few adverse reactions when compared with placebo.
Assuntos
Antiparkinsonianos/uso terapêutico , Benzilaminas/uso terapêutico , Doença de Parkinson , Alanina/análogos & derivados , Antiparkinsonianos/efeitos adversos , Benzilaminas/efeitos adversos , Consenso , Humanos , Doença de Parkinson/tratamento farmacológico , EspanhaRESUMO
Andean uplift played a fundamental role in shaping South American climate and species distribution, but the relationship between the rise of the Andes, plant composition, and local climatic evolution is poorly known. We investigated the fossil record (pollen, leaves, and wood) from the Neogene of the Central Andean Plateau and documented the earliest evidence of a puna-like ecosystem in the Pliocene and a montane ecosystem without modern analogs in the Miocene. In contrast to regional climate model simulations, our climate inferences based on fossil data suggest wetter than modern precipitation conditions during the Pliocene, when the area was near modern elevations, and even wetter conditions during the Miocene, when the cordillera was around ~1700 meters above sea level. Our empirical data highlight the importance of the plant fossil record in studying past, present, and future climates and underscore the dynamic nature of high elevation ecosystems.
RESUMO
Safinamide is a new add-on drug to levodopa for the treatment of Parkinson's disease (PD) with motor fluctuations. Due to the recent incorporation of safinamide into routine clinical practice, no post-authorisation phase IV studies on the safety of safinamide have been conducted to date. This study provides clinical management guidelines for safinamide based on the opinion of a group of experts in movement disorders. This project was developed in 2 phases: 16 local meetings in phase 1 and a national meeting in phase 2. The meetings followed a pre-established agenda. The present clinical practice guidelines are based on the main conclusions reached during the national meeting. The group concluded that safinamide is effective in reducing motor and non-motor fluctuations. PD patients with mild-to-moderate fluctuations benefit most from treatment, although the drug may also improve the clinical status of patients with advanced PD. The dose of other dopaminergic drugs may be reduced after introducing safinamide, which would contribute to reducing such adverse reactions as impulse control disorder. At doses higher than those usually prescribed, safinamide may also improve dyskinesia. The experts agreed that safinamide is well tolerated and causes few adverse reactions when compared with placebo.
RESUMO
OBJECTIVE: To generate normative data on the Stroop Test across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the Stroop Test, as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained 14-36% of the variance in Stroop Word scores, 12-41% of the variance in the Stoop Color, 14-36% of the variance in the Stroop Word-Color scores, and 4-15% of variance in Stroop Interference scores. Although t-tests showed significant differences between men and women on the Stroop test, none of the countries had an effect size larger than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America to create norms for the Stoop Test in a Spanish-Speaking sample. This study will therefore have important implications for the future of neuropsychology research and practice throughout the region.
Assuntos
Cor , Teste de Stroop/normas , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Testes de Percepção de Cores , Escolaridade , Feminino , Humanos , Idioma , América Latina , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores Sexuais , Fatores Socioeconômicos , Adulto JovemRESUMO
OBJECTIVE: To generate normative data on the Boston Naming Test (BNT) across 10 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,779 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the BNT as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained between 3-32% of the variance in BNT scores. Although t-tests showed significant differences between men and women for Mexico, Argentina, Chile, Cuba, Guatemala, and Bolivia on the BNT, none of the six countries had an effect size larger than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America to generate norms for the BNT; this study will have substantial repercussions for the practice of neuropsychology throughout the global region.
Assuntos
Testes Neuropsicológicos/normas , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Interpretação Estatística de Dados , Feminino , Humanos , Idioma , América Latina , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores Sexuais , Fatores Socioeconômicos , Adulto JovemRESUMO
OBJECTIVE: To generate normative data on the Symbol Digit Modalities Test (SDMT) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the SDMT as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained 29-56% of the variance in SDMT scores. Although there were gender differences on the SDMT in Mexico, Honduras, Paraguay, and Guatemala, none of the four countries had an effect size greater than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America to create norms for the SDMT; this study will have an impact on the future practice of neuropsychology throughout the global region.
Assuntos
Testes Neuropsicológicos/normas , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Escolaridade , Feminino , Humanos , Idioma , América Latina , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores Sexuais , Fatores Socioeconômicos , Adulto JovemRESUMO
OBJECTIVE: To generate normative data on the Brief Test of Attention (BTA) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Mexico, Argentina, Peru, Paraguay, Honduras, Chile, Cuba, Puerto Rico, Guatemala, El Salvador, and Bolivia. Each subject was administered the BTA as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained between 11-41% of the variance in BTA scores. Although men had higher scores on the BTA in Honduras, there were no other significant gender differences, and this one effect size was small. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America to create norms for the BTA; this study will have an impact on the future practice of neuropsychology throughout Latin America.
Assuntos
Atenção , Testes Neuropsicológicos/normas , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Escolaridade , Feminino , Humanos , Idioma , América Latina , Masculino , Pessoa de Meia-Idade , Valores de Referência , Análise de Regressão , Fatores Sexuais , Fatores Socioeconômicos , Adulto JovemRESUMO
OBJECTIVE: To generate normative data on the Rey-Osterrieth Complex Figure Test (ROCF) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the ROCF as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained 7-34% of the variance in ROCF copy scores and 21-41% of the variance in immediate recall scores. Although t-tests showed significant differences between men and women on ROCF copy and immediate recall scores, none of the countries had an effect size larger than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: The present study is the first to create norms for the ROCF in Latin America. As a result, this study will have important implications for the formation and practice of neuropsychology in this region.
Assuntos
Rememoração Mental , Testes Neuropsicológicos/normas , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Escolaridade , Feminino , Humanos , Idioma , América Latina , Modelos Lineares , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Fatores Sexuais , Fatores Socioeconômicos , Adulto JovemRESUMO
OBJECTIVE: To generate normative data for the Verbal Fluency Tests across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the Verbal Fluency Test as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models for the letter F explained 8-30% of the variance, 7-32% for letter A, 8-32% for the letter S, and 16-43% for the animal category in Verbal Fluency Test scores. Although t-tests showed significant differences between men and women on the Verbal Fluency Test, they did not have an effect size larger than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America aiming to create norms for the Verbal Fluency Test; this study will have important outcomes for the future of neuropsychology in the region.
Assuntos
Fala , Comportamento Verbal , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Escolaridade , Feminino , Identidade de Gênero , Humanos , Idioma , América Latina , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores Sexuais , Fatores Socioeconômicos , Adulto JovemRESUMO
OBJECTIVE: To generate normative data on the Trail Making Test (TMT) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Mexico, Argentina, Peru, Paraguay, Honduras, Chile, Cuba, Puerto Rico, Guatemala, El Salvador, and Bolivia. Each subject was administered the TMT as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models for the TMT-A explained 23- 50% of the variance, and the final multiple linear models for the TMT-B explained 22- 49% of the variance. Although there were gender differences on the TMT in Mexico, Peru, Paraguay, and Honduras, only Honduras had an effect size greater than 0.3. As a result, gender-adjusted norms were generated for the Trail Making Test-A, but not B, in this country. CONCLUSIONS: The present study is the first to create norms for the TMT in Latin America. As a result, this study will have important implications for the practice of neuropsychology in the future.
Assuntos
Teste de Sequência Alfanumérica/normas , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Escolaridade , Feminino , Humanos , Idioma , América Latina , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores Sexuais , Fatores Socioeconômicos , Adulto JovemRESUMO
OBJECTIVE: To generate normative data on the Modified Card Sorting Test (M-WCST) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico. Each subject was administered the M-WCST as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained between 2-33% of the variance in M-WCST scores. Although t-tests showed significant differences between men and women from seven different countries on the M-WCST, the effect sizes were small. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in in Latin America aiming to create norms for the M-WCST; this study will have important implications for the future of neuropsychology in the region.
Assuntos
Testes Neuropsicológicos/normas , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Escolaridade , Função Executiva , Feminino , Humanos , Idioma , América Latina , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores Sexuais , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVE: To generate normative data on the Hopkins Verbal Learning Test- Revised (HVLT-R) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the HVLT-R as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained 17- 45% of the variance in HVLT-R scores. Although t-tests showed significant differences between men and women in Guatemala on the HVLT-R, it was a small effect size. As a result, gender-adjusted norms were not generated. CONCLUSIONS: The results from this study will have a substantial impact on the practice of neuropsychology in Latin America, as this is the first normative multicenter study to develop norms for the HVLT-R in this region.
Assuntos
Testes Neuropsicológicos/normas , Aprendizagem Verbal , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Escolaridade , Feminino , Humanos , Idioma , América Latina , Masculino , Pessoa de Meia-Idade , Desempenho Psicomotor , Valores de Referência , Fatores Sexuais , Fatores Socioeconômicos , Adulto JovemRESUMO
BACKGROUND: The Test of Memory Malingering (TOMM) is an instrument used to assess purposeful embellishment or fabrication of memory difficulties for personal gain. Although the TOMM can be use in non-English speaking cultures, it has not been validated in Spanish-speaking Central and South American contexts. OBJECTIVE: To generate normative data on TOMM across 7 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 2,266 healthy adults who were recruited from Argentina, Bolivia, Chile, Mexico, Paraguay, Peru, and Puerto Rico. Each subject was administered the TOMM as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: t-tests did not show significant differences in TOMM performance between men and women in any countries of the TOMM Trial 1 or 2. As a result, gender-adjusted norms were not generated. CONCLUSIONS: The results from this study will have a large impact on the practice of neuropsychology in Latin America, as this is the first normative multicenter study to create norms for the TOMM in this global region.
Assuntos
Simulação de Doença/diagnóstico , Simulação de Doença/psicologia , Transtornos da Memória/diagnóstico , Transtornos da Memória/psicologia , Testes Neuropsicológicos/normas , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Escolaridade , Feminino , Humanos , Idioma , América Latina , Masculino , Pessoa de Meia-Idade , Valores de Referência , Análise de Regressão , Fatores Sexuais , Fatores Socioeconômicos , Adulto JovemRESUMO
In a previous work we demonstrated that toxic aggregates of the protein ß-amyloid (ATAß) involved in the Alzheimer's disease (AD) can be destabilized upon electromagnetic irradiation of the peptide Cys-Leu-Pro-Phe-Phe-Asp (CLPFFD) adsorbed on gold nanospheres (AuNSs). For a selective recognition of the therapeutic target (i.e. ATAß) of AD by the conjugates peptide-nanoparticle it is relevant to understand how the interaction between attached ligands and nanoparticles occurs. In this work a surface enhanced Raman scattering spectroscopy (SERS) study of the interactions of CLPFFD with AuNSs of 10nm average diameter was carried out. The SERS data suggest that phenylalanine displays its aromatic ring coplanar to the surface which is supported by theoretical data obtained from molecular mechanics (MM) and Extended Hückel Theory (EHT) calculations.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Ouro/química , Nanosferas/química , Peptídeos/química , Ácido Aspártico/química , Cisteína/química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas Metálicas/química , Modelos Moleculares , Peptídeos/farmacologia , Fenilalanina/química , Conformação Proteica , Espectrofotometria Ultravioleta , Análise Espectral Raman/métodosRESUMO
INTRODUCTION: Extracorporeal Shock Wave Lithotripsy (ESWL) is currently the recommended treatment for intra-renal calculi smaller than 2 cm. However the low Stone Free Rate (SFR) in lower pole calculi gives rise to new techniques, such us retrograde intrarenal surgery (RIRS), for improve the surgery outcomes. OBJECTIVE: To compare the efficacy of a treatment with ESWL with RIRS, in terms of SFR after surgery, in patients with kidney stones up to 15 mm in the lower pole. MATERIAL AND METHODS: A prospective study was carried out in order to assess the results of ESWL and RIRS in patients with lower pole stones less than 15 mm. Among a total of 55 patients, 31 were underwent to ESWL (Group 1) and the remaining 24 to RIRS (Group 2). Clinical data recorded, including general characteristics of each patient, were: calculi size, side, operative time, complications according to Clavien scale, SFR and the presence of residual fragments at 2 months post-treatment assessed by a CT scan. STATA 11 was used to perform the statistical analysis. RESULTS: There were no differences for general descriptors among groups with the exception of a significantly longer operative time for RIRS. The rates of SFR and residual fragments lesser than 3 mm. were lower in the RIRS group than in ESWL ones. RIRS also showed a lower rate of clinically significant fragments (0% vs 42.3%. P < .05). In the subgroup of patients with stones between 10/15 mm RIRS showed higher SFR (75% vs. 41.2%) and a lower rate of stones>3 mm (0% vs. 58.8%), being statistically significant (P < .05). Clavien III or higher complications were not reported in any of the groups. CONCLUSIONS: In the treatment of lower pole stone RIRS has the same results than ESWL in terms of SFR. Regarding absence of a clinically significant residual fragment, RIRS was superior to ESWL. A bigger sample size is required in order to confirm this results.
Assuntos
Litotripsia , Ureteroscopia/métodos , Adulto , Feminino , Humanos , Cálculos Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Resultado do TratamentoRESUMO
Prismatic silver nanoparticles (PNps) were used in the surface enhanced Raman scattering (SERS) study of the antioxidant alkaloid boldine (5,6,6a,7-tetrahydro-1,10-dimethoxy-6-methyl-4H-dibenzo[de,g]quinoline-2,9-diol). Prismatic and quasi-spherical (QsNps) silver nanoparticles were synthesized and characterized by UV-Vis spectra, topographic profile (AFM) and zeta potential measurements. Raman and infrared (IR) spectra of the boldine were registered. Theoretical model calculations of the boldine onto the Ag surface predict a nearly coplanar orientation of the benzo[de]quinoline moiety and non-bonded interactions (electrostatic).
Assuntos
Antioxidantes/química , Aporfinas/química , Nanopartículas Metálicas/química , Prata/química , Análise Espectral Raman/métodos , Modelos MolecularesRESUMO
Raman and surface-enhanced Raman scattering (SERS) spectra of the synthetic carboxy terminal peptide of human chorionic gonadatropin ß-subunit free of carbohydrate moieties(P37) are reported. The spectral analysis is performed on the basis of our reported Raman spectrum and SERS data of oligopeptides displaying selected amino acids sequences MRKDV, ADEDRDA, and LGRGISL. SERS samples of P37 were prepared by coating the solid peptide with metal colloids on a quartz slide. This treatment makes possible to obtain high spectral batch to batch reproducibility. Amino acids components of P37 display net charges and hydrophobic characteristics, which are related to particular structural aspects of the adsorbate-substrate interaction. The spectroscopic results are supported by quantum chemical calculations performed by using extended Hückel theory method for a model of P37 interacting with an Ag surface. The P37-metal interaction is drove by positively charged fragments of selected amino acids,mainly threonine 109, lysine 122, and arginine in positions 114 and 133. Data here reported intend to contribute to the knowledge about the antigen-antibody interaction and to the drugs delivery research area
Assuntos
Gonadotropina Coriônica Humana Subunidade beta/química , Sequência de Aminoácidos , Gonadotropina Coriônica Humana Subunidade beta/genética , Humanos , Interações Hidrofóbicas e Hidrofílicas , Técnicas In Vitro , Nanopartículas Metálicas , Modelos Moleculares , Oligopeptídeos/química , Oligopeptídeos/genética , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Análise Espectral Raman/métodos , Eletricidade EstáticaRESUMO
TLN-4601 is a farnesylated dibenzodiazepinone isolated from Micromonospora sp. with an antiproliferative effect on several human cancer cell lines. Although the mechanism of action of TLN-4601 is unknown, our earlier work indicated that TLN-4601 binds the PBR (peripheral benzodiazepine receptor; more recently known as the translocator protein or TSPO), an 18 kDa protein associated with the mitochondrial permeability transition (mPT) pore. While the exact function of the PBR remains a matter of debate, it has been implicated in heme and steroid synthesis, cellular growth and differentiation, oxygen consumption and apoptosis. Using the Jurkat immortalized T-lymphocyte cell line, documented to have negligible PBR expression, and Jurkat cells stably transfected with a human PBR cDNA, the present study demonstrates that TLN-4601 induces apoptosis independently of PBR expression. As PBRs are overexpressed in brain tumors compared to normal brain, we examined if TLN-4601 would preferentially accumulate in tumors using an intra-cerebral tumor model. Our results demonstrate the ability of TLN-4601 to effectively bind the PBR in vivo as determined by competitive binding assay and receptor occupancy. Analysis of TLN-4601 tissue and plasma indicated that TLN-4601 preferentially accumulates in the tumor. Indeed, drug levels were 200-fold higher in the tumor compared to the normal brain. TLN-4601 accumulation in the tumor (176 µg/g) was also significant compared to liver (24.8 µg/g; 7-fold) and plasma (16.2 µg/mL; 11-fold). Taken together our data indicate that while PBR binding does not mediate cell growth inhibition and apoptosis, PBR binding may allow for the specific accumulation of TLN-4601 in PBR positive tumors.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Dibenzazepinas/farmacologia , Receptores de GABA/metabolismo , Animais , Antineoplásicos/sangue , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Ligação Competitiva , Western Blotting , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Sobrevivência Celular/efeitos dos fármacos , Dibenzazepinas/sangue , Dibenzazepinas/farmacocinética , Dibenzazepinas/uso terapêutico , Relação Dose-Resposta a Droga , Glioma/tratamento farmacológico , Glioma/metabolismo , Glioma/patologia , Humanos , Células Jurkat , Ligantes , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estrutura Molecular , Transplante de Neoplasias , Tomografia por Emissão de Pósitrons , Ligação Proteica , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Receptores de GABA/genética , TransfecçãoRESUMO
Arginine amino acid (Arg) has been vibrationally studied through its infrared, Raman and surface-enhanced Raman scattering (SERS) spectra, and theoretical calculations. Net charge is used to predict the possibility to obtain the SERS spectrum of Arg in colloidal solution. The interpretation of the SERS spectral data suggests that the Arg-Ag nanoparticles interaction in a colloidal solution and in the case of the Arg coated by Ag is mainly verified through the guanidinium moiety. Theoretical calculations performed by using extended Hückel theory method for a model of Arg interacting with an Ag cluster support the observed SERS experimental result.