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1.
J Couns Psychol ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38358675

RESUMO

On September 20, 2017, Hurricane Maria made landfall in Puerto Rico, devastating the archipelago and forcing thousands of Puerto Ricans to migrate to the U.S. mainland. Guided by a cultural stress theory framework, the present mixed method study examined how various cultural stressors impact participants' daily interactions and mental health outcomes. A total of 319 adult Hurricane Maria survivors residing on the U.S. mainland participated in the study. A mixed method sequential explanatory design was used. First, we used latent profile analysis (LPA) and multinomial logistic regression to identify the varied cultural stress experiences that participants had. Then we used data from semistructured interviews to better understand the experiences of participants classified into the different LPA profiles. Four profiles were identified: "moderate cultural stress" (35%), "overall low" (29%), "high cultural stress" (26%), and "low language stress" (10%). Multinomial regression indicated that members of the moderate cultural stress, high cultural stress, and low language stress profiles all reported significantly higher depressive and anxiety symptoms compared to members of the overall low profile. Qualitative data exemplified the daily experiences of participants placed into each profile, demonstrating that participants have rich and varied experiences that can contribute to their mental health symptoms. The present study documents the contributions of hurricane trauma and cultural stress vis-à-vis current mental health symptoms. Clinicians working with Hurricane Maria survivors should be cognizant of and inquire about migration-related cultural stressors including discrimination, feelings of being unwelcomed, and difficulty communicating in the destination community's dominant language. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

2.
Artigo em Inglês | MEDLINE | ID: mdl-38780597

RESUMO

OBJECTIVES: A growing body of research points to a relationship between exposure to migration-related cultural stress and mental health problems. However, such research is often conducted with the tacit assumption that postmigration experiences are the primary-if not singular-driver of psychological distress. In the present study, we aim to extend the cultural-stress paradigm by examining the influences of both premigration crisis exposure and postmigration cultural stress on depression in a sample of Venezuelan crisis migrants in Colombia. METHOD: Survey data for the present study were collected from Venezuelan youth (N = 429, ages 12-17, Mage = 14.0 years, 49% female) and adults (N = 566, ages 18+, Mage = 35.1 years, 82% female) in Bogota and Medellin, Colombia between April and June 2023. RESULTS: Both crisis exposure and discrimination were independently related to depressive symptoms. However, when examined in a multivariate model along with discrimination, crisis exposure was not a significant predictor of depressive symptoms among youth, and its influence weakened considerably among adults. Among both youth and adults, a Crisis Exposure × Discrimination interaction term significantly predicted depressive symptoms, indicating that discrimination was a more robust predictor of depressive symptoms among those endorsing lower levels of crisis exposure than among those reporting high levels of crisis exposure. CONCLUSION: Our research provides new insights into the experiences of Venezuelan migrant youth and adults in Colombia. It provides further support for the importance of drawing from a crisis-informed cultural-stress framework when working with crisis migrant populations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

3.
Fam Process ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632594

RESUMO

Hurricane María caused significant devastation on the island of Puerto Rico, impacting thousands of lives. Puerto Rican crisis migrant families faced stress related to displacement and relocation (cultural stress), often exhibited mental health symptoms, and experienced distress at the family level. Although cultural stress has been examined as an individual experience, little work has focused on the experience as a family. To address this gap, we conducted a mixed-methods study designed to examine the predictive effects of cultural stress on family conflict and its mental health implications among Puerto Rican Hurricane María parent and child dyads living on the U.S. mainland. In the quantitative phase of the study, 110 parent-child dyads completed an online survey assessing cultural stress, family dynamics, and mental health. As part of our primary analysis, we estimated a structural equation path model. Findings from the quantitative phase showed a significant positive relationship between family cultural stress and family conflict, as well as individual parent and child mental health symptoms. In the qualitative phase of the study, 35 parent-child dyads participated in individual interviews. Findings from the interviews revealed variations in difficulties related to language, discrimination, and financial burdens, with some participants adapting more quickly and experiencing fewer stressors. Findings also highlight the impact on mental health for both parents and youth, emphasizing the family-level nature of cultural stress, while noting a potential discrepancy between qualitative and quantitative findings in the discussion of family conflict.

4.
Mol Pharm ; 20(5): 2702-2713, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37013916

RESUMO

Glioblastoma (GBM), as the most central nervous system (CNS) intractable disease, has spoiled millions of lives due to its high mortality. Even though several efforts have been made, the existing treatments have had limited success. In this sense, we studied a lead compound, the boron-rich selective epidermal growth factor receptor (EGFR)-inhibitor hybrid 1, as a potential drug for GBM treatment. For this end, we analyzed the in vitro activity of hybrid 1 in a glioma/primary astrocytes coculture, studying cellular death types triggered by treatment with this compound and its cellular localizations. Additionally, hybrid 1 concentrated boron in glioma cells selectively and more effectively than the boron neutron capture therapy (BNCT)-clinical agent 10B-l-boronophenylalanine and thus displayed a better in vitro-BNCT effect. This encouraged us to analyze hybrid 1 in vivo. Therefore, immunosuppressed mice bearing U87 MG human GBM were treated with both 1 and 1 encapsulated in a modified liposome (recognized by brain-blood barrier peptide transporters), and we observed a potent in vivo per se antitumor activity (tumor size decrease and animal survival increase). These data demonstrate that 1 could be a promising new targeted therapy for GBM.


Assuntos
Terapia por Captura de Nêutron de Boro , Neoplasias Encefálicas , Glioblastoma , Glioma , Camundongos , Humanos , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/metabolismo , Boro , Compostos de Boro/farmacologia , Compostos de Boro/uso terapêutico , Glioma/tratamento farmacológico , Glioma/radioterapia , Glioma/metabolismo , Glioblastoma/tratamento farmacológico
5.
Cogn Neuropsychiatry ; 28(2): 102-115, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36695101

RESUMO

Introduction: One of the main contributors to cognitive reserve (CR) is the involvement in cognitively stimulating activities (CSAs), including education, work, leisure, social and physical activities. Personality traits are plausible determinants of CR, influencing the tendency to engage in CSAs. The goal of this study was to evaluate the association between personality and CR, operationalised as self-rated involvement in CSAs, in a sample of individuals aged 18-50 or more. Method: We collected two-wave non-probabilistic online data throughout Mexico. The instruments were the Big Five Inventory-2 for the baseline, its extra-short form for the follow-up and the Self-Rating of Cognitive Reserve (SRCR). Confirmatory factor analyses (CFAs) were performed to test the unifactorial structure of the SRCR, and multiple regressions were conducted with personality factors as predictors of CR. Results: For the baseline, 2025 participants were recruited, and 610 for the follow-up, most of them female and aged 18-40. CFAs showed excellent goodness-of-fit, and the regression analyses proved Negative Emotionality and Extraversion to be the main predictors of CR. Conclusions: Our study highlights the need to identify personality profiles at high risk of underdevelopment of CR in ages where it is still feasible to promote engagement in CSAs.


Assuntos
Reserva Cognitiva , Humanos , Feminino , México , Personalidade , Atividades de Lazer , Motivação
6.
Artigo em Inglês | MEDLINE | ID: mdl-37091741

RESUMO

The political climate often changes following the installment of a new president. This volatility presents opportunities for examining how elections might affect vulnerable subgroups such as Hispanic/Latino (HL) adolescents. The present study explored the perception of negative political climate among HL adolescents before and after the 2020 U.S. presidential election and its association with internalizing symptoms and substance use. We conducted the study in Los Angeles and Miami between 2020-2021, with a sample of 304 HL adolescents (Females = 60.8%), aged 15.3 years on average. Participants completed measures of negative political climate (pre- post-election) and measures of depressive symptoms, anxiety, substance misuse, and substance use intentions after the election. We used paired tests and linear mixed-effects modeling to explore changes in perceived negative climate before and after the election. Structural equation modeling was used to determine predictors of negative political climate and its associations with internalizing symptoms and substance use. Results indicated that following the election negative political climate increased significantly in Miami and among Cuban-origin adolescents but not in Los Angeles or among Mexican-origin adolescents. Pre-election perceived negative political climate was significantly predicted by gender, study site, and mother's nativity. Pre-election negative political climate predicted post-election internalizing symptoms and substance use intentions indirectly through post-election negative political climate. HL youth's perceived political climate is a complex construct that might vary across different sociopolitical contexts and populational sub-groups. Exploring variations in politically-based cultural stressors and their role as mental health and substance use risk factors is crucial to addressing HL disparities. KEY WORDS: Adolescence, Hispanic/Latino, political climate, presidential election, internalizing symptoms, substance use.

7.
J Couns Psychol ; 69(4): 416-429, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35129997

RESUMO

The present study was designed to examine the extent to which, in a sample of 873 Hispanic college students, daily levels of, and variability in, well-being would mediate the predictive effects of culturally related stressors (discrimination, negative context of reception, and bicultural stress) on internalizing and externalizing symptoms 11 days later. A 12-day daily diary design was utilized, where reports of cultural stressors were gathered on Day 1, daily well-being reports were gathered on Days 2-11, and outcomes were measured on Day 12 (with controls for Day 1 levels of these same outcomes). Structural equation modeling results indicated that daily means of, and variability in, well-being significantly mediated the predictive effect of Day 1 ethnic/racial discrimination, negative context of reception, and bicultural stress on Day 12 symptoms of anxiety and depression. No effects emerged for externalizing symptoms. When we decomposed the latent well-being variability construct into its component indicators (self-esteem, life satisfaction, psychological well-being/self-acceptance, and eudaimonic well-being), daily variability in life satisfaction and self-acceptance appeared to be primarily responsible for the mediated predictive effects we observed. These results are discussed in terms of implications for further research, for counseling practice, and for the development of more inclusive university practices and policies. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Hispânico ou Latino , Racismo , Estresse Psicológico/etnologia , Cultura , Etnicidade , Hispânico ou Latino/psicologia , Humanos , Racismo/psicologia , Autoimagem , Estresse Psicológico/epidemiologia , Estresse Psicológico/etiologia , Estudantes , Adulto Jovem
8.
Molecules ; 27(10)2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35630543

RESUMO

Plant polyphenols offer several benefits for the prevention of diverse illnesses. Fruit's edible and inedible parts (pulp, seeds, peels, stems, flowers) are important sources of polyphenols. Different industrial processes for fruit treatment and commercialization affect the total polyphenol content (TPC), and probably the biological activity. The purpose of the present work was to determine the TPC and antioxidant activity (by DPPH) of polyphenols extracted from the pulp and seeds of Mauritia flexuosa (aguaje), in fresh and dehydrated forms, in order to determine the possible connection with the quantity of polyphenols and their specific antioxidant activity. The highest phenolic content for M. flexuosa seeds in fresh form (non-dehydrated) was 270.75 mg GAE/100 g with a 96-h extraction. With respect to the dehydrated samples, the best yield was quantified in the 96-h dehydrated seed sample. For all pulp and seeds, dehydrated for 24, 48, and 96 h, TPC showed a slightly decreasing pattern. The DPPH results were the highest in the 96-h dehydrated samples and the differences among all dehydrated pulp and seed samples were minimal. More studies testing the presence of other antioxidant components could help in understanding the detailed antioxidant activity, and related more to the specific action, rather than only total polyphenol content.


Assuntos
Arecaceae , Polifenóis , Antioxidantes/química , Arecaceae/química , Desidratação , Frutas/química , Polifenóis/química
9.
New Dir Child Adolesc Dev ; 2021(176): 41-59, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33634569

RESUMO

Crisis migration refers to displacement of large numbers of individuals and families from their home countries due to wars, dictatorial governments, and other critical hazards (e.g., hurricanes). Although crisis migration can adversely influence direct and indirect effects on the mental health of adults and their children collectively as families, there is a deficiency in theory that addresses family level processes in this crisis migration context. We propose the Family Crisis Migration Stress Framework, which consolidates what is known about the multiple factors affecting mental health outcomes of crisis migrants into one cohesive model. In our article, we synthesize relevant theories and models of disaster, migration, and family resilience in order to create a framework in which to organize the complex processes that occur within families as a result of migration and that affect the mental health of children. We include examples from various national settings to illustrate the tenets of our framework. Future policy and intervention for crisis migrant should focus on the family as a unit, instead of parents and children as individual entities.


Assuntos
Desastres , Resiliência Psicológica , Migrantes , Adulto , Criança , Saúde da Família , Humanos , Saúde Mental
10.
Environ Res ; 181: 108893, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31784077

RESUMO

Inhabitants of Sibaté (Colombia) report that between approximately 1975 and 1985 asbestos-containing materials (ACM) were dumped at different locations in the urban area of the municipality. Starting in around 1986, the dumping of materials resulted in landfilled zones, on top of which different facilities were then constructed. In a previous study, an underground friable asbestos layer was discovered in these landfilled zones. However, potential exposure to asbestos on the surface of landfilled zones in Sibaté has not been determined. In the current study, the U.S. EPA Activity-Based Sampling (ABS) methodology was adapted and applied in three scenarios located on potential landfilled areas in Sibaté, to estimate the current risk of exposure to asbestos through inhalation, and the resulting excess lifetime cancer risk (ELCR). For this purpose, generic ABS in a football stadium, and specific ABS in both a public playground and a school courtyard were conducted. Personal, area and blank samples were collected and analyzed using phase contrast microscopy (PCM) and transmission electron microscopy (TEM) following NIOSH 7400 and ISO 13794 methods, respectively. Exposure point concentrations were determined and compared against the action level for asbestos in air (ALAA), and were also used to calculate the ELCR of each scenario. A total of 25 airborne asbestos samples were collected, and 22 of these (12 personal samples, 7 area samples and 3 blank samples) were analyzed using PCM. Eighteen of these samples (12 personal, 3 area samples and 3 blank samples) were analyzed using TEM. The total asbestos structures concentration of personal samples ranged from non-detected to 0.326 S/cc (i.e., total asbestos structures counts ranged from 0 to 12). All samples had PCM-Equivalent asbestos structures concentrations below analytical sensitivity. Of the 22 samples analyzed, 18 were overloaded with particles. Although chrysotile and actinolite were identified in some personal samples, suggesting a potential risk of asbestos exposure, the ELCR was at U.S. EPA acceptable risk levels. Since the ABS methodology was applied in a limited number of scenarios and a small number of samples were collected, these results should be interpreted with caution and additional sampling campaigns are required to fully understand the risk of asbestos exposure in Sibaté. Methodological and analytical challenges encountered in the current study are discussed in detail, which could inform future ABS studies, not only in Sibaté, but also in other areas with asbestos-contaminated soils.


Assuntos
Poluentes Ocupacionais do Ar , Amianto , Exposição Ocupacional , Cidades , Colômbia , Monitoramento Ambiental , Exposição por Inalação , Instalações de Eliminação de Resíduos
11.
Environ Res ; 191: 110182, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32971078

RESUMO

INTRODUCTION: Sibaté is a municipality located in the central region of Colombia, where the first asbestos-cement facility of the country has been in operation since 1942. Both a malignant pleural mesothelioma cluster and landfilled zones with the presence of an underground friable asbestos layer have been identified in Sibaté. There is still limited knowledge regarding the history of the construction of landfilled zones, and what kinds of materials were deposited. The current study aims to improve our understanding of the history and characteristics of the landfilled zones present in Sibaté. METHODS: Two participatory workshops with inhabitants of Sibaté were conducted to determine when the landfilled zones were built and their location. Information collected in participatory workshops was crossed with both topographic maps and aerial photographs, giving special attention to zones within the urban area of the municipality that in the past were inundated with water from El Muña Reservoir. An opportunistic soil sampling campaign was conducted in suspected landfilled zones that had not been previously sampled, during the replacement of pipelines of the drainage system ordered by the municipality. RESULTS: The analysis of historical topographic maps, combined with the interpretation of aerial photographs, confirmed the disposal of residues in areas that were previously inundated with water from El Muña Reservoir, creating landfilled zones in the urban area of Sibaté. On top of these landfilled zones, a football stadium and a football field with an athletic track were built. The location of landfilled zones identified using geographic analysis was similar to the location identified analyzing maps constructed by inhabitants of Sibaté in participatory workshops. The four soil samples collected during an opportunistic sampling campaign confirmed the presence in new locations of the underground friable asbestos layer discovered in previous studies. DISCUSSION: Based on the extension of the landfilled zones, the presence of friable asbestos in these areas, and the close proximity to a school and residential dwellings, there could have been major dispersion events of asbestos fibers in the urban area of Sibaté during the disposal of residue materials and the construction of the landfilled zones. Thus, important asbestos exposures may have occurred among residents of Sibaté, which is aggravated by the fact that during those years, more than 50% of the population of Sibaté was 25 years old or younger. Although the results of the current study improved our understanding of the processes and chronology associated with the landfilled zones, the uncertainty regarding their exact location remains significant. It is important to continue investigating the adverse health effects resulting from this potential asbestos exposure source.


Assuntos
Amianto , Exposição Ocupacional , Cidades , Colômbia , Exposição Ambiental , Instalações de Eliminação de Resíduos
12.
Dis Aquat Organ ; 138: 185-194, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32213666

RESUMO

In bivalve mollusk aquaculture, massive disease outbreaks with high mortality and large economic losses can occur, as in northwest Mexico in the 1990s. A range of pathogens can affect bivalves; one of great concern is ostreid herpesvirus 1 (OsHV-1), of which there are several strains. This virus has been detected in the Gulf of California in occasional or sporadic samplings, but to date, there have been few systematic studies. Monthly samples of Crassostrea gigas, water, and sediment were taken in the La Cruz coastal lagoon and analyzed by PCR. The native mollusk, Dosinia ponderosa, which lives outside the lagoon, was sampled as a control. The virus was found throughout the year only in C. gigas, with prevalence up to 60%. In total, 9 genotype variants were detected, and genetic analysis suggests that linear genotypic evolution has occurred from strain JF894308, present in La Cruz in 2011. There has been no evidence of the entry of new viral genotypes in the recent past, thus confinement of the virus within the lagoons of the Gulf of California could promote a native genotypic diversity in the short term.


Assuntos
Crassostrea , Animais , California , Vírus de DNA , Genótipo , México , Prevalência
13.
Environ Res ; 176: 108464, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31229775

RESUMO

INTRODUCTION: The asbestos industry began operations in Colombia in 1942, with an asbestos-cement facility located in the municipality of Sibaté. In recent years residents from Sibaté have been complaining about what they consider is an unusually large number of people diagnosed with asbestos-related diseases in the town. A study to analyze the situation of Sibaté started in 2015, to verify if the number of asbestos related diseases being diagnosed were higher than expected, and to identify potential asbestos exposure sources in the town. METHODS: A health and socioeconomic survey was implemented door-to-door to identify potential asbestos-related diseases. Several self-reported mesothelioma cases were identified, and for confirmation purposes, copies of the medical record with the histopathology report were obtained. A panel of six physicians analyzed the medical records. Information of validated cases was used to estimate the male and female age-adjusted incidence rate for Sibaté. Based on reports of the existence of potential asbestos-contaminated landfills, topographic maps, a digital elevation model, and current satellite images were crossed using a geographic information system to identify potential landfilled areas, and soils samples were collected in some of these areas. RESULTS: A total of 355 surveys were completed, and 29 self-reported mesothelioma cases were identified. Twenty-five of these cases have been persons who had lived at some moment of their lives in Sibaté. It was possible to obtain copies of the medical diagnosis for 17 cases. Of these, the panel of physicians classified 15 cases as certain pleural mesothelioma, one as probable, and one as not mesothelioma. Based on this information, the estimated age-adjusted incidence rate of mesothelioma in Sibaté was 3.1 × 105 persons-year for males and 1.6 × 105 persons-year for females. These rates are high in comparison to those reported in other cities, regions, and countries of the world. Using geographic information systems, landfilled zones in the urban area of Sibaté were identified, on top of which a school and different sports facilities were built. The analysis of four soil samples collected in landfilled zones, confirmed the existence of an underground layer of friable and non-friable asbestos. CONCLUSION: The collected evidence suggests the presence of a malignant pleural mesothelioma cluster in Sibaté.


Assuntos
Amianto , Mesotelioma , Exposição Ocupacional , Adulto , Amianto/toxicidade , Cidades , Colômbia , Exposição Ambiental , Feminino , Humanos , Incidência , Masculino , Mesotelioma/epidemiologia , Pessoa de Meia-Idade
14.
Int J Immunogenet ; 46(2): 59-66, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30681271

RESUMO

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by chronic and symmetrical inflammation of synovial tissue with subsequent joint destruction. SUMO1 is an important regulator of apoptosis through non-canonical mechanism in synovial fibroblasts, and POU2AF1 is a known B-cell transcriptional co-activator. The specific objective of this study was to measure the expression of SUMO1 and POU2AF1 on first-degree relatives of patients with RA and also in the preclinical and clinical stages of RA and describe their possible role in RA physiopathology. Blood samples were collected from ACPA+, ACPA-, early and established RA subjects recruited. ACPAs and CarP autoantibodies were determined by ELISA Eurodiagnostica CCplus kit according to previously described protocols. RNA was isolated from blood samples; the purity as integrity was determined. Gene expression analysis was made by RT-qPCR using specific primers for SUMO1 and POU2AF1 mRNAs; relative expression was determined according to the 2-ΔΔct method procedure. Significant differences in the expression of both, SUMO1 and POU2AF1 were identified when comparing arthritis versus healthy or ACPA+ individuals, suggesting that the down regulation of such genes starts after the onset of symptoms in RA patients. Also, a significant correlation was identified for POU2AF1 and disease progression whit a downward trend for those with established RA. The implications of such gene down regulation are discussed in the context of RA physiopathology.


Assuntos
Artrite Reumatoide/sangue , Família , Proteína SUMO-1/sangue , Transativadores/sangue , Adulto , Artrite Reumatoide/genética , Regulação para Baixo/genética , Feminino , Redes Reguladoras de Genes , Humanos , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Risco , Proteína SUMO-1/genética , Transativadores/genética
15.
Chemistry ; 24(13): 3122-3126, 2018 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-29194843

RESUMO

New 1,7-closo-carboranylanilinoquinazoline hybrids have been identified as EGFR inhibitors, one of them with higher affinity than the parent compound erlotinib. The comparative docking analysis with compounds bearing bioisoster-substructures, demonstrated the relevance of the 3D aromatic-boron-rich moiety for interacting into the EGFR ATP binding region. The capability to accumulate in glioma cells, the ability to cross the blood-brain barrier and the stability on simulated biological conditions, render these molecules as lead compounds for further structural modifications to obtain dual action drugs to treat glioblastoma.


Assuntos
Boro/análise , Receptores ErbB/antagonistas & inibidores , Glioma/tratamento farmacológico , Quinazolinas/uso terapêutico , Compostos de Anilina , Barreira Hematoencefálica/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Inibidores de Proteínas Quinases/química , Quinazolinas/química
16.
Org Biomol Chem ; 16(29): 5275-5285, 2018 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-29974915

RESUMO

Pretargeted imaging, based on the highly reactive process between [1,2,4,5]tetrazines with trans-cyclooctene (TCO), appears as an attractive strategy to overcome disadvantages associated with traditional radioimmunoconjugates. To be successful, the radiolabeled component should react in vivo with the conjugated antibody and the non reactive excess clear fast from the organism. Herein, we explore the in vivo effects of hydrophilic linker incorporation into [1,2,4,5]tetrazine systems bearing a 6-hydrazinonicotinyl (HYNIC) moiety for technetium-99m coordination. Incorporation of a polypeptide chain containing hydrophilic aminoacids, resulted in a derivative with renal clearance. Pretargeted bevacizumab imaging was used as proof of concept.

17.
Oncology ; 92(4): 229-242, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28196364

RESUMO

INTRODUCTION: Rituximab was the first monoclonal antibody approved for the treatment of B-cell non-Hodgkin lymphoma (NHL) expressing CD20 antigen. This antibody has also the potential to be used as a specific fluorescent and radiolabel agent for targeting NHL. OBJECTIVE: To radiolabel rituximab with technetium-99m (99mTc) or Cy7 and evaluate both probes as potential imaging agents for NHL. METHODS: Rituximab was derivatized with the trifluoroacetyl hydrazino protected form of succinimidyl ester of HYNIC and radiolabeled with 99mTc. Radiochemical stability and in vitro cell assays were evaluated. Biodistribution and single-photon emission computed tomography/computed tomography (SPECT/CT) were performed. Raji cells were transfected with luciferase for bioluminescent NHL imaging up to 21 days. Rituximab was labeled with Cy7 for in vivo noninvasive fluorescence imaging up to 96 h. RESULTS: Radiolabeling was carried out in a fast, reproducible, easy, and stable way with high radiochemical purity and did not interfere with epitope recognition. Biodistribution and SPECT/CT studies showed high liver and discrete tumor uptake. Bioluminescence and fluorescence studies helped us evaluate rituximab-Cy7 in Raji subcutaneous engraftment in BALB/c nude mice. CONCLUSIONS: Our results support the potential use of rituximab labeled either with 99mTc or Cy7 as a molecular imaging tool for staging, restaging, and guiding surgical excision of tumors, which merits further evaluation.


Assuntos
Carbocianinas , Linfoma não Hodgkin/diagnóstico por imagem , Imagem Molecular/métodos , Rituximab , Tecnécio , Animais , Antígenos CD20/metabolismo , Carbocianinas/farmacocinética , Linhagem Celular Tumoral , Usos Diagnósticos de Compostos Químicos , Feminino , Humanos , Camundongos Endogâmicos BALB C , Compostos Radiofarmacêuticos/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Rituximab/química , Rituximab/metabolismo , Rituximab/farmacocinética , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tecnécio/farmacocinética , Distribuição Tecidual
19.
Bioorg Med Chem ; 24(6): 1209-15, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26875936

RESUMO

Metal-free click chemistry has become an important tool for pretargeted approaches in the molecular imaging field. The application of bioorthogonal click chemistry between a pretargeted trans-cyclooctene (TCO) derivatized monoclonal antibody (mAb) and a (99m)Tc-modified 1,2,4,5-tetrazine for tumor imaging was examined in vitro and in vivo. The HYNIC tetrazine compound was synthesized and structurally characterized, confirming its identity. Radiolabeling studies demonstrated that the HYNIC tetrazine was labeled with (99m)Tc at an efficiency of >95% and was radiochemically stable. (99m)Tc-HYNIC tetrazine reacted with the TCO-CC49 mAb in vitro demonstrating its selective reactivity. In vivo biodistribution studies revealed non-specific liver and GI uptake due to the hydrophobic property of the compound, however pretargeted SPECT imaging studies demonstrated tumor visualization confirming the success of the cycloaddition reaction in vivo. These results demonstrated the potential of (99m)Tc-HYNIC-tetrazine for tumor imaging with pretargeted mAbs.


Assuntos
Química Click , Imagem Molecular/métodos , Sondas Moleculares/química , Compostos de Organotecnécio/química , Tetrazóis/química , Animais , Anticorpos Monoclonais/química , Linhagem Celular Tumoral , Ciclo-Octanos/química , Humanos , Camundongos , Sondas Moleculares/farmacocinética , Neoplasias Experimentais/diagnóstico , Neoplasias Experimentais/metabolismo , Compostos de Organotecnécio/farmacocinética , Tetrazóis/farmacocinética , Distribuição Tecidual
20.
Ann Occup Hyg ; 60(8): 1020-35, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27234376

RESUMO

Asbestos and non-asbestos containing brake products are currently used in low- and middle-income countries like Colombia. Because brake products are distributed detached from their supports, they require manipulation before installation, which release fibers and expose workers. Previous studies of our research group have documented exposures in excess of the widely accepted 0.1 f/cm(3) exposure guideline. The aim of this study is to identify factors associated with non-compliance of the 8-h time weighted average (TWA) 0.1 f/cm(3) asbestos occupational limit among brake mechanics (i.e. riveters). Eighteen brake repair shops (BRS) located in Bogotá (Colombia) were sampled during 3 to 6 consecutive days for the entire work-shift. Personal and short-term personal samples were collected following NIOSH methods 7400 and 7402. Longitudinal based logistic regression models were used to determine the association between the odds of exceeding the 8-h TWA 0.1 f/cm(3) asbestos occupational limit and variables such as type of tasks performed by workers, workload (number of products manipulated daily), years of experience as riveters, and shop characteristics. These models can be used to estimate the odds of being currently or historically overexposed when sampling data do not exist. Since the information required to run the models can vary for both retrospective and current asbestos occupational exposure studies, three models were constructed with different information requirements. The first model evaluated the association between the odds of non-compliance with variables related to the workload, the second model evaluated the association between the odds of non-compliance with variables related to the manipulation tasks, and the third model evaluated the association between the odds of non-compliance with variables related with both the type of tasks performed by workers and the workload. Variables associated with the odds of non-compliance included conducting at least one manipulation activity with beveling and grinding of asbestos and non-asbestos containing brake products during the work shift, the location of the worker in the shop during non-manipulation activities, cleaning activities of the manipulation area, the years of experience working as riveters, and the number of asbestos and non-asbestos containing brake products manipulated daily. These models could be useful for current and retrospective occupational studies, in determining the odds of non-compliance of the asbestos occupational limit among brake mechanics.


Assuntos
Asbestos Serpentinas/efeitos adversos , Monitoramento Ambiental/métodos , Exposição por Inalação/análise , Exposição Ocupacional/análise , Poluentes Ocupacionais do Ar/análise , Automóveis , Colômbia , Humanos , Manufaturas , National Institute for Occupational Safety and Health, U.S. , Exposição Ocupacional/normas , Estudos Retrospectivos , Fatores de Risco , Estados Unidos
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