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Disparities in patient care and outcomes are well-documented in medicine but have received comparatively less attention in anesthesiology. Those disparities linked to racial and ethnic identity are pervasive, with compelling evidence in operative anesthesiology, obstetric anesthesiology, pain medicine, and critical care. This narrative review presents an overview of disparities in perioperative patient care that is grounded in historical context followed by potential solutions for mitigating disparities and inequities.
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Anestesiologia , Etnicidade , Disparidades em Assistência à Saúde , Humanos , Disparidades em Assistência à Saúde/etnologia , História do Século XX , História do Século XXI , Grupos Raciais , Anestesiologistas , Assistência PerioperatóriaRESUMO
Scaffolds can be considered as one of the most promising treatments for bone tissue regeneration. Herein, blends of chitosan, poly(vinyl alcohol), and hydroxyapatite in different ratios were used to synthesize scaffolds via freeze-drying. Mechanical tests, FTIR, swelling and solubility degree, DSC, morphology, and cell viability were used as characterization techniques. Statistical significance of the experiments was determined using a two-way analysis of variance (ANOVA) with p < 0.05. Crosslinked and plasticized scaffolds absorbed five times more water than non-crosslinked and plasticized ones, which is an indicator of better hydrophilic features, as well as adequate resistance to water without detriment of the swelling potential. Indeed, the tested mechanical properties were notably higher for samples which were undergone to crosslinking and plasticized process. The presence of chitosan is determinant in pore formation and distribution which is an imperative for cell communication. Uniform pore size with diameters ranging from 142 to 519 µm were obtained, a range that has been described as optimal for bone tissue regeneration. Moreover, cytotoxicity was considered as negligible in the tested conditions, and viability indicates that the material might have potential as a bone regeneration system.
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Desenvolvimento Ósseo/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Engenharia Tecidual , Alicerces Teciduais/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Osso e Ossos/química , Proliferação de Células/efeitos dos fármacos , Quitosana/síntese química , Quitosana/química , Quitosana/uso terapêutico , Durapatita/síntese química , Durapatita/química , Durapatita/uso terapêutico , Humanos , Osteoblastos/efeitos dos fármacos , Álcool de Polivinil/síntese química , Álcool de Polivinil/química , Álcool de Polivinil/uso terapêuticoRESUMO
BACKGROUND/OBJECTIVES: With aging, people commonly develop motor slowing (bradykinesia). Although this slowness with aging may be entirely related to degradation of the cerebral networks important in motor programing, it is possible that, at least in part, it may be a learned procedure for enhancing the accuracy and/or precision of movements. The goal of this study is to test these contradictory hypotheses. METHODS: Twenty-four healthy adults, 12 younger than age 26 and 12 older than age 65 were asked to make alternative marks with a pen between a card centered in front of them and a series of circles distributed across a page. Performance was timed, and participants were instructed to complete the task as quickly as possible while not sacrificing accuracy for speed. The circle sizes and hand used varied by trial. RESULTS: The older adults performed the task more slowly for all target circle diameters. As the circles decreased in size, the younger adults performed the task more rapidly than did the older participants, but the younger participants also had a greater decline in accuracy. CONCLUSIONS: During this aiming task, healthy older adults were less likely than younger adults to sacrifice accuracy for speed. Thus, at least in part, their slowing may be a learned adaptive strategy.
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Envelhecimento/fisiologia , Função Executiva/fisiologia , Atividade Motora/fisiologia , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Percepção Espacial/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Adulto JovemRESUMO
AIMS: In this study, we examined the relationship between 131 suicide related Google search terms, grouped into nine categories, and the number of suicide cases per month in Ecuador from January 2011 to December 2021. METHODS: First, we applied time-series analysis to eliminate autocorrelation and seasonal patterns to prevent spurious correlations. Second, we used Pearson's correlation to assess the relationship between Google search terms and suicide rates. Third, cross-correlation analysis was used to explore the potential delayed effects between these variables. Fourth, we extended the correlation and cross-correlation analyses by three demographic characteristics - gender, age, and region. RESULTS: Significant correlations were found in all categories between Google search trends and suicide rates in Ecuador, with predominantly positive and moderate correlations. The terms 'stress' (.548), 'prevention' (.438), and 'disorders' (.435) showed the strongest associations. While global trends indicated moderate correlations, sensitivity analysis revealed higher coefficients in men, young adults, and the Highlands region. Specific patterns emerged in subgroups, such as 'digital violence' showing significant correlations in certain demographics, and 'trauma' presenting a unique temporal pattern in women. In general, cross correlation analysis showed an average negative correlation of -.191 at lag 3. CONCLUSION: Google search data do not provide further information about users, such as demographics or mental health records. Hence, our results are simply correlations and should not be interpreted as causal effects. Our findings highlight a need for tailored suicide prevention strategies that recognize the complex dynamics of suicide risk across demographics and time periods.
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BACKGROUND: Conceptual apraxia (CA), a feature of Alzheimer disease (AD), can be detected by asking participants to identify the correct tool to act on an object. Assessment can be based on either learned associations (a tool selection test) or the mechanical properties that the tool needs to alter the target object (an alternative tool selection test). OBJECTIVES: We wanted to determine whether knowledge of semantic taxonomic relations (intrinsic properties shared by items) correlated with performance on tests for CA in people with AD or amnestic mild cognitive impairment (aMCI). METHODS: We tested 10 participants with AD, 12 with aMCI, and 18 healthy older adults for CA using an alternative tool selection test, a tool selection test, and a test of taxonomic relations. RESULTS: The aMCI group did not differ from the control group on the CA tests. The patients with AD were impaired on all tests except tool selection; their performance on the alternative tool selection test correlated significantly with their performance on the taxonomic relations test. CONCLUSIONS: The correlation between performances on the alternative tool selection test and the taxonomic relations test in AD suggests a common pathophysiologic substrate, either impairment in accessing conceptual-semantic representations or a degradation of these representations.
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Doença de Alzheimer/psicologia , Apraxias/psicologia , Disfunção Cognitiva/psicologia , Conhecimento , Idoso , Doença de Alzheimer/complicações , Apraxias/complicações , Comportamento de Escolha , Disfunção Cognitiva/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
The eXtensible Markup Language (XML) files are widely used by the industry due to their flexibility in representing numerous kinds of data. Multiple applications such as financial records, social networks, and mobile networks use complex XML schemas with nested types, contents, and/or extension bases on existing complex elements or large real-world files. A great number of these files are generated each day and this has influenced the development of Big Data tools for their parsing and reporting, such as Apache Hive and Apache Spark. For these reasons, multiple studies have proposed new techniques and evaluated the processing of XML files with Big Data systems. However, a more usual approach in such works involves the simplest XML schemas, even though, real data sets are composed of complex schemas. Therefore, to shed light on complex XML schema processing for real-life applications with Big Data tools, we present an approach that combines three techniques. This comprises three main methods for parsing XML files: cataloging, deserialization, and positional explode. For cataloging, the elements of the XML schema are mapped into root, arrays, structures, values, and attributes. Based on these elements, the deserialization and positional explode are straightforwardly implemented. To demonstrate the validity of our proposal, we develop a case study by implementing a test environment to illustrate the methods using real data sets provided from performance management of two mobile network vendors. Our main results state the validity of the proposed method for different versions of Apache Hive and Apache Spark, obtain the query execution times for Apache Hive internal and external tables and Apache Spark data frames, and compare the query performance in Apache Hive with that of Apache Spark. Another contribution made is a case study in which a novel solution is proposed for data analysis in the performance management systems of mobile networks.
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BACKGROUND: Chikungunya (CHIKV), is an endemic RNA virus in some regions of Asia and Africa. In Colombia in 2014, its spread started explosively and quickly. The presentation of CHIKV is a febrile condition, with musculoskeletal symptoms, which can progress to erosive arthropathy and polyarticular deformity. The purpose of this study is to evaluate symptomatic and serological behaviour in patients suffering from CHIKV infection in Neiva, Huila who attend the Rheumatology clinic, and to describe the comorbidities associated with the chronic phase of the disease. METHODS: An observational, longitudinal and retrospective analysis of data collected in 410 patients afflicted with the CHIKV virus, with symptoms lasting more than 3 months, who persisted with musculoskeletal and joint symptoms. The patients were classified according to their commitment in post-viral arthralgias, polyarthritis post viral, Rheumatoid Arthritis (RA) post CHIKV, Spondyloarthritis postCHIKV, and soft tissue rheumatism. The statistical analysis was performed using SPSS software (version 24). A descriptive analysis was carried out to evaluate quantitative variables such as the mean (standard deviation), and categorical variables such as frequency (%). The categorical variables were compared using the Chi-square equation. As a statistical significance, a p less than .05 was considered. RESULTS: Of the 410 patients, 89.23% were women, with polyarticular involvement in 92.26% of the cases. Of the patients, 49.83% had osteoarthritis. At the time of the evaluation in the Rheumatology clinic, 46.3% of the cases presented persistent non-inflammatory arthralgias, and 53.7% of the patients underwent arthritis on physical examination, of which, remarkably, 20.3% met the criteria for rheumatoid arthritis postCHIKV. CONCLUSIONS: The development of musculoskeletal symptoms after CHIKV infection is a very serious public health problem, with persistent complications and long-term morbidity risk in real life. The presence of net postviral arthritis is noteworthy, however the development of postCHIKV rheumatoid arthritis usually requires more advanced pharmacological measures, including, in some cases, transition to biological therapy. The presence of symptoms of venous insufficiency in the lower limbs that developed with CHIKV infection was an incidental finding that requires a more precise study.
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Artrite Reumatoide , Febre de Chikungunya , Vírus Chikungunya , Reumatologia , Artrite Reumatoide/epidemiologia , Febre de Chikungunya/epidemiologia , Feminino , Humanos , Estudos RetrospectivosRESUMO
Decellularized membranes (DM) were obtained from bovine amniotic membranes (BAM) using four different decellularization protocols, based on physical, chemical, and mechanical treatment. The new material was used as a biological scaffold for in vitro skin cell culture. The DM were characterized using hematoxylin-eosin assay, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR-ATR), and differential scanning calorimetry (DSC). The in vitro cytotoxicity of DM was evaluated using MTT. The efficacy of decellularization process was assessed through DNA quantification and electrophoresis. All the used protocols showed a high effectiveness in terms of elimination of native cells, confirmed by DNA extraction and quantification, electrophoresis, and SEM, although protocol IV removes the cellular contents and preserve the native extracellular matrix (ECM) architecture which it can be considered as the most effective in terms of decellularization. FTIR-ATR and DSC on the other hand, revealed the effects of decellularization on the biochemical composition of the matrices. There was no cytotoxicity and the biological matrices obtained were a source of collagen for recellularization. The matrices of protocols I, II, and III were degraded at day 21 of cell culture, forming a gel. The biocompatibility in vitro was demonstrated; hence these matrices may be deemed as potential scaffold for epithelial tissue regeneration.
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BACKGROUND: Chikungunya (CHIKV), is an endemic RNA virus in some regions of Asia and Africa. In Colombia in 2014, its spread starts explosively and quickly. The presentation of CHIKV is a febrile condition, with musculoskeletal symptoms, which can progress to erosive arthropathy and polyarticular deformity. The purpose of this study is to evaluate in patients suffering from CHIKV infection in Neiva, Huila who attend the Rheumatology clinic, the symptomatic and serological behavior, and to describe comorbidities associated to the chronic phase of the disease. METHODS: An observational, longitudinal and retrospective analysis of data collected in 410 patients afflicted with the CHIKV virus, with symptoms lasting more than 3 months, who persisted with musculoskeletal and joint symptoms. The patients were classified according to their commitment in post-viral arthralgias, polyarthritis post viral, Rheumatoid Arthritis (RA) post CHIKV, Spondyloarthritis postCHIKV, and soft tissue rheumatism. The statistical analysis was performed using SPSS software (version 24). A descriptive analysis was carried out to evaluate quantitative variables such as the mean (standard deviation), and categorical variables such as frequency (%). The categorical variables were compared using the Chi-square equation. As a statistical significance, a p less than .05 was considered. RESULTS: Of the 410 patients, 89.23% were women, with polyarticular involvement in 92.26% of the cases. Of the patients, 49.83% had osteoarthritis. At the time of the evaluation in the Rheumatology clinic, 46.3% of the cases presented persistent non-inflammatory arthralgias, and 53.7% of the patients underwent arthritis on physical examination, of which, remarkably, 20.3% met the criteria for rheumatoid arthritis postCHIKV. CONCLUSIONS: The development of musculoskeletal symptoms after CHIKV infection is a very serious public health problem, with persistent complications and long-term morbidity risk in real life. The presence of net postviral arthritis is noteworthy, however the development of postCHIKV rheumatoid arthritis usually requires more advanced pharmacological measures, including, in some cases, transition to biological therapy. The presence of symptoms of venous insufficiency in the lower limbs that developed with CHIKV infection was an incidental finding that requires a more precise study.
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Acute intermittent porphyria (AIP) is an autosomal dominant metabolic disorder characterized by a deficiency in heme biosynthesis. Heme biosynthesis occurs throughout the body, but it is most prominent in the erythroblastic system and liver. AIP is a hepatic porphyria whereby the liver is the source of toxic heme metabolites. Clinical manifestations of AIP result from a genetic mutation that leads to partial function of porphobiliogen deaminase (PBGD). This causes an accumulation of upstream, neurotoxic metabolites. Symptoms include but are not limited to peripheral neuropathies, autonomic neuropathies and psychiatric manifestations. AIP can be life threatening and clinical signs and symptoms are often heterogeneous and non-specific. Therefore, it is important to be able to recognize these patients to make a prudent diagnosis and offer appropriate therapy. Here, we review the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of AIP including the role of liver transplantation.
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BACKGROUND/OBJECTIVES: Compound horizontal lines are composed of 2 segments of unequal length and width. Line bisection requires that the participants attend to the entire line (global attention). The longer segment often distracts participants, suggesting that attention directed to this segment (focal attention) disrupts the allocation of global attention. This study attempted to learn whether the allocation of focal attention to a line segment is distracted by global attention allocated to the entire line and whether there are right-left distraction asymmetries when allocating focal or global attention. METHOD: Twenty-four healthy adults (12 > 65 years old) attempted to bisect horizontal lines composed of 2 segments of unequal length, with the larger segment placed to the right or left. They were also asked to bisect the longer segment of these lines. RESULTS: When allocating focal attention to the larger segment, healthy participants were more distracted when the smaller segment was on the left than on the right. In contrast, when attempting to allocate global attention to the entire line, participants were more distracted when the larger segment was on the right side. There were no significant differences between older and younger participants. CONCLUSIONS: The asymmetrical global distraction during segment bisection might be related to the right hemisphere's dominance in mediating global attention and allocating attention leftward. In contrast, the asymmetrical focal distraction during full-line bisection might be related to the left hemisphere's dominance in mediating focal attention and allocating attention toward the right. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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Atenção/fisiologia , Lateralidade Funcional/fisiologia , Percepção Espacial/fisiologia , Percepção Visual/fisiologia , Adolescente , Adulto , Idoso , Envelhecimento/psicologia , Dominância Cerebral/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Adulto JovemRESUMO
Background-objectives: When vertical lines are positioned above or below the center of the page, line bisection deviates toward the center of the page, suggesting that the edges of the page distract the allocation of attention to the line. A letter-character line (LCL) bisection requires both global and focal attention, to identify the target letter closest to the line's center. If more focal and less global attention is allocated to a LCL, more global attentional resources may be available and inadvertently allocated to the page. Alternatively, if the allocation of focal attention to a LCL inhibits global attentional processing, there may be less distraction by the page. METHOD: Twenty-four healthy adults (12 older) bisected vertical solid and character lines centered, or positioned closer to the top or bottom of the page. RESULTS: There was no difference between bisection of solid and character lines centered on the page. Page-related deviations were greater with character lines than solid line bisections, and greater for lines positioned toward the top than the bottom of the page. With lines positioned toward the top, the older participants' attempted bisections were higher than those of the younger participants. CONCLUSIONS: These results suggest that the allocation of focal attention increases global attentional distractibility and that global-background attentional distraction is greater when the vertical lines are placed in the upper part of the page. Older participants appeared to be less distracted when lines were placed toward the top of the page, but the reason for this age difference requires further research.
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Atenção/fisiologia , Percepção Espacial/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Estimulação Luminosa , Adulto JovemRESUMO
The efficacy and safety of two whole IgG polyvalent antivenoms (A and B) were compared in a randomised, blinded clinical trial in 67 patients systemically envenomed by Bothrops asper in Colombia. Both antivenoms were fractionated by caprylic acid precipitation and had similar neutralising potencies, protein concentrations and aggregate contents. Antivenom B was additionally treated with beta-propiolactone to lower its anticomplementary activity. Analysing all treatment regimens together, there were no significant differences between the two antivenoms (A=34 patients; B=33 patients) in the time taken to reverse venom-induced bleeding and coagulopathy, to restore physiological fibrinogen concentrations and to clear serum venom antigenaemia. Blood coagulability was restored within 6-24 h in 97% of patients, all of whom had normal coagulation and plasma fibrinogen levels 48 h after the start of antivenom treatment. Two patients (3.0%) had recurrent coagulopathy and eight patients suffered recurrence of antigenaemia within 72 h of treatment. None of the dosage regimens of either antivenom used guaranteed resolution of venom-induced coagulopathy within 6 h, nor did they prevent recurrences. A further dose of antivenom at 6 h also did not guarantee resolution of coagulopathy within 12-24 h in all patients. The incidence of early adverse reactions (all mild) was similar for both antivenoms (15% and 24%; P>0.05).
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Antivenenos/uso terapêutico , Bothrops , Venenos de Crotalídeos/sangue , Mordeduras de Serpentes/tratamento farmacológico , Adolescente , Adulto , Idoso , Animais , Antivenenos/sangue , Antivenenos/química , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Caprilatos/farmacologia , Fracionamento Químico/métodos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Fibrinogênio/metabolismo , Humanos , Imunoglobulina G , Masculino , Camundongos , Pessoa de Meia-Idade , Propiolactona/farmacologia , Recidiva , Mordeduras de Serpentes/sangue , Resultado do Tratamento , Tempo de Coagulação do Sangue TotalRESUMO
Introducción: Chikungunya (CHIKV) es un virus RNA endémico en algunas regiones de Asia y África. En Colombia en el año 2014 inicia su dispersión de manera explosiva y rápida. La presentación del CHIKV es una condición febril con síntomas musculoesqueléticos que pueden progresar a artropatía erosiva y deformidad poliarticular. El propósito de este estudio es evaluar en pacientes aquejados por la infección por CHIKV en Neiva, Huila que acuden a la consulta de Reumatología, el comportamiento sintomático y serológico, y describir comorbilidades asociadas a la fase crónica de la enfermedad. Métodos: Se realizó un análisis observacional, longitudinal y retrospectivo, de datos recolectados en 410 pacientes aquejados por el virus CHIKV con síntomas de más de tres meses de duración que persistían con afecciones musculoesqueléticas y articulares. Los pacientes fueron clasificados según su compromiso en: artralgias postvirales, poliartritis postviral, artritis reumatoide (AR) postCHIKV, espondiloartritis postCHIKV y reumatismo de tejidos blandos. El análisis estadístico fue realizado usando SPSS software (versión 24). Se llevó a cabo análisis descriptivo para evaluar variables cuantitativas como la media (desviación estándar) y variables categóricas como la frecuencia (%). Las variables categóricas fueron comparadas usando la ecuación X2. Como significancia estadística se consideró una p < 0,05. Resultados: De los 410 pacientes, 89,23% fueron mujeres, con compromiso poliarticular en 92,26% de los casos. El 49,83% de los pacientes presentaban de base osteoartritis. Al momento de la evaluación en la consulta de Reumatología, 46,3% de los pacientes cursaron con artralgias no inflamatorias persistentes y 53,7% de los casos presentaban artritis al examen físico, de los cuales, de manera remarcable 20,3% cumplieron criterios para AR postCHIKV.(AU)
Background: Chikungunya (CHIKV), is an endemic RNA virus in some regions of Asia and Africa. In Colombia in 2014, its spread starts explosively and quickly. The presentation of CHIKV is a febrile condition, with musculoskeletal symptoms, which can progress to erosive arthropathy and polyarticular deformity. The purpose of this study is to evaluate in patients suffering from CHIKV infection in Neiva, Huila who attend the Rheumatology clinic, the symptomatic and serological behavior, and to describe comorbidities associated to the chronic phase of the disease. Methods: An observational, longitudinal and retrospective analysis of data collected in 410 patients afflicted with the CHIKV virus, with symptoms lasting more than 3 months, who persisted with musculoskeletal and joint symptoms. The patients were classified according to their commitment in post-viral arthralgias, polyarthritis post viral, Rheumatoid Arthritis (RA) post CHIKV, Spondyloarthritis postCHIKV, and soft tissue rheumatism. The statistical analysis was performed using SPSS software (version 24). A descriptive analysis was carried out to evaluate quantitative variables such as the mean (standard deviation), and categorical variables such as frequency (%). The categorical variables were compared using the Chi-square equation. As a statistical significance, a p less than .05 was considered. Results: Of the 410 patients, 89.23% were women, with polyarticular involvement in 92.26% of the cases. Of the patients, 49.83% had osteoarthritis. At the time of the evaluation in the Rheumatology clinic, 46.3% of the cases presented persistent non-inflammatory arthralgias, and 53.7% of the patients underwent arthritis on physical examination, of which, remarkably, 20.3% met the criteria for rheumatoid arthritis postCHIKV.(AU)
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Humanos , Masculino , Feminino , Fenômenos Fisiológicos Musculoesqueléticos , Febre de Chikungunya , Avaliação de Sintomas , Sorologia , Comorbidade , Artralgia , Artrite , Artrite Reumatoide , Reumatologia , Doenças Reumáticas , Colômbia , Estudos Longitudinais , Estudos RetrospectivosRESUMO
The mechanism of neurotoxicity produced by the interaction of melanin with manganese was investigated in PC12-derived neuronal cell cultures. The cells were incubated with melanin (25-500 microg/ml), MnCl2 (10 ng/ml-100 microg/ml) and a combination of both substances for 24 and 72 h. Incubation with either toxicant alone resulted in a minimal decrease in cell viability. The combination of melanin and manganese caused significant (up to 60%) decreases in viability of PC12 cells in a dose-dependent manner. Increases in oxidative DNA damage, indicated by levels of 8-hydroxy-2'deoxyguanosine (8-oxodG), was associated with decreased cell viability. Melanin alone, but not manganese alone, resulted in increased oxidative DNA damage. The maximal increase in 8-oxodG caused by melanin was about seven times higher than control after 24 h of exposure. The activity of the DNA repair enzyme, 8-oxoguanine DNA glycosylase (OGG1), was increased in cells incubated with single toxicants and their combinations for 24 h. On the third day of incubation with the toxicants, activity of OGG1 declined below control levels and cell viability significantly decreased. Melanin was observed to have an inhibitory effect on OGG1 activity. Study of the regulation of OGG1 activity in response to melanin and manganese may provide insights into the vulnerability of nigral neurons to oxidative stress in Parkinson's disease.
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Dano ao DNA , Reparo do DNA/efeitos dos fármacos , Guanina/análogos & derivados , Manganês/farmacologia , Melaninas/toxicidade , Neurônios/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , DNA/análise , DNA/química , DNA Glicosilases/antagonistas & inibidores , DNA Glicosilases/metabolismo , Guanina/análise , Guanina/química , Peroxidação de Lipídeos/efeitos dos fármacos , Melaninas/metabolismo , Neurônios/metabolismo , Células PC12 , Ratos , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
The expression and activity of 8-oxoguanosine DNA-glycosylase (Ogg1), a key enzyme responsible forthe clearance of the oxidized DNA base 8-hydroxy-2'-deoxyguanosine (oxo8dG), was determined in the cerebellum (CB) and the caudate and the putamen (CP) of male Balb/c, ICR, and C57BL/J mice. There was no significant difference in the protein expression of Ogg1 in the CB or CP. The activity of Ogg1 was not significantly different in the CB; however, in the CP of ICR mice, the activity of Ogg1 was 34% and 31% lower than Balb/c and C57BL/J, respectively. In contrast, the levels of oxo8dG in the CB and CP of C57BL/J mice were nearly twice as high as the values in both regions of Balb/c and ICR mice. The activity of superoxide dismutases (SOD) appeared to account for the differences in the levels of oxo8dG in the C57BL/J strain. Total SOD in the C57BL/J strain was two- and fourfold higher in the CB and CP, respectively, versus the other strains. These results suggest that the enhanced vulnerability of the C57BL/J strain to neurotoxicants may not be due to a decreased capacity for DNA repair, but rather, the significantly higher activity of SODs, which may cause these pathways to become more readily saturated.
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Encéfalo/enzimologia , DNA-Formamidopirimidina Glicosilase/metabolismo , Desoxiguanosina/análogos & derivados , Neurônios/enzimologia , 8-Hidroxi-2'-Desoxiguanosina , Animais , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/genética , Desoxiguanosina/metabolismo , Tolerância a Medicamentos/genética , Regulação Enzimológica da Expressão Gênica/fisiologia , Predisposição Genética para Doença/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Doenças Neurodegenerativas/enzimologia , Doenças Neurodegenerativas/genética , Neurotoxinas/farmacologia , Especificidade da Espécie , Superóxido Dismutase/metabolismoRESUMO
Ethylene dibromide (EDB) has been used as a model compound for eliciting hepato- and nephrotoxicity. Conjugation with glutathione (GSH) has been shown to play a role in the bioactivation of EDB. The aim of this study was to determine whether activation of alpha(1)-adrenergic receptors, which causes a decrease in cellular GSH levels, could modulate the nephrotoxicity of EDB. For this purpose, male ICR mice were treated with EDB and/or the alpha-adrenergic agonist, phenylephrine (Pe), or the alpha-adrenergic antagonist, phentolamine (Phe). Animals treated with EDB (40 mg/kg, i.p.) had a 9.3-fold increase in urinary gamma-glutamyltranspeptidase (GGTP: EC 2.3.2.2) activity and a 38% decrease in renal non-protein bound sulfhydryl (NPSH) levels; however, animals co-treated with EDB and Pe (50 mg/kg, i.p.) exhibited a 27.8-fold increase in urinary GGTP activity and a 60% decrease in NPSH levels. The enhanced presence of urinary GGTP and decrease in cellular levels of NPSH was nearly blocked by treating animals concomitantly with EDB and Phe (10 mg/kg, i.p.) or EDB, Pe, and Phe. Histopathological examination revealed the enhanced degree of tissue damage and necrosis following treatment with EDB and Pe, and the protective effect of Phe at ameliorating EDB toxicity. These results indicate that factors that can influence alpha-adrenergic receptors may be critical in assessing dose-response data used in the risk assessment process.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 1 , Agonistas alfa-Adrenérgicos/toxicidade , Dibrometo de Etileno/toxicidade , Inseticidas/toxicidade , Nefropatias/induzido quimicamente , Antagonistas Adrenérgicos alfa/toxicidade , Animais , Catecolaminas/sangue , Sinergismo Farmacológico , Rim/efeitos dos fármacos , Rim/enzimologia , Rim/metabolismo , Nefropatias/enzimologia , Nefropatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fentolamina/toxicidade , Fenilefrina/toxicidade , Compostos de Sulfidrila/metabolismo , gama-Glutamiltransferase/urinaRESUMO
The efficacy and safety of two polyvalent horse-derived antivenoms in Bothrops asper envenomings were tested in a randomized, double-blind, clinical trial performed in Colombia. Both antivenoms were manufactured from the same pool of hyperimmune plasma. Antivenom A was made of F(ab')2 fragments, generated by pepsin digestion and caprylic acid precipitation, whereas antivenom B consisted of whole IgG molecules produced by caprylic acid precipitation followed by ion-exchange chromatography. Besides the different nature of the active substance, antivenom B had higher protein concentration, slightly higher turbidity and aggregate content. No significant differences were observed in the efficacy of antivenoms. Both halted local and systemic bleeding (P = 0.40) within 6-12 h of treatment in 100% of the cases, and restored blood coagulation (P = 0.87) within 6-24 h in 84.7% of patients, and within 48 h in all of them, in agreement with restoration of plasma fibrinogen concentration. Venom concentrations in serum dropped significantly (P < 0.001), to very low levels, 1 h after antivenom infusion. Nevertheless, eight patients (11.1%), four for each antivenom, presented recurrence of venom antigenaemia at different times, from 6 to 96 h, with clinical significance (recurrent coagulopathy) only in one group B patient (2.9%). Serum creatine kinase (CK) activity was increased, as a consequence of local myonecrosis. There was no significant difference (P = 0.51) in the incidence of early adverse reactions to antivenom administration (28.9% for patients of group A and 20.6% for patients of group B), most of the reactions being mild, mainly cutaneous. The most frequent complications were cellulitis (16.7%), abscess formation (5.6%), acute renal failure (8.3%), and compartmental syndrome (5.6%). In conclusion, IgG and F(ab')2 antivenoms, prepared by caprylic acid fractionation, presented similar efficacy and safety profiles for the treatment of B. asper envenomings in Colombia.