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Over the COVID-19 pandemic, the impact of enduring mental health on healthcare workers has become increasingly evident. This review focuses on post-pandemic mental health challenges faced by healthcare personnel in Latin America. This highlights the persistent burden on healthcare workers, especially women, which is exacerbated by economic disparities, inadequacies in the healthcare system, and ongoing occupational stressors. Our literature review, utilizing databases such as PubMed, Scopus, and Google Scholar, scrutinized the mental health status of healthcare professionals in the region after the pandemic's peak. The analysis indicated sustained levels of psychological distress, with frontline workers and women continuing to be affected disproportionately. These findings emphasize the urgent need for personalized interventions to effectively address the complex mental health challenges in this context. This review advocates strategic interventions, including tailored psychological support, innovative diagnostics, and technological solutions, integrated into patient-centered care models. Such approaches aim to enhance the mental resilience and overall well-being of healthcare professionals across Latin America in the post-COVID era.
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BACKGROUND AND AIMS: Stress-related to self-isolation during the COVID-19 pandemic has shown a strong correlation with issues in the diet and health of the population. In this study, we aimed to relate the perceived stress of a group of Ecuadorian adults with emotional eating. METHODS: Cross-sectional design study. We applied validated questionnaires of perceived stress and emotional eating to adults of both sexes who virtually completed a form between the months of January and March 2021. The analyzes were carried out using Chi2 statistical tests, Student's t-tests and a multiple linear regression model., the analyzes were performed using the statistical software R. RESULTS: The sample was composed of 2333 participants, the median age was 25 years (interquartile range 21-37 years). Females reported more perceived stress than males (77.91% vs. 22.09%). Nearly 64% of participants who displayed perceived stress were emotional eaters. A statistically significant association was found between the emotional eating score and perceived stress (p < 0.001), the effect was an elevation of 0.44 points in the emotional eating score for each stress point perceived. For each unit increase in BMI the emotional eating score increased 0.26 units (p < 0.001) and for each unit increase in age the emotional eating score decreased by 0.27 units (p = 0.03). CONCLUSIONS: It is concluded that stress is associated to emotional eating. Dietary intake that responds to emotions and not to physiological hunger may have long-term problems related to unhealthy diet. It is recommended to consider stress and emotional eating in the nutritional care process of people.
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COVID-19 , Comportamento Alimentar , Adulto , Estudos Transversais , Emoções , Comportamento Alimentar/psicologia , Feminino , Humanos , Masculino , Pandemias , Estresse Psicológico/psicologia , Adulto JovemRESUMO
BACKGROUND: Acute psychological stressors such as anger can precipitate ventricular arrhythmias, but the mechanism is incompletely understood. Quantification of regional myocardial sympathetic activity with 123I-metaiodobenzylguanidine (123I-mIBG) SPECT imaging in conjunction with perfusion imaging during mental stress may identify a mismatch between perfusion and sympathetic activity that may exacerbate a mismatch between perfusion and sympathetic activity that could create a milieu of increased vulnerability to ventricular arrhythmia. METHODS: Five men with ischemic cardiomyopathy (ICM), and five age-matched healthy male controls underwent serial 123I-mIBG and 99mTc-Tetrofosmin SPECT/CT imaging during an anger recall mental stress task and dual isotope imaging was repeated approximately 1 week later during rest. Images were reconstructed using an iterative reconstruction algorithm with CT-based attenuation correction. The mismatch of left ventricular myocardial 123I-mIBG and 99mTc-Tetrofosmin was assessed along with radiotracer heterogeneity and the 123I-mIBG heart-to-mediastinal ratios (HMR) were calculated using custom software developed at Yale. RESULTS: The hemodynamic response to mental stress was similar in both groups. The resting-HMR was greater in healthy control subjects (3.67 ± 0.95) than those with ICM (3.18 ± 0.68, P = .04). Anger recall significantly decreased the HMR in ICM patients (2.62 ± 0.3, P = .04), but not in normal subjects. The heterogeneity of 123I-mIBG uptake in the myocardium was significantly increased in ICM patients during mental stress (26% ± 8.23% vs. rest: 19.62% ± 9.56%; P = .01), whereas the 99mTc-Tetrofosmin uptake pattern was unchanged. CONCLUSION: Mental stress decreased the 123I-mIBG HMR, increased mismatch between sympathetic activity and myocardial perfusion, and increased the heterogeneity of 123I-mIBG uptake in ICM patients, while there was no significant change in myocardial defect size or the heterogeneity of 99mTc-Tetrofosmin perfusion. The changes observed in this proof-of-concept study may provide valuable information about the trigger-substrate interaction and the potential vulnerability for ventricular arrhythmias.
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Cardiomiopatias , Isquemia Miocárdica , 3-Iodobenzilguanidina , Ira , Arritmias Cardíacas , Coração/diagnóstico por imagem , Humanos , Radioisótopos do Iodo , Masculino , Isquemia Miocárdica/diagnóstico por imagem , Miocárdio , Compostos Radiofarmacêuticos , Estresse Psicológico/diagnóstico por imagem , Sistema Nervoso Simpático/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
The reduction of hours of sleep affects the physical and mental health of people. Having unhealthy sleep habits are associated with a greater occurrence of daytime sleepiness, which in turn has been related to poorer nutritional status. The objective of this study was to relate food intake, anthropometric measurements, and daytime sleepiness in Ecuadorian adults. Non-experimental, cross-sectional study, the sample included 400 men and women between 18 and 65 years of age, who attended an outpatient consultation of general medicine, family medicine, and traumatology services of a public hospital in Quito-Ecuador. Anthropometric and body composition measurements were measured using tetrapolar bio-impedance, following the recommendations of the International Society for the Advancement of Anthropometry (ISAK). Caloric intake was measured using a 24-hour recall and for daytime sleepiness (DS) the Epworth questionnaire was used. Statistical analyzes were performed using R. From the sample 56.5% presented DS, which affected women more frequently compared to men (p < 0.05). Differences were found between body measurements and dietary intake between groups of people with and without DS. Caloric intake, waist circumference, percentage of fat mass were higher in people with DS (p < 0.05), while muscle mass was higher in subjects without DS (p <0.05). No differences were found concerning visceral fat. We conclude that SD is related to less healthy values in terms of dietary intake and anthropometric measures(AU)
La reducción de las horas de sueño afecta la salud física y mental de las personas. Tener hábitos de sueño poco saludables se asocia a una mayor ocurrencia de somnolencia diurna, lo que a su vez se ha relacionado con un peor Estado Nutricional. El objetivo de este estudio fue relacionar la ingesta de alimentos, las medidas antropométricas y la somnolencia diurna en adultos ecuatorianos. Estudio no experimental, transversal n=400 hombres y mujeres entre 18 y 65 años, que acudieron a consulta externa de los servicios de medicina general, medicina familiar y traumatología de un hospital público de Quito, Ecuador tomado como referencia. Se tomaron medidas antropométricas siguiendo las recomendaciones de la Sociedad Internacional para el Avance de la Antropometría (ISAK) y de composición corporal a través de la bioimpedancia tetrapolar. La ingesta calórica se midió mediante un recordatorio de 24 horas y para somnolencia diurna (SD)se utilizó el cuestionario de Epworth. Los análisis estadísticos se realizaron utilizando el software R. 56,5% de la muestra presenta SD, que afectó con mayor frecuencia a las mujeres en comparación con los hombres (p <0,05). Se encontraron diferencias entre las medidas corporales y la ingesta dietética entre grupos de personas con SD y sin ella. La ingesta calórica, la circunferencia de la cintura, el porcentaje de masa grasa fue mayor en personas con SD (p <0.05), mientras que la masa muscular fue mayor en sujetos sin SD (p <0.05). No se encontraron diferencias en relación con la grasa visceral. Concluimos que SD está relacionada con valores menos saludables en cuanto a ingesta dietética y medidas antropométricas(AU)
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Pesos e Medidas Corporais , Ingestão de Alimentos , Comportamento Alimentar , Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Composição Corporal , Estado Nutricional , Estudos Transversais , Distribuição por Sexo , Equador/epidemiologia , Fatores de Risco CardiometabólicoRESUMO
A theoretical physicochemical and thermodynamic investigation of the adsorption of heavy metals Zn2+, Cd2+, Ni2+, and Cu2+on carbon-based adsorbents was performed with statistical physics fundaments. Particularly, the experimental adsorption isotherms of heavy metal removal, at 30°C and pH 5, using adsorbents obtained from the pyrolysis of three biomasses (cauliflower cores, broccoli stalks, and coconut shell) were modelled and interpreted with a homogeneous statistical physics adsorption model. Calculations indicated that the heavy metal adsorption with these carbon-based materials was a multi-ionic process where several ions interact simultaneously with the same carboxylic functional group on the adsorbent surface. Adsorption capacities for these metal ions and adsorbents were correlated with electronegativity theory, which established that the adsorbate with the highest electronegativity was more readily adsorbed by the carboxylic functional groups available on the adsorbent surfaces. Also, the chemical compositions of biomass precursors explained achieved adsorption capacities for these metallic ions. The best adsorbent for heavy metal removal was obtained from CC biomass pyrolysis. Calculated adsorption energies for heavy metal removal could be associated with physisorption-type forces. Finally, the adsorption mechanism analysis was complemented with the determination of adsorption thermodynamic functions using the statistical physics.
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Metais Pesados , Poluentes Químicos da Água , Adsorção , Cádmio , Carbono , Concentração de Íons de Hidrogênio , Íons , Cinética , ZincoRESUMO
BACKGROUND: Planar equilibrium radionuclide angiocardiography (ERNA) has been used as the gold standard for assessment of left ventricular (LV) function for over three decades. However, this imaging modality has recently gained less favor due to growing concerns about radiation exposure. We developed a novel approach that involves integrating short axis slices of gated bloodpool SPECT for quantification of LV function with improved signal-to-noise ratio and reduced radioactive dose while maintaining image quality and quantitative precision. METHODS: Twenty patients referred for ERNA underwent standard in vitro 99mTc-labeling of red blood cells (RBC), and were initially imaged following a low-dose (~ 8 mCi) injection using a dedicated cardiac SPECT camera, and then had planar imaging following a high-dose (~ 25 mCi) injection. Four different quantification methods were utilized to assess the LV function and were compared for quantitative precision and inter-observer reproducibility of the quantitative assessments. RESULTS: The Yale method resulted in the most consistent assessment of LV function compared with the gold standard high-dose ERNA method, along with excellent inter-observer reproducibility. CONCLUSIONS: The new low-dose 99mTc-RBC imaging method provides precise quantification of LV function with a greater than 67% reduction in dose and may potentially improve assessment of regional function.
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Tomografia Computadorizada por Emissão de Fóton Único de Sincronização Cardíaca/métodos , Imagem do Acúmulo Cardíaco de Comporta/métodos , Compostos Radiofarmacêuticos , Pertecnetato Tc 99m de Sódio , Disfunção Ventricular Esquerda/diagnóstico por imagem , Idoso , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Volume Sistólico , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND: Quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) has shown diagnostic and prognostic values for the assessment of coronary artery disease (CAD). This study aimed to evaluate in patients a highly automatic Yale-MQ (myocardial blood flow quantification) software incorporated with a novel image segmentation approach for quantification of global and regional MBF and MFR from dynamic 82Rb cardiac positron emission tomography (PET). METHODS: Global and regional MBFs and MFRs were quantified in 80 patients (18 normal and 62 CAD subjects) by two different observers using the Yale-MQ software. Lower limits of normal (LLN) values and intra- and inter-observer variabilities of MBFs and MFRs were calculated for the assessment of quantitative precision. The Yale-MQ was compared with a commercially available software (Corridor 4DM) being used as a reference. RESULTS: The Yale-MQ method provided precise assessments of LLNs of MBF and MFR. The global and regional MBFs and MFR quantified via Yale-MQ were correlated strongly with those via Corridor4DM (R ≥ 0.867). The intra- and inter-observer variabilities of MBFs and MFRs quantified via Yale-MQ were small (≤ 7.7% for MBFs and ≤ 10.0% for MFRs) with excellent correlations (R ≥ 0.980 for MBFs and R ≥ 0.976 for MFRs). CONCLUSIONS: The new Yale-MQ software associated with the automatic processing scheme provides a highly reproducible clinical tool for precise quantification of MBF and MFR in patients with reliable LLN values.
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Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Processamento de Imagem Assistida por Computador , Imagem de Perfusão do Miocárdio , Tomografia por Emissão de Pósitrons , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , SoftwareRESUMO
Children from out-of-home care are a vulnerable population that faces high stress and anxiety levels due to stressful experiences, such as being abused, being raped, and violence. This problem could have negative effects on their bio-psycho-social well-being if they are not provided with comprehensive psychological treatment. Numerous methods have been developed to help them relax, but there are no current approaches for assessing the relaxation level they reach. Based on this, a novel smart sensor that can evaluate the level of relaxation a child experiences is developed in this paper. It evaluates changes in thermal biomarkers (forehead, right and left cheek, chin, and maxillary) and heart rate (HR). Then, through a k-nearest neighbors (K-NN) intelligent classifier, four possible levels of relaxation can be obtained: no-relax, low-relax, relax, and very-relax. Additionally, an application (called i-CARE) for anxiety management, which is based on biofeedback diaphragmatic breathing, guided imagery, and video games, is evaluated. After testing the developed smart sensor, an 89.7% accuracy is obtained. The smart sensor used provides a reliable measurement of relaxation levels and the i-CARE application is effective for anxiety management, both of which are focused on children exposed to out-of-home care conditions.
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Serviços de Assistência Domiciliar , Biorretroalimentação Psicológica , Criança , Frequência Cardíaca , Humanos , Jogos de VídeoRESUMO
The aim of this work was to evaluate the bioenergy potential of cocoa residue via anaerobic digestion. Batch and fed-batch lab-scale reactors were operated under low and high solids conditions. In the batch tests, 59⯱â¯4% of Chemical Oxygen Demand (COD) was recovered as methane. This corresponded with an average methane yield of 174 (wet) and 193 (dry)â¯Lâ¯kg-1 volatile solids fed, whereas a series of fed-batch reactors produced 70⯱â¯24 (wet) and 107⯱â¯39 (dry)â¯Lâ¯CH4â¯kg-1 volatile solids fed during stable conditions. A case study was developed for canton Balao (Ecuador) based on our experimental data, operational estimates and available cocoa waste in the area. Annually, 8341â¯MWh could be produced, meeting 88% of the current electricity demand in Balao. This case study proves the potential for cocoa waste as a source of renewable energy in rural areas.
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Biocombustíveis , Metano/biossíntese , Energia Renovável , Anaerobiose , Análise da Demanda Biológica de Oxigênio , Biomassa , Reatores BiológicosRESUMO
Assessment of cardiac 123I-meta iodobenzylguanidine (123I-mIBG) uptake relies on the heart-to-mediastinum ratio (HMR) derived from planar images. We have developed novel semiautomated quantitative methodologies for assessing HMR from SPECT images using a dedicated cardiac multipinhole SPECT/CT system and determined the lower limit of normal (LLN) SPECT-derived HMR and the correlation to planar-derived HMR. Methods: Twenty-one healthy volunteers were injected with 123I-mIBG and imaged using 2 different cameras. Planar images were acquired using a conventional SPECT camera equipped with parallel hole collimators, and hybrid SPECT/CT images were acquired using a dedicated cardiac SPECT system with 19 pinhole collimators interfaced with 64-slice CT. Planar HMR was calculated as per standard guidelines (manual traditional method) and elliptic region-of-interest (Elip-ROI) and region-growing (RG-ROI) techniques. SPECT HMR was quantified using a new method that incorporates various cardiac and mediastinal segmentation schemes in which upper and lower limits of the heart were determined from CT and the left ventricular ROI, and mean counts were calculated using Elip-ROI and RG-ROI techniques. Mean counts in mediastinal ROI were computed from a fixed volume in 3 different regions: upper mediastinum (UM), lower mediastinum (LM), and contralateral lung (CL). HMRs were processed by 2 observers, and reproducibility was assessed by intraclass correlation coefficient and Bland-Altman analysis. Results: Planar HMR calculated using the RG-ROI method showed highest intra- and interobserver levels of agreement compared with Elip-ROI and manual traditional methods. SPECT HMR calculated on the basis of UM, LM, and CL background regions showed excellent intra- and interobserver agreement. SPECT HMR with UM resulted in highest correlation (R = 0.91) with planar HMR compared with that with LM (R = 0.74) and CL (R = 0.73). The LLN of SPECT HMR with UM and that of planar HMR was calculated as 5.5 and 1.6, respectively. The normal values of SPECT-derived HMR and planar-derived HMR were correlated linearly. Conclusion: We reconfirmed the previous planar HMR threshold and determined SPECT LLN HMR for SPECT. Planar HMR can be estimated from SPECT HMR via a simple linear regression equation, allowing use of the new cardiac-dedicated SPECT camera for 123I-mIBG imaging.
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3-Iodobenzilguanidina/farmacocinética , Coração/diagnóstico por imagem , Mediastino , Miocárdio/metabolismo , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/normas , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
PURPOSE: Segmentation of contrast-enhanced CT and measurement of SPECT point spread function (PSF) are usually required for conventional partial volume correction (PVC). This study was to develop a segmentation-free method with blind deconvolution (BD) and anatomical-based filtering for SPECT PVC. METHODS: The proposed method was implemented using an iterative BD algorithm to estimate the restored image and the PSF simultaneously. An anatomical-based filtering was implemented at each iteration to reduce Gibbs artifact and suppress noise amplification in the deconvolution process. The proposed method was validated with 123 I-metaiodobenzylguanidine (123 I-mIBG) SPECT/CT imaging of NCAT phantoms with and without myocardial perfusion defect and a physical cardiac phantom. Fifteen heart-to-mediastinum ratios (HMRs) were configured in the NCAT and physical phantoms. Correlations between SPECT-quantified and true HMRs were calculated from images without PVC as well as from BD restored images. The proposed method was also performed on a human 123 I-mIBG study. RESULTS: Relative bias and standard deviation images of NCAT phantoms showed that the proposed method reduced both bias and noise. Mean relative bias in the simulated normal myocardium was markedly improved (-16.8% ± 0.4% versus -0.8% ± 0.6% for low noise level; -16.7% ± 0.7% versus -2.3% ± 0.9% for high noise level). Mean relative bias in the simulated myocardial defect was also noticeably improved (-12.7% ± 1.2% versus 1.2% ± 1.6% for low noise level; -13.5% ± 2.4% versus -0.9% ± 2.8% for high noise level). The signal to noise ratio (SNR) of the defect was improved from 2.95 ± 0.09 to 4.07 ± 0.16 for low noise level (38% increase of mean), and from 2.56 ± 0.15 to 3.62 ± 0.22 for high noise level (41% increase of mean). For both NCAT and physical phantoms, HMRs calculated from images without PVC were underestimated (correlations between SPECT-quantified and true HMRs: y = 0.81x + 0.1 for NCAT phantom; y = 0.82x + 0.14 for physical phantom). HMRs from BD restored images were markedly improved (correlations between SPECT-quantified and true HMRs: y = x + 0.05 for NCAT phantom; y = 0.97x - 0.12 for physical phantom). After applying the proposed PVC method, the estimation error between the SPECT-quantified and true HMRs was significantly reduced from -0.75 ± 0.57 to 0.04 ± 0.17 for NCAT phantom (P = 8e-05), and from -0.68 ± 0.67 to -0.26 ± 0.42 for physical phantom (P = 0.005). The human study demonstrated that the HMR increased by 8% with PVC. CONCLUSIONS: The proposed segmentation-free PVC method has the potential of improving SPECT quantification accuracy and reducing noise without the need for premeasuring the image PSF.
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3-Iodobenzilguanidina , Coração/anatomia & histologia , Coração/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Imagens de Fantasmas , Razão Sinal-RuídoRESUMO
Chronic renal disease (CRD) in its pre-dialysis stage is an important risk factor for mortality among adults. The aim of this study was to assess the effects of CRD on mortality among consultants in Chilean public primary care clinics. We obtained information about serum creatinine, urinary albumin excretion (UAE), blood pressure, and body mass index of 5224 consultants [3379 females aged 67 (59-75) years and 1845 males aged 68 (59-75) years] in three clinics of Metropolitan Santiago. Kaplan-Meier curves and Cox proportional hazard regression models were used to determine risk factors for mortality, determined 41 months after obtaining the blood samples. During the follow-up period, 262 patients died (33% due to circulatory causes and 29% due to tumors). Kaplan-Meier curves showed that there was a significant association between survival, estimated glomerular filtration rate, and UAE. Cox models showed that serum creatinine, UAE, a lower body mass index, and a history of diabetes were significant mortality predictors. A sensitivity analysis performed eliminating extreme ages (less than 50 and more than 80 years), included high diastolic pressure as a predictor of survival. We conclude that among patients with CRD in its pre-dialysis stage, UAE is an important predictor of survival, along with serum creatinine. A low body mass index was associated with a higher mortality.
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Albuminúria/epidemiologia , Creatinina/sangue , Diabetes Mellitus/epidemiologia , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/mortalidade , Idoso , Pressão Sanguínea , Índice de Massa Corporal , Chile/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde , Prognóstico , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
The monoamine vesicular transporter 2 (VMAT-2) has been associated with dopamine (DA) sequestration and protection against neurodegeneration caused by the intracellular oxidation of this monoamine. The data presented herein suggest that methylphenidate treatment enhances the amount of VMAT-2 protein and possibly its activity in the presynaptic cytosol, where it is able to increase the sequestration of DA and likely protect against its instability. In contrast, methamphetamine (METH) has an opposite effect on cytosolic VMAT-2 resulting in degradation of DA terminals. The fact that posttreatment of methylphenidate after a neurotoxic regimen of METH protects against resulting loss of DA parameters suggests that treatment with methylphenidate, or other DA transporter blockers, may be protective against degenerative disorders of DA pathways, such as Parkinson's disease.
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Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Metanfetamina/farmacologia , Metanfetamina/uso terapêutico , Metilfenidato/farmacologia , Metilfenidato/uso terapêutico , Animais , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Masculino , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Transporte Proteico/efeitos dos fármacos , Transporte Proteico/fisiologia , Ratos , Ratos Sprague-Dawley , Proteínas Vesiculares de Transporte de Aminas BiogênicasRESUMO
It has been hypothesized that high-dose methamphetamine treatment rapidly redistributes cytoplasmic dopamine within nerve terminals, leading to intraneuronal reactive oxygen species formation and well characterized persistent dopamine deficits. We and others have reported that in addition to this persistent damage, methamphetamine treatment rapidly decreases vesicular dopamine uptake, as assessed in purified vesicles prepared from treated rats; a phenomenon that may contribute to aberrant intraneuronal dopamine redistribution proposedly caused by the stimulant. Interestingly, post-treatment with dopamine transporter inhibitors protect against the persistent dopamine deficits caused by methamphetamine; however, mechanisms underlying this phenomenon have not been elucidated. Also of interest are findings that dopamine transporter inhibitors, including methylphenidate, rapidly increase 1) vesicular dopamine uptake, 2) vesicular monoamine transporter-2 (VMAT-2) ligand binding, and 3) VMAT-2 immunoreactivity in a vesicular subcellular fraction prepared from treated rats. Therefore, we hypothesized that methylphenidate post-treatment might protect against the persistent striatal dopamine deficits caused by methamphetamine by rapidly affecting VMAT-2 and vesicular dopamine content. Results reveal that methylphenidate post-treatment both prevents the persistent dopamine deficits and reverses the acute decreases in vesicular dopamine uptake and VMAT-2 ligand binding caused by methamphetamine treatment. In addition, methylphenidate post-treatment reverses the acute decreases in vesicular dopamine content caused by methamphetamine treatment. Taken together, these findings suggest that methylphenidate prevents persistent methamphetamine-induced dopamine deficits by redistributing vesicles and the associated VMAT-2 protein and presumably affecting dopamine sequestration. These findings not only provide insight into the neurotoxic effects of methamphetamine but also mechanisms underlying dopamine neurodegenerative disorders, including Parkinson's disease.
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Inibidores da Captação Adrenérgica/farmacologia , Corpo Estriado/efeitos dos fármacos , Dopamina/metabolismo , Metanfetamina/antagonistas & inibidores , Metilfenidato/farmacologia , Animais , Monoaminas Biogênicas/metabolismo , Transporte Biológico , Corpo Estriado/metabolismo , Técnicas In Vitro , Masculino , Metanfetamina/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores Dopaminérgicos/metabolismoRESUMO
Previous studies indicate that reserpine may disrupt dopamine transporter activity. Results presented herein reveal that it also inhibits potently synaptosomal [3H]dopamine uptake. In addition, reserpine administration to rats decreased the V(max) of synaptosomal dopamine transport, as assessed ex vivo 12 h after treatment. This decrease appeared, at least in part, dissociated from concurrent inhibition of the vesicular monoamine transporter-2 (VMAT-2). In separate experiments, synaptosomal dopamine uptake did not differ between wild-type and heterozygous VMAT-2 knockout mice, and reserpine treatment did not inhibit [3H]dopamine uptake into cells heterogously expressing the human dopamine transporter. Taken together, these data suggest that reserpine may transiently alter dopamine transporter function in a noncompetitive, indirect manner.
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Proteínas de Membrana Transportadoras/fisiologia , Proteínas do Tecido Nervoso , Neuropeptídeos , Reserpina/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Dopamina/farmacocinética , Proteínas da Membrana Plasmática de Transporte de Dopamina , Humanos , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/fisiologia , Camundongos , Camundongos Knockout , Ratos , Ratos Sprague-Dawley , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Fatores de Tempo , Trítio , Células Tumorais Cultivadas , Proteínas Vesiculares de Transporte de Aminas Biogênicas , Proteínas Vesiculares de Transporte de MonoaminaRESUMO
It is well accepted that methylphenidate (MPD) inhibits dopamine (DA) transporter function. In addition to this effect, this study demonstrates that MPD increases vesicular [3H]DA uptake and binding of the vesicular monoamine transporter-2 (VMAT-2) ligand dihydrotetrabenazine (DHTBZ) in a dose- and time-dependent manner in purified striatal vesicles prepared from treated rats. This change did not result from residual MPD introduced by the original in vivo treatment, because application of MPD in vitro (< or =1 miccrom) was without effect, and higher concentrations decreased vesicular [3H]DA uptake. In addition, MPD treatment increased and decreased VMAT-2 immunoreactivity in striatal vesicle subcellular and plasmalemmal membrane fractions, respectively. The MPD-induced increase in both VMAT-2 immunoreactivity and DHTBZ binding was attenuated by pretreatment in vivo with either the DA D(1) receptor antagonist SCH23390 or the DA D2 receptor antagonist eticlopride. Coadministration of these antagonists in vivo inhibited completely the MPD-induced increase in DHTBZ binding in the purified vesicular preparation. These observations suggest a role for DA in the MPD-induced redistribution of VMAT-2. The implications of this phenomenon will be discussed.
Assuntos
Corpo Estriado/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras , Metilfenidato/farmacologia , Neuropeptídeos , Receptores Dopaminérgicos/metabolismo , Sinaptossomos/metabolismo , Tetrabenazina/análogos & derivados , Animais , Ligação Competitiva/efeitos dos fármacos , Western Blotting , Corpo Estriado/química , Dopamina/metabolismo , Dopamina/farmacocinética , Dopaminérgicos/farmacologia , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Masculino , Glicoproteínas de Membrana/química , Transporte Proteico/efeitos dos fármacos , Ratos , Frações Subcelulares/química , Frações Subcelulares/metabolismo , Sinaptossomos/química , Tetrabenazina/farmacocinética , Proteínas Vesiculares de Transporte de Aminas Biogênicas , Proteínas Vesiculares de Transporte de MonoaminaRESUMO
Recent studies demonstrated that vesicular dopamine (DA) uptake can be rapidly altered in synaptic vesicles purified from the striata of stimulant-treated rats. Specifically, a single administration of the plasmalemmal DA transporter inhibitor, cocaine, or the DA D(2) agonist, quinpirole, increases vesicular DA uptake in vesicles purified from the striata of treated rats. These effects of cocaine are prevented by pretreatment with a D(2), but not D(1), DA receptor antagonist. The purpose of the present study was to characterize the effect of a mechanistically different psychostimulant, methamphetamine (METH), on vesicular DA uptake. Results demonstrated that a single administration of this DA-releasing agent rapidly and reversibly decreased vesicular DA uptake. The METH-related decrease in vesicular DA uptake was attenuated by pretreatment with the D(2) antagonist, eticlopride, but not the D(1) antagonist, SCH23390 (R-[+]-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine). Core body temperature did not contribute to the effects of METH on vesicular DA uptake. Neither quinpirole nor cocaine increased vesicular DA uptake when rats were concurrently treated with METH. These studies provide further evidence that psychostimulants rapidly and differentially modify vesicular DA uptake. In addition, these studies demonstrate a complex role for D(2) DA receptors in altering vesicular DA transport.
Assuntos
Antagonistas de Dopamina/farmacologia , Dopamina/metabolismo , Glicoproteínas de Membrana , Moduladores de Transporte de Membrana , Proteínas de Membrana Transportadoras/antagonistas & inibidores , Metanfetamina/farmacologia , Proteínas do Tecido Nervoso , Animais , Estimulantes do Sistema Nervoso Central/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina , Cinética , Masculino , Quimpirol/farmacologia , Ratos , Ratos Sprague-Dawley , Valores de ReferênciaRESUMO
Administration of a high-dose regimen of methamphetamine (METH) rapidly and profoundly decreases plasmalemmal and vesicular dopamine (DA) transport in the striatum, as assessed in synaptosomes and purified vesicles, respectively. To determine whether these responses were common to other amphetamines of abuse, effects of methylenedioxymethamphetamine (MDMA) on the plasmalemmal DA transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2) were assessed. Similar to effects of METH reported previously, multiple high-dose MDMA administrations rapidly (within 1 h) decreased plasmalemmal DA uptake, as assessed ex vivo in synaptosomes prepared from treated rats. Unlike effects of multiple METH injections, this deficit was reversed completely 24 h after drug treatment. Also in contrast to effects of multiple METH injections, 1) MDMA caused little or no decrease in binding of the DAT ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of DA prevented the MDMA-induced reduction in plasmalemmal DA transport. However, a role for phosphorylation was suggested because pretreatment with protein kinase C inhibitors attenuated the deficit caused by MDMA in an in vitro model system. In addition to affecting DAT function, MDMA rapidly decreased vesicular DA transport as assessed in striatal vesicles prepared from treated rats. Unlike effects of multiple METH injections reported previously, this decrease partially recovered by 24 h after drug treatment. Taken together, these results reveal several differences between effects of MDMA and previously reported METH on DAT and VMAT-2; differences that may underlie the dissimilar neurotoxic profile of these agents.
Assuntos
Cocaína/análogos & derivados , Dopamina/metabolismo , Alucinógenos/toxicidade , N-Metil-3,4-Metilenodioxianfetamina/toxicidade , Proteínas do Tecido Nervoso , Neuropeptídeos , Neurotoxinas/toxicidade , Vesículas Sinápticas/efeitos dos fármacos , Tetrabenazina/análogos & derivados , Animais , Transporte Biológico/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Cocaína/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina , Inibidores da Captação de Dopamina/toxicidade , Cinética , Masculino , Glicoproteínas de Membrana/biossíntese , Proteínas de Membrana Transportadoras/biossíntese , Metanfetamina/toxicidade , Ratos , Ratos Sprague-Dawley , Tetrabenazina/farmacocinética , Proteínas Vesiculares de Transporte de Aminas Biogênicas , Proteínas Vesiculares de Transporte de MonoaminaRESUMO
Antecedentes: el tétanos es una enfermedad cada vez menos frecuente y con mejor pronóstico. Sin embargo, la supervivencia de estos pacientes nos enfrenta a nuevas complicaciones. Objetivo: reporta un caso de tétanos que, además de las complicaciones pulmonares esperadas, desarrolló hipercalcemia relacionada con la inmovilización prolongada. Material y métodos: ingresó un paciente con herida punzocortante en el antebrazo; se manejó con sedación, relajación muscular, antibióticos, apoyo ventilatorio mecánico, insulina y nutrición parenteral. Resultados: egresó a los 128 días de hospitalización y permaneció en programa de diálisis peritoneal continua ambulatoria (DPCA) y rehabilitación física. Conclusiones: en la actualidad, los pacientes con diagnóstico de tétanos severo pueden recibir apoyo multisistémico, por lo cual las complicaciones relacionadas tienen una mejor evolución y disminuye la mortalidad. Ahora se deben enfrentar otras complicaciones que repercuten en el pronóstico de estos pacientes