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Objectives: Dementia is an oxidative stress-related disease. Coenzyme Q10 is a nutrient that occurs naturally in the human body and acts as an antioxidant. The purpose of this study was to investigate the relationships of coenzyme Q10 status, biomarkers for dementia (amyloid ß and tau protein), and antioxidant capacity in patients with dementia. Methods: Eighty dementia patients aged ≥60 years and with a mini mental state examination (MMSE) score ≤ 26 were enrolled. The levels of coenzyme Q10, total antioxidant capacity (TAC), amyloid ß, and tau protein were measured. Results: A total of 73% of patients had a low coenzyme Q10 status. Patients with low coenzyme Q10 status had a significantly higher level of serum amyloid ß-42 and amyloid ß-42/40 ratio (p < 0.05). Coenzyme Q10 status was significantly correlated with the values of TAC, MMSE score, amyloid ß-42, and amyloid ß-42/40 ratio (p < 0.05) but not with tau protein. Additionally, a high proportion of moderate dementia patients were found to have low coenzyme Q10 status (p = 0.07). Conclusion: Patients with dementia suffered from coenzyme Q10 deficiency, and the degree of deficiency was related to the level of amyloid-ß and antioxidant capacity. Since adequate level of coenzyme Q10 may delay the progression of dementia, monitoring coenzyme Q10 status in patients with dementia is necessary.
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Cognitive dysfunction is associated with functional impairment of patients with Major Depressive Disorder (MDD). The goals were to explore the associated factors of cognitive impairment in MDD and to develop and validate a brief and culture-relevant questionnaire, the Taiwan Cognition Questionnaire (TCQ), among patients with MDD. This was a cross-sectional, multi-center observational study of MDD patients in Taiwan. Participants of Group 1 from 10 centers contributed to the validation of the TCQ by their response and sociodemographics. The participants of Group 2 from one center received an objective cognitive assessment for clarification of the relationship between the TCQ score and its associated factors. In Group 1, 493 participants were recruited. As for Group 2, an extra 100 participants were recruited. The global Cronbach's alpha for the TCQ was 0.908. According to the coordinates of the ROC curve, 9/10 was the ideal cut-off point. With the criteria, the sensitivity/specificity of the TCQ was 0.610/0.689. The TCQ score was positively associated with a history of being admitted to acute psychiatric care and the severity of depression and negatively associated with objective cognitive measures. The TCQ provides a reliable, valid, and convenient measure of subjective cognitive dysfunction in patients with MDD.
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The purpose of this study was to investigate the nutritional status of dementia patients and examine the correlation with sarcopenia, frailty, depression, and quality of life. We enrolled patients aged 60 years and over with Mini Mental State Examination (MMSE) scores ≤ 26 (Taiwan), and dementia diagnosed by a neurologist or psychiatrist. Nutritional status was assessed with the Mini Nutritional Assessment (MNA). Muscle mass was measured by dual-energy X-ray absorptiometry. Muscle strength and endurance were evaluated by handgrip, leg-back strength, dumbbell curls, sit to stand test, and gait speed. Quality of life, frailty, and depression status were measured by questionnaires. Patients with moderate dementia (MMSE ≤ 20) had a significantly lower MNA score, muscle function, and quality of life than patients with mild dementia (p < 0.01). A lower MNA score was significantly associated with the risk of frailty (odds ratio: 4.76, p < 0.01), depression (odds ratio: 3.17, p = 0.03), and poor quality of life (odds ratio: 2.73, p < 0.05), and sarcopenia (odds ratio: 3.97, p = 0.03) after adjusting for potential confounders. In conclusion, patients with dementia were at risk of malnutrition, and nutritional status was associated to the risk of sarcopenia, frailty, depression, and quality of life.
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Demência , Fragilidade , Desnutrição , Sarcopenia , Idoso , Estudos Transversais , Demência/epidemiologia , Depressão/epidemiologia , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Avaliação Geriátrica , Força da Mão , Humanos , Desnutrição/diagnóstico , Pessoa de Meia-Idade , Estado Nutricional , Obesidade , Qualidade de Vida , Sarcopenia/complicações , Sarcopenia/diagnóstico , Sarcopenia/epidemiologiaRESUMO
OBJECTIVE: The TREVIDA study aimed to evaluate vortioxetine for the treatment of major depressive disorder (MDD) in Taiwanese adults. METHODS: Patients with active depressive episode were recruited in this non-interventional, prospective, multi-site study conducted between June 2019 and August 2020 in Taiwan. Patient eligibility was independent of the physician's decision to prescribe vortioxetine for an MDD episode. Vortioxetine was initiated on the first visit. Depression severity, cognitive function, work productivity, functioning and safety were evaluated over 3 months. RESULTS: Overall, 242 patients were analyzed. At baseline, 70.7% and 90.4% of patients had moderately severe-to-severe depression based on PHQ-9 (Patient Health Questionnaire-9) and TDQ (Taiwanese Depression Questionnaire), respectively. By Month 3, significant improvements from baseline in depression severity (mean [SD] changes in PHQ-9, TDQ and CGI-S [Clinical Global Impression-Severity]: -6.3 [7.3]; -13.2 [14.0]; -1.5 [1.3], respectively), cognitive function (mean [SD] change in PDQ-D: -8.0 [17.5]), functioning (mean [SD] change in SDS: -5.4 [7.6]), and presenteeism (38.9% from 56.3%), work productivity loss (40.9% from 58.7%) and activity impairment (43.2% from 61.0%) were observed (p < .001 for all). By month 3, patient-reported (PHQ-9) response and remission rates were 43.4% and 52.9%, respectively; physician-reported (CGI-S) response and remission rates were 29.0% and 31.6%, respectively. Vortioxetine was well-tolerated and no unexpected side effects were reported. CONCLUSIONS: Vortioxetine reduced depression severity and improved cognitive function, work productivity, and functioning in Taiwanese patients with MDD in the real-world setting. Vortioxetine was well-tolerated in this Taiwanese population.
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Transtorno Depressivo Maior , Adulto , Antidepressivos/efeitos adversos , Ásia , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Método Duplo-Cego , Humanos , Estudos Prospectivos , Sulfetos/efeitos adversos , Vortioxetina/uso terapêuticoRESUMO
Introduction: The interaction between hyperuricemia and the cognitive system is still under debate, with studies presenting somewhat conflicting results. Objectives: This study aimed to investigate the risk of dementia in patients with gout who are administered anti-inflammatory drug treatment. Methods: Gouty arthritis patients aged 50 years and older, who received at least one of the background therapy drugs (colchicine, corticosteroids, or nonsteroidal anti-inflammatory drugs for 6 months), were divided into the following groups and compared: patients who had dementia over a period of 5 years (n = 2,292) and matched patients without dementia (n = 2,292). Results: We found that the most significant risk factors for dementia were stroke (OR, 2.66; 95% C.I., 2.33-3.03; AOR, 2.39; 95% C.I., 2.08-2.75) and depression (OR, 3.72; 95% C.I., 3.01-4.6; AOR, 3.25; 95% C.I., 2.60-4.05). The results of anti-gout drug administration, which impacted the dementia risk among patients of all ages (but especially in 50-64-year-old patients), demonstrated a higher risk ratio after 90 days of corticosteroid use (OR, 3.39; 95% C.I., 1.15-9.99), which was further increased after 180 days (OR, 3.61; 95% C.I., 1.31-9.94). We revealed that female patients experienced a significant increase in dementia risk after 90 days of corticosteroid administration, whereas male patients experienced a significant increase only after 180 days (OR, 1.52; 95% C.I., 1.06-2.17). Conclusion: We had identified that > 90-day corticosteroid administration is a significant dementia risk factor in both female and male patients of all ages, especially in the 50-60-year-old group.
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Antirreumáticos/efeitos adversos , Demência/epidemiologia , Glucocorticoides/efeitos adversos , Gota/tratamento farmacológico , Hiperuricemia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Demência/sangue , Demência/diagnóstico , Demência/etiologia , Feminino , Gota/sangue , Gota/complicações , Humanos , Hiperuricemia/sangue , Hiperuricemia/complicações , Hiperuricemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Prednisolona/efeitos adversos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/epidemiologia , Taiwan/epidemiologia , Fatores de Tempo , Ácido Úrico/sangueRESUMO
Amyloid ß (Aß) is a peptide fragment of the amyloid precursor protein that triggers the progression of Alzheimer's Disease (AD). It is believed that Aß contributes to neurodegeneration in several ways, including mitochondria dysfunction, oxidative stress and brain insulin resistance. Therefore, protecting neurons from Aß-induced neurotoxicity is an effective strategy for attenuating AD pathogenesis. Recently, applications of stem cell-based therapies have demonstrated the ability to reduce the progression and outcome of neurodegenerative diseases. Particularly, Nanog is recognized as a stem cell-related pluripotency factor that enhances self-renewing capacities and helps reduce the senescent phenotypes of aged neuronal cells. However, whether the upregulation of Nanog can be an effective approach to alleviate Aß-induced neurotoxicity and senescence is not yet understood. In the present study, we transiently overexpressed Nanog-both in vitro and in vivo-and investigated the protective effects and underlying mechanisms against Aß. We found that overexpression of Nanog is responsible for attenuating Aß-triggered neuronal insulin resistance, which restores cell survival through reducing intracellular mitochondrial superoxide accumulation and cellular senescence. In addition, upregulation of Nanog expression appears to increase secretion of neurotrophic factors through activation of the Nrf2 antioxidant defense pathway. Furthermore, improvement of memory and learning were also observed in rat model of Aß neurotoxicity mediated by upregulation of Nanog in the brain. Taken together, our study suggests a potential role for Nanog in attenuating the neurotoxic effects of Aß, which in turn, suggests that strategies to enhance Nanog expression may be used as a novel intervention for reducing Aß neurotoxicity in the AD brain.
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Peptídeos beta-Amiloides/toxicidade , Resistência à Insulina , Proteína Homeobox Nanog/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Células-Tronco Pluripotentes/metabolismo , Animais , Apoptose/efeitos dos fármacos , Encéfalo/patologia , Linhagem Celular Tumoral , Senescência Celular/efeitos dos fármacos , Transtornos Cognitivos/complicações , Transtornos Cognitivos/patologia , Humanos , Insulina/metabolismo , Masculino , Transtornos da Memória/complicações , Transtornos da Memória/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Neuroproteção/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Superóxidos/metabolismo , Regulação para Cima/efeitos dos fármacos , Proteínas tau/metabolismoRESUMO
Chondroitin sulfate synthases, a family of enzyme involved in chondroitin sulfate (CS) polymerization, are dysregulated in various human malignancies, but their roles in glioma remain unclear. We performed database analysis and immunohistochemistry on human glioma tissue, to demonstrate that the expression of CHSY1 was frequently upregulated in glioma, and that it was associated with adverse clinicopathologic features, including high tumor grade and poor survival. Using a chondroitin sulfate-specific antibody, we showed that the expression of CHSY1 was significantly associated with CS formation in glioma tissue and cells. In addition, overexpression of CHSY1 in glioma cells enhanced cell viability and orthotopic tumor growth, whereas CHSY1 silencing suppressed malignant growth. Mechanistic investigations revealed that CHSY1 selectively regulates PDGFRA activation and PDGF-induced signaling in glioma cells by stabilizing PDGFRA protein levels. Inhibiting PDGFR activity with crenolanib decreased CHSY1-induced malignant characteristics of GL261 cells and prolonged survival in an orthotopic mouse model of glioma, which underlines the critical role of PDGFRA in mediating the effects of CHSY1. Taken together, these results provide information on CHSY1 expression and its role in glioma progression, and highlight novel insights into the significance of CHSY1 in PDGFRA signaling. Thus, our findings point to new molecular targets for glioma treatment.
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Transtorno Bipolar/terapia , Serviços Comunitários de Saúde Mental , Transtorno Depressivo/terapia , Reabilitação Psiquiátrica , Esquizofrenia/terapia , Austrália , Centros Comunitários de Saúde Mental/organização & administração , Centros Comunitários de Saúde Mental/normas , Serviços Comunitários de Saúde Mental/organização & administração , Serviços Comunitários de Saúde Mental/normas , Congressos como Assunto , Ásia Oriental , Humanos , Índia , Direitos do Paciente , Reabilitação Psiquiátrica/organização & administração , Reabilitação Psiquiátrica/normas , Sociedades , TurquiaRESUMO
When studying the range of toxic substances triggering dementia, special attention should be paid to the materials used in dental practice, particularly to dental fillings containing amalgam. This necessitated conducting large-scale epidemiologic studies. The aim of our research was to determine the risk factors for developing dementia when filling materials containing amalgam are used in dental practice. In order to achieve the set goals, the following tasks were undertaken: (1) The social and demographic characteristics of the examined patients were studied; (2) the spectrum of concomitant somatic diseases was determined in patients of different gender and age; and (3) the relationship between dementia incidence and the volume of dental filling material containing amalgam was identified in patients with different somatic diseases. In general, the research conducted did not reveal any direct relationship between the development of dementia and the volume of filling material containing amalgam. However, among the people with dementia, there were persons for whom its progression was accelerated in cases where a large volume of dental filling material containing amalgam was present.
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Demência/induzido quimicamente , Amálgama Dentário/intoxicação , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Restauração Dentária Permanente , Estudos Epidemiológicos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores Sexuais , TaiwanRESUMO
The effective dose (HE) and organ or tissue equivalent dose (HT) for use in brain computed tomography (CT) examinations with various body weights were evaluated. Thermoluminescent dosimeters (TLD-100H) were inserted into Rando and five anthropomorphic phantoms. These phantoms were made of polymethylmethacrylate (PMMA), according to the specifications of ICRU 48, with masses from 10 to 90 kg. Brain CT examinations were conducted, scanning the maxillae from the external auditory meatus to the parietal bone using a 128-slice multi-detector CT (MDCT) scanner. To reduce errors, three independent trials were conducted. Calculated HE,TLD, based on the weighting factor recommended by ICRP 103, was 1.72 ± 0.28 mSv, which slightly exceeds the HE,DLP of 1.70 mSv, that was calculated from the dose-length product (DLP) of the Rando phantom. This experiment yielded HE,TLD values of ICRP 103 from the highest 1.85 ± 0.28 (90 kg) to the lowest 1.47 ± 0.22 (10 kg) mSv. HE,TLD (mSv) = 5.45×10-3 W(kg) + 1.361, with an R2 of 0.87667. Using the DLP protocol, HE,DLP was estimated from CTDIvol that was recorded directly from the console display of the CT unit and multiplied by the conversion coefficient (k) recommended by the ICRP 103. Finally, the experimental results obtained herein are compared with those in the literature. Physicians should choose and adjust protocols to prevent the exposure of patients to unnecessary radiation, satisfying the as low as reasonably achievable (ALARA) principle. These findings will be valuable to patients, physicians, radiologists and the public.
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Peso Corporal , Encéfalo/efeitos da radiação , Imagens de Fantasmas , Algoritmos , Antropometria , Calibragem , Feminino , Humanos , Masculino , Doses de Radiação , Dosimetria Termoluminescente , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer's type. This study assessed the short- and long-term effectiveness and safety of rivastigmine in patients with mild-to-moderate Alzheimer's disease (AD) in a real-world clinical setting in Taiwan. METHODS: This was a 48-week, single-arm, open-label, prospective, observational, post-marketing surveillance, multicenter study. The primary outcomes were change from baseline to week 48 in the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) scores. One-year persistence to treatment, effect on activities of daily living, and incidence of adverse events (AEs) were also assessed. RESULTS: Overall, 151 patients were enrolled in the study, of which 91 (60.26%) completed this study. At the end of the study, the mean rivastigmine dose received by the patients was 6.59 mg/day. At week 48, the changes in mean [standard deviation (SD)] MMSE and CDR scores in the intent-to-treat (ITT) population from baseline were - 1.00 (3.8; p = 0.0344) and 0.07 (0.29; p = 0.0403), respectively. The most frequently reported AEs by preferred term were dizziness (12.58%) and nausea (9.27%). No new or unexpected AEs were observed, and 30 (20.13%) patients in the ITT population were on rivastigmine therapy for 1 year without treatment discontinuation. CONCLUSION: Despite the low 1-year persistence rate, rivastigmine showed a stabilizing effect on declining cognition in patients with mild-to-moderate AD in a real-world scenario. Rivastigmine is well tolerated at 6.0-9.0 mg/day with no unexpected safety concerns. FUNDING: Novartis Co. Ltd., Taipei, Taiwan.
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Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/uso terapêutico , Rivastigmina/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Inibidores da Colinesterase/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Projetos de Pesquisa , Rivastigmina/administração & dosagem , Taiwan/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Surfactant-induced skin barrier disruption can enhance blood flow and water content in the superficial skin. The effect of therapeutic ultrasound on accelerating the recovery of superficial skin after skin barrier disruption has seldom been studied. OBJECTIVE: To understand the effects of therapeutic ultrasound on barrier recovery, we used the sodium lauryl sulfate irritation model and treatment with ultrasound intervention. METHODS: The study allocated 30 healthy subjects into an ultrasound group (nâ¯=â¯15) and a control group (nâ¯=â¯15), each divided into three subgroups (sodium lauryl sulfate at concentrations of 1.0%, 0.5%, and 0%). Pulsed ultrasound (1â¯MHz, 0.3â¯W/cm2SATA) was applied to ultrasound subgroups. The treatment effect was evaluated by the recovery rate of enhanced blood flow and water content. RESULTS: The results indicated a surfactant dose-dependent effect on blood flow, but not on water content. The recovery rates of enhanced blood flow were higher in the 0.5% and 1.0% ultrasound subgroups than in the control subgroups throughout the experiment. However, recovery rates of water content were higher in the ultrasound subgroups than in the control subgroups only on Day2. CONCLUSIONS: Pulsed ultrasound accelerated the barrier recovery by reducing the enhanced blood flow and water content after skin barrier disruption.
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Dermatite Irritante/terapia , Dodecilsulfato de Sódio/efeitos adversos , Tensoativos/efeitos adversos , Terapia por Ultrassom , Adulto , Dermatite Irritante/etiologia , Feminino , Humanos , Masculino , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Testes de Irritação da Pele , Fenômenos Fisiológicos da Pele , Adulto JovemRESUMO
The 6-minute walk test (6MWT) has been applied to assess postsurgical recovery in cardiac populations. This study mainly investigated whether the 6MWT could serve as an indicator for physical functioning in patients undergoing cardiac surgery.Participants completed the 6MWT and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) at baseline, discharge, and 3 months postoperatively, in order to analyze the construct validity and responsiveness of the 6MWT. The participants in this study were 125 patients (92 males and 33 females) with an average age of 65.1â±â11.1 years. The mean 6MWT was 308.9â±â77.3 m in the preoperative phase, decreased to 277.3â±â85.7 m at discharge, and returned to 378.1â±â95.2 m at 3-month follow-up. The results showed that the 6-minute walk distances at baseline and at 3-month follow-up were moderately to highly correlated with the physical functioning subscale of the SF-36 (rsâ=â.44 and .54, respectively) and had weak correlation with the nonphysical functioning subscales. The recovery level of physical functioning is meaningfully associated with the 6MWT change from baseline to discharge and from baseline to 3-month follow-up. Patients with higher New York Heart Association (NYHA) Functional Classification levels had lower 6MWT. Additionally, the 6MWT was sensitive to change during the perioperative period (effect sizes from -0.51 to 1.72).The supporting evidence includes the construct validity and responsiveness of the 6MWT. This study supports the feasibility of the 6MWT as an evaluation tool of physical functioning for assessment of postcardiac surgical recovery.
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Procedimentos Cirúrgicos Cardíacos/reabilitação , Avaliação de Resultados em Cuidados de Saúde/normas , Teste de Caminhada/normas , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Alta do Paciente , Período Pós-Operatório , Estudos Prospectivos , Recuperação de Função Fisiológica , Reprodutibilidade dos Testes , Resultado do Tratamento , CaminhadaRESUMO
Dementia with Lewy bodies (DLB) is characterized by neuronal deficits and α-synuclein inclusions in the brain. Ceftriaxone (CEF), a ß-lactam antibiotic, has been suggested as a therapeutic agent in several neurodegenerative disorders for its abilities to counteract glutamate-mediated toxicity and to block α-synuclein polymerization. By using manganese-enhanced magnetic resonance imaging (MEMRI) and immunohistochemistry, we measured the effects of CEF on neuronal activity and α-synuclein accumulation in the brain in a DLB rat model. The data showed that CEF corrected neuronal density and activity in the hippocampal CA1 area, suppressed hyperactivity in the subthalamic nucleus, and reduced α-synuclein accumulation, indicating that CEF is a potential agent in the treatment of DLB.
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Ceftriaxona/uso terapêutico , Doença por Corpos de Lewy/terapia , Animais , Encéfalo/patologia , Ceftriaxona/farmacologia , China , Demência/terapia , Modelos Animais de Doenças , Hipocampo/metabolismo , Corpos de Lewy/efeitos dos fármacos , Imageamento por Ressonância Magnética/métodos , Masculino , Doenças Neurodegenerativas/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Wistar , alfa-Sinucleína/efeitos dos fármacos , alfa-Sinucleína/metabolismoRESUMO
Huntington's disease (HD) is a progressive and fatal neurodegenerative disease caused by CAG repeat expansion in the coding region of huntingtin (HTT) protein. The accumulation of mutant HTT (mHTT) contributes to neurotoxicity by causing autophagy defects and oxidative stress that ultimately lead to neuronal death. Interestingly, epidemiologic studies have demonstrated that the prevalence of type-2 diabetes, a metabolic disease mainly caused by defective insulin signaling, is higher in patients with HD than in healthy controls. Although the precise mechanisms of mHTT-mediated toxicity remain unclear, the blockade of brain insulin signaling may initiate or exacerbate mHTT-induced neurodegeneration. In this study, we used an in vitro HD model to investigate whether neuronal insulin signaling is involved in mHTT-mediated neurotoxicity. Our results demonstrated that mHTT overexpression significantly impairs insulin signaling and causes apoptosis in neuronal cells. However, treatment with liraglutide, a GLP-1 analogue, markedly restores insulin sensitivity and enhances cell viability. This neuroprotective effect may be attributed to the contribution of the upregulated expression of genes associated with endogenous antioxidant pathways to oxidative stress reduction. In addition, liraglutide stimulates autophagy through AMPK activation, which attenuates the accumulation of HTT aggregates within neuronal cells. Our findings collectively suggest that liraglutide can rescue impaired insulin signaling caused by mHTT and that GLP-1 may potentially reduce mHTT-induced neurotoxicity in the pathogenesis of HD.
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Proteína Huntingtina/genética , Insulina/metabolismo , Liraglutida/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Humanos , Proteína Huntingtina/metabolismo , Hipoglicemiantes/farmacologia , Imuno-HistoquímicaRESUMO
BACKGROUND: Studies on second-generation antipsychotics (SGA) augmentation treatment for older adults with major depressive disorder (MDD) remain limited. We aimed to investigate the effectiveness of SGA augmentation for overall and older patients with MDD inpatient history by assessing the change in 1-year hospitalization before and after SGA augmentation using the latest National Health Insurance Research Database (NHIRD) in Taiwan. METHODS: The samples were MDD patients (ICD-9 CM code: 296.2 and 296.3) who had psychiatric inpatient history. A total of 2602 MDD patients including 430 elderly subjects (age ≥ 60 years) who received SGA augmentation for 8 weeks between January 1998 and December 2012 were included in this 1-year mirror-image study. Outcome measures included number and length of psychiatric and all-cause hospitalizations. RESULTS: After 8-week continuous SGA augmentation in the study subjects, the total number and days of psychiatric hospitalizations among overall patients reduced by 33.57% (p < .0001) and 18.24% (p < .0001), respectively; the total number and days of psychiatric hospitalizations among older patients (age ≥ 60) reduced by 44.52% (p < .0001) and 27.95% (p < .0001), respectively. Similarly, the total number and days of all-cause hospitalizations were significantly reduced. LIMITATIONS: MDD patients without inpatient history were not included due to data limitation; hence, the results may not be generalized to all patients. CONCLUSIONS: The results support that SGA may be effective in reducing psychiatric and all-cause hospitalization among overall and elderly MDD patients. More studies focusing on the safety of SGA among older MDD patients is warranted.
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Antipsicóticos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Hospitalização/tendências , Idoso , Bases de Dados Factuais , Feminino , Hospitais Psiquiátricos/estatística & dados numéricos , Humanos , Seguro Saúde/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Taiwan , Resultado do TratamentoRESUMO
AIM: α-Synuclein (αSyn) is known as a small soluble protein abundantly expressed in neuronal cells. Although its physiological role is still unclear, the aggregation of αSyn has been recognized as responsible for some neurodegenerative disorders such as dementia with Lewy bodies (DLB). In most cases, intracellular abnormal aggregates are caused by protein-coding mutations that alter primary structure and therefore increase propensity toward aggregation. However, no pathogenic alterations or polymorphisms in αSyn are found in DLB patients so far, suggesting genetic mutations may not play a major role in DLB pathogenesis. In contrast, emerging evidence reveals that amyloid ß (Aß) may contribute to aggregate formation and exacerbate neurotoxicity of αSyn. However, the underlying mechanism of action has remained unclear. METHODS: To investigate molecular pathways involved in Aß-mediated αSyn pathology, we established an in vitro model for inducible αSyn overexpression in SK-N-MC human neuronal cells. RESULTS: Our results demonstrated that Aß treatment in αSyn-overexpressed neuronal cells significantly increases αSyn intracellular aggregation and cytotoxicity. Moreover, Aß also caused AMP-activated protein kinase (AMPK) inhibition and impaired insulin sensitivity, which leads to significant downregulation of nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase 1 (HO-1) antioxidant signaling to elicit αSyn aggregation. CONCLUSIONS: This raised the possibility that insulin resistance could be one of the causative factors of αSyn toxicity, and the strategies for insulin sensitization may have therapeutic potential for synucleinopathies including DLB.
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Peptídeos beta-Amiloides/toxicidade , Insulina/metabolismo , Neurônios/efeitos dos fármacos , Fragmentos de Peptídeos/toxicidade , Transdução de Sinais/efeitos dos fármacos , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Quinases Proteína-Quinases Ativadas por AMP , Linhagem Celular Transformada , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Antagonistas de Hormônios/farmacologia , Humanos , Insulina/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mifepristona/farmacologia , Mutação/genética , Estresse Oxidativo/efeitos dos fármacos , Proteínas Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fatores de Tempo , TransfecçãoRESUMO
PURPOSE: The effective dose (HE) and organ or tissue equivalent dose (HT) of a Rando phantom undergoing two brain computed tomography (CT) examination protocols were evaluated using thermoluminescent dosimeters (TLD-100H) and dose length product (DLP) methods. MATERIALS AND METHODS: TLDs were inserted into the correlated positions of an organ or tissue of Rando phantom, such as thyroid, brain, and salivary gland, using (A) axial scan: scanning the maxillae ranging from external auditory meatus to the parietal bone, and (B) helical scan: scanning from the mandible to the parietal bone. CT examinations were performed on a Philips computer tomography (Brilliance CT) at Lukang Christian Hospital. TLDs were measured using a Harshaw 3500 TLD reader. The HT of organ and tissue during the two protocols was discussed. RESULTS AND CONCLUSION: HE were calculated using ICRP 60 and 103 at 2.67 ± 0.18 and 1.89 ± 0.23 mSv based on an axial scan, and 4.70 ± 0.38 and 4.39 ± 0.37 mSv based on a helical scan, respectively. In the DLP method, HE was estimated from CTDIvol that was recorded directly from the console display of the CT unit and then calculated using AAPM 96. Finally, experimental results are compared with those in literature. Radiologists should choose and adjust protocols to prevent unnecessary radiation to patients and satisfying the as low as reasonably achievable (ALARA) principle. These findings will be valuable to patients, physicians, radiologists, and the public.
Assuntos
Encéfalo/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Imagens de Fantasmas , Doses de Radiação , Dosimetria Termoluminescente/métodos , Relação Dose-Resposta à Radiação , Feminino , Humanos , Sensibilidade e EspecificidadeRESUMO
Objectives: Menopausal transition in women initiates with declining estrogen levels and is followed by significant changes in their physiological characteristics. These changes often lead to medical conditions, such as obesity, which is correlated with chronic low-grade/subclinical inflammation. Ocimum gratissimum L. is a food spice or traditional herb in many countries; the plant is rich in antioxidants, which possess anti-inflammation activities and multitude of other therapeutic functions. Methods: In this study, we evaluated effects of O. gratissimum extract (OGE) in preventing obesity by using ovariectomized (OVX) animal models to mimic menopausal women. Methods: OVX rats showed increase in body weight and in adipocyte size in perigonadal adipose tissue (p <0.05) and decrease in uterus weight. By contrast, OGE (0.2 mg/ml) significantly reduced body weight gain and adipocyte in OVX rats and showed insignificant changes in uterus weight. Further investigation indicated that OGE exerted no influence on levels of dorsal fat, serum total cholesterol, and serum triacylglycerol and on serum biochemical factors, calcium, phosphorus, and glucose. Conclusion: These findings suggested that OGE dietary supplements may be useful in controlling body weight of menopausal women.