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1.
Neurobiol Learn Mem ; 205: 107840, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37805119

RESUMO

Environmental enrichment (EE) is known to improve memory and cognition and modulate the impact of aversive stimuli in animals, promoting the development of resilience to stressful situations. Likewise, it is known that EE can modulate synaptic plasticity as is the case of long-term potentiation (LTP). These findings have been described initially in ex vivo preparations, suggesting that the effects of EE are the result of an early modification of the synaptic excitability and transmission. In this regard, it is known that metaplasticity refers to the persistent modification, by previous activity, in the ability to induce synaptic plasticity. Our previous studies have shown that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of LTP in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC) in vivo. In addition, we have shown that CTA extinction allows the induction but not the maintenance of IC-LTP of the Bla-IC pathway. Recently, we also showed that prior exposure to environmental enrichment for three weeks reduces the strength of CTA, restoring the brain-derived neurotrophic factor (BDNF) levels in the IC. The present study aimed to analyze the effects of brief exposure to an enriched environment on the strength of aversive memory, as well as on the in vivo IC-LTP. To do so, adult rats were exposed for seven days to an EE, either before CTA training or LTP induction in the Bla-IC pathway. Our results demonstrate that a seven-day exposure to an enriched environment attenuates the aversive response to a strong CTA and allows the induction but not the maintenance of LTP in the insular cortex. These findings provide evidence that metaplastic regulation in a neocortical region takes part in the mechanisms through which brief exposure to enriched environments attenuates an aversive response.


Assuntos
Córtex Insular , Paladar , Animais , Ratos , Aprendizagem da Esquiva/fisiologia , Córtex Cerebral/fisiologia , Condicionamento Clássico/fisiologia , Plasticidade Neuronal , Paladar/fisiologia
2.
Neurobiol Learn Mem ; 193: 107647, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35679998

RESUMO

Currently, it is widely accepted that memory extinction involves the formation of a new associative memory rather than unlearning of the information previously acquired. Nonetheless, the cellular and molecular mechanisms underlying this process are still unclear. In this regard, it has been suggested that while kinases modulate conditioning and LTP, phosphatases are relevant for extinction and LTD. In particular, the protein phosphatase calcineurin (CaN) has been involved in the extinction of some behavioral tasks along with LTD. Indeed, studies of our research group have demonstrated that induction of LTD in the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC) pathway facilitates the extinction of conditioned taste aversion (CTA), while the induction of LTP in this pathway slows it down. In addition, we have shown that the extinction of CTA elicits an increase of CaN. The aim of the present study was to evaluate the participation of calcineurin in the extinction of CTA and in the expression of in vivo LTD in the Bla-IC pathway. For this purpose, we chemically inhibited calcineurin in the IC of adult male Wistar rats, either during CTA-extinction or thirty minutes after LTD induction in the Bla-IC pathway. Our results show that calcineurin inhibition slows down the CTA-extinction and blocks the maintenance of LTD. Furthermore, we show that CaN levels increase after LTD induction. These findings support the idea that calcineurin is a key molecular actor for both CTA extinction and LTD expression in the IC, a highly relevant neocortical area for the processing of aversively motivated learning tasks, suggesting that both processes are associated at a molecular level.


Assuntos
Aprendizagem da Esquiva , Calcineurina , Animais , Aprendizagem da Esquiva/fisiologia , Calcineurina/metabolismo , Córtex Cerebral/fisiologia , Córtex Insular , Masculino , Ratos , Ratos Wistar , Paladar/fisiologia
3.
Issues Ment Health Nurs ; 40(9): 760-767, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31194606

RESUMO

This paper explores culturally-related concerns that arose during a multi-year study of obsessive-compulsive disorder (OCD) along the U.S.-Mexico border and describes adaptations made to better connect the research process to study participants. The purpose of this exploration is two-fold: (1) to offer suggestions for culturally sensitive borderland mental health research; and (2) to enhance dialog focused on culture, mental health research and the U.S.-Mexico border. Systematic coding of the written record of weekly research team meetings identified six recurring cultural concerns: emotionally charged and poorly understood terminology; differing meanings of ethnicity and acculturation; quality of life-regional variation and uncertainty; overlap of research and care; hopeful but hesitant; and fatalism. We conclude that diligence in the initial planning phase of a study is only part of the challenge in doing culturally sensitive research. Equally important is an ongoing process of evaluation to make explicit cultural concerns that arise during research, as well as a readiness to implement culturally sensitive research adaptations.


Assuntos
Comparação Transcultural , Assistência à Saúde Culturalmente Competente , Emigrantes e Imigrantes/psicologia , Americanos Mexicanos/psicologia , Transtorno Obsessivo-Compulsivo/etnologia , Transtorno Obsessivo-Compulsivo/enfermagem , Enfermagem Psiquiátrica , Aculturação , Pesquisa sobre Serviços de Saúde , Humanos , México , Transtorno Obsessivo-Compulsivo/psicologia , Qualidade de Vida/psicologia , Estados Unidos
4.
Behav Brain Res ; 430: 113947, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35644274

RESUMO

It has been shown that exposure to an enriched environment (EE) can modulate the physiological impact of aversive stimuli in animals, promoting adaptive attitudes, as well as the development of resilience to stressful situations. These changes are known to be related to increased levels of some trophic factors, such as brain-derived neurotrophic factor (BDNF), which has been considered a regulatory protein for synaptic plasticity in the adult brain. Our previous studies have demonstrated that in the insular cortex (IC), a brain region of the temporal lobe implicated in the acquisition, consolidation, and retention of conditioned taste aversion (CTA) task, BDNF can reverse the CTA memory deficit caused by a protein synthesis inhibitor. Likewise, our research group have also shown that BDNF is required for the maintenance of CTA long-term memory. Here we evaluate the effects of the exposure to an enriched environment on the CTA memory strength, using a weak and strong version of this paradigm. The exposure to an EE for 21 days was able to attenuate the strong-CTA response through the restoration of BDNF levels in the IC of adult rats. These results provide evidence that environmental enrichment is capable of reducing the strength of an aversive memory trace, restoring the BDNF levels in a neocortical region of the adult brain.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Paladar , Animais , Aprendizagem da Esquiva , Córtex Cerebral/fisiologia , Córtex Insular , Ratos , Ratos Wistar
5.
Physiol Behav ; 254: 113878, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35700814

RESUMO

Several factors, including environmental modifications, stimulate neuroplasticity. One type of neuroplasticity consists in the generation of new neurons in the dentate gyrus of the hippocampus. Neurogenesis is modulated by environmental enrichment (ENR, tunnels plus running wheel) and affected by the time of exposure to ENR. Despite the wide use of ENR to stimulate neuroplasticity, the degree to which ENR variations modeled by temporally changing the level of environmental complexity affect hippocampal neurogenesis and anxiety is still unclear. Thus, we investigated the effects of five housing conditions on young adult male Balb/C mice exposed for 42 days. The groups were as follows: standard conditions without ENR, constant ENR complexity, gradual increase of ENR complexity followed by a gradual decrease of ENR complexity, gradual increase of ENR complexity followed by constant ENR complexity, and constant ENR complexity followed by a gradual decrease of ENR complexity. On day 44, mice were exposed to the elevated plus-maze to evaluate anxiety. Further, we analyzed neurogenesis and quantified corticosterone levels. In an additional experiment, we explored the effect of voluntary physical activity on anxiety, neurogenesis, and corticosterone during the variations in ENR complexity. Our results showed that any change in ENR complexity over time reduced anxiety. Also, voluntary physical activity alone or in the context of a complex environment increased doublecortin cell maturation in the granular cell layer of the hippocampus. Finally, our study supports that physical activity acts proneurogenic, whereas any change in environmental complexity decreases anxiety-like behavior. However, the decrease in corticosterone levels elicited by physical activity was lower than the decrease produced by the decrement in environmental complexity.


Assuntos
Corticosterona , Meio Ambiente , Animais , Ansiedade , Hipocampo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neurogênese/fisiologia
6.
Sci Rep ; 8(1): 945, 2018 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-29343740

RESUMO

Evening chronotype associates with health complications possibly via lifestyle factors, while the contribution of genetics is unknown. The aim was to study the relative contributions of genetics, lifestyle, and circadian-related physiological characteristics in metabolic risk of evening chronotype. In order to capture a biological contribution to chronotype, a genetic-risk-score (GRS), comprised of 15 chronotype-related variants, was tested. Moreover, a wide range of behavioral and emotional eating factors was studied within the same population. Chronotype, lifestyle, and metabolic syndrome (MetS) outcomes were assessed (n = 2,126), in addition to genetics (n = 1,693) and rest-activity/wrist-temperature rhythms (n = 100). Evening chronotype associated with MetS and insulin resistance (P < 0.05), and several lifestyle factors including poorer eating behaviors, lower physical activity and later sleep and wake times. We observed an association between higher evening GRS and evening chronotype (P < 0.05), but not with MetS. We propose a GRS as a tool to capture the biological component of the inter-individual differences in chronotype. Our data show that several modifiable factors such as sedentary lifestyle, difficulties in controlling the amount of food eaten, alcohol intake and later wake and bed times that characterized evening-types, may underlie chronotype-MetS relationship. Our findings provide insights into the development of strategies, particularly for evening chronotype.


Assuntos
Ritmo Circadiano/fisiologia , Síndrome Metabólica/etiologia , Síndrome Metabólica/fisiopatologia , Sono/fisiologia , Adulto , Feminino , Humanos , Estilo de Vida , Masculino , Fatores de Risco , Inquéritos e Questionários
7.
Food Funct ; 8(8): 2702-2711, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28703832

RESUMO

Quercitrin (quercetin 3-rhamnoside) is a bioflavonoid with anti-inflammatory activity in experimental colitis. Several studies have suggested that vascular injury might be a primary process in Crohn's disease, but there is no information about the function of the mesenteric bed in the experimental models of colitis. The aims of this study were to analyse whether the reactivity to vasoconstrictor agents is altered in the mesenteric vascular bed from animals with colitis induced by administration of trinitrobenzenesulfonic acid (TNBS) in the early stages of this pathology, and to determine the effects of quercitrin on such vascular alterations. Contraction of mesenteric beds produced by vasoconstrictor agents such as noradrenaline and KCl is reduced in rats in the early stages of experimental TNBS-induced colitis. This alteration was partially reverted by non-selective nitric oxide synthase (NOS) inhibition with N-nitro-l-arginine methylester, and enhanced by non-selective cyclooxygenase (COX) inhibition with indomethacin. However, the endothelium-dependent relaxant responses to acetylcholine were not significantly altered. iNOS, COX-2, NOX-1, tumor necrosis factor α (TNFα) and interleukin 1ß (IL1ß) expressions were higher in the mesenteric arteries from TNBS-treated rats, without changes in both eNOS expression and eNOS-Ser1177 phosphorylation. The in vivo pre-treatment with 5 mg kg-1 of the flavonoid quercitrin reverts both the early hyporesponse of mesenteric arteries to noradrenaline and the up-regulation of iNOS, COX2, NOX1, TNFα and IL1ß in colitic rats. In conclusion, quercitrin improves the impaired mesenteric vascular reactivity in the acute phase of this colitis model, at least in part by reducing NO overproduction from iNOS.


Assuntos
Colite/tratamento farmacológico , Artérias Mesentéricas/efeitos dos fármacos , Óxido Nítrico/metabolismo , Quercetina/análogos & derivados , Animais , Anti-Inflamatórios/administração & dosagem , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Feminino , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Artérias Mesentéricas/metabolismo , NADPH Oxidase 1/genética , NADPH Oxidase 1/metabolismo , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Quercetina/administração & dosagem , Ratos , Ratos Wistar , Ácido Trinitrobenzenossulfônico/efeitos adversos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
8.
Mol Nutr Food Res ; 61(11)2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28766852

RESUMO

SCOPE: The biggest challenge for losing weight is the ability to control the amount of food eaten; the tendency to overeat is called disinhibition. Our aims were to determine whether (a) the SLC6A4-promoter variant (5-HTTLPR) relates to disinhibition; (b) this association could affect total weight-loss during a behavioral/dietary treatment for obesity. METHODS AND RESULTS: A total of 2961 subjects attended voluntarily five weight-loss clinics; a subsample (n = 624) was recruited for SLC6A4 genotyping. Total weight-loss, emotional-eating-score and disinhibition-score were examined. We observed that: (a) the reduced ability to control food intake (disinhibition) is implicated in the impairment to lose weight; (b) SLC6A4-promoter variant is implicated in disinhibition. S carriers (low-expressing) of the SLC6A4-promoter variant had a lower inhibition capacity and showed more failure (1.6 times) to control the amount of food eaten than LL (p < 0.05); other factors such as eating while bored, overeating after work at night, or craving for specific foods were associated to the SLC6A4 genotype (p < 0.05); (c) The combination of disinhibition (high disinhibition) and genetics (S carrier) had a higher impact on total weight loss than each factor separately. CONCLUSIONS: SLC6A4-promoter variant is associated with the ability to control food intake and interacts with emotional eating to modulate total weight loss.


Assuntos
Regulação do Apetite , Obesidade/terapia , Sobrepeso/terapia , Polimorfismo Genético , Regiões Promotoras Genéticas , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Programas de Redução de Peso , Adulto , Alelos , Dieta Mediterrânea , Ingestão de Energia , Retroalimentação Fisiológica , Feminino , Frequência do Gene , Estudos de Associação Genética , Estilo de Vida Saudável , Humanos , Inibição Psicológica , Masculino , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/psicologia , Sobrepeso/genética , Sobrepeso/psicologia , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Espanha , Redução de Peso
9.
Am J Clin Nutr ; 104(4): 1160-1166, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27629052

RESUMO

BACKGROUND: We propose that eating lunch late impairs the mobilization of fat from adipose tissue, particularly in carriers of PERILIPIN1 (PLIN1) variants. OBJECTIVE: The aim was to test the hypothesis that PLIN1, a circadian lipid-stabilizing protein in the adipocyte, interacts with the timing of food intake to affect weight loss. DESIGN: A total of 1287 overweight and obese subjects [229 men and 1058 women; mean ± SD body mass index (in kg/m2): 31 ± 5] who attended outpatient obesity clinics were enrolled in the ONTIME (Obesity, Nutrigenetics, Timing, Mediterranean) study. Timing of food intake was estimated with a validated questionnaire. Anthropometric variables and PLIN1 genotypes were analyzed, including 6209T>C (rs2289487), 11482G>A (rs894160), 13041A>G (rs2304795), and 14995A>T (rs1052700). The main outcomes were effectiveness of the program and weight-loss progression during 28 wk of treatment. RESULTS: The PLIN1 locus was associated with variability in response to a weight-loss program. Specifically, carrying the minor C allele at the PLIN1 6209T>C was associated with better weight-loss response (P = 0.035). The probability of being a better responder [percentage of weight loss ≥7.5% (median)] was 33% higher among C than among TT carriers (OR: 1.32; 95% CI: 1.05, 1.67; P = 0.017). We found an interaction of PLIN1 × food timing between the 14995A>T variant and timing of lunch eating for total weight loss (P = 0.035). Among AA carriers, eating late was associated with less weight loss (P < 0.001), whereas time of eating did not influence weight loss among TT carriers (P = 0.326). CONCLUSIONS: Variability at the PLIN1 locus is associated with variability in weight loss. Moreover, eating late is related to lower weight-loss effectiveness among carriers of the AA genotype at the PLIN1 14995A>T variant. These results contribute to our ability to implement more precise and successful obesity treatments. The ONTIME study was registered at clinicaltrials.gov as NCT02829619.


Assuntos
Comportamento Alimentar , Genótipo , Almoço , Obesidade/genética , Perilipina-1/genética , Polimorfismo de Nucleotídeo Único , Redução de Peso/genética , Adulto , Alelos , Índice de Massa Corporal , Ritmo Circadiano , Inquéritos sobre Dietas , Dieta Redutora , Ingestão de Alimentos , Feminino , Interação Gene-Ambiente , Humanos , Masculino , Pessoa de Meia-Idade , Nutrigenômica , Obesidade/dietoterapia , Sobrepeso , Avaliação de Programas e Projetos de Saúde , Programas de Redução de Peso
10.
Dement Neuropsychol ; 10(3): 198-203, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29213455

RESUMO

BACKGROUND: Delirium is a neuropsychiatric syndrome with multiple etiological factors. Evaluation of delirium in different settings, especially the Emergency Department (ED) pertaining to different regions of the world with patients from different cultural and educational backgrounds is needed. OBJECTIVE: To determine the prevalence of delirium and its association with education in an ED in Brazil during a 6-month period. Methods: Patients aged >18 years were randomly selected from ED admissions. The instruments Confusion Assessment. METHOD: (CAM) scale, Mini-Mental State Examination (MMSE), Wechsler Logical Memory (WLM) and Charlson comorbidity score were applied to evaluate delirium, cognitive status, and comorbidities. RESULTS: The prevalence of delirium was10.7%. Delirium patients had significantly lower education, MMSE and WLM (immediate and delayed) scores, with 97.4% presenting episodic memory impairment. Patients with delirium had more history of neurological disorders. Three logistic regression models evaluating the association of variables with delirium were developed. Age and MMSE were retained in the first model, WLM scores in the second, and education in the third. CONCLUSION: To the best of our knowledge, this is the first study estimating the prevalence of delirium in a Brazilian ED. Lower education was associated with the occurrence of delirium.


INTRODUÇÃO: Delirium é uma síndrome neuropsiquiátrica, com fatores etiológicos múltiplos. A avaliação de delirium em diferentes ambientes, especialmente no Serviço de Emergência (SE) de diferentes regiões do mundo e com diferentes características culturais e educacionais é necessária. OBJETIVO: Determinar a prevalência de delirium e associação com educação em um SE no Brasil, durante seis meses. MÉTODOS: Foram randomizados aleatoriamente no SE os pacientes com idade acima de 18 anos. Escala Confusion Assessment Method (CAM), Mini Exame do Estado Mental (MEEM), o teste de Memória Lógica de Wechsler (MLW), e o escore de comorbidade de Charlson foram aplicados para avaliar delirium, status cognitivo, e comorbidades. RESULTADOS: A prevalência de delirium foi 10,7%. Os pacientes com delirium apresentaram significativamente menor escolaridade, escores mais baixos no MEEM e MLW (imediato e tardio), sendo que 97,4% apresentava comprometimento de memória episódica. Pacientes com delirium apresentaram mais história de transtorno neurológico prévio. Três modelos de regressão logística para delirium foram realizados. No primeiro, idade e MEEM foram mantidos no modelo final. No segundo, MLW imediato e tardio; e no terceiro, apenas educação. CONCLUSÃO: Este é o primeiro estudo brasileiro, de acordo com nosso melhor conhecimento, a estimar a prevalência de delirium em serviço de emergência. Nível educacional mais baixo foi associado com ocorrência de delirium.

12.
PLoS One ; 11(1): e0147211, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26808201

RESUMO

Despite the recent advances in the development of antitumor therapies, the prognosis for patients with malignant gliomas remains dismal. Therapy with tumor-selective viruses is emerging as a treatment option for this devastating disease. In this study we characterize the anti-glioma effect of VCN-01, an improved hyaluronidase-armed pRB-pathway-selective oncolytic adenovirus that has proven safe and effective in the treatment of several solid tumors. VCN-01 displayed a significant cytotoxic effect on glioma cells in vitro. In vivo, in two different orthotopic glioma models, a single intra-tumoral administration of VCN-01 increased overall survival significantly and led to long-term survivors free of disease.


Assuntos
Adenovírus Humanos/fisiologia , Neoplasias Encefálicas/terapia , Glioma/terapia , Terapia Viral Oncolítica , Vírus Oncolíticos/fisiologia , Proteínas E1A de Adenovirus/genética , Adenovírus Humanos/genética , Animais , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Efeito Citopatogênico Viral , Fator de Transcrição E2F1/genética , Genes Sintéticos , Genes Virais , Glioma/patologia , Humanos , Hialuronoglucosaminidase/genética , Injeções Intralesionais , Camundongos , Células-Tronco Neoplásicas , Oligopeptídeos/genética , Vírus Oncolíticos/genética , Organismos Geneticamente Modificados , Replicação Viral , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Clin Cancer Res ; 22(9): 2217-25, 2016 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-26603261

RESUMO

PURPOSE: Osteosarcoma is the most common malignant bone tumor in children and adolescents. Despite aggressive chemotherapy, more than 30% of patients do not respond and develop bone or lung metastasis. Oncolytic adenoviruses engineered to specifically destroy cancer cells are a feasible option for osteosarcoma treatment. VCN-01 is a replication-competent adenovirus specifically engineered to replicate in tumors with a defective RB pathway, presents an enhanced infectivity through a modified fiber and an improved distribution through the expression of a soluble hyaluronidase. The aim of this study is to elucidate whether the use of VCN-01 would be an effective therapeutic strategy for pediatric osteosarcoma. EXPERIMENTAL DESIGN: We used osteosarcoma cell lines established from patients with metastatic disease (531MII, 678R, 588M, and 595M) and a commercial cell line (143B). MTT assays were carried out to evaluate the cytotoxicity of VCN-01. Hexon assays were used to evaluate the replication of the virus. Western blot analysis was performed to assess the expression levels of viral proteins and autophagic markers. The antitumor effect of VCN-01 was evaluated in orthotopic and metastatic osteosarcoma murine animal models. RESULTS: This study found that VCN-01, a new generation genetically modified oncolytic adenovirus, administered locally or systemically, had a potent antisarcoma effect in vitro and in vivo in mouse models of intratibial and lung metastatic osteosarcoma. Moreover, VCN-01 administration showed a safe toxicity profile. CONCLUSIONS: These results uncover VCN-01 as a promising strategy for osteosarcoma, setting the bases to propel a phase I/II trial for kids with this disease. Clin Cancer Res; 22(9); 2217-25. ©2015 AACR.


Assuntos
Adenoviridae/genética , Neoplasias Ósseas/virologia , Vírus Oncolíticos/genética , Osteossarcoma/virologia , Animais , Neoplasias Ósseas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Feminino , Terapia Genética/métodos , Células HEK293 , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/virologia , Camundongos , Camundongos Nus , Terapia Viral Oncolítica/métodos , Pediatria , Replicação Viral/genética , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
14.
Neuro Oncol ; 18(8): 1109-19, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26951384

RESUMO

BACKGROUND: Endoplasmic reticulum (ER) stress results from protein misfolding imbalance and has been postulated as a therapeutic strategy. ER stress activates the unfolded protein response which leads to a complex cellular response, including the upregulation of aberrant protein degradation in the ER, with the goal of resolving that stress. O(6)-methylguanine DNA methyltransferase (MGMT), N-methylpurine DNA glycosylase (MPG), and Rad51 are DNA damage repair proteins that mediate resistance to temozolomide in glioblastoma. In this work we sought to evaluate whether ER stress-inducing drugs were able to downmodulate DNA damage repair proteins and become candidates to combine with temozolomide. METHODS: MTT assays were performed to evaluate the cytotoxicity of the treatments. The expression of proteins was evaluated using western blot and immunofluorescence. In vivo studies were performed using 2 orthotopic glioblastoma models in nude mice to evaluate the efficacy of the treatments. All statistical tests were 2-sided. RESULTS: Treatment of glioblastoma cells with ER stress-inducing drugs leads to downregulation of MGMT, MPG, and Rad51. Inhibition of ER stress through pharmacological treatment resulted in rescue of MGMT, MPG, and Rad51 protein levels. Moreover, treatment of glioblastoma cells with salinomycin, an ER stress-inducing drug, and temozolomide resulted in enhanced DNA damage and a synergistic antitumor effect in vitro. Of importance, treatment with salinomycin/temozolomide resulted in a significant antiglioma effect in 2 aggressive orthotopic intracranial brain tumor models. CONCLUSIONS: These findings provide a strong rationale for combining temozolomide with ER stress-inducing drugs as an alternative therapeutic strategy for glioblastoma.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/metabolismo , Dacarbazina/análogos & derivados , Estresse do Retículo Endoplasmático , Glioblastoma/metabolismo , Piranos/administração & dosagem , Animais , Antineoplásicos Alquilantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , DNA Glicosilases/metabolismo , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Dacarbazina/administração & dosagem , Dacarbazina/farmacologia , Regulação para Baixo , Humanos , Camundongos , Piranos/farmacologia , Rad51 Recombinase/metabolismo , Análise de Sobrevida , Temozolomida , Proteínas Supressoras de Tumor/metabolismo
15.
Carbohydr Polym ; 122: 376-86, 2015 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-25817682

RESUMO

Sulfated and pyruvylated galactans were isolated from three tropical species of the Bryopsidales, Penicillus capitatus, Udotea flabellum, and Halimeda opuntia. They represent the only important sulfated polysaccharides present in the cell walls of these highly calcified seaweeds of the suborder Halimedineae. Their structural features were studied by chemical analyses and NMR spectroscopy. Their backbone comprises 3-, 6-, and 3,6-linkages, constituted by major amounts of 3-linked 4,6-O-(1'-carboxy)ethylidene-d-galactopyranose units in part sulfated on C-2. Sulfation on C-2 was not found in galactans from other seaweeds of this order. In addition, a complex sulfation pattern, comprising also 4-, 6-, and 4,6-disulfated galactose units was found. A fraction from P. capitatus, F1, showed a moderate anticoagulant activity, evaluated by general coagulation tests and also kinetics of fibrin formation was assayed. Besides, preliminary results suggest that one of the possible mechanisms involved is direct thrombin inhibition.


Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Bryopsida/química , Galactanos/química , Galactanos/farmacologia , Ácido Pirúvico/metabolismo , Alga Marinha/química , Sulfatos/química , Anticoagulantes/química , Cálcio/metabolismo , Parede Celular/efeitos dos fármacos , Clorófitas/efeitos dos fármacos , Fibrina/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Cinética , Espectroscopia de Ressonância Magnética/métodos , Polissacarídeos/química , Polissacarídeos/farmacologia
16.
Rev Psiquiatr Salud Ment ; 7(2): 72-9, 2014.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-24054065

RESUMO

OBJECTIVES: To verify food consumption patterns and presence of risk anthropometric parameters in schizophrenic patients, trying to assess some modifiable cardiovascular risk. METHOD: Twenty-five schizophrenic outpatients, attended at the Hospital de Clínicas de Porto Alegre, Brazil, and 25 healthy controls matched by sex, age and body mass index (BMI) were included. Demographic (age, sex and socioeconomic status), anthropometric (weight, height and waist circumference), clinical (antipsychotics) and dietary consumption data (food frequency questionnaire) were obtained. RESULTS: There was a 40% frequency of overweight and 40% of obesity as verified by BMI, and 80% of increased risk of metabolic complications as measured by waist circumference. Most of the patients (68%) used atypical antipsychotics and no association was found between the distribution of the nutritional status according to BMI and type of antipsychotic used. There was a higher intake of total calories, calories and protein per kilogram of body weight, percentage of carbohydrates, and lower intake of omega-6, phytosterols, vitamin A and α-tocopherol by cases. Cholesterol and sodium intake did not differ between groups (365 ± 152 mg of cholesterol in cases and 313 ± 146 mg in controls; (3499 ± 1695 mg sodium by cases and 2874 ± 800 by controls). CONCLUSION: In this sample of schizophrenic patients there was a higher intake of calories and lower consumption of α-tocoferol and phitosterols, compared to controls. There was also elevated sodium, and cholesterol intake, and high frequency of overweight and central obesity.


Assuntos
Doenças Cardiovasculares/etiologia , Dieta , Estado Nutricional , Sobrepeso/etiologia , Esquizofrenia/complicações , Adolescente , Adulto , Brasil , Estudos de Casos e Controles , Inquéritos sobre Dietas , Ingestão de Energia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/etiologia , Fatores de Risco , Adulto Jovem
17.
J Bone Miner Res ; 29(10): 2287-96, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24737304

RESUMO

Osteosarcoma is the most common malignant bone tumor in children and adolescents. The presence of metastases and the lack of response to conventional treatment are the major adverse prognostic factors. Therefore, there is an urgent need for new treatment strategies that overcome both of these problems. Our purpose was to elucidate whether the use of the oncolytic adenovirus Δ24-RGD alone or in combination with standard chemotherapy would be effective, in vitro and in vivo, against osteosarcoma. Our results showed that Δ24-RGD exerted a potent antitumor effect against osteosarcoma cell lines that was increased by the addition of cisplatin. Δ24-RGD osteosarcoma treatment resulted in autophagy in vitro that was further enhanced when combined with cisplatin. Of importance, administration of Δ24-RGD and/or cisplatin, in novel orthotopic and two lung metastatic models in vivo resulted in a significant reduction of tumor burden meanwhile maintaining a safe toxicity profile. Together, our data underscore the potential of Δ24-RGD to become a realistic therapeutic option for primary and metastatic pediatric osteosarcoma. Moreover, this study warrants a future clinical trial to evaluate the safety and efficacy of Δ24-RGD for this devastating disease.


Assuntos
Adenoviridae/fisiologia , Cisplatino/uso terapêutico , Oligopeptídeos/uso terapêutico , Vírus Oncolíticos/fisiologia , Osteossarcoma/terapia , Adolescente , Animais , Autofagia/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Criança , Cisplatino/farmacologia , Terapia Combinada , Humanos , Concentração Inibidora 50 , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Camundongos Nus , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Osteossarcoma/ultraestrutura , Ensaios Antitumorais Modelo de Xenoenxerto
18.
CCH, Correo cient. Holguín ; 21(3): 748-763, jul.-set. 2017. tab
Artigo em Espanhol | LILACS | ID: biblio-889516

RESUMO

Introducción: el método clínico es un proceder científico y sistematizado que el médico ha empleado desde sus inicios y continúa vigente, es el arma primordial para el ejercicio de su profesión, considerado como un sistema de pensamiento lógico, ordenado y científico con la finalidad de establecer un diagnóstico e instaurar un tratamiento. Objetivo: comprobar el dominio y aplicación del método clínico de los estudiantes de tercer año de la carrera de Medicina en Moa, durante la rotación de Propedéutica, durante el curso escolar 2015-2016. Método: se realizó un estudio descriptivo observacional, con una muestra integrada por 52 estudiantes, los que constituyeron el 100% de la población estudiada. Se consideraron los resultados por los estudiantes en los exámenes prácticos de la asignatura de Propedéutica. Resultados: El 36,5% obtuvo resultados insatisfactorios en los exámenes, con un índice de calidad del 42,4%; el 65,3% presentó dificultades en el interrogatorio, el 57,6% en el examen físico y el 50,0% de los profesores valoró de regular la interrelación entre: interrogatorio, examen físico, resumen sindromológico y complementarios, considerando que el local de los exámenes tenía buena privacidad en el 85,7%, higiene en el 78,5% e iluminación en el 71,4%. Conclusiones: se demostró que existen dificultades en los estudiantes de tercer año de la carrera de medicina para desarrollar habilidades que reflejen dominio y aplicación del método clínico.


Introduction: the clinical method is a systematized and scientific practice; the doctor has ever used it up to nowadays. This method is of high importance, since it denotes a system of logical, well-ordered and scientific thought to make a diagnosis and give the treatment. Objective: to check the mastery and application of the clinical method of the students of third year of the career of Medicine in Moa, in the Propaedeutic cycle in 2015-2016 school year. Method: an observational descriptive study was carried out, with a sample of 52 students who represented the 100% of the population. The students´ results achieved in the practical exams of the Propaedeutic subject were considered. Results: insufficient results were obtained in the exam in 36.5% of the students, with an index of quality of 42.4%, 65.3% presented difficulties in the medical interview, 57.6% in the physical exam and. The interrelation among medical interview, physical exam, syndromological summary and complementary were assessed as medium by 50.0% of the professors, considering that the place where the exams were developed had good privacy in 85.7%, hygiene in 78.5% and illumination in 71.4%. Conclusions: the study demonstrated that there were difficulties in the students of third year of the medicine career, to develop abilities that show knowledge and use of the clinical method.

19.
Ciênc. cuid. saúde ; 16(2)abr. -jun.2017.
Artigo em Inglês, Português | LILACS, BDENF - enfermagem (Brasil) | ID: biblio-966808

RESUMO

Este estudo teve como objetivo identificar ações de cuidado de enfermagem ao paciente com risco de suicídio internado em uma Unidade de Internação Psiquiátrica do Sul do Brasil. Trata-se de um estudo qualitativo, descritivo. Os dados foram coletados entre outubro de 2013 e março de 2014, por meio de entrevistas com 20 profissionais de enfermagem na referida Unidade. Na análise das entrevistas, observou-se que os cuidados de enfermagem a pacientes com risco de suicídio são centrados basicamente na formação de vínculos, no estabelecimento de contrato terapêutico com o paciente e na organização das rotinas assistenciais da equipe. Formação de vínculos e estabelecimento de contrato terapêutico fazem parte do cuidado mais singular, exercido tanto por técnicos como por enfermeiros, no sentido de conhecer melhor as experiências de vida dos pacientes e ajudá-los a lidar com o risco de suicídio. Em relação à organização das rotinas, cabe ao enfermeiro esse processo, de forma a oportunizar que o vínculo e o contrato terapêutico se efetivem no cotidiano da internação. Conclui-se que a assistência aos pacientes com risco de suicídio possui especificidades. Ressalta-se que os dados obtidos possibilitaram a construção de um protocolo institucional para avaliação do risco de suicídio, que está sendo utilizado pela equipe de enfermagem da Unidade de Internação estudada.


This study aimed to identify actions of nursing care to patients at risk of suicide hospitalized in a Psychiatric Internment Unit of the South of Brazil. This is a qualitative, descriptive study. Data were collected between October 2013 and March 2014, through interviews with 20 nursing professionals at the Unit. In the analysis of the interviews, it was observed that the nursing care for patients at risk of suicide is basically centered on the formation of bonds, the establishment of therapeutic contract with the patient and the organization of the staff's care routines. Linking and establishing a therapeutic contract are part of the more unique care, carried out by both technicians and nurses, in order to better understand patients' life experiences and to help them in dealing with the risk of suicide. Regarding the organization of routines, the nurse is responsible for this process, so that the bond and the therapeutic contract become effective in the daily hospitalization. It is concluded that assistance to patients at risk of suicide has specificities. It should be emphasized that the data obtained allowed the construction of an institutional protocol for the evaluation of suicide risk, which is being used by the nursing team of the hospitalization unit studied


Este estudio tuvo como objetivo identificar acciones de cuidado de enfermería al paciente con riesgo al suicidio ingresado en una Unidad de Internación Psiquiátrica del sur de Brasil. Se trata de un estudio cualitativo, descriptivo. Los datos fueron recolectados entre octubre de 2013 y marzo de 2014, por medio de entrevistas con 20 profesionales de enfermería en la referida Unidad. En el análisis de las entrevistas, se observó que los cuidados de enfermería a pacientes con riesgo al suicidio son centrados básicamente en la formación de vínculos, en el establecimiento de contrato terapéutico con el paciente y en la organización de las rutinas asistenciales del equipo. Formación de vínculos y establecimiento de contrato terapéutico hacen parte del cuidado más singular, ejercido tanto por técnicos como por enfermeros, en el sentido de conocer mejor las experiencias de vida de los pacientes y ayudarlos a lidiar con el riesgo al suicidio. Con relación a la organización de las rutinas, cabe al enfermero este proceso, a fin de llevar a cabo que el vínculo y el contrato terapéutico se efectúen en el cotidiano de la internación. Se concluye que la asistencia a los pacientes con riesgo al suicidio posee especificidades. Se destaca que los datos obtenidos posibilitaron la construcción de un protocolo institucional para evaluación del riesgo al suicidio, que está siendo utilizado por el equipo de enfermería de la Unidad de Internación estudiada..


Assuntos
Humanos , Enfermagem Psiquiátrica , Saúde Mental , Suicídio , Hospitalização , Equipe de Enfermagem
20.
Dement. neuropsychol ; 10(3): 198-203, July-Sept. 2016. tab
Artigo em Inglês | LILACS | ID: lil-795280

RESUMO

ABSTRACT. Background: Delirium is a neuropsychiatric syndrome with multiple etiological factors. Evaluation of delirium in different settings, especially the Emergency Department (ED) pertaining to different regions of the world with patients from different cultural and educational backgrounds is needed. Objective: To determine the prevalence of delirium and its association with education in an ED in Brazil during a 6-month period. Methods: Patients aged >18 years were randomly selected from ED admissions. The instruments Confusion Assessment Method (CAM) scale, Mini-Mental State Examination (MMSE), Wechsler Logical Memory (WLM) and Charlson comorbidity score were applied to evaluate delirium, cognitive status, and comorbidities. Results: The prevalence of delirium was10.7%. Delirium patients had significantly lower education, MMSE and WLM (immediate and delayed) scores, with 97.4% presenting episodic memory impairment. Patients with delirium had more history of neurological disorders. Three logistic regression models evaluating the association of variables with delirium were developed. Age and MMSE were retained in the first model, WLM scores in the second, and education in the third. Conclusion: To the best of our knowledge, this is the first study estimating the prevalence of delirium in a Brazilian ED. Lower education was associated with the occurrence of delirium.


RESUMO Introdução: Delirium é uma síndrome neuropsiquiátrica, com fatores etiológicos múltiplos. A avaliação de delirium em diferentes ambientes, especialmente no Serviço de Emergência (SE) de diferentes regiões do mundo e com diferentes características culturais e educacionais é necessária. Objetivo: Determinar a prevalência de delirium e associação com educação em um SE no Brasil, durante seis meses. Métodos: Foram randomizados aleatoriamente no SE os pacientes com idade acima de 18 anos. Escala Confusion Assessment Method (CAM), Mini Exame do Estado Mental (MEEM), o teste de Memória Lógica de Wechsler (MLW), e o escore de comorbidade de Charlson foram aplicados para avaliar delirium, status cognitivo, e comorbidades. Resultados: A prevalência de delirium foi 10,7%. Os pacientes com delirium apresentaram significativamente menor escolaridade, escores mais baixos no MEEM e MLW (imediato e tardio), sendo que 97,4% apresentava comprometimento de memória episódica. Pacientes com delirium apresentaram mais história de transtorno neurológico prévio. Três modelos de regressão logística para delirium foram realizados. No primeiro, idade e MEEM foram mantidos no modelo final. No segundo, MLW imediato e tardio; e no terceiro, apenas educação. Conclusão: Este é o primeiro estudo brasileiro, de acordo com nosso melhor conhecimento, a estimar a prevalência de delirium em serviço de emergência. Nível educacional mais baixo foi associado com ocorrência de delirium.


Assuntos
Humanos , Delírio , Educação , Emergências
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