Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 176
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
Retina ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39151183

RESUMO

PURPOSE: To evaluate high-risk histopathological features (HRHF) following primary enucleation of eyes with retinoblastoma (RB) and assess the patient outcomes across continents. METHODS: Retrospective study of 1426 primarily enucleated RB eyes from five continents. RESULTS: Of all, 923 (65%) were from Asia (AS), 27 (2%) from Australia (AUS), 120 (8%) from Europe (EUR), 162 (11%) from North America (NA), and 194 (14%) from South America (SA). Based on the continent (AS vs. AUS vs. EUR vs. NA vs. SA), the histopathology features included massive choroidal invasion (31% vs. 7% vs. 13% vs. 19% vs. 27%, p=0.001), post-laminar optic nerve invasion (27% vs. 0% vs. 16% vs. 21% vs. 19%, p=0.0006), scleral infiltration (5% vs. 0% vs. 4% vs. 2% vs. 7%, p=0.13), and microscopic extrascleral infiltration (4% vs. 0% vs. <1% vs. <1% vs. 4%, p=0.68). Adjuvant chemotherapy with/without orbital radiotherapy was given in 761 (53%) patients. Based on Kaplan-Meier estimates in different continents (AS vs. AUS vs. EUR vs. NA vs. SA), the 6-year risk of orbital tumor recurrence was 5% vs. 2% vs. 0% vs. 0% vs. 12% (p<0.001), systemic metastasis was reported in 8% vs. 5% vs. 2% vs. 0% vs. 13% (p=0.001), and death in 10% vs. 3% vs. 2% vs. 0% vs. 11% (p<0.001) patients. CONCLUSION: There is a wide variation in the infiltrative histopathology features of RB across continents, resulting in variable outcomes. SA and AS had a higher risk of orbital tumor recurrence, systemic metastasis, and death compared to AUS, EUR, and NA.

2.
Int J Mol Sci ; 25(18)2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39337526

RESUMO

The objective of this review is to provide a comprehensive examination of the role of microbial metabolites in the progression of neurodegenerative diseases, as well as to investigate potential therapeutic interventions targeting the microbiota. A comprehensive literature search was conducted across the following databases: PubMed, Scopus, Web of Science, ScienceDirect, and Wiley. Key terms related to the gut microbiota, microbial metabolites, neurodegenerative diseases, and specific metabolic products were used. The review included both preclinical and clinical research articles published between 2000 and 2024. Short-chain fatty acids have been demonstrated to play a crucial role in modulating neuroinflammation, preserving the integrity of the blood-brain barrier, and influencing neuronal plasticity and protection. Furthermore, amino acids and their derivatives have been demonstrated to exert a significant influence on CNS function. These microbial metabolites impact CNS health by regulating intestinal permeability, modulating immune responses, and directly influencing neuroinflammation and oxidative stress, which are integral to neurodegenerative diseases. Therapeutic strategies, including prebiotics, probiotics, dietary modifications, and fecal microbiota transplantation have confirmed the potential to restore microbial balance and enhance the production of neuroprotective metabolites. Furthermore, novel drug developments based on microbial metabolites present promising therapeutic avenues. The gut microbiota and its metabolites represent a promising field of research with the potential to advance our understanding of and develop treatments for neurodegenerative diseases.


Assuntos
Microbioma Gastrointestinal , Doenças Neurodegenerativas , Probióticos , Humanos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/terapia , Doenças Neurodegenerativas/microbiologia , Animais , Probióticos/uso terapêutico , Prebióticos , Transplante de Microbiota Fecal , Progressão da Doença , Barreira Hematoencefálica/metabolismo , Estresse Oxidativo , Ácidos Graxos Voláteis/metabolismo
3.
Int J Mol Sci ; 25(16)2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39201684

RESUMO

Parkinson's Disease (PD) is a prevalent neurodegenerative disorder characterized by motor and non-motor symptoms. Emerging evidence suggests that gut microbiota alterations, specifically involving short-chain fatty acids (SCFAs) like butyrate, may influence PD pathogenesis and symptomatology. This Systematic Review aims to synthesize current research on the role of butyrate in modulating motor symptoms and its neuroprotective effects in PD, providing insights into potential therapeutic approaches. A systematic literature search was conducted in April 2024 across databases, including ScienceDirect, Scopus, Wiley, and Web of Science, for studies published between 2000 and 2024. Keywords used were "neuroprotective effects AND butyrate AND (Parkinson disease OR motor symptoms)". Four authors independently screened titles, abstracts, and full texts, applying inclusion criteria focused on studies investigating butyrate regulation and PD motor symptoms. A total of 1377 articles were identified, with 40 selected for full-text review and 14 studies meeting the inclusion criteria. Data extraction was performed on the study population, PD models, methodology, intervention details, and outcomes. Quality assessment using the SYRCLE RoB tool highlighted variability in study quality, with some biases noted in allocation concealment and blinding. Findings indicate that butyrate regulation has a significant impact on improving motor symptoms and offers neuroprotective benefits in PD models. The therapeutic modulation of gut microbiota to enhance butyrate levels presents a promising strategy for PD symptom management.


Assuntos
Butiratos , Microbioma Gastrointestinal , Fármacos Neuroprotetores , Doença de Parkinson , Transdução de Sinais , Doença de Parkinson/metabolismo , Doença de Parkinson/tratamento farmacológico , Humanos , Butiratos/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais
4.
Int J Mol Sci ; 25(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38474254

RESUMO

This systematic review addresses the use of Lactiplantibacillus (Lactobacillus) plantarum in the symptomatological intervention of neurodegenerative disease. The existence of gut microbiota dysbiosis has been associated with systemic inflammatory processes present in neurodegenerative disease, creating the opportunity for new treatment strategies. This involves modifying the strains that constitute the gut microbiota to enhance synaptic function through the gut-brain axis. Recent studies have evaluated the beneficial effects of the use of Lactiplantibacillus plantarum on motor and cognitive symptomatology, alone or in combination. This systematic review includes 20 research articles (n = 3 in human and n = 17 in animal models). The main result of this research was that the use of Lactiplantibacillus plantarum alone or in combination produced improvements in symptomatology related to neurodegenerative disease. However, one of the studies included reported negative effects after the administration of Lactiplantibacillus plantarum. This systematic review provides current and relevant information about the use of this probiotic in pathologies that present neurodegenerative processes such as Alzheimer's disease, Parkinson's disease and Multiple Sclerosis.


Assuntos
Doenças Neurodegenerativas , Probióticos , Humanos , Doenças Neurodegenerativas/terapia , Doenças Neurodegenerativas/microbiologia , Probióticos/uso terapêutico , Animais , Microbioma Gastrointestinal , Lactobacillus plantarum/fisiologia , Terapias Complementares/métodos , Disbiose/terapia , Disbiose/microbiologia
5.
Nutr Health ; 29(2): 277-285, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35023408

RESUMO

Background: The adaptation of Parenteral Nutrition (PN) to actual energy requirements of hospitalised patients is essential, since excessive and insufficient nutritional intake have been associated with poor clinical outcomes. Aim: To evaluate the adaptation of prescribed PN to the estimated nutritional requirements using three predictive equations and the influence of excessive/insufficient nutrient intake on patient clinical outcomes (nutritional parameters, metabolic and infectious complications). Methods: Prospective, observational study in hospitalised patients nutritionally assessed. Data was collected the first and fifth/sixth day of PN with clinical (infection, length of hospital stay), biochemical (visceral proteins, cholesterol, glucose, triglycerides, lymphocytes, CRP) and anthropometric parameters (skin folds, height, weight). Theoretical requirements were calculated using Harris-Benedict (HB), Mifflin-St Jeor (MF) and 25 Kcal/Kg/day formulas. The HB formula was used to compare estimated and provided requirements. Results: A total of 94 patients (mean: 72 ± 13.7 years old) were included with initial mean weight and height of 69.2 Kg and 162.8 cm, respectively (mean BMI: 26.1 Kg/m2). No statistically significant differences were found between the actual (1620 Kcal/day) and estimated caloric mean calculated with HB (1643 Kcal/day) and MF (1628 Kcal/day). When comparing with the caloric estimation, 31.9% of patients were underfed, while 14.9% were overfed. Intergroup analysis demonstrated significant variations in albumin, prealbumin, glucose, cholesterol, triglycerides and MUAC, with a significant increase of hyperglycaemia (+37.86; p < 0.05) and hypertriglyceridemia (+63.10; p < 0.05), being higher in overfed patients. Conclusion: In our study, inadequate nutrient intake was associated with a higher degree of hyperglycaemia and hypertriglyceridemia, without positive impact on anthropometric parameters.


Assuntos
Ingestão de Energia , Hipertrigliceridemia , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Prospectivos , Nutrição Parenteral , Triglicerídeos
6.
Int J Mol Sci ; 24(17)2023 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-37686104

RESUMO

The comprehensive narrative review conducted in this study delves into the mechanisms of communication and action at the molecular level in the human organism. The review addresses the complex mechanism involved in the microbiota-gut-brain axis as well as the implications of alterations in the microbial composition of patients with neurodegenerative diseases. The pathophysiology of neurodegenerative diseases with neuronal loss or death is analyzed, as well as the mechanisms of action of the main metabolites involved in the bidirectional communication through the microbiota-gut-brain axis. In addition, interventions targeting gut microbiota restructuring through fecal microbiota transplantation and the use of psychobiotics-pre- and pro-biotics-are evaluated as an opportunity to reduce the symptomatology associated with neurodegeneration in these pathologies. This review provides valuable information and facilitates a better understanding of the neurobiological mechanisms to be addressed in the treatment of neurodegenerative diseases.


Assuntos
Microbioma Gastrointestinal , Doenças Neurodegenerativas , Humanos , Disbiose/terapia , Transplante de Microbiota Fecal , Doenças Neurodegenerativas/terapia , Metaboloma
7.
Appl Psychophysiol Biofeedback ; 47(2): 77-84, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34958443

RESUMO

Drug treatment centres provide the highest level of rehab services for patients diagnosed with drug addictions. Most inpatient drug rehab programs focus on medical detox and mental health interventions. However, how to optimize the later remains a challenge. The aim of this study was to examine the psychophysiological and psychosocial profile of patients attending drug addiction centres in comparation with the general population. A total of 105 inpatient drug rehab patients and 50 participants from the general population were compared based on standardized psychophysiological and psychosocial measures. Results of this study suggest that patients attending drug addiction centers differ from general population in several different psychophysiological and psychosocial factors. Patients reported significantly lower levels of physical activity and increased sympathetic responsiveness, and significantly higher levels in loneliness, psychologically inflexibility and neuroticism. The results of this study highlight the importance of address healthy lifestyle behaviors such as sport practice and psychological variables such as loneliness, psychological (in)flexibility and neuroticism to improve current programs aim to prevent or reduce problematic drug consumptions.


Assuntos
Solidão , Transtornos Relacionados ao Uso de Substâncias , Humanos , Psicofisiologia
8.
Epilepsy Behav ; 114(Pt A): 107560, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33243680

RESUMO

OBJECTIVE: To determine the usefulness and efficacy of radiofrequency ablations (RFA) of the Centromedian thalamic nucleus (CMN) to control primarily generalized or multifocal seizures in refractory epilepsy. METHODS: Six patients with clinical diagnosis of multifocal or primarily generalized drug-resistant epilepsy were included. Bilateral RFA of the CMN was performed through a monopolar 1.8 mm. tip electrode with a temperature of 80 °C during 90 seconds. Patients were followed in every 3 months visit for 20 to 36 months and kept a monthly seizure count calendar. We also compared maximal paroxysmal electroencephalogram (EEG) activity and neuropsychological evaluation pre and 6 months postoperatively. RESULTS: A significant reduction in the number of generalized seizures was observed in all subjects in the range of 79-98%, starting the first post-operative month. Although focal aware seizures remained unchanged throughout follow-up, there was an important reduction on paroxysmal activity between the pre and postoperative EEG. No major changes on cognitive status were detected. There was post-operative dysphagia and odynophagia lasting one week and there was no mortality in this group of patients. CONCLUSION: Preliminary results of CMN RFA suggest safety and a trend toward reduction of some seizure types, it may reduce the seizure frequency like other palliative procedures since the first post-operative month, but a larger, controlled study would be needed to establish the value of this therapy.


Assuntos
Epilepsia Resistente a Medicamentos , Núcleos Intralaminares do Tálamo , Preparações Farmacêuticas , Ablação por Radiofrequência , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia , Humanos
9.
Acta Derm Venereol ; 101(11): adv00597, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34643739

RESUMO

BRAF/V600E mutation and other cell growth/growth-control mechanisms are involved in naevogenesis and melanomagenesis. Immunoexpression of BRAF/V600E and other molecules (p16, phosphatase and tensin homologue (PTEN), Ki67, hTERT and Cav3.1 and 3.2 calcium channels) were investigated in 80 histopatho-logically and dermoscopically classified acquired naevi. Regarding BRAF/V600E, dysplastic naevi showed lower immunostaining than common naevi, which was significant in comparison with intradermal naevi, which showed the highest BRAF/V600E histoscore. Junctional naevi showed the lowest BRAF/V600E levels. Globular/cobblestone and reticular dermoscopic patterns were consistently associated with high and low BRAF/V600E immunoexpression, respectively, but Zalaudek's peripheral globule pattern (CR/PG) showed the highest BRAF/V600E immunoexpression. Among global patterns, the previously not investigated multicomponent pattern showed the lowest BRAF/V600E immunoexpression. Regarding the remaining biomarkers, new immunohistochemical features were found, in particular p16 and PTEN low expression in multicomponent pattern; and Ki67, hTERT and Cav.3.1 high expression in CR/PG. In conclusion, histopathology and dermoscopy provide complementary information regarding the biology of melanocytic naevi.


Assuntos
Canais de Cálcio Tipo T , Nevo Pigmentado , Neoplasias Cutâneas , Biomarcadores , Dermoscopia , Humanos , PTEN Fosfo-Hidrolase , Proteínas Proto-Oncogênicas B-raf/genética
10.
Stereotact Funct Neurosurg ; 99(1): 40-47, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33113540

RESUMO

INTRODUCTION: Evidence has been provided that the subiculum may play an important role in the generation of seizures. Electrical stimulation at this target has been reported to have anticonvulsive effects in kindling and pilocarpine rat models, while in a clinical study of hippocampal deep brain stimulation (DBS), contacts closest to the subiculum were associated with a better anticonvulsive effect. OBJECTIVES: To evaluate the effect of electrical stimulation of the subiculum in patients with refractory mesial temporal lobe epilepsy (MTLE) who have hippocampal sclerosis (HS). METHODS: Six patients with refractory MTLE and HS, who had focal impaired awareness seizures (FIAS) and focal to bilateral tonic-clonic seizures (FBTCS), had DBS electrodes implanted in the subiculum. During the first month after implantation, all patients were OFF stimulation, then they all completed an open-label follow-up of 24 months ON stimulation. DBS parameters were set at 3 V, 450 µs, 130 Hz, cycling stimulation 1 min ON, 4 min OFF. RESULTS: There was a mean reduction of 49.16% (±SD 41.65) in total seizure number (FIAS + FBTCS) and a mean reduction of 67.93% (±SD 33.33) in FBTCS at 24 months. FBTCS decreased significantly with respect to baseline, starting from month 2 ON stimulation. CONCLUSIONS: Subiculum stimulation is effective for FBTCS reduction in patients with MTLE and HS, suggesting that the subiculum mediates the generalization rather than the genesis of mesial temporal lobe seizures. Better results are observed at longer follow-up times.


Assuntos
Estimulação Encefálica Profunda/métodos , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/terapia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/terapia , Hipocampo/diagnóstico por imagem , Adolescente , Adulto , Animais , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Ratos , Esclerose , Resultado do Tratamento , Adulto Jovem
11.
Int J Cancer ; 147(1): 277-284, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31953839

RESUMO

Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Although most patients are diagnosed at early stages, 15-20% will relapse despite local treatment. Presently, there are no reliable markers to identify patients with worse outcomes who may benefit from adjuvant treatments, such as chemotherapy, and liquid biopsies may be of use in this setting. Peritoneal lavages are systematically performed during endometrial surgery but little data are available about their potential as liquid biopsies. We analyzed KRAS and PIK3CA mutations in paired surgical biopsies, blood and cytology-negative peritoneal lavages in a cohort of 50 EC patients. Surgical biopsies were submitted to next-generation sequencing (NGS) while circulating-free DNA (cfDNA) purified from plasma and peritoneal lavages was analyzed for KRAS and PIK3CA hotspot mutations using a sensitive quantitative polymerase chain reaction (PCR) assay. NGS of biopsies revealed KRAS, PIK3CA or concomitant KRAS + PIK3CA mutations in 33/50 (66%) EC patients. Of those, 19 cases carried hotspot mutations. Quantitative PCR revealed KRAS and/or PIK3CA mutations in the lavages of 9/19 (47.4%) hotspot EC patients. In contrast, only 2/19 (10.5%) blood samples from hotspot EC patients were positive. Mutations found in cfDNA consistently matched those in paired biopsies. One of the two patients positive in plasma and lavage died in less than 6 months. In conclusion, mutational analysis in peritoneal lavages and blood from early stage EC is feasible. Further studies are warranted to determine if it might help to identify patients with worse prognosis. Human genes discussed: KRAS, KRAS proto-oncogene, GTPase; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha.


Assuntos
Neoplasias do Endométrio/genética , Mutação , Idoso , Idoso de 80 Anos ou mais , Alelos , Classe I de Fosfatidilinositol 3-Quinases/genética , Análise Mutacional de DNA , DNA Circular/sangue , DNA Circular/genética , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Biópsia Líquida , Pessoa de Meia-Idade , Lavagem Peritoneal/métodos , Estudo de Prova de Conceito , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas p21(ras)/genética , Reação em Cadeia da Polimerase em Tempo Real
12.
Histopathology ; 76(3): 447-460, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31550396

RESUMO

AIMS: Endometrial serous carcinoma (ESC) represents the most aggressive subtype of endometrial carcinoma (EC). According to The Cancer Genome Atlas (TCGA), ESC exhibits a genomic profile characterised by frequent TP53 mutations and somatic copy-number alterations (SCNA). Several studies have suggested the role of intratumour heterogeneity (ITH) in tumour progression and therapy resistance, highlighting ITH as a challenge for personalised medicine. ITH is described as the co-existence of clonal and subclonal cellular populations within a single tumour. To date, the extent and prevalence of ITH in ESC have not been fully evaluated. The aim of this study was to address ITH analysis in ESC. We performed a descriptive integrated molecular approach using targeted sequencing and multiplex ligation-dependent probe amplification (MLPA) to identify mutations and SCNA patterns, respectively. METHODS AND RESULTS: Eight ESC were examined, selecting three tumour regions per case and their corresponding normal tissue. For targeted sequencing a gene panel of 40 genes based on TCGA and other survey data was performed. For MLPA different probe mixes were used to detect SCNA in 106 genes. Analysis of mutations and SCNA were performed in each sample and comparative analysis of the three tumour regions was also conducted. Targeted sequencing showed that mutations in TP53, PIK3CA and PPP2R1A were ubiquitous in all tumour regions. Moreover, MLPA results demonstrated a high frequency of SCNA, according to the already known presence of genomic instability in ESC. Unlike the homogeneous distribution of somatic mutations, SCNA exhibited ITH affecting targetable genes such as ERBB2. CONCLUSIONS: Our study suggests that somatic gene copy-number alterations are the main source of ITH in ESC.


Assuntos
Biologia Computacional , Variações do Número de Cópias de DNA , Neoplasias do Endométrio/genética , Medicina de Precisão , Idoso , Idoso de 80 Anos ou mais , Instabilidade Cromossômica , Neoplasias do Endométrio/patologia , Endométrio/patologia , Feminino , Dosagem de Genes , Humanos , Reação em Cadeia da Polimerase Multiplex , Mutação
13.
J Nutr ; 150(6): 1631-1643, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32243527

RESUMO

BACKGROUND: The cognitive impairments that characterize Down syndrome (DS) have been attributed to brain hypocellularity due to neurogenesis impairment during fetal stages. Thus, enhancing prenatal neurogenesis in DS could prevent or reduce some of the neuromorphological and cognitive defects found in postnatal stages. OBJECTIVES: As fatty acids play a fundamental role in morphogenesis and brain development during fetal stages, in this study, we aimed to enhance neurogenesis and the cognitive abilities of the Ts65Dn (TS) mouse model of DS by administering oleic or linolenic acid. METHODS: In total, 85 pregnant TS females were subcutaneously treated from Embryonic Day (ED) 10 until Postnatal Day (PD) 2 with oleic acid (400 mg/kg), linolenic acid (500 mg/kg), or vehicle. All analyses were performed on their TS and Control (CO) male and female progeny. At PD2, we evaluated the short-term effects of the treatments on neurogenesis, cellularity, and brain weight, in 40 TS and CO pups. A total of 69 TS and CO mice were used to test the long-term effects of the prenatal treatments on cognition from PD30 to PD45, and on neurogenesis, cellularity, and synaptic markers, at PD45. Data were compared by ANOVAs. RESULTS: Prenatal administration of oleic or linolenic acid increased the brain weight (+36.7% and +45%, P < 0.01), the density of BrdU (bromodeoxyuridine)- (+80% and +115%; P < 0.01), and DAPI (4',6-diamidino-2-phenylindole)-positive cells (+64% and +22%, P < 0.05) of PD2 TS mice with respect to the vehicle-treated TS mice. Between PD30 and PD45, TS mice prenatally treated with oleic or linolenic acid showed better cognitive abilities (+28% and +25%, P < 0.01) and a higher density of the postsynaptic marker PSD95 (postsynaptic density protein 95) (+65% and +44%, P < 0.05) than the vehicle-treated TS animals. CONCLUSION: The beneficial cognitive and neuromorphological effects induced by oleic or linolenic acid in TS mice suggest that they could be promising pharmacotherapies for DS-associated cognitive deficits.


Assuntos
Síndrome de Down/fisiopatologia , Exposição Materna , Ácido Oleico/administração & dosagem , Ácido alfa-Linolênico/administração & dosagem , Animais , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Modelos Animais de Doenças , Síndrome de Down/patologia , Feminino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurogênese/efeitos dos fármacos , Ácido Oleico/farmacologia , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ácido alfa-Linolênico/farmacologia
14.
J Pathol ; 247(1): 72-85, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30206933

RESUMO

Many human cancers present Phosphatase and tensin homolog (PTEN) deficiency and between 20 and 30% of colorectal tumors show PTEN loss. The transcription factor, E2 promoter binding factor 1 (E2F-1), exhibits tumor promoter or suppressive functions depending on cellular type and tissue context, but its role in the progression and development of colorectal carcinogenesis was largely unknown. Here, using a tamoxifen-inducible PTEN knockout mouse model, we have demonstrated that loss of PTEN leads to the development of colorectal tumorigenesis through the serrated pathway. Next, we studied PTEN loss-driven colorectal lesions in the context of E2F-1 deficiency in vivo. Our results revealed that monoallelic and biallelic absence of E2F-1 led to an increased incidence and progression of serrated tumorigenesis induced by PTEN loss. Finally, we investigated the mechanisms by which double PTEN/E2F-1 deficiency leads to enhanced tumorigenesis. We found that colorectal tumors from PTEN/E2F-1 double knockout mice and the human colorectal carcinoma cell line HT29 with shRNA-mediated downregulation of PTEN and E2F-1 exhibit hyperactivation of the RAS-MAPK pathway, accumulation of DNA damage and resistance to apoptosis. To date, this is the first preclinical study evaluating the effect of genetic deletion of E2F-1 in colorectal malignancies driven by PTEN deficiency. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Carcinogênese , Neoplasias Colorretais/enzimologia , Fator de Transcrição E2F1/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Apoptose , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Dano ao DNA , Fator de Transcrição E2F1/genética , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Camundongos Knockout , Proteínas Quinases Ativadas por Mitógeno/metabolismo , PTEN Fosfo-Hidrolase/genética , Transdução de Sinais , Proteínas Supressoras de Tumor/genética , Proteínas ras/metabolismo
15.
Appl Psychophysiol Biofeedback ; 45(1): 23-29, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31612295

RESUMO

The simulation scenarios are increasingly being used to assess professional competences in health sciences at university level. The objective of this study was to explore the effect of differences in the stress psychophysiological response of Psychology degree students from Spain and Colombia undergoing to clinical practice. Multiple psychophysiological measures were obtained in a sample of 25 Colombian and Spanish Psychology students undergoing to simulation scenario. Differences in the initial level of stress and habituation process as reported by self-reported and psychophysiological measurements as discussed. Differences in stress-related psychological traits are also analyzed and further discussed.


Assuntos
Comparação Transcultural , Estresse Psicológico/etnologia , Adulto , Colômbia/etnologia , Feminino , Humanos , Masculino , Projetos Piloto , Espanha/etnologia , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Estudantes , Universidades , Adulto Jovem
16.
Addict Biol ; 24(5): 1019-1033, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30277635

RESUMO

Chronic alcohol consumption is associated with neurocognitive and memory deficits, dramatically affecting plasticity and connectivity, with maximal expression as dementia. Neurotrophic factors may contribute to alcohol-related cognitive decline. For further investigation, a cross-sectional study was performed to evaluate the association of cognitive impairment, by using frontal assessment battery, and memory loss, using memory failures everyday, with the circulating levels of the neurotrophin brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) in abstinent subjects with alcohol use disorders (AUDs, N = 58, average of 17.9 years of problematic use and 4.3 months of abstinence) compared with healthy control subjects (N = 22). This association was also explored in a pre-clinical model of adolescent rats chronically exposed to alcohol up to adulthood (~77 days old) in a three-bottle free-choice (5-10-20 percent), repeated abstinence and relapse paradigm. AUD subjects had low educational level and cognitive impairment associated with teenage consumption and lower circulating levels of BDNF and NT-3. Only BDNF concentration showed a positive correlation with frontal assessment battery in AUD patients. In the ethanol-exposed rats, the plasma levels of BDNF and NT-3 were also decreased, and a negative correlation between hippocampal Bdnf mRNA levels and recognition memory was found. The ethanol-exposed rat hippocampus showed a decrease in the mRNA levels of neurotrophic (Bdnf and Ntf-3) and neurogenic (Mki67, Sox2, Dcx, Ncam1 and Calb1) factors, associated to a deactivation of the neurogenic regulator mitogen-activated protein kinase extracellular signal-regulated kinase. Results suggest a relevant role of BDNF/extracellular signal-regulated kinase 2 signaling in alcohol-induced cognitive impairment and suggest that early alcohol exposure-derived effects on cognition are associated with neurotrophin signaling deficits.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Alcoolismo/complicações , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Neurotrofina 3/metabolismo , Adolescente , Adulto , Idoso , Abstinência de Álcool , Alcoolismo/sangue , Animais , Biomarcadores/metabolismo , Depressores do Sistema Nervoso Central/toxicidade , Disfunção Cognitiva/sangue , Disfunção Cognitiva/induzido quimicamente , Estudos Transversais , Discriminação Psicológica/efeitos dos fármacos , Modelos Animais de Doenças , Proteína Duplacortina , Etanol/toxicidade , Feminino , Hipocampo/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Transtornos da Memória/induzido quimicamente , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Ratos Wistar , Reconhecimento Psicológico/efeitos dos fármacos , Recidiva , Adulto Jovem
17.
Stereotact Funct Neurosurg ; 97(4): 232-240, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31722358

RESUMO

BACKGROUND: Positron emission tomography (PET) imaging in epilepsy is an in vivo technique that allows the localization of a possible seizure onset zone (SOZ) during the interictal period. Stereo-electro-encephalography (SEEG) is the gold standard to define the SOZ. The objective of this research was to evaluate the accuracy of PET imaging in localizing the site of SOZ compared with SEEG. METHODS: Seven patients with refractory temporal lobe epilepsy (Ep) and 2 healthy controls (HC) underwent 2 PET scans, one with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and another with 2'-[18F]fluoroflumazenil (FFMZ), acquired 1 day apart. FDG was acquired for 10 min (static scan) 1 h after administration. An FFMZ scan was acquired for 60 min from radiopharmaceutical administration in a dynamic mode. Each brain PET image was segmented using a standard template implemented in PMOD 3.8. The pons was used as the reference region for modeling of the nondisplaceable binding potential (BPND)for FFMZ, and to obtain uptake ratios for FDG. SEEG studies of patients were performed as a part of their surgical evaluation to define the SOZ. RESULTS: Well-defined differences between HC and Ep were found with both radiopharmaceuticals, showing the utility to identify abnormal brain regions using quantitative PET imaging. Lateralization of the SOZ findings by PET (lower uptake/binding in a specific brain hemisphere) matched in 86% for FFMZ and 71% for FDG with SEEG data. CONCLUSION: Quantitative PET imaging is an excellent complementary tool that matches reasonably well with SEEG to define SOZ in presurgical evaluation.


Assuntos
Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia do Lobo Temporal/diagnóstico por imagem , Flumazenil/análogos & derivados , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Adolescente , Adulto , Mapeamento Encefálico/métodos , Epilepsia Resistente a Medicamentos/metabolismo , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/cirurgia , Feminino , Flumazenil/metabolismo , Radioisótopos de Flúor/metabolismo , Fluordesoxiglucose F18/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Convulsões/diagnóstico por imagem , Convulsões/metabolismo , Convulsões/cirurgia
18.
J Med Syst ; 43(3): 68, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30734084

RESUMO

The aim of this study was to analyze the psychophysiological response of Physiotherapy degree students during a complete clinical practice as well as their psychological profile in relation to coping style in stressful situations, and its impact on academic performance. We analysed in 15 students heart rate variability (HRV) to analyse autonomic modulation in three moments during the entire clinical practices of 3 months (4 h per day, 3 days per week), first session, middle session and last session; perceived stress, personality, life engagement, cognitive flexibility before starting the clinical practice the academic performance after the clinical practice. Results based on HRV and related indexes parameters fail to indicate the expected autonomic adaptation during the practice. A complete clinical practice of Physiotherapy degree students did not produce an habituation process since a high sympathetic autonomic nervous system modulation was measured in the beginning, at the middle and at the final of the clinical practice. Below-average scores are presented in a personality factor associated with traditional and non-adaptive coping styles that could explain the non-habituation of the students. Finally, none of the analyzed indexes has been able to relate to academic performance.


Assuntos
Adaptação Psicológica , Avaliação Educacional , Estudantes de Medicina/psicologia , Adulto , Educação de Graduação em Medicina , Feminino , Frequência Cardíaca , Humanos , Masculino , Personalidade , Especialidade de Fisioterapia/educação , Adulto Jovem
19.
Epilepsy Behav ; 79: 138-145, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29287217

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the relation between cognitive performance and white matter (WM) integrity in patients with temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS). METHODS: We included 26 patients with TLE (10 right, 16 left onset) as well as 24 healthy controls matched for age, gender, and years of education. In addition to quantitative hippocampal volume and transverse relaxation (T2) evaluation, whole-brain WM was analyzed using fractional anisotropy (FA) maps, derived from the diffusion tensor model. Average FA values were obtained from 38 regions of interest (ROI) of the main WM fascicles using an atlas-based approach. All subjects underwent extensive coFignitive assessments, Wechsler Adult Intelligence Scale (WAIS-IV) and Wechsler Memory Scale (WMS-IV). Fractional anisotropy was correlated with neuropsychological scores, and group effects were evaluated. Finally, patients were clustered based on their cognitive performance to evaluate if clinical and structural variables relate to specific cognitive profiles. RESULTS: Patients had differential alterations in the integrity of the WM dependent on seizure laterality and presence of hippocampal sclerosis. Patients with TLE showed, on average, lower scores in most of the cognitive assessments. Correlations between cognition and WM followed specific trajectories per group with TLE, particularly in Left-TLE, in which we found a marked association between cognitive abilities and WM abnormalities. Cluster analysis of cognitive performance revealed three cognitive profiles, which were associated with the degree and spread of WM abnormalities. SIGNIFICANCE: White matter diffusion characteristics differ between patients, particularly in relation to seizure laterality and hippocampal damage. Moreover, WM abnormalities are associated with cognitive performance. The extent of WM alterations leads to disrupted cerebral intercommunication and therefore negatively affects cognition.


Assuntos
Transtornos Cognitivos/patologia , Cognição/fisiologia , Epilepsia do Lobo Temporal/patologia , Hipocampo/diagnóstico por imagem , Convulsões , Lobo Temporal/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Anisotropia , Estudos de Casos e Controles , Transtornos Cognitivos/etiologia , Imagem de Tensor de Difusão , Epilepsia do Lobo Temporal/complicações , Feminino , Lateralidade Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose/diagnóstico por imagem
20.
Stereotact Funct Neurosurg ; 96(1): 54-59, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29408817

RESUMO

BACKGROUND: Selective improvement of symptoms may be required when treating Parkinson disease (PD) patients with a predominantly monosymptomatic clinical picture. OBJECTIVE: To define a target in prelemniscal radiation fibers (Raprl) related to the physiopathology of tremor evidenced by tractography. CASE REPORT: We report a patient with predominant unilateral rest and postural tremor, diagnosed as PD based on 80% improvement induced by the administration of L-DOPA/carbidopa, subsequently complicated by motor fluctuations, L-DOPA dyskinesia, and a reduced ON period. A stereotactic radiofrequency lesion was made for tremor control, and postoperative diffusion-weighted imaging (DWI) demonstrated the precise location and extension of the lesioned tract. RESULTS: Perfect control of the tremor was achieved with the patient OFF medication; this has lasted for 5 years, without hypotonia in the treated extremities. DWI revealed a 3.0-mm lesion at the base of the nucleus ventralis intermedius (Vim) interrupting cerebellar-Vim fibers sparing the cerebellar ventralis oralis posterior nucleus component. CONCLUSION: Selective improvement of symptoms is feasible in patients with a predominantly monosymptomatic PD clinical presentation.


Assuntos
Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/cirurgia , Tremor/diagnóstico por imagem , Tremor/cirurgia , Núcleos Ventrais do Tálamo/diagnóstico por imagem , Núcleos Ventrais do Tálamo/cirurgia , Idoso , Carbidopa/uso terapêutico , Combinação de Medicamentos , Humanos , Levodopa/uso terapêutico , Masculino , Doença de Parkinson/tratamento farmacológico , Resultado do Tratamento , Tremor/tratamento farmacológico
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa