RESUMO
Several studies have demonstrated that stroke subjects present impairment of functions related to decision-making and timing, involving the information processing in the neural circuits of the cerebellum in association with the prefrontal cortex. This review is aimed to identify the gaps, and demonstrate a better understanding of decision-making and timing functions in the patients with stroke. Electronic literature database was searched and the findings of relevant studies were used to explore the mechanisms of decision-making and timing in patients with stroke, as well as the circuit connections in timing mediated by prefrontal cortex and cerebellum. A literature review was conducted with 65 studies that synthesized findings on decision-making and time perception in individuals with stroke. Types of neurobiological modalities in this study included: Relationships among decision-making, time perception, related cognitive aspects (such as discrimination tasks, verbal estimation, bisection tasks, time production and motor reproduction), and motor control. We demonstrate that the timing processes are important for the performance in cognitive tasks and that the cerebellum and prefrontal cortex are involved in decision-making and time perception. In the context, the decision-making is impaired in stroke patients has a great impact on executive functions, and this seems to be important in determining neurobiological aspects relevant to the time interval interpretation.
Assuntos
Comportamento/fisiologia , Transtornos Cognitivos/etiologia , Tomada de Decisões/fisiologia , Vias Neurais/fisiologia , Acidente Vascular Cerebral/complicações , Percepção do Tempo/fisiologia , Cerebelo/patologia , Cerebelo/fisiologia , Cognição/fisiologia , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Humanos , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologiaRESUMO
The subversion mechanisms employed by Helicobacter pylori (H. pylori) to escape from immune surveillance and to establish persistent infection are poorly understood. Growing evidence indicates that expression of HLA-G, a non-classical major histocompatibility complex molecule, negatively regulates immune responses in pathological conditions, including infectious diseases. In this context, we aimed to evaluate HLA-G expression in the gastric microenvironment of individuals harbouring H. pylori and to correlate it with histological variables. Fifty-four gastric specimens from patients harbouring H. pylori infection were evaluated by immunohistochemistry using anti-HLA-G monoclonal antibody. As a result, HLA-G expression was detected in 43 of 54 specimens harbouring H. pylori. The presence of HLA-G was significantly associated with milder colonization by H. pylori (P < 0.02), milder inflammatory activity (P < 0.02) and bacterium histological location in the gastric antrum. This study is the first to explore HLA-G expression in the context of bacterial infection. Whether the biological role of HLA-G during H. pylori infection is beneficial or hazardous for patients remains to be defined.
Assuntos
Mucosa Gástrica/metabolismo , Antígenos HLA-G/biossíntese , Infecções por Helicobacter/metabolismo , Mucosa Gástrica/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori , Humanos , Imuno-Histoquímica , Isoformas de Proteínas/biossíntese , Estudos Retrospectivos , Regulação para CimaRESUMO
WHAT IS KNOWN: Documentation is a process indicator utilized to evaluate quality clinical pharmacist services. In this framework, documentation of dispensing, besides supporting patient care, allows evaluation of the impact of counselling. OBJECTIVE: To identify and assess studies of documentation by pharmacists in the dispensing process. METHOD: A systematic review was carried out according to the following steps: (i) identification of studies in the following databases: PubMed/Medline, Web of Science, Scopus and Lilacs, using the descriptors 'counselling', 'dispensing', 'community pharmacy services', 'pharmacies' and 'pharmacists' in different combinations; (ii) evaluation of studies, in which the title, abstract and full text of the studies, and the evaluation of the methodological quality of the selected studies were analysed. RESULTS: In total, 26 articles met the specific criteria. Few studies addressed documentation as part of the dispensing working process (3), and 16 articles reported documentation using non-electronic systems. The main variables documented were patient information, drug therapy problems and clinical interventions. Furthermore, 20 studies showed the effects of documentation in the dispensing process and 23 studies included statistical evidence. Eight articles met between 42% and 75% of the 28 items recommended by the STROBE initiative, and two articles met approximately 60% of the 36 items recommended by the CONSORT initiative. WHAT IS NEW AND CONCLUSION: Few studies address documentation as part of the dispensing working process. Thus, researchers should be concerned with standardizing documentation and implementing more robust designs and multicenter studies.
Assuntos
Serviços Comunitários de Farmácia/normas , Documentação , Farmácias/normas , Serviço de Farmácia Hospitalar/normas , Humanos , FarmacêuticosRESUMO
Yoga is believed to have beneficial effects on cognition, attenuation of emotional intensity and stress reduction. Previous studies were mainly performed on eastern experienced practitioners or unhealthy subjects undergoing concomitant conventional therapies. Further investigation is needed on the effects of yoga per se, as well as its possible preventive benefits on healthy subjects. We investigated the effects of yoga on memory and psychophysiological parameters related to stress, comparing yoga practice and conventional physical exercises in healthy men (previously yoga-naïve). Memory tests, salivary cortisol levels and stress, anxiety, and depression inventories were assessed before and after 6 months of practice. Yoga practitioners showed improvement of the memory performance, as well as improvements in psychophysiological parameters. The present results suggest that regular yoga practice can improve aspects of cognition and quality of life for healthy individuals. An indirect influence of emotional state on cognitive improvement promoted by yoga practice can be proposed.
Assuntos
Yoga/psicologia , Adulto , Ansiedade/prevenção & controle , Cognição , Depressão/prevenção & controle , Humanos , Hidrocortisona/análise , Masculino , Memória , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Saliva/química , Estresse Psicológico/prevenção & controle , Adulto JovemRESUMO
Insulin-like growth factor (IGF)-1 has shown some interesting results in studies examining its use as a hair-loss treatment. IGF-1 works by regulating cellular proliferation and migration during the development of hair follicles. Hepatotoxicity and myelotoxicity were evaluated in hamsters (Mesocricetus auratus) after topical application of the liquid gel vehicle (placebo), 1% IGF-1 or 3% IGF-1. No significant difference in the levels of aspartate aminotransferase or alanine aminotransferase was found between the control and treated groups. ELISA did not shown any increase in the plasma level of IGF-1. A haematopoietic niche was found, but it was not associated with myelotoxicity. Efficacy was determined by dermatoscopy analysis of hair density and microscopy analysis of hair diameter, with hair found to be thicker and with more rapid growth in the 3% group than in either the 1% group or the control group. These results strongly suggest that liposomal IGF-1 in a liquid gel formulation is a safe and efficient treatment for hair loss.
Assuntos
Alopecia/tratamento farmacológico , Folículo Piloso/crescimento & desenvolvimento , Cabelo/crescimento & desenvolvimento , Fator de Crescimento Insulin-Like I/farmacologia , Administração Tópica , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Cricetinae , Géis , Cabelo/efeitos dos fármacos , Folículo Piloso/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/efeitos adversos , Fator de Crescimento Insulin-Like I/metabolismo , Modelos Animais , Pele/efeitos dos fármacosRESUMO
Obesity is rampant in modern society and growth hormone (GH) could be useful as adjunct therapy to reduce the obesity-induced cardiovascular damage. To investigate GH effects on obesity, initially 32 male Wistar rats were divided into two groups (n=16): control (C) was fed standard-chow and water and hypercaloric (H) was fed hypercaloric chow and 30% sucrose in its drinking water. After 45 days, both C and H groups were divided into two subgroups (n=8): C+PL was fed standard-chow, water and received saline subcutaneously; C+GH was fed standard-chow, water, and received 2 mg/kg/day GH subcutaneously; H+PL was fed hypercaloric diet, 30% sucrose in its drinking water, and received saline subcutaneously; and H+GH was fed hypercaloric diet, 30% sucrose in its drinking water, and received GH subcutaneously. After 75 days of total experimental period, H+PL rats were considered obese, having higher body weight, body mass index, Lee-index, and atherogenic index (AI) compared to C+PL. Obesity was accompanied by enhanced myocardial lipid hydroperoxide (LH) and lactate dehydrogenase (LDH), as well of depressed energy expenditure (RMR) and oxygen consumption(VO (2))/body weight. H+GH rats had higher fasting RMR, as well as lower AI and myocardial LH than H+PL. Comparing C+GH with C+PL, despite no effects on morphometric parameters, lipid profile, myocardial LH, and LDH activity, GH enhanced fed RMR and myocardial pyruvate dehydrogenase. In conclusion, the present study brought new insights into the GH effects on obesity related cardiovascular damage demonstrating, for the first time, that GH regulated cardiac metabolic pathways, enhanced energy expenditure and improved the lipid profile in obesity condition. Growth hormone in standard fed condition also offered promising therapeutic value enhancing pyruvate-dehydrogenase activity and glucose oxidation in cardiac tissue, thus optimizing myocardial energy metabolism.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Hormônio do Crescimento/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Miocárdio/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Humanos , Masculino , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
SUMMARY: Chagas' disease is a debilitating but comparatively neglected illness that affects about 15 million people. There is an urgent need to develop new, more effective, and less-toxic compounds. In this study, we assessed the in vitro anti-trypanosomal activity of the sesquiterpene elatol from the Brazilian red seaweed Laurencia dendroidea. We used electron microscopy to evaluate the effect of elatol on the morphology and ultrastructure of the parasite. Elatol showed a dose-dependent effect against the epimastigote, trypomastigote, and amastigote forms, with IC50 values of 45.4, 1.38, and 1.01 microm, respectively. Observation of treated intracellular amastigotes by light microscopy demonstrated a total elimination of the infection at a dose of 3.0 microm. In addition, the compound did not affect the red blood cells, and the CC50 value for LLCMK2 cells was 27.0 microm. Transmission and scanning electron micrographs showed aberrant-shaped cells and breaks in the plasma membrane, prominent swollen mitochondria, and extensive formation of cytoplasmic vacuoles in all the forms. This is the first report of the anti-trypanosomal effect of the sesquiterpene elatol.
Assuntos
Laurencia/metabolismo , Compostos de Espiro/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Linhagem Celular , Eritrócitos/efeitos dos fármacos , Eritrócitos/fisiologia , Humanos , Concentração Inibidora 50 , Laurencia/classificação , Microscopia Eletrônica , Testes de Sensibilidade Parasitária , Compostos de Espiro/química , Compostos de Espiro/metabolismo , Tripanossomicidas/química , Tripanossomicidas/metabolismo , Trypanosoma cruzi/crescimento & desenvolvimento , Trypanosoma cruzi/ultraestruturaRESUMO
The potential of microalgae Spirulina platensis to the production of nitrogenous compounds in liquid fraction via slow pyrolysis was evaluated. Aiming to identify the best condition which maximized liquid yield, the effects of operational conditions mass load, temperature, and heating rate were evaluated using Experimental Design and Response Surface Methodology techniques and optimized with Differential Evolution methodology. The composition of liquid fraction was analyzed by GC-MS and the effect of the same operational conditions in nitrogenous compounds formation was analyzed. The separation of nitrogenous compounds was evaluated by extraction and adsorption techniques. The results indicated that the heating rate significantly impacted both the liquid yield and the formation of the nitrogenous compounds. At optimal conditions, a maximum liquid yield of 64.59% was obtained. The extraction and adsorption processes showed to be promising routes for the purification of nitrogenous compounds, however, extraction was more selective to separate them.
Assuntos
Microalgas , Spirulina , Biocombustíveis , Compostos de Nitrogênio , PiróliseRESUMO
Caloric restriction (CR) reduces body weight and systemic inflammation, but the effects on adipose tissue under dietary lipid overload are controversial. We evaluated the effects of CR-induced weight loss with a high-fat diet on adipose tissue inflammation of obese mice. Male mice were assigned into low-fat diet (LF) and high-fat diet (HF) groups. After 8 weeks, the mice in the HF group were reassigned for another 7 weeks into the following 3 conditions: (i) kept in the HF condition; (ii) changed to low-fat diet ad libitum (LFAL); and (iii) changed to high-fat calorie-restricted (RHF) diet to reach LFAL body weight. Serum markers, adipocytokines, morphology, and inflammatory infiltrates in retroperitoneal adipose tissue (RAT) were accessed. The body weights of the LFAL and RHF groups were reduced, equaling the body weights of the LF group. The LFAL mice had restored almost all inflammatory markers as the LF mice, except tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and adiponectin. Compared with the HF group, the RHF group had lowered visceral adiposity, retroperitoneal adipocyte sizes, and RAT inflammatory cell infiltration, as well as TNF-α, interleukin-6, and hepatic and serum C-reactive protein, which were higher than that of the LFAL group; adiponectin and MCP-1 did not change. CR with high-fat diet reduced body weight and attenuated visceral adiposity but did not fully recover visceral tissue inflammation. Novelty Caloric restriction in a high-fat diet ameliorated visceral adiposity. Caloric restriction in a high-fat diet did not recover visceral adipose tissue inflammation.
Assuntos
Restrição Calórica , Dieta Hiperlipídica , Inflamação/patologia , Gordura Intra-Abdominal/patologia , Redução de Peso , Adipocinas , Adiposidade , Animais , Dieta com Restrição de Gorduras , Masculino , Camundongos Endogâmicos C57BL , ObesidadeRESUMO
We present the first comprehensive study, to our knowledge, on genomic chromosomal analysis in syndromic craniosynostosis. In total, 45 patients with craniosynostotic disorders were screened with a variety of methods including conventional karyotype, microsatellite segregation analysis, subtelomeric multiplex ligation-dependent probe amplification) and whole-genome array-based comparative genome hybridisation. Causative abnormalities were present in 42.2% (19/45) of the samples, and 27.8% (10/36) of the patients with normal conventional karyotype carried submicroscopic imbalances. Our results include a wide variety of imbalances and point to novel chromosomal regions associated with craniosynostosis. The high incidence of pure duplications or trisomies suggests that these are important mechanisms in craniosynostosis, particularly in cases involving the metopic suture.
Assuntos
Aberrações Cromossômicas , Segregação de Cromossomos , Craniossinostoses/genética , Repetições de Microssatélites , Humanos , Cariotipagem , Hibridização de Ácido Nucleico/métodos , Polimorfismo GenéticoRESUMO
The objective of this study was to evaluate the effects of different environment conditions on productive performance and surface temperatures of Japanese quail (Coturnix coturnix japonica) during the initial stage of laying. In environmental controlled chambers, the birds were subjected to different temperatures and air velocities at the feeder. A total of 216 Japanese quails were distributed randomly in 2 galvanized wire cages, with 3 partitions each and 27 birds/cage. The experimental design consisted of randomized blocks with 2 treatments (air velocity at the feeder: 0, 1, 2, and 3 m/s and air temperature: 17, 23, 29, and 35°C) and 6 replicates. The productive performance was analyzed statistically (Sigma Plot 12.0) by 2-way ANOVA, with treatment means separated by the Tukey test (P < 0.05). To evaluate the main effects and interactions of the factors, the Holm-Sidak multiple comparisons test was performed using a mild condition as the control group (0 m/s). Feed intake did not differ (P > 0.05) among birds reared at temperatures of 23, 29, and 35°C, but higher feed intake was noted at 17°C. The mean values of egg production increased significantly (P < 0.05) with increased air velocity levels. It was observed that there was an increase in egg production and feed intake with the intensification of air velocity at the feeder, regardless of ambient temperature. Egg weight and feed conversion were not affected by air velocity treatments (P > 0.05). There was a significant positive correlation between air temperature and mean surface temperature and head surface temperature. In contrast, a significant negative correlation was observed between air velocity and mean surface temperature and head surface temperature. Productive performance was affected by temperature and air velocity, except for egg weight and feed conversion, which was not influenced by air velocity. Air velocity is important in removing heat from the surface of birds.
Assuntos
Movimentos do Ar , Coturnix/fisiologia , Resposta ao Choque Térmico/fisiologia , Criação de Animais Domésticos/métodos , Animais , Ovos/análise , Feminino , Oviposição/fisiologia , Distribuição Aleatória , Temperatura Cutânea/fisiologia , TemperaturaRESUMO
Cancer is a disease that effects cell metabolism causing an imbalance in the health of the patient. On the other hand, malnutrition, presented by oncological patients, is caused by both the disease and its treatment. Some serum biochemical parameters cannot be determined by the traditional method of laboratory blood analysis (spectrophotometry). Among the various techniques that could be used for blood biochemical analysis, we opted for the Z-scan technique, due to its sensitivity to the reading of blood components. Our objective in this work was to compare the data obtained by the Z-scan technique and the spectrophotometry of the serological samples of children with solid tumors and leukemia under treatment, receiving or not selenium supplementation in a randomized, double-blind clinical trial. The biochemical parameters were read based on blood. These blood sampling made at different stages of chemotherapy and selenium supplementation. At each of these stages, the cholesterol, glucose and triglycerides parameters were read using the Z-scan and spectrophotometry techniques. We observed that selenium helps in balancing the health of these patients, and corroborates with our hypothesis that the Z-scan technique may be an alternative for the determination of biochemical parameters.
Assuntos
Biomarcadores/sangue , Análise Química do Sangue/métodos , Neoplasias/tratamento farmacológico , Imagem Óptica/métodos , Selênio/sangue , Selênio/uso terapêutico , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Leucemia/sangue , Leucemia/tratamento farmacológico , Masculino , Neoplasias/sangue , Sensibilidade e Especificidade , Espectrofotometria , Adulto JovemRESUMO
Several evidences point for beneficial effects of growth hormone (GH) in heart failure (HF). Taking into account that HF is related with changes in myocardial oxidative stress and in energy generation from metabolic pathways, it is important to clarify whether GH increase or decrease myocardial oxidative stress and what is its effect on energetic metabolism in HF condition. Thus, this study investigated the effects of two different doses of GH on energetic metabolism and oxidative stress in myocardium of rats with HF. Male Wistar rats (n=25) were submitted to aortic stenosis (AS). The HF was evidenced by tachypnea and echocardiographic criteria around 28 weeks of AS. The rats were then randomly divided into three groups: (HF) with HF, treated with saline (0.9% NaCl); (HF-GH1), treated with 1 mk/kg/day recombinant human growth hormone (rhGH), and (HF-GH2) treated with 2 mg/kg/day rhGH. GH was injected, subcutaneously, daily for 2 weeks. A control group (sham; n=12), with the same age of the others rats was evaluated to confirm data for AS. HF had lower IGF-I (insulin-like growth factor-I) than sham-operated rats, and both GH treatments normalized IGF-I level. HF-GH1 animals had lower lipid hydroperoxide (LH), LH/total antioxidant substances (TAS) and glutathione-reductase than HF. Glutathione peroxidase (GSH-Px), hydroxyacyl coenzyme-A dehydrogenase, lactate dehydrogenase(LDH) were higher in HF-GH1 than in HF. HF-GH2 compared with HF, had increased LH/TAS ratio, as well as decreased oxidized glutathione and LDH activity. Comparing the two GH doses, GSH-Px, superoxide dismutase and LDH were lower in HF-GH2 than in HF-GH1. In conclusion, GH effects were dose-dependent and both tested doses did not aggravate the heart dysfunction. The higher GH dose, 2 mg/kg exerted detrimental effects related to energy metabolism and oxidative stress. The lower dose, 1mg/kg GH exerted beneficial effects enhancing antioxidant defences, reducing oxidative stress and improving energy generation in myocardium of rats with heart failure.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Hormônio do Crescimento/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Ecocardiografia , Hormônio do Crescimento/administração & dosagem , L-Lactato Desidrogenase/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
Existem poucos estudos sobre doenças infecciosas em animais silvestres. O objetivo deste estudo foi pesquisar DNA de Leptospira spp. em sangue de tartarugas mantidas em cativeiro, pertencentes ao Bosque Rodrigues Alves (Jardim Zoobotânico da Amazônia). O DNA foi isolado das amostras de sangue coletadas de 148 tartarugas pertencentes a seis espécies diferentes. A reação em cadeia da polimerase (PCR) foi realizada utilizando-se iniciadores específicos para DNA de Leptospira spp. Nenhuma das amostras apresentou resultado positivo para Leptospira spp.(AU)
Assuntos
Animais , Tartarugas/microbiologia , Leptospira/isolamento & purificação , Reação em Cadeia da Polimerase/veterinária , Animais SelvagensRESUMO
INTRODUCTION: In pharmacotherapeutic follow-up a pharmacist is responsible for drug-related patient needs (DRPN) by detecting, preventing and solving medication-related problems aiming at specific results to improve patient quality of life. Drug-related problems are pharmacotherapy failures leading to failed therapeutic goals or undesirable events. MATERIAL AND METHODS: In this study, Daders methodology for pharmacotherapeutic follow-up was used in patients admitted to the Internal Medicine Department of Hospital Infanta Margarita, Cabra-Córdoba, Spain. RESULTS: In all, 85 DRPNs (2.7 DRPNs per patient) were identified, and 36 pharmaceutical procedures were performed, with physicians accepting 92% of said procedures. Forty-nine percent of drug-related problems were related to need, 40% to effectiveness, and 11% to safety. CONCLUSIONS: The presence of a pharmacist at the Internal Medicine Department allows the detection of DRPNs that are mostly related to need and effectiveness. Pharmaceutical procedures are widely accepted by medical teams.
Assuntos
Monitoramento de Medicamentos/normas , Tratamento Farmacológico/normas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Unidades Hospitalares/normas , Hospitalização , Medicina Interna/normas , Serviço de Farmácia Hospitalar/normas , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Estudos Prospectivos , EspanhaRESUMO
The mechanisms that regulate programmed cell death, such as apoptosis, and the cellular "self-eating" phenomenon of autophagy, share many regulatory systems and common pathways. These mechanisms have been extensively investigated over the last few years. Some intracellular structures may determine and control the autophagic fate of the cell such as the endoplasmic reticulum, mitochondria, and lysosomes. The coordination and interrelation of these organelles are crucial in maintaining calcium levels and general cellular homeostasis, as well as in regulating cell life and death under physiological and pathological conditions, including cancer, neurodegeneration, and aging. In this review, we discuss the crosstalk between the aforementioned organelles and their influence in apoptotic and autophagic processes.
Assuntos
Envelhecimento/genética , Cálcio/metabolismo , Retículo Endoplasmático/metabolismo , Lisossomos/metabolismo , Mitocôndrias/metabolismo , Envelhecimento/metabolismo , Animais , Apoptose/genética , Autofagia/genética , Retículo Endoplasmático/genética , Regulação da Expressão Gênica , Homeostase , Humanos , Lisossomos/genética , Mitocôndrias/genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Transdução de SinaisRESUMO
Glutamate is an important neurotransmitter in neurons and glial cells and it is one of the keys to the neuron-glial interaction in the brain. Glutamate transmission is strongly dependent on calcium homeostasis and on mitochondrial function. In the present work we presented several aspects related to the role of mitochondria in glutamate signaling and in brain diseases. We focused on glutamateinduced calcium signaling and its relation to the organelle dysfunction with cell death processes. In addition, we have discussed how alterations in this pathway may lead or aggravate a variety of neurodegenerative diseases. We compiled information on how mitochondria can influence cell fate during glutamate stimulation and calcium signaling. These organelles play a pivotal role in neuron and glial exchange, in synaptic plasticity and several pathological conditions related to Aging, Alzheimer's, Parkinson's and Huntington's diseases. We have also presented autophagy as a mechanism activated during mitochondrial dysfunction which may function as a protective mechanism during injury. Furthermore, some new perspectives and approaches to treat these neurodegenerative diseases are offered and evaluated.
Assuntos
Metabolismo Energético , Ácido Glutâmico/metabolismo , Mitocôndrias/metabolismo , Neuroglia/metabolismo , Neurônios/metabolismo , Transmissão Sináptica , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Autofagia/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Fármacos Atuantes sobre Aminoácidos Excitatórios/metabolismo , Fármacos Atuantes sobre Aminoácidos Excitatórios/farmacologia , Humanos , Doença de Huntington/tratamento farmacológico , Doença de Huntington/metabolismo , Mitocôndrias/efeitos dos fármacos , Neuroglia/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/prevenção & controle , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Transmissão Sináptica/efeitos dos fármacosRESUMO
The 2008 World Health Organization (WHO) proposed revision of the classification of MDS recognizes a deletion (5q) subtype with mutation of Janus kinase-2 (JAK2(V617F)). We investigated the clonal origin of this gene mutation in a patient with del(5q) MDS presenting with thrombocytosis and normal hemoglobin. Analysis of colony forming units-granulocyte-monocyte (CFU-GM) and erythropoietin-independent growth of bone marrow (BM) and peripheral blood (PB) burst forming units-erythroid (BFU-E) showed that del(5q) and JAK2(V617F) existed in progenitors derived from independent clones. Fifty percent of endogenous erythroid colonies (EEC) harbored the JAK2(V617F) mutation whereas fluorescent in situ hybridization (Fish) with a chromosome 5 (q31.1) probe showed only a diploid allele compliment. Assessment of transcriptional clonality by iduronate-2-sulfatase (IDS) gene polymorphism suggested that JAK2(V617F) was acquired in at least two independent multipotent stem cell progeny. Our findings indicate that JAK2(V617F) mutant clones may arise in genetically discordant clones independent of del(5q).
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 5 , Células Clonais/patologia , Janus Quinase 2/genética , Síndromes Mielodisplásicas/genética , Substituição de Aminoácidos , Células Clonais/metabolismo , Células Precursoras Eritroides/metabolismo , Células Precursoras Eritroides/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Mutação de Sentido Incorreto/fisiologia , Síndromes Mielodisplásicas/patologia , Fenilalanina/genética , Valina/genéticaRESUMO
The beneficial action of moderate wine consumption is increasingly being attributed to resveratrol (trans-3,4',5-trihydroxystilbene). To test the safety of resveratrol use as a dietary supplement, 24 male Wistar rats were initially divided into three groups: (C, n=6) was given standard chow and water; (R, n=6) received standard chow and 6 mg/l resveratrol in its drinking water (1mg/kg/day), and (HFD, n=12) received high-fat diet and water. In order to more appropriately study the effects of resveratrol on high-fat diet, after 30 days of treatments, HFD-rats were divided into two subgroups (n=6/group):(HFD) remained receiving high-fat diet and water; (HFD-R) given high-fat diet and 6 mg/l resveratrol in its drinking water (1mg/kg/day). The total experimental period was 45 days. The resveratrol dose took into account its average concentration in wine, the time variability of wine ingestion, and so of resveratrol consumption in humans. HFD-rats had hyperglycaemia, dyslipidemia, increased serum oxidized-LDL (ox-LDL) and hepatic oxidative stress. Comparing HFD-R and HFD-rats, resveratrol improved lipid profile and glucose level, enhanced superoxide dismutase, thus reducing ox-LDL and hepatic oxidative stress. Resveratrol, in standard-fed-rats reduced glutathione-antioxidant defense system and enhanced hepatic lipid hydroperoxide. In conclusion, based on the results of this single dose preliminary study with resveratrol in the drinking water of male Wistar rats for 30 days, it may be concluded that resveratrol may have beneficial effects in high-fat diets (e.g. ox-LDL, decreased serum and hepatic oxidativestress), but not in standard-fed diets (effects produced include enhanced hepatic oxidative stress). Further studies are indicated.