RESUMO
Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) transcriptional coactivators are key regulators of energy metabolism-related genes and are expressed in energy-demanding tissues. There are several PGC-1α variants with different biological functions in different tissues. The brain is one of the tissues where the role of PGC-1α isoforms remains less explored. Here, we used a toxin-based mouse model of Parkinson's disease (PD) and observed that the expression levels of variants PGC-1α2 and PGC-1α3 in the nigrostriatal pathway increases at the onset of dopaminergic cell degeneration. This increase occurs concomitant with an increase in glial fibrillary acidic protein levels. Since PGC-1α coactivators regulate cellular adaptive responses, we hypothesized that they could be involved in the modulation of astrogliosis induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Therefore, we analysed the transcriptome of astrocytes transduced with expression vectors encoding PGC-1α1 to 1α4 by massively parallel sequencing (RNA-seq) and identified the main cellular pathways controlled by these isoforms. Interestingly, in reactive astrocytes the inflammatory and antioxidant responses, adhesion, migration, and viability were altered by PGC-1α2 and PGC-1α3, showing that sustained expression of these isoforms induces astrocyte dysfunction and degeneration. This work highlights PGC-1α isoforms as modulators of astrocyte reactivity and as potential therapeutic targets for the treatment of PD and other neurodegenerative disorders.
Assuntos
Astrócitos , Fatores de Transcrição , Camundongos , Animais , Astrócitos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Dopamina/metabolismo , Encéfalo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismoAssuntos
Anodontia/genética , Ectodisplasinas/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Mutação , Anodontia/metabolismo , Brasil , Criança , Simulação por Computador , Análise Mutacional de DNA , Ectodisplasinas/química , Ectodisplasinas/metabolismo , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Humanos , Masculino , Modelos Moleculares , Linhagem , Conformação Proteica , Sequenciamento do ExomaRESUMO
The Brazilian Water Resources Policy (Law 9433/1997) establishes participatory and decentralized management, involving civil society, water users and governmental bodies, with the basin committees as the basis of this process. Fifteen years after its implementation, it is possible to perceive accomplishments, but, at the same time, there are some difficulties in regards to the operation of the basin committees in the country. Considering the North Paraíba River Basin - which is completely included in the State of Paraíba, Northeastern Brazil, and presents great social and economic importance for the state - this article analyzes the process of formation, installation and functioning of its Basin Committee (CBH-PB), focusing on its composition, the reasons for the mobilization and demobilization of its members, the intra-relations between segments, and the inter-relations between the CBH-PB and other entities of the State Water Management System (the Water Executive Agency and the State Water Resources Council). The level of decentralization and the quality of participatory management (as it is being performed at the CBH-PB) are discussed and guidelines are suggested in order to allow greater effectiveness to the committee.
Assuntos
Conservação dos Recursos Naturais/métodos , Brasil , Conservação dos Recursos Naturais/legislação & jurisprudência , Órgãos Governamentais , Formulação de Políticas , RiosRESUMO
HIV-1 infection is a global epidemic whose treatment is limited majorly by viral resistance and adverse effects. Natural products from algae have been studied for many years, including antiviral, being an alternative to anti-HIV drug design. Since the isolation of natural products can be a hurdle, molecular modeling is an important tool to study these compounds. Herein, structure-activity relationship, molecular docking, and molecular dynamic studies were performed to direct the studies of ten marine natural products with anti-HIV activity. In the structure-activity relationship, descriptors were identified associating the anti-HIV activity of five diterpenes with possible action on the reverse transcriptase allosteric site. These diterpenes were evaluated by molecular docking, and it was identified that only dolabelladienetriol interacted in the allosteric site. Molecular dynamics suggested that the dolabelladienetriol might interfere with the viral RNA binding to HIV-1 RT by inducing a conformational change of the enzyme. Also, in silico ADMET simulations predicts that the dolabelladienetriol present a high potential to be successfully developed as a drug. Thus, applying in silico approaches was possible to suggest potential anti-HIV compounds derived from marine natural products.Communicated by Ramaswamy H. Sarma.
Assuntos
Fármacos Anti-HIV , Produtos Biológicos , Diterpenos , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Produtos Biológicos/farmacologia , Diterpenos/farmacologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Relação Quantitativa Estrutura-Atividade , Relação Estrutura-AtividadeRESUMO
The purpose of this study was to test the hypotheses that in obese children: 1) hypocaloric diet (D) improves both heart rate recovery at 1 min (Δ HRR1) cfter an exercise test, and cardiac autonomic nervous system activity (CANSA) in obese children; 2) Diet and exercise training (DET) combined leads to greater improvement in both Δ HRR1 after an exercise test and in CANSA, than D alone. Moreover, we examined the relationships among Δ HRR1, CANSA, cardiorespiratory fitness and anthropometric variables (AV) in obese children submitted to D and to DET. 33 obese children (10 ± 0.2 years; body mass index (BMI) >95 (th) percentile) were divided into 2 groups: D (n=15; BMI=31 ± 1 kg/m²)) and DET (n=18; 29 ± 1 kg/m²). All children performed a maximal cardiopulmonary exercise test on a treadmill. The Δ HRR1 or LF/HF ratio (P>0.05). In contrast, the DET group showed increased peak VO2 ( P=0.01) and improved Δ HRR1 (Δ HRR1=37.3 ± 2.6; P=0.01) and LF/HF ratio ( P=0.001). The DET group demonstrated significant relationships among Δ HRR1, peak VO2 and CANSA (P<0.05). In conclusion, DET, in contrast to D, promoted improved ÄΔ HRR1 and CANSA in obese children, suggesting a positive influence of increased levels of cardiorespiratory fitness by exercise training on cardiac autonomic activity.
Assuntos
Terapia por Exercício/métodos , Frequência Cardíaca/fisiologia , Obesidade/terapia , Consumo de Oxigênio/fisiologia , Antropometria , Sistema Nervoso Autônomo/fisiologia , Pesos e Medidas Corporais , Criança , Teste de Esforço , Humanos , Obesidade/dietoterapia , Aptidão Física/fisiologiaRESUMO
Increasing evidence supports the beneficial effects of ischemic preconditioning (IPC) of organs on subsequent ischemia. The aim of this study was to assess the effects of IPC of the pancreas on islet cell recovery after cold preservation using a rat model. The pancreas was deprived of perfusion (celiac artery and superior mesenteric artery occlusion) for 10 minutes followed by 10 minutes of reperfusion. Islet isolation was performed after 18 hours of cold ischemia. Glands undergoing IPC yielded significantly greater numbers of islets than controls. Following overnight culture, a significantly greater proportion of islets was recovered from IPC-treated pancreata. Microarray genomic analysis of pancreatic tissue revealed a significant differential expression of approximately 600 unique mRNA strands within IPC pancreata compared to only <100 unique mRNA strands within non-IPC pancreata (>2-fold change; P < .05). Proteomic analysis revealed significant differential expression of at least 5 proteins >1.5-fold change; P < .05) within the IPC vs control group. Our data indicated that IPC of the pancreas prior to cold preservation was associated with improved islet cell recovery after cold ischemia. IPC of the pancreas may represent a viable therapeutic intervention to increase islet transplantation success from a single donor and to maximize organ utilization.
Assuntos
Diabetes Mellitus Experimental/cirurgia , Precondicionamento Isquêmico/métodos , Ilhotas Pancreáticas/fisiologia , Preservação de Órgãos/métodos , Pâncreas/citologia , Animais , Regulação da Expressão Gênica , Ilhotas Pancreáticas/citologia , Camundongos , Camundongos Nus , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , Ratos , Transplante Heterólogo/fisiologiaRESUMO
The purpose of this study was to test the hypothesis that in obese children: 1) Ventilatory efficiency (VentE) is decreased during graded exercise; and 2) Weight loss through diet alone (D) improves VentE, and 3) diet associated with exercise training (DET) leads to greater improvement in VentE than by D. Thirty-eight obese children (10+/-0.2 years; BMI >95th percentile) were randomly divided into two study groups: D (n=17; BMI=30+/-1 kg/m (2)) and DET (n=21; 28+/-1 kg/m (2)). Ten lean children were included in a control group (10+/-0.3 years; 17+/-0.5 kg/m (2)). All children performed maximal treadmill testing with respiratory gas analysis (breath-by-breath) to determine the ventilatory anaerobic threshold (VAT) and peak oxygen consumption (VO (2) peak). VentE was determined by the VE/VCO (2) method at VAT. Obese children showed lower VO (2) peak and lower VentE than controls (p<0.05). After interventions, all obese children reduced body weight (p<0.05). D group did not improve in terms of VO (2) peak or VentE (p>0.05). In contrast, the DET group showed increased VO (2) peak (p=0.01) and improved VentE (DeltaVE/VCO (2)=-6.1+/-0.9; p=0.01). VentE is decreased in obese children, where weight loss by means of DET, but not D alone, improves VentE and cardiorespiratory fitness during graded exercise.
Assuntos
Terapia por Exercício/métodos , Obesidade/terapia , Redução de Peso , Limiar Anaeróbio , Dióxido de Carbono/metabolismo , Criança , Teste de Esforço , Humanos , Obesidade/fisiopatologia , Consumo de Oxigênio , Troca Gasosa PulmonarRESUMO
Lucina pectinata is an important economic resource in the Brazilian coast. This study reports parasitism caused by a Digenea in this species. The specimens (n = 470) were collected in December 2012 in a mangrove swamp of the Cachoeira River estuary, Bahia, Brazil. They were measured along the anterior-posterior axis (length), and after macroscopic analysis for parasites and diseases cuts of 5 mm were fixated in Carnoy's solution and processed by routine histology technique wherein sessions of 7 µm were stained with Harris hematoxylin and eosin (H&E). The tissues were examined using an optical microscope. The mean length of L. pectinata was 4.0 ± 0.53 cm. Microscopic analysis showed sporocysts containing both germ balls as cercariae of an unidentified Digenea (Platyhelminthes), these in various stages of development. The prevalence was 1.48% (7/470). In a parasitized specimen was macroscopic evidence of tissue densification of gills. The sporocysts were observed in mantle, gills, digestive gland and gonads, with evident alteration/destruction of tissues, including parasitic castration. There were no other parasites found, which is probably related to inaccessibility and chemical conditions in which lives L. pectinata, i.e., between 10 and 20 cm in mangrove sediment.
Assuntos
Bivalves/parasitologia , Trematódeos/patogenicidade , Animais , Brasil , Estuários , Interações Hospedeiro-Parasita , RiosRESUMO
The aim of this study was to jointly show the results of three independent ecotoxicological studies performed to investigate pollutants in three Brazilian tropical reservoirs undergoing accelerated eutrophication. In order to accomplish this goal, the full toxicity identification and evaluation procedure (TIE approach) was performed, at Pampulha (Minas Gerais State) and Salto Grande and Barra Bonita reservoirs (São Paulo State). Acute and chronic toxicity tests were performed using the cladocerans Daphnia similis and Ceriodaphnia dubia (exotic) and Daphnia laevis and Ceriodaphnia silvestrii (native) as test organisms. Results from TIE procedure stage I indicated the existence of nonpolar organic and filterable compounds in the water from Pampulha, probably cyanotoxins, and oxidants as part of the toxic agents. TIE results for sediments identified ammonia (Pampulha and Salto Grande), organic compounds (Pampulha), metals (Pampulha, Barra Bonita, and Salto Grande), and acidity (Salto Grande) as responsible for toxicity. Whole-sediment remediation experiments for Pampulha reservoir confirmed, through reproduction decrease, ammonia and organic compounds as contaminants. Such pollutants represent threats to aquatic biota and must be prevented. Higher temperatures as predicted from global climate change will severely affect tropical shallow reservoirs, accelerating eutrophication, the release of contaminants from sediments, and increasing toxicity.
Assuntos
Eutrofização , Água Doce/análise , Sedimentos Geológicos/química , Animais , Brasil , Cladocera/efeitos dos fármacos , Daphnia/efeitos dos fármacos , Ecotoxicologia , Clima Tropical , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
The authors analyzed twelve patients with symptomatic essential throthrombocythemia (E.T.) diagnosed from 1983 to 1991. Haemorrhagic and thrombotic phenomena were the main presenting features. Treatment consisted mostly of alpha-interferon (IFN-alpha 2b) subcutaneously in dosage ranging from 3 to 5 MU/m2 and hydroxyurea (HU) in conventional dosage. A clinical response was seen in seven patients treated with IFN-alpha 2b (4 CR and 2 PR), and in four patients treated with HU (3 CR and 1 PR). No significant side effects were observed. Our findings indicate that IFN-alpha 2b offers a non-leukaemogenic and very promising therapeutic alternative for E.T.
Assuntos
Hidroxiureia/uso terapêutico , Interferon-alfa/uso terapêutico , Trombocitemia Essencial/terapia , Idoso , Feminino , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Proteínas Recombinantes , Indução de Remissão , Trombocitemia Essencial/sangueRESUMO
Islet transplantation has become an accepted method to treat type 1 diabetes. To succeed and achieve normal levels of glucose in transplant recipients, the quality of the transplanted islets is of the utmost importance. Lack of oxygen during organ procurement, islet isolation, and subsequent culture triggers apoptosis or necrosis and loss of islet function, causing the yield and quality to diminish. A promising candidate for cytoprotection against oxygen deprivation is neuroglobin (Ngb). Ngb is a recently described member of globin family and is expressed in neurons, retina, and pancreatic islets. To overexpress this protein in the islets and study its ability to protect them, we utilized protein transduction. Protein transduction is achieved by fusing Ngb to the TAT/PTD transduction domain, a peptide originated from the HIV transcriptional transactivator protein. Our study proved that TAT-Ngb is an efficient fusion protein capable of protecting the human islets in culture from loss of cell mass and function, thus increasing the quality of transplantable islets. If the islets could be cultured for a longer period of time without suffering harmful effects, it would be possible to precondition the recipient and there would be more time to assess their quality and function before transplantation.
Assuntos
Globinas/metabolismo , Ilhotas Pancreáticas/citologia , Proteínas do Tecido Nervoso/metabolismo , Automação , Hipóxia Celular , Separação Celular/métodos , Sobrevivência Celular , Células Cultivadas , Citometria de Fluxo , Produtos do Gene tat/genética , Produtos do Gene tat/metabolismo , Globinas/genética , Humanos , Ilhotas Pancreáticas/fisiologia , Transplante das Ilhotas Pancreáticas/fisiologia , Microscopia Confocal , Proteínas do Tecido Nervoso/genética , Neuroglobina , Consumo de Oxigênio , Transporte ProteicoRESUMO
The present work describes the expression of extracellular proteins in the thymus and skeletal muscle of the X-linked dystrophic MDX mouse which corresponds to an experimental model for the human disease Duchenne muscular dystrophy. MDX dystrophic mice showed marked alterations in the thymic cytoarchitecture including cortical atrophy that was paralleled by denser epithelial cell network with intense immunolabelling for cytokeratins pair 8/18 and increased vascularization assessed with monoclonal antibody anti-desmin. Consistent augmentation of intrathymic extracellular matrix components (ECM) was observed especially at weaning and by the onset of disease. Interestingly, the amount of ECM elements in the gastrocnemius muscle of MDX wild-type dystrophic mice also showed a prominent difference as compared to age-matched non-dystrophic BALB/cAn animals. A marked but uneven overdeposition of reticulin and collagen fibres (type I, type IV), laminin and fibronectin were often present in the skeletal muscle of dystrophic mice, mostly around lesioned fibres. Alterations in both organs positively correlated with the degree of dystrophy thus suggesting that similar stimuli may be enhancing ECM production in both thymus and skeletal muscle. Although the thymus gland might not be directly involved in the development of the murine X-linked muscular dystrophy, it should be considered as a further target in this disease.
Assuntos
Proteínas da Matriz Extracelular/metabolismo , Músculo Esquelético/patologia , Distrofia Muscular Animal/metabolismo , Timo/metabolismo , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Distrofia Muscular Animal/patologia , Timo/patologiaRESUMO
To study the relationship between the sympathetic nerve activity and hemodynamic alterations in obesity, we simultaneously measured muscle sympathetic nerve activity (MSNA), blood pressure, and forearm blood flow (FBF) in obese and lean individuals. Fifteen normotensive obese women (BMI = 32.5 +/- 0.5 kg/m2) and 11 age-matched normotensive lean women (BMI = 22.7 +/- 1.0 kg/m2) were studied. MSNA was evaluated directly from the peroneal nerve by microneurography, FBF was measured by venous occlusion plethysmography, and blood pressure was measured noninvasively by an autonomic blood pressure cuff. MSNA was significantly increased in obese women when compared with lean control women. Forearm vascular resistance and blood pressure were significantly higher in obese women than in lean women. FBF was significantly lower in obese women. BMI was directly and significantly correlated with MSNA, blood pressure, and forearm vascular resistance levels, but inversely and significantly correlated with FBF levels. Obesity increases sympathetic nerve activity and muscle vascular resistance, and reduces muscle blood flow. These alterations, taken together, may explain the higher blood pressure levels in obese women when compared with lean age-matched women.
Assuntos
Pressão Sanguínea/fisiologia , Antebraço/irrigação sanguínea , Músculo Esquelético/inervação , Obesidade/fisiopatologia , Sistema Nervoso Simpático/fisiologia , Adulto , Feminino , Frequência Cardíaca/fisiologia , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/irrigação sanguínea , Fluxo Sanguíneo Regional/fisiologia , Resistência Vascular/fisiologiaRESUMO
Twenty-four mongrel dogs, weighing 13 to 24 kg, were used to study the effectiveness of anastomosis by Argon Laser beam. After anesthesia, intubation and controlled ventilation, they were submitted to three types of vascular anastomoses: saphenous vein intercarotid artery bypass; left mammary artery/left anterior descending coronary artery bypass; and veno-venous anastomosis. In all groups, 0.8 to 1.5 watts of Argon Laser power were applied for a total time of 90 to 300 seconds. The lower power was for veno-venous anastomoses and the greater was applied for arterial anastomoses. The mean values of resistance of the laser anastomosis to pressure-induced repture were 730 mm Hg in the immediate postoperative study, but increased to 2,500 mm Hg 30 days after surgery. No signs of occlusion were demonstrated at the anastomotic sites by the angiographic and anatomopathological studies performed.
RESUMO
Abstract Lucina pectinata is an important economic resource in the Brazilian coast. This study reports parasitism caused by a Digenea in this species. The specimens (n = 470) were collected in December 2012 in a mangrove swamp of the Cachoeira River estuary, Bahia, Brazil. They were measured along the anterior-posterior axis (length), and after macroscopic analysis for parasites and diseases cuts of 5 mm were fixated in Carnoy's solution and processed by routine histology technique wherein sessions of 7 μm were stained with Harris hematoxylin and eosin (H&E). The tissues were examined using an optical microscope. The mean length of L. pectinata was 4.0 ± 0.53 cm. Microscopic analysis showed sporocysts containing both germ balls as cercariae of an unidentified Digenea (Platyhelminthes), these in various stages of development. The prevalence was 1.48% (7/470). In a parasitized specimen was macroscopic evidence of tissue densification of gills. The sporocysts were observed in mantle, gills, digestive gland and gonads, with evident alteration/destruction of tissues, including parasitic castration. There were no other parasites found, which is probably related to inaccessibility and chemical conditions in which lives L. pectinata, i.e., between 10 and 20 cm in mangrove sediment.
Resumo Lucina pectinata é um importante recurso econômico na costa brasileira. Este estudo relata parasitismo causado por um Digenea nesta espécie. Os exemplares (n = 470) foram coletados em dezembro de 2012 em um manguezal do estuário do Rio Cachoeira, Ilhéus, Bahia. Estes foram medidos quanto ao eixo ântero-posterior (comprimento) e após análise macroscópica quanto a parasitos e enfermidades, cortes transversais de 5 mm foram fixados em solução de Carnoy e processados por técnica rotineira de histologia, sendo que sessões de 7 μm foram coradas com hematoxilina de Harris e eosina (HE). Os tecidos foram examinados em microscopia de luz. A média de comprimento de L. pectinata foi de 4,0 ± 0,53 cm. A análise microscópica evidenciou esporocistos de um Digenea (Platyhelminthes) não identificado, contendo massas germinativas e cercárias, estas em vários estágios de desenvolvimento. A prevalência foi de 1,48% (7/470). Um dos exemplares parasitado apresentou adensamento dos tecidos nas brânquias. Os esporocistos foram observados no manto, brânquias, glândula digestiva e gônadas, causando evidente alteração/destruição de tecidos, inclusive castração parasitária. Não foram observados outros parasitos, o que está provavelmente associado à inacessibilidade e condições químicas em que vive este hospedeiro, isto é, entre 10 e 20 cm no sedimento do manguezal.
Assuntos
Animais , Trematódeos/patogenicidade , Bivalves/parasitologia , Brasil , Estuários , Rios , Interações Hospedeiro-ParasitaRESUMO
Drug delivery to the central nervous system (CNS) is a timely and challenging issue: 95 percent; of the pharmacological drugs cannot be delivered to the brain. This is mainly due to the blood-brain barrier (BBB), a highly selective boundary that hampers the passage of most compounds into the CNS. To overcome this problem, several approaches exist to deliver a therapeutic drug to the brain that takes into account not only the chemical properties of the drug but also the type of transport used at the BBB. One of those strategies is the glucose-mediated drug delivery which will be the focus of the present review. Glucose-mediated drug delivery requires the attachment of glycosyl moieties to a drug and the use of endogenous glucose transporters as a way to circumvent the blood-brain barrier. Glycosylated drugs display improved cell penetrability, enhanced biodistribution, stability and low toxicity. Examples such as glycosylation of ibuprofen and different opioids result in an enhanced central effect and will be discussed.
Assuntos
Encéfalo/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Glucose/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encefalopatias/tratamento farmacológico , Encefalopatias/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Glicosilação , HumanosRESUMO
BACKGROUND AND PURPOSE: Kyotorphin (KTP; L-Tyr-L-Arg), an endogenous neuropeptide, is potently analgesic when delivered directly to the central nervous system. Its weak analgesic effects after systemic administration have been explained by inability to cross the blood-brain barrier (BBB) and detract from the possible clinical use of KTP as an analgesic. In this study, we aimed to increase the lipophilicity of KTP by amidation and to evaluate the analgesic efficacy of a new KTP derivative (KTP-amide - KTP-NH(2) ). EXPERIMENTAL APPROACH: We synthesized KTP-NH(2) . This peptide was given systemically to assess its ability to cross the BBB. A wide range of pain models, including acute, sustained and chronic inflammatory and neuropathic pain, were used to characterize analgesic efficacies of KTP-NH(2) . Binding to opioid receptors and toxicity were also measured. KEY RESULTS: KTP-NH(2) , unlike its precursor KTP, was lipophilic and highly analgesic following systemic administration in several acute and chronic pain models, without inducing toxic effects or affecting motor responses and blood pressure. Binding to opioid receptors was minimal. KTP-NH(2) inhibited nociceptive responses of spinal neurons. Its analgesic effects were prevented by intrathecal or i.p. administration of naloxone. CONCLUSIONS AND IMPLICATIONS: Amidation allowed KTP to show good analgesic ability after systemic delivery in acute and chronic pain models. The indirect opioid-mediated actions of KTP-NH(2) may explain why this compound retained its analgesic effects although the usual side effects of opioids were absent, which is a desired feature in next-generation pain medications.
Assuntos
Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Dipeptídeos/administração & dosagem , Dipeptídeos/uso terapêutico , Endorfinas/administração & dosagem , Endorfinas/uso terapêutico , Dor/tratamento farmacológico , Doença Aguda , Administração Oral , Analgésicos/síntese química , Analgésicos/farmacocinética , Animais , Barreira Hematoencefálica/metabolismo , Doença Crônica , Dipeptídeos/síntese química , Dipeptídeos/farmacocinética , Modelos Animais de Doenças , Endorfinas/síntese química , Endorfinas/farmacocinética , Injeções Intraperitoneais , Injeções Espinhais , Masculino , Ligação Proteica , Ratos , Ratos Wistar , Receptores Opioides/metabolismoRESUMO
The first generation of in vitro models providing successful isolation of viable brain endothelial cells from different species, which could be maintained in cell culture, have emerged around thirty years ago. However, the time consuming and the difficulty of working with primary culture cells led to the development of simpler models employing cell lines with blood-brain barrier properties. The creation, in late nineties, of a transgenic mouse harboring the temperature sensitive simian virus 40 large T-antigen as a source of conditionally immortalized brain endothelial cell lines circumvented the problems of in vitro transfection of tumour inducing gene in primary cells. These different ways to obtain cultures of brain endothelial cells have profited from the discovery of different cellular factors that allow the growth of differentiated cells on plastic filters. Although cell preparations and culture conditions of brain endothelial cells are based on the same principle, there are two main models for studying the blood-brain barrier: the static and the more recently described dynamic model. Dynamic models were created in order to replicate the physiological in vivo environment of the blood-brain barrier. The large pool of in vitro models is being enlarged since each laboratory improves its model adding small differences adapted to the research interests. The great impact of blood-brain barrier studies in the development of therapies related to the central nervous system supports the interests of this review about in vitro models.