RESUMO
Three new species of harvestmen are described based on morphology. Taito mayoruna spec. nov. from Jenaro Herrera province, Loreto, Peru is differentiated from other species of Taito Kury Barros, 2014 by features such as anal operculum armed, and femur IV with two retro-distal spines. Taito curupira spec. nov. from Porto Velho, Rondonia, Brazil is recognized by an H-shaped color pattern, femur IV curved dorsally and armed with medial prolateral and retrolateral tubercles. A third species herein described, Eulibitia chacuamarei spec. nov., from Trinidad, Casanare, Colombia is distinguished by the absence of a ladder mask and by the presence of blunt tubercles on areas I, III and the posterior margin. Penial morphology is described, and SEM micrographs are included.
Assuntos
Aracnídeos/anatomia & histologia , Aracnídeos/classificação , Animais , Brasil , Colômbia , PeruRESUMO
The genus Platymessa Mello-Leitão, 1941 is represented by two species in the Andes of Colombia: P. h-inscriptum Mello-Leitão, 1941 and P. ectroxantha Mello-Leitão, 1941. Platymessa victoriae Pinzón-M. & Townsend, sp. n. is described on the basis of somatic morphological characters and the structure of the penis. The placement of this new species in the genus Platymessa is based upon multiple characters including the outline of dorsal scutum, the presence of a blunt spine on coxa IV, having short and strong legs with femora III and IV having five longitudinal rows of small tubercles, the shape of the basitarsomeres of male leg I, the distribution and relative sizes of the marginal setae on the ventral plate of the penis, and the morphology of the chelicerae and cheliceral sockets. In contrast to other members of the genus, P. victoriae has a pair of triangular tubercles on scutal area III, lacks paired paramedian tubercles on scutal area V, and does not have a ladder mask color pattern on the dorsal scutum. The description of this species expands the distribution of the genus to north of the Oriental Cordillera in the Cesar Department of Colombia.
RESUMO
Parkinson's disease (PD) is the second most frequent neurodegenerative disorder afflicting 2% of the population older than 65 years worldwide. Recently, brain organotypic slices have been used to model neurodegenerative disorders, including PD. They conserve brain three-dimensional architecture, synaptic connectivity and its microenvironment. This model has allowed researchers a simple and rapid method to observe cellular interactions and mechanisms. In the present study, we developed an organotypic PD model from rat brains that includes all the areas involved in the nigrostriatal pathway in a single slice preparation, without using neurotoxins to induce the dopaminergic lesion. The mechanical transection of the nigrostriatal pathway obtained during slice preparation induced PD-like histopathology. Progressive nigrostriatal degeneration was monitored combining innovative approaches, such as diffusion tensor magnetic resonance imaging (DT-RMI) to follow fiber degeneration and mass spectrometry to quantify striatal dopamine content, together with bright-field and fluorescence microscopy imaging. A substantia nigra dopaminergic cell number decrease was observed by immunohistochemistry against rat tyrosine hydroxylase (TH) reaching 80% after 2 days in culture associated with a 30% decrease of striatal TH-positive fiber density, a 15% loss of striatal dopamine content quantified by mass spectrometry and a 70% reduction of nigrostriatal fiber fractional anisotropy quantified by DT-RMI. In addition, a significant decline of medium spiny neuron density was observed from days 7 to 16. These sagittal organotypic slices could be used to study the early stage of PD, namely dopaminergic degeneration, and the late stage of the pathology with dopaminergic and GABAergic neuron loss. This novel model might improve the understanding of PD and may represent a promising tool to refine the evaluation of new therapeutic approaches.
Assuntos
Corpo Estriado/patologia , Modelos Animais de Doenças , Doenças Neurodegenerativas/patologia , Substância Negra/patologia , Animais , Animais Recém-Nascidos , Imagem de Tensor de Difusão , Dopamina/metabolismo , Feminino , Humanos , Espectrometria de Massas , Feixe Prosencefálico Mediano/patologia , Vias Neurais , Técnicas de Cultura de Órgãos , Fosfopiruvato Hidratase/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Protein kinase C (PKC) is a family of serine/threonine-isozymes that are involved in many signaling events in normal and disease states. Previous studies from our lab have demonstrated that ÉPKC plays a pivotal role in neuroprotection induced by ischemic preconditioning. However, the role of ÉPKC during and after brain ischemia is not clearly defined. Therefore, in the present study, we tested the hypothesis that activation of ÉPKC during an ischemic event is neuroprotective. Furthermore, other studies have demonstrated that ÉPKC mediates cerebral ischemic tolerance in the rat brain by decreasing vascular tone. Thus, we also tested the effects of ÉPKC activation during ischemia on cerebral blood flow (CBF). We found that ψÉ-Receptors for Activated C Kinase (RACK), a ÉPKC-selective peptide activator, injected intravenously 30min before induction of global cerebral ischemia conferred neuroprotection in the CA1 region of the rat hippocampus. Moreover, measurements of CBF before, during, and after cerebral ischemia revealed a significant reduction in the reperfusion phase of rats pretreated with ψÉRACK as compared to Tat peptide (vehicle). Our results suggest that ÉPKC can protect the rat brain against ischemic damage by regulating CBF. Thus, ÉPKC may be one of the treatment modalities against ischemic injury.
Assuntos
Isquemia Encefálica/enzimologia , Isquemia Encefálica/prevenção & controle , Circulação Cerebrovascular/fisiologia , Hipocampo/irrigação sanguínea , Hipocampo/enzimologia , Fármacos Neuroprotetores/metabolismo , Proteína Quinase C-épsilon/metabolismo , Animais , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Hipocampo/efeitos dos fármacos , Masculino , Fármacos Neuroprotetores/administração & dosagem , Proteína Quinase C-épsilon/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores de Quinase C Ativada , Receptores de Superfície Celular/administração & dosagem , Fatores de TempoRESUMO
The long-term consequences of forebrain ischemia include delayed Parkinson's syndrome. This study revealed delayed neurodegeneration in the substantia nigra 8 weeks after 12.5 minutes of global ischemia in rat brain. Following neuronal loss of 30-40% in central and dorsolateral striatum at day 3, neuronal damage in the substantia nigra (SN) was assessed at 4-8 weeks using immunohistochemistry for glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (VGAT), and calretinin (CR). At day 56, the optical density of GAD67-, but not VGAT-, immunoreactivity in substantia nigra pars reticulata (SNR)-significantly decreased. CR-neurons concentrated in substantia nigra pars compacta (SNC) were reduced by 27% from day 3 (n = 5) to day 56 (n = 7, ANOVA, p < .01). Movement coordination was impaired at day 56, as evaluated using beam-walking test (time-to-traverse 5.6 ± 1.2 sec versus 11.8 ± 5.4 sec; sham versus ischemia, p < .05, n = 5, and 7, resp.). Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.
RESUMO
Cerebral ischemia causes blood flow derangements characterized by hyperemia (increased cerebral blood flow, CBF) and subsequent hypoperfusion (decreased CBF). We previously demonstrated that protein kinase C delta (δPKC) plays an important role in hippocampal neuronal death after ischemia. However, whether part of this protection is due to the role of δPKC on CBF following cerebral ischemia remains poorly understood. We hypothesized that δPKC exacerbates hyperemia and subsequent hypoperfusion resulting in CBF derangements following ischemia. Sprague-Dawley (SD) rats pretreated with a δPKC specific inhibitor (δV1-1, 0.5 mg/kg) exhibited attenuation of hyperemia and latent hypoperfusion characterized by vasoconstriction followed by vasodilation of microvessels after 2-vessel occlusion plus hypotension measured by 2-photon microscopy. In an asphyxial cardiac arrest model (ACA), SD rats treated with δV1-1 (pre- and post-ischemia) exhibited improved perfusion after 24 h and less hippocampal CA1 neuronal death 7 days after ACA. These results suggest possible therapeutic potential of δPKC in modulating CBF and neuronal damage after cerebral ischemia.
Assuntos
Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular , Proteína Quinase C-delta/fisiologia , Animais , Asfixia/complicações , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Encéfalo/patologia , Isquemia Encefálica/patologia , Sobrevivência Celular/efeitos dos fármacos , Parada Cardíaca/etiologia , Parada Cardíaca/fisiopatologia , Hiperemia/prevenção & controle , Masculino , Microcirculação , Neurônios/efeitos dos fármacos , Neurônios/patologia , Proteína Quinase C-delta/antagonistas & inibidores , Transporte Proteico , Ratos , Ratos Sprague-DawleyRESUMO
The trigemino-cardiac reflex (TCR) may be classified as a sub-phenomenon in the group of the so-called 'oxygen-conserving reflexes'. Within seconds after the initiation of such a reflex, there is neither a powerful and differentiated activation of the sympathetic system with subsequent elevation in regional cerebral blood flow (CBF) with no changes in the cerebral metabolic rate of oxygen (CMRO(2)) or in the cerebral metabolic rate of glucose (CMRglc). Such an increase in regional CBF without a change of CMRO(2) or CMRglc provides the brain with oxygen rapidly and efficiently and gives substantial evidence that the TCR is an oxygen-conserving reflex. This system, which mediates reflex protection projects via currently undefined pathways from the rostral ventrolateral medulla oblongata to the upper brainstem and/or thalamus which finally engage a small population of neurons in the cortex. This cortical centre appears to be dedicated to reflexively transduce a neuronal signal into cerebral vasodilatation and synchronization of electrocortical activity. Sympathetic excitation is mediated by cortical-spinal projection to spinal pre-ganglionic sympathetic neurons whereas bradycardia is mediated via projections to cardiovagal motor medullary neurons. The integrated reflex response serves to redistribute blood from viscera to brain in response to a challenge to cerebral metabolism, but seems also to initiate a preconditioning mechanism. Better and more detailed knowledge of the cascades, transmitters and molecules engaged in such endogenous (neuro) protection may provide new insights into novel therapeutic options for a range of disorders characterized by neuronal death and into cortical organization of the brain.
Assuntos
Encéfalo/fisiologia , Oxigênio/metabolismo , Reflexo/fisiologia , Encéfalo/fisiopatologia , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/prevenção & controle , Humanos , Conhecimento , Estimulação FísicaRESUMO
Resveratrol is a natural polyphenol found in grapes and wine and has been associated with protective effects against cardiovascular diseases. In vitro, both resveratrol preconditioning (RPC) and ischemic preconditioning (IPC) require activation of sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, to induce neuroprotection against cerebral ischemia. In the present study, we tested two hypotheses: (a) that neuroprotection against cerebral ischemia can be induced by RPC in vivo; and (b) that RPC neuroprotection involves alterations in mitochondrial function via the SIRT1 target mitochondrial uncoupling protein 2 (UCP2). IPC was induced by 2 min of global ischemia (temporary bilateral carotid artery occlusion with hypotension), and RPC, by i.p. injection of resveratrol at 10, 50 and 100 mg/kg dosages. Forty-eight hours later, we compared the neuroprotective efficacy of RPC and IPC in vulnerable cornu ammonis 1 hippocampal pyramidal neurons using a rat model of asphyxial cardiac arrest (ACA). SIRT1 activity was measured using a SIRT1-specific fluorescent enzyme activity assay. In hippocampal mitochondria isolated 48 h after IPC or RPC, we measured UCP2 levels, membrane potential, respiration, and the mitochondrial ATP synthesis efficiency (ADP/O ratio). Both IPC and RPC induced tolerance against brain injury induced by cardiac arrest in this in vivo model. IPC increased SIRT1 activity at 48 h, while RPC increased SIRT1 activity at 1 h but not 48 h after treatment in hippocampus. Resveratrol significantly decreased UCP2 levels by 35% compared to sham-treated rats. The SIRT1-specific inhibitor sirtinol abolished the neuroprotection afforded by RPC and the decrease in UCP2 levels. Finally, RPC significantly increased the ADP/O ratio in hippocampal mitochondria reflecting enhanced ATP synthesis efficiency. In conclusion, in vivo resveratrol pretreatment confers neuroprotection similar to IPC via the SIRT1-UCP2 pathway.
Assuntos
Isquemia Encefálica/prevenção & controle , Hipocampo/efeitos dos fármacos , Canais Iônicos/metabolismo , Proteínas Mitocondriais/metabolismo , Sirtuínas/metabolismo , Estilbenos/farmacologia , Trifosfato de Adenosina/biossíntese , Animais , Asfixia , Benzamidas/farmacologia , Doenças das Artérias Carótidas/prevenção & controle , Modelos Animais de Doenças , Parada Cardíaca , Hipocampo/fisiopatologia , Hipotensão/prevenção & controle , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/fisiologia , Naftóis/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/fisiopatologia , Ratos , Ratos Sprague-Dawley , Respiração/efeitos dos fármacos , Resveratrol , Transdução de Sinais , Sirtuína 1 , Sirtuínas/antagonistas & inibidores , Estilbenos/administração & dosagem , Proteína Desacopladora 2RESUMO
Estradiol-17beta is released from the ovaries in a cyclic manner during the normal estrous cycle in rats. During the transition from the diestrous to proestrous stage, the 17beta-estradiol increases in blood circulation. We hypothesized that a higher serum level of endogenous 17beta-estradiol would protect hippocampal pyramidal neurons against global cerebral ischemia via activation of the cyclic-AMP response element binding protein (CREB)-mediated signaling cascade. Furthermore, we asked if a single 17beta-estradiol bolus provides protection against ischemia in the absence of endogenous estradiol. To test these hypotheses, rats were subjected to global cerebral ischemia at different stages of the estrous cycle. Ischemia was produced by bilateral carotid occlusion and systemic hypotension. Brains were examined for histopathology at 7 days of reperfusion. Higher serum levels of 17beta-estradiol (at proestrus and estrus stages) correlated with increased immunoreactivity of pCREB in hippocampus and ischemic tolerance. At diestrus, when circulating gonadal hormone concentrations were lowest, the pCREB protein content of hippocampus was reduced and showed the least number of normal neurons after ischemia compared to other stages of the estrous cycle. A similar phosphorylation pattern was also observed for mitogen-activated protein kinase (MAPK) and calcium-calmodulin-dependent protein kinase (CaMKII) in hippocampus. The cyclic variation in ovarian hormones did not reflect phosphorylation of protein kinase B (Akt). To test the efficacy of a single bolus of 17beta-estradiol before ischemia, ovariectomized rats were treated with 17beta-estradiol (5/10/50 microg/kg) or vehicle (oil) and 48/72/96 h later rats were exposed to cerebral ischemia. A single 17beta-estradiol bolus treatment in ovariectomized rats significantly increased CREB mRNA activation and protected CA1 pyramidal neurons against ischemia. These results suggest that an exogenous bolus of 17beta-estradiol to ovariectomized rats protects hippocampus against ischemia via activation of the CREB pathway in a manner similar to the endogenous estrous cycle.
Assuntos
Isquemia Encefálica/patologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Estradiol/administração & dosagem , Hipocampo/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Células Piramidais/patologia , Análise de Variância , Animais , Ciclo Estral/fisiologia , Feminino , Hipocampo/citologia , Ovariectomia , Células Piramidais/metabolismo , Ratos , Ratos Sprague-Dawley , Sistemas do Segundo Mensageiro/fisiologia , Transdução de Sinais/fisiologia , Estatísticas não ParamétricasRESUMO
The signaling pathway of cyclooxygenase-2 (COX-2) induction following ischemic preconditioning (IPC) in brain remains undefined. To determine role of COX-2 in ischemic preconditioning, we used two in vitro models: mixed cortical neuron/astrocyte cell cultures and organotypic hippocampal slice cultures. We simulated IPC by exposing cell or slice cultures to 1 h or 15 min of oxygen/glucose deprivation (OGD), respectively, 48 h prior to ischemia. To mimic ischemia in vitro, we exposed cell or slice cultures to OGD of 4 h or 40 min, respectively. In cell cultures, these experiments revealed that COX-2 induction peaked at 24 h following IPC in cell culture. Inhibition of COX-2 activation with 50 microM NS-398 (a COX-2 selective inhibitor) abolished IPC-mediated neuroprotection in both in vitro models. Next, we tested whether epsilon protein kinase C (epsilonPKC) and extracellular signal regulated kinase 1/2 (ERK1/2) activation was involved in IPC-mediated neuroprotection and COX-2 expression in cell culture. Cell cultures were treated with an epsilonPKC-specific activating peptide (psiepsilonRACK, 100 nM) for 1 h, and 48 h later were exposed to OGD. epsilonPKC activation increased ERK1/2 phosphorylation and COX-2 induction and conferred neuroprotection similar to IPC. Additionally, inhibition of either epsilonPKC or ERK1/2 activation abolished COX-2 expression and neuroprotection due to ischemic preconditioning. These results demonstrate a crucial role for the epsilonPKC-->ERK1/2-->COX-2 pathway in the induction of neuroprotection via ischemic preconditioning.
Assuntos
Astrócitos/fisiologia , Ciclo-Oxigenase 2/metabolismo , Hipocampo/fisiologia , Precondicionamento Isquêmico , Neurônios/fisiologia , Proteína Quinase C-épsilon/metabolismo , Animais , Astrócitos/citologia , Técnicas de Cultura de Células , Morte Celular , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ativação Enzimática , Hipocampo/irrigação sanguínea , Cinética , L-Lactato Desidrogenase/análise , Masculino , N-Metilaspartato/farmacologia , Neurônios/citologia , Técnicas de Cultura de Órgãos , Ratos , Ratos Sprague-Dawley , ReperfusãoRESUMO
Estrogen is neuroprotective against ischemia in both in vivo and in vitro injury models. Because of the promising preclinical data on neuroprotection, the Women's Estrogen for Stroke Trial was initiated. The outcomes from this trial were, however, unsuccessful and questions emerged about the safety of chronic estrogen treatment in women. In contrast to the chronic estrogen treatment strategy, the present study aims to investigate: (1) the neuroprotective efficacy of single estrogen pretreatment/preconditioning; and (2) the existence of a similarity between estrogen- and ischemic preconditioning-induced neuroprotection against cerebral ischemia. The efficacy of estrogen was tested in an in vitro model of cerebral ischemia using hippocampal organotypic slice culture system. The hippocampal organotypic slice cultures were generated from female neonatal (9-11 days old) Sprague-Dawley rats. The slices were exposed to estradiol-17beta (0.5, 1, 5 nM) for various durations (1, 2 or 4 h) 48 h prior to ischemia (40 min of oxygen-glucose deprivation). For ischemic preconditioning, slices were exposed to sublethal oxygen-glucose deprivation (15 min), 48 h prior to lethal oxygen-glucose deprivation. Quantification of cell death in hippocampal CA1 region was conducted by using propidium iodide fluorescence staining technique. Results demonstrated that estrogen preconditioning significantly protects the hippocampal CA1 region against ischemia (P<0.001) and mimicked ischemic preconditioning-induced neuroprotection. The propidium iodide fluorescence values of estrogen preconditioning, ischemic preconditioning and ischemia groups were 21+/-2 (mean+/-S.E.M.) (1 nM; 2 h; n=15), 18+/-2 (5 nM; 4 h; n=12), 32+/-3 (n=8), 65+/-3 (n=27), respectively. Further, estrogen preconditioning initiated a calcium-mediated signaling pathway leading to protection of CA1 neurons against ischemia. Future investigations in estrogen preconditioning may suggest new estrogen regimens that avoid potential side effects of chronic estrogen treatment for stroke patients.
Assuntos
Estradiol/administração & dosagem , Hipocampo/efeitos dos fármacos , Isquemia/prevenção & controle , Análise de Variância , Animais , Animais Recém-Nascidos , Western Blotting/métodos , Morte Celular/efeitos dos fármacos , Quelantes/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Inibidores Enzimáticos/farmacologia , Glucose/deficiência , Hipocampo/patologia , Hipóxia , Imuno-Histoquímica/métodos , Técnicas In Vitro , Isquemia/patologia , Modelos Biológicos , Fosfopiruvato Hidratase/metabolismo , Propídio , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
The Wobbler mouse is a model of human motor neuron disease. Recently we reported the impairment of mitochondrial complex IV in Wobbler mouse CNS, including motor cortex and spinal cord. The present study was designed to test the effect of hyperbaric oxygen therapy (HBOT) on (1) mitochondrial functions in young Wobbler mice, and (2) the onset and progression of the disease with aging. HBOT was carried out at 2 atmospheres absolute (2 ATA) oxygen for 1 h/day for 30 days. Control groups consisted of both untreated Wobbler mice and non-diseased Wobbler mice. The rate of respiration for complex IV in mitochondria isolated from motor cortex was improved by 40% (P<0.05) after HBOT. The onset and progression of the disease in the Wobbler mice was studied using litters of pups from proven heterozygous breeding pairs, which were treated from birth with 2 ATA HBOT for 1 h/day 6 days a week for the animals' lifetime. A "blinded" observer examined the onset and progression of the Wobbler phenotype, including walking capabilities ranging from normal walking to jaw walking (unable to use forepaws), and the paw condition (from normal to curled wrists and forelimb fixed to the chest). These data indicate that the onset of disease in untreated Wobbler mice averaged 36+/-4.3 days in terms of walking and 40+/-5.7 days in terms of paw condition. HBOT significantly delayed (P<0.001 for both paw condition and walking) the onset of disease to 59+/-8.2 days (in terms of walking) and 63+/-7.6 days (in terms of paw condition). Our data suggest that HBOT significantly ameliorates mitochondrial dysfunction in the motor cortex and spinal cord and greatly delays the onset of the disease in an animal model of motor neuron disease.
Assuntos
Oxigenoterapia Hiperbárica/métodos , Mitocôndrias/metabolismo , Doença dos Neurônios Motores/metabolismo , Doença dos Neurônios Motores/prevenção & controle , Animais , Progressão da Doença , Camundongos , Camundongos Mutantes Neurológicos , Doenças Mitocondriais/genética , Doenças Mitocondriais/metabolismo , Doenças Mitocondriais/prevenção & controle , Córtex Motor/metabolismo , Doença dos Neurônios Motores/genética , Oxirredução , Fenótipo , Medula Espinal/metabolismoRESUMO
El Hospital de San José como pionero del manejo del trauma facial en Colombia presenta una enorme experiencia en el manejo de las fracturas orbitarias, en el cual se incluyen 25 pacientes. Se decidió recopilar en este trabajo descriptivo, de los casos manejados mediante cirugía en los últimos cinco años, el comportamiento epidemiológico de esta patología, su manejo al igual que las secuelas.
Assuntos
Fraturas OrbitáriasRESUMO
Introducción: Las indicaciones tradicionales de la cirugía ortognática son el tratamiento de los desarreglos oclusales no susceptibles de tratamiento exclusivamente ortodóntico, y de las alteraciones de desarrollo del esqueleto facial. Desde hace unos años, la reconstrucción de la vía aérea superior es la nueva indicación surgida para la realización de este tipo de procedimientos. Pacientes y métodos: Realizamos una revisión de 10 pacientes clase II intervenidos de genioplastias y mandibulotomías de avance, por indicaciones estéticas y oclusales. Medimos las dimensiones de los espacios faríngeos superior e inferior en la radiografía lateral de cráneo siguiendo el método de McNamara. Resultados: La media de incremento en el espacio faríngeo superior fue de un 19,1 por ciento. La media de avance en el espacio faríngeo inferior fue de un 41,2 por ciento. Discusión / conclusiones: La cirugía ortognática, gracias a las modificaciones esqueléticas que produce en el maxilar superior y la mandíbula, es un método eficaz para aumentar las dimensiones de la vía aérea superior. Los cambios en el armazón óseo de puntos concretos de esta región tienen repercusiones generalizadas en el espacio aéreo surpraglótico.
Assuntos
Apneia Obstrutiva do Sono/cirurgia , Apneia Obstrutiva do Sono/diagnósticoRESUMO
Ischemic tolerance in brain develops when sublethal ischemic insults occur before "lethal" cerebral ischemia. Two windows for the induction of tolerance by ischemic preconditioning (IPC) have been proposed: one that occurs within 1 hour after IPC, and another that occurs 1 or 2 days after IPC. The authors tested the hypotheses that IPC would reduce or prevent ischemia-induced mitochondrial dysfunction. IPC and ischemia were produced by bilateral carotid occlusions and systemic hypotension (50 mm Hg) for 2 and 10 minutes, respectively. Nonsynaptosomal mitochondria were harvested 24 hours after the 10-minute "test" ischemic insult. No significant changes were observed in the oxygen consumption rates and activities for hippocampal mitochondrial complexes I to IV between the IPC and sham groups. Twenty-four hours of reperfusion after 10 minutes of global ischemia (without IPC) promoted significant decreases in the oxygen consumption rates in presence of substrates for complexes I and II compared with the IPC and sham groups. These data suggest that IPC protects the integrity of mitochondrial oxidative phosphorylation after cerebral ischemia.
Assuntos
Isquemia Encefálica/metabolismo , Hipocampo/metabolismo , Precondicionamento Isquêmico , Mitocôndrias/enzimologia , Animais , Isquemia Encefálica/patologia , Morte Celular , Corpo Estriado/metabolismo , Complexo I de Transporte de Elétrons , Complexo II de Transporte de Elétrons , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Radicais Livres/metabolismo , Hipocampo/patologia , Masculino , Complexos Multienzimáticos/metabolismo , NADH NADPH Oxirredutases/metabolismo , Oxirredutases/metabolismo , Consumo de Oxigênio , Ratos , Ratos Wistar , Succinato Desidrogenase/metabolismoRESUMO
Mild cerebral anoxic/ischemic/stress insults promote 'tolerance' and thereby protect the brain from subsequent 'lethal' anoxic/ischemic insults. We examined whether specific activation of PKC alpha, delta, epsilon, or zeta isoforms is associated with ischemic preconditioning (IPC) in rat brain. IPC was produced by a 2-minute global cerebral ischemia. Membrane and cytosolic fractions of the hippocampi were immunoblotted using specific antibodies for PKCalpha, delta, epsilon, and zeta. PKCalpha showed a significant translocation to the membrane fraction from 30 min to 4 h and PKCdelta at 4 h following IPC. In contrast, the membrane/cytosol ratio of PKCepsilon showed a tendency to decrease at 30 min and 8 h, and the membrane/cytosol ratio of PKCzeta was significantly decreased from 30 min to 24 h following IPC. These findings indicate PKC isoform-specific membrane translocations in the hippocampus after brief global brain ischemia and suggest that activation of PKCalpha and PKCdelta may be associated with IPC-induced tolerance in the rat hippocampus.
Assuntos
Encéfalo/enzimologia , Precondicionamento Isquêmico , Proteína Quinase C/metabolismo , Animais , Glicemia/metabolismo , Pressão Sanguínea , Temperatura Corporal , Isoenzimas/metabolismo , Cinética , Masculino , Oxigênio/sangue , Proteína Quinase C-alfa , Proteína Quinase C-delta , Proteína Quinase C-épsilon , Transporte Proteico , Ratos , Ratos WistarRESUMO
Non overlapping 20-mer peptides, covering the complete sequence of acid basic repeat antigen (ABRA) of Plasmodium falciparum, were synthesised and tested in binding assays to erythrocytes. Five peptides localised in the N-terminal region coded 2148 (121LQSHKKLIKALKKNIESYQN(140)), 2149 (141KKHLIYKNKSYNPLLLSCVK(160)), 2150 (161KMNMLKENVDYIQKNQNLFK(180)), 2152 (201YKSQGHKKETSQNQNENNDN(220)) and 2153 (221QKYQEVNDEDDVNDEEDTND(240)) specifically bind to erythrocytes. These peptides bind independently of the peptide and erythrocyte charge, with high affinity (Kd between 70 and 180 nM) and the hydrophobic interaction is important for this binding ( approximately 30% hydrophobic critical residues). These results allow us define a specific erythrocyte binding region (residues 121-240), which may bound to at least three different binding sites on erythrocytes. Peptide 2153 shares the underlined sequence 221QKYQEVNDEDDVNDEEDTND(240) with an earlier 18-mer peptide recognised by human exposed sera. Peptides number 2148 and 2149 in vitro inhibit erythrocyte invasion by merozoites. We found that 2149 peptide and some of its glycine analogues show specific haemolytic and/or antimicrobial activity. We discuss a possible role of ABRA or its regions in the merozoite invasion of erythrocyte.
Assuntos
Eritrócitos/metabolismo , Fragmentos de Peptídeos/metabolismo , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo , Sequência de Aminoácidos , Animais , Antígenos de Protozoários/metabolismo , Eritrócitos/parasitologia , Humanos , Dados de Sequência Molecular , Ligação ProteicaRESUMO
Two hours of transient focal brain ischemia causes acute neuronal death in the striatal core region and a somewhat more delayed type of neuronal death in neocortex. The objective of the current study was to investigate protein aggregation and neuronal death after focal brain ischemia in rats. Brain ischemia was induced by 2 hours of middle cerebral artery occlusion. Protein aggregation was analyzed by electron microscopy, laser-scanning confocal microscopy, and Western blotting. Two hours of focal brain ischemia induced protein aggregation in ischemic neocortical neurons at 1 hour of reperfusion, and protein aggregation persisted until neuronal death at 24 hours of reperfusion. Protein aggregates were found in the neuronal soma, dendrites, and axons, and they were associated with intracellular membranous structures during the postischemic phase. High-resolution confocal microscopy showed that clumped protein aggregates surrounding nuclei and along dendrites were formed after brain ischemia. On Western blots, ubiquitinated proteins (ubi-proteins) were dramatically increased in neocortical tissues in the postischemic phase. The ubi-proteins were Triton-insoluble, indicating that they might be irreversibly aggregated. The formation of ubi-protein aggregates after ischemia correlated well with the observed decrease in free ubiquitin and neuronal death. The authors concluded that proteins are severely damaged and aggregated in neurons after focal ischemia. The authors propose that protein damage or aggregation may contribute to ischemic neuronal death.
Assuntos
Ataque Isquêmico Transitório/metabolismo , Proteínas do Tecido Nervoso/química , Reperfusão , Animais , Axônios/química , Western Blotting , Núcleo Celular/química , Corantes , Constrição , Dendritos/química , Etanol , Ataque Isquêmico Transitório/patologia , Masculino , Microscopia Confocal , Microscopia Eletrônica , Artéria Cerebral Média , Neocórtex/química , Proteínas do Tecido Nervoso/análise , Neurônios/química , Neurônios/ultraestrutura , Ácido Fosfotúngstico , Ratos , Ratos Wistar , Ubiquitinas/análise , Ubiquitinas/químicaRESUMO
The involvement of mitochondrial dysfunction promoting neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), has been suggested. Histopathological and biochemical mitochondrial abnormalities have been reported in both sporadic and familial patients and suggest the contention that mitochondria may play a key role promoting ALS. Animal models of ALS provide a unique opportunity to study this incurable and fatal human disease. In the present study we tested the hypothesis that alterations in mitochondrial physiology occur in the brain of wobbler mice. No significant difference was found in the respiratory control index or adenosine diphosphate/oxygen ratio values between isolated mitochondria of wobbler and control mice. When pyruvate and malate were used as substrates, oxygen consumption was decreased significantly by approximately 33% in mitochondria isolated from wobbler mouse brain compared to controls. Oxygen consumption in the presence of ascorbate and N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) was decreased significantly by approximately 21% in wobbler brain mitochondria compared to controls, which suggests impairment in the function of complex IV. These findings are the first demonstration of mitochondrial respiratory chain dysfunction in the brain of the wobbler mouse.
Assuntos
Esclerose Lateral Amiotrófica/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças , Mitocôndrias/metabolismo , Consumo de Oxigênio/fisiologia , Animais , Ácido Ascórbico/metabolismo , Respiração Celular/fisiologia , Transporte de Elétrons/fisiologia , Malatos/metabolismo , Camundongos , Camundongos Mutantes Neurológicos , Ácido Pirúvico/metabolismoRESUMO
Traumatic brain injury (TBI) can produce chronic cognitive learning/memory deficits that are thought to be mediated, in part, by impaired hippocampal function. Experimentally induced TBI is associated with deficits in hippocampal synaptic plasticity (long-term potentiation, or LTP) at acute post-injury intervals but plasticity has not been examined at long-term survival periods. The present study was conducted to assess the temporal profile of LTP after injury and to evaluate the effects of injury severity on plasticity. Separate groups of rats were subjected to mild (1.1-1.4 atm), moderate (1.8-2.1 atm), or severe (2.2-2.7 atm) fluid percussion (FP) injury (or sham surgery) and processed for hippocampal electrophysiology in the first or eighth week after injury. LTP was defined as a lasting increase in field excitatory post-synaptic potential (fEPSP) slope in area CA1 following tetanic stimulation of the Schaffer collaterals. The fEPSP slope was measured for 60 min after tetanus. Assessment of LTP at the acute interval (6 days) revealed modest peak slope potentiation values (129-139%), which declined in each group (including sham) over the hour-long recording session and did not differ between groups. Eight weeks following injury, slices from all groups exhibited robust maximal potentiation (134-147%). Levels of potentiation among groups were similar at the 5-min test interval but differed significantly at the 30- and 60-min test intervals. Whereas sham slices showed stable potentiation for the entire 60-min assessment period, slices in all of the injury groups exhibited a significant decline in potentiation over this period. These experiments reveal a previously unknown effect of TBI whereby experimentally induced injury results in a chronic inability of the CA1 hippocampus to maintain synaptic plasticity. They also provide evidence that sham surgical procedures can significantly influence hippocampal physiology at the acute post-TBI intervals. The results have implications for the mechanisms underlying the impaired synaptic plasticity following TBI.