RESUMO
During the consumption of alkanes, Alcanivorax borkumensis will form a biofilm around an oil droplet, but the role this plays during degradation remains unclear. We identified a shift in biofilm morphology that depends on adaptation to oil consumption: Longer exposure leads to the appearance of dendritic biofilms optimized for oil consumption effected through tubulation of the interface. In situ microfluidic tracking enabled us to correlate tubulation to localized defects in the interfacial cell ordering. We demonstrate control over droplet deformation by using confinement to position defects, inducing dimpling in the droplets. We developed a model that elucidates biofilm morphology, linking tubulation to decreased interfacial tension and increased cell hydrophobicity.
Assuntos
Alcanivoraceae , Alcanos , Biofilmes , Petróleo , Alcanivoraceae/metabolismo , Alcanos/metabolismo , Petróleo/metabolismo , Biodegradação AmbientalRESUMO
Layer V neurons in the primary motor cortex (M1) are important for motor skill learning. Since pretreatment of either CNQX or APV in rat M1 layer V impaired rotor rod learning, we analysed training-induced synaptic plasticity by whole-cell patch-clamp technique in acute brain slices. Rats trained for 1 day showed a decrease in small inhibitory postsynaptic current (mIPSC) frequency and an increase in the paired-pulse ratio of evoked IPSCs, suggesting a transient decrease in presynaptic GABA release in the early phase. Rats trained for 2 days showed an increase in miniature excitatory postsynaptic current (mEPSC) amplitudes/frequency and elevated AMPA/NMDA ratios, suggesting a long-term strengthening of AMPA receptor-mediated excitatory synapses. Importantly, rotor rod performance in trained rats was correlated with the mean mEPSC amplitude and the frequency obtained from that animal. In current-clamp analysis, 1-day-trained rats transiently decreased the current-induced firing rate, while 2-day-trained rats returned to pre-training levels, suggesting dynamic changes in intrinsic properties. Furthermore, western blot analysis of layer V detected decreased phosphorylation of Ser408-409 in GABAA receptor ß3 subunits in 1-day-trained rats, and increased phosphorylation of Ser831 in AMPA receptor GluA1 subunits in 2-day-trained rats. Finally, live-imaging analysis of Thy1-YFP transgenic mice showed that the training rapidly recruited a substantial number of spines for long-term plasticity in M1 layer V neurons. Taken together, these results indicate that motor training induces complex and diverse plasticity in M1 layer V pyramidal neurons. KEY POINTS: Here we examined motor training-induced synaptic and intrinsic plasticity of layer V pyramidal neurons in the primary motor cortex. The training reduced presynaptic GABA release in the early phase, but strengthened AMPA receptor-mediated excitatory synapses in the later phase: acquired motor performance after training correlated with the strength of excitatory synapses rather than inhibitory synapses. As to the intrinsic property, the training transiently decreased the firing rate in the early phase, but returned to pre-training levels in the later phase. Western blot analysis detected decreased phosphorylation of Ser408-409 in GABAA receptor ß3 subunits in the acute phase, and increased phosphorylation of Ser831 in AMPA receptor GluA1 subunits in the later phase. Live-imaging analysis of Thy1-YFP transgenic mice showed rapid and long-term spine plasticity in M1 layer V neurons, suggesting training-induced increases in self-entropy per spine.
Assuntos
Córtex Motor , Receptores de GABA-A , Camundongos , Ratos , Animais , Receptores de GABA-A/metabolismo , Receptores de AMPA/metabolismo , Córtex Motor/fisiologia , Células Piramidais/fisiologia , Sinapses/fisiologia , Plasticidade Neuronal/fisiologia , Ácido gama-Aminobutírico , Camundongos TransgênicosRESUMO
OBJECTIVE: To systematically review evidence on the effects of nutrition therapy in older stroke patients undergoing rehabilitation and identify its effectiveness using meta-analysis. METHODS: PubMed (MEDLINE), EMBASE (via Dialog), Cochrane Central Register of Controlled Trial, World Health Organization International Clinical Trials Registry Platform and Ichu-shi Web were searched for relevant articles. Randomized controlled trials investigating the effects of nutrition therapy compared to control interventions in older stroke patients undergoing rehabilitation were considered eligible. The primary outcome was activities of daily living (ADL), and secondary outcomes were all-cause mortality, infections, pneumonia incidence, disability level, walking ability, fall, stroke recurrence, and quality of life. The risk of bias of each trial was assessed using the Cochrane Collaboration Tool, and the quality of the body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Eight randomized controlled trials with a total of 5484 participants were included in the meta-analysis. The meta-analysis for ADL showed no significant effects (mean difference, 4.16; 95% confidence interval [CI], -0.88 to 9.20; I2=53%, low-quality evidence). The meta-analyses for secondary outcomes revealed a significant effect of reduced infections (risk ratio, 0.65; 95% CI, 0.51 to 0.84; I2=0%; low-quality evidence), with no significant effects on the other outcomes. CONCLUSION: Nutrition therapy had no statistically significant effect on ADL. However, it reduced the incidence of infections. More high-quality trials are warranted to clarify the effects of nutrition therapy in older stroke patients undergoing rehabilitation.
Assuntos
Apoio Nutricional/métodos , Qualidade de Vida/psicologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/dietoterapia , Idoso , Idoso de 80 Anos ou mais , HumanosRESUMO
A total of 211 neurons that discharged at the highest rate during sleep (sleep-active neurons) were recorded in non-anesthetized, head-restrained mice during the complete wake-sleep cycle in, and around, the laterodorsal (LDT) and sublaterodorsal (SubLDT) tegmental nuclei, which contain both cholinergic and non-cholinergic neurons. For the first time in mice, I reveal the presence, mainly in the SubLDT, of sleep-specific neurons displaying sustained tonic discharge either (i) just prior to, and during, paradoxical sleep (PS) (PS-on neurons) or (ii) during both slow-wave sleep (SWS) and PS (SWS/PS-on neurons). Both the PS-on and SWS/PS-on neurons showed either a low (< 10 Hz) or high (⩾ 10 Hz) rate of spontaneous firing and exhibited a biphasic narrow or medium-to-broad action potential, a characteristic of non-cholinergic neurons. At the transition from SWS to waking (W), the PS-on and SWS/PS-on neurons simultaneously ceased firing shortly before the onset of W, whereas, at the transition from W to SWS, only the SWS/PS-on neurons fired shortly after the onset of sleep. At the transition from SWS to PS, only the PS-on neurons exhibited a significant increase in discharge rate before PS onset, while, at the transition from PS to W, the SWS/PS-on neurons, then the PS-on neurons, displayed a significant decrease in the discharge rate before the end of PS. The SWS/PS-on neurons were more sensitive to the change in the electroencephalogram (EEG) than the PS-on neurons, as, during a PS episode, the slightest interruption of rhythmic theta activity resulted in cessation of discharge of the SWS/PS-on neurons. These findings support the view that, in the mouse SubLDT, PS-on neurons play an important role in the induction, maintenance, and cessation of PS, while SWS/PS-on neurons play a role in the maintenance of the PS state in particular and the sleep state in general.
Assuntos
Neurônios/fisiologia , Tegmento Pontino/fisiologia , Sono REM/fisiologia , Vigília/fisiologia , Potenciais de Ação , Animais , Eletroencefalografia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fases do Sono/fisiologia , Tálamo/fisiologiaRESUMO
We recorded 872 single units across the complete sleep-waking cycle in the mouse preoptic area (POA) and basal forebrain (BFB), which are deeply involved in the regulation of sleep and wakefulness (W). Of these, 552 were sleep-active, 96 were waking-active, 106 were active during both waking and paradoxical sleep (PS), and the remaining 118 were state-indifferent. Among the 872, we distinguished slow-wave sleep (SWS)-specific, SWS/PS-specific, PS-specific, W-specific, and W/PS-specific neurons, the last group being further divided into specific tonic type I slow (TI-Ss) and specific tonic type I rapid (TI-Rs) both discharging specifically in association with cortical activation during both W and PS. Both the SWS/PS-specific and PS-specific neurons were distributed throughout a wide region of the POA and BFB, whereas the SWS-specific neurons were mainly located in the middle and ventral half of the POA and adjacent BFB, as were the W-specific and W/PS-specific neurons. At the transition from waking to sleep, the majority of SWS-specific and all SWS/PS-specific neurons fired after the onset of cortical synchronization (deactivation), whereas all W-specific and W/PS-specific neurons showed a significant decrease in firing rate >0.5 s before the onset. At the transition from SWS to W, the sleep-specific neurons showed a significant decrease in firing rate 0.1 s before the onset of cortical activation, while the W-specific and W/PS-specific neurons fired >0.5 s before the onset. TI-Ss neurons were characterized by a triphasic broad action potential, slow single isolated firing, and an antidromic response to cortical stimulation, whereas TI-Rs neurons were characterized by a narrow action potential and high frequency burst discharge in association with theta waves in PS. These data suggest that the forebrain sleep/waking switch is regulated by opposing activities of sleep-promoting (SWS-specific and SWS/PS-specific) and waking-promoting (W-specific and W/PS-specific) neurons, that the initiation of sleep is caused by decreased activity of the waking-promoting neurons (disfacilitation), and that the W/PS-specific neurons are deeply involved in the processes of cortical activation/deactivation.
Assuntos
Neurônios/fisiologia , Prosencéfalo/citologia , Sono , Vigília , Estimulação Acústica , Potenciais de Ação , Animais , Mapeamento Encefálico , Estimulação Elétrica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Área Pré-Óptica/citologia , Área Pré-Óptica/fisiologia , Prosencéfalo/fisiologia , Fases do SonoRESUMO
Using extracellular single unit recordings alone or in combination with neurobiotin juxtacellular labeling and orexin (hypocretin) immunohistochemistry in the mouse, we have recorded a total of 452 neurons in the orexin neuron field of the posterior hypothalamus. Of these, 76 exhibited tonic discharge highly specific to wakefulness, referred to as waking-active neurons. They showed differences from each other in terms of spike shape, activity profile, and response to an arousing sound stimulus and could be classified into three groups on the basis of spike shape as: 1) biphasic broad; 2) biphasic narrow; and 3) triphasic. Waking-active neurons characterized by biphasic broad spikes were orexin-immunopositive, whereas those characterized by either biphasic narrow or triphasic broad spikes were orexin-immunonegative. Unlike waking-specific histamine neurons, all orexin and non-orexin waking-active neurons exhibited slow (<10 Hz) tonic discharges during wakefulness and ceased firing shortly after the onset of electroencephalogram (EEG) synchronization (deactivation), the EEG sign of sleep (drowsy state). They remained virtually silent during slow-wave sleep, but displayed transient discharges during paradoxical (or rapid eye movement) sleep. During the transition from sleep to wakefulness, both orexin and triphasic non-orexin neurons fired in clusters prior to the onset of EEG activation, the EEG sign of wakefulness, and responded with a short latency to an arousing sound stimulus given during sleep. In contrast, the biphasic narrow non-orexin neurons fired in single spikes either prior to, or after, EEG activation during the same transition and responded to the stimulus with a longer latency. The activity of all waking-active neurons preceded the return of muscle tonus at the transition from paradoxical sleep to wakefulness. These data support the view that the activity of orexin and non-orexin waking-active neurons in the posterior hypothalamus plays an important wake-promoting role and that their activity antagonizes cortical deactivation and loss of muscle tone.
Assuntos
Hipotálamo/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neurônios/fisiologia , Neuropeptídeos/metabolismo , Sono/fisiologia , Vigília/fisiologia , Animais , Sincronização Cortical , Eletroencefalografia , Eletromiografia , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tono Muscular/fisiologia , Orexinas , Técnicas de Patch-ClampRESUMO
This paper reports a 59 year old woman with paraneoplastic limbic encephalitis associated with diffuse large B cell lymphoma. Her brain magnetic resonance imaging scan showed bilateral posterior thalamic hyperintensities, similar to the "pulvinar sign". Her symptoms included progressive psychiatric disturbance and resembled the initial symptoms of variant Creutzfeldt-Jakob disease (vCJD). Clinicians should consider this treatable disorder in the differential diagnosis of vCJD.
Assuntos
Encefalite Límbica/patologia , Linfoma não Hodgkin/patologia , Pulvinar/patologia , Axila , Síndrome de Creutzfeldt-Jakob/diagnóstico , Diagnóstico Diferencial , Feminino , Hipocampo/patologia , Humanos , Encefalite Límbica/complicações , Linfonodos/patologia , Linfoma não Hodgkin/complicações , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Lobo Temporal/patologia , Tálamo/patologiaRESUMO
BACKGROUND: Although a number of studies on traditional eastern or Chinese medicine, such as acupuncture, moxibustion, and herbal drugs, have been reported, few reports describe electroacupuncture (EAC) effects on drug- and alcohol-seeking behaviors in animal models. The purpose of the present study was to investigate the effect of EAC on changes in alcohol-drinking behavior in rats challenged with restriction and immobilization stress. MATERIAL AND METHODS: Male Sprague Dawley rats (260-280 g) were tightly hung and immobilized in restriction models for 10 min. These immobilization stresses were performed twice a week for 1 week and for 3 consecutive weeks for the short- and long-restricted stress groups, respectively. EAC was applied for 10 min to the hindlimb point, Tsu-San-Li (ST 36), and the lumbar point, Shen-Shu (BL 23). These points are used to treat mental and psychosomatic disorders and are known clinically to produce a sedation effect. Time-access alcohol-drinking behavior was determined at 24 hr after the termination of EAC. Finally, brain dopamine (DA) levels were assayed in the two groups. A sham-control group underwent only restricted stress without EAC. RESULTS: Time-access alcohol-drinking behavior increased significantly in the long-restricted group compared with the short-restricted group and controls. EAC applied to the ST 36 (Tsu-San-Li) point suppressed the increased alcohol-drinking behavior in restricted rats. However, EAC applied to the Shen-Shu (BL 23) point was not effective, because alcohol-drinking behavior was significantly increased in long-restricted rats compared with short-restricted rats. Striatal DA levels of restricted rats with EAC stimulated at Tsu-San-Li were increased significantly compared with the rats with EAC applied to the Shen-Shu point. CONCLUSION: These findings suggest that EAC applied at ST 36 (Tsu-San-Li) was more effective for reducing the increased alcohol-drinking behavior in restricted rats, and they showed that a point specific in EAC procedure was associated with an increase of striatal DA levels. These findings provide new information for understanding alcohol-drinking behavior and for treating human alcoholics.
Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Comportamento Animal , Eletroacupuntura , Estresse Fisiológico/fisiopatologia , Animais , Química Encefálica , Dopamina/análise , Masculino , Ratos , Ratos Sprague-Dawley , Restrição FísicaRESUMO
The effects of three chronically administered antipsychotic drugs on selected neurochemical markers of dopaminergic and GABAergic transmission were compared within the cerebral regions making up the basal ganglia-thalamocortical parallel processing neuronal pathways. All three drugs reduce psychosis in humans, whereas only haloperidol, but not olanzapine or sertindole, induce purposeless oral chewing movements (CMs) in rats or cause high rates of parkinsonism or tardive dyskinesia in humans. Male Sprague Dawley rats were treated with haloperidol, sertindole, or olanzapine delivered in drinking water for 6 months at doses which produce drug plasma levels in rat in the human therapeutic range. Results show the expected dopamine D2 receptor upregulation in striatum predominantly with haloperidol, although mild D2 upregulation was apparent in striatum after olanzapine. GAD67 mRNA was increased in striatum and decreased in globus pallidus by haloperidol and sertindole, but not by olanzapine. In the substantia nigra pars reticulata (SNR), both olanzapine and sertindole failed to induce GABA(A) receptor upregulation or D1 receptor downregulation, but haloperidol did both, confirming a previous report. In thalamus, all three drugs increased GAD expression in the reticular nucleus, whereas only haloperidol decreased GABA(A) binding in the mediodorsal nucleus, actions consistent with a reduction in nigrothalamic, GABA-mediated neural transmission. These results are consistent with the idea that the two new antipsychotics tested have mild and regionally restricted actions within the basal ganglia nuclei and a common action on increasing GAD expression in the reticular nucleus of the thalamus (RtN). Haloperidol, in contrast, has a broad and potent action in basal ganglia, causing changes in SNR and in the mediodorsal nucleus, while also altering GAD mRNA in RtN, potentially reflective of its dyskinetic and antipsychotic actions.
Assuntos
Antipsicóticos/farmacologia , Encéfalo/efeitos dos fármacos , Neurotransmissores/metabolismo , Pirenzepina/análogos & derivados , Animais , Benzodiazepinas , Encéfalo/citologia , Encéfalo/metabolismo , Corpo Estriado/citologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Haloperidol/farmacologia , Imidazóis/farmacologia , Indóis/farmacologia , Masculino , Olanzapina , Pirenzepina/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D1/efeitos dos fármacos , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/efeitos dos fármacos , Receptores de Dopamina D2/metabolismo , Tálamo/citologia , Tálamo/efeitos dos fármacos , Tálamo/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
We have analyzed oligosaccharide chains in brain microsomes of rats fed an n-3 polyunsaturated fatty acid-deficient (safflower oil group; S group) or -rich (perilla oil group; P group) diet before and after brightness-discrimination learning tasks. The amount of concanavalin A-binding sites (mainly mannoside) of the brain microsomes was found to be significantly less in the S group than the P group before the learning task. Detailed analysis of glycoprotein glycans demonstrated that high mannose type oligosaccharides were dominant in brain microsomes before the learning task in both dietary groups, whereas multiantennary complex-type oligosaccharides became dominant after the learning task and especially a tetra-antennary glycan, that had a core structure of the glycan of neural cell adhesion molecule, was more increased in the S-group than the P group. When polysialylated glycans were analyzed on serotonin-conjugated HPLC column, the glycans in the S-group microsomes before the learning task contained larger amount of higher affinity-polysialylated glycans to serotonin column than those in the P-group, and also contained larger amount of phosphoglycans that showed also high affinity to serotonin column than the P-group. Removal of mannoside from microsomes by alpha-mannosidase-treatment changed the membrane surface physical property, especially permittivity, as revealed by analysis of the interaction with 1-anilinonaphthalene-8-sulfonate. These results suggest that high mannose content and several multiantennary glycans including polysialylated and phospho-glycans were changed by dietary n-3 fatty acid deficiency and learning task in rat brain microsomal glycoproteins and that these changes may affect membrane functions through changes of membrane surface physical properties and reactivity against serotonin.
Assuntos
Encéfalo/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Alimentos Formulados/efeitos adversos , Aprendizagem/fisiologia , Microssomos/metabolismo , Oligossacarídeos/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Glicoproteínas/metabolismo , Deficiências da Aprendizagem/metabolismo , Deficiências da Aprendizagem/fisiopatologia , Manose/metabolismo , Potenciais da Membrana/fisiologia , Fosforilação , Ratos , Receptores de Concanavalina A/metabolismo , Ácidos Siálicos/metabolismo , Sialoglicoproteínas/metabolismoRESUMO
We describe the serial changes of magnetic resonance imaging (MRI) in a patient with chronic cryptococcus meningo-encephalitis. In the subacute phase, MRI revealed a focal lesion with hyperintensity on T2-weighted image (WI) in the left thalamus. At 11 months after the onset, MRI showed a focal lesion with hyperintensity on T2-WI in the right pons that was enhanced with gadolinium (Gd). At 13 months after the onset, the lesion in the left thalamus became rim enhanced with Gd. After antifungal therapy (amphotericin B and 5-flucytosine), the rim enhancement in the left thalamus and the high signal intensity area in the right pons decreased. Cryptococcoma should be in the differential from other ring enhancing lesions.
Assuntos
Imageamento por Ressonância Magnética , Meningite Criptocócica/patologia , Ponte/patologia , Tálamo/patologia , Doença Crônica , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Although isoflurane has been shown to cause coronary and systemic vasodilation through KATP channel activation, the interaction of KATP channel openers and isoflurane has not been fully investigated. The present study was carried out to determine the haemodynamic actions of cromakalim, a KATP channel opener, under the conscious state and during isoflurane anaesthesia in chronically instrumented dogs. METHODS: Fourteen dogs were chronically instrumented to measure systemic and coronary haemodynamics. Each dog was randomly assigned to receive doses of either cromakalim, 4 and 10 microg x kg(-1) i.v., or isoflurane, 2.1% end-tidal (1.5 MAC), plus cromakalim, 4 and 10 microg x kg(-1) i.v. RESULTS: Cromakalim dose-relatedly decreased mean arterial pressure and systemic vascular resistance and increased coronary blood flow in both conscious and anaesthetized states. With isoflurane, the duration of effects of cromakalim were prolonged. Isoflurane exerted an additive effect on the increase in coronary blood flow induced by a low-dose cromakalim, whereas it did not influence the effect of a high-dose cromakalim. The maximum rate of increase in left ventricular pressure and segment shortening were increased by cromakalim in the conscious state but unchanged during isoflurane anaesthesia. CONCLUSION: The results suggest that the coronary vasodilating effects of isoflurane and cromakalim are basically additive until cromakalim exerts the maximal effect, and that the action of cromakalim on the coronary vasculature is prolonged by isoflurane.
Assuntos
Anestésicos Inalatórios/farmacologia , Circulação Coronária/efeitos dos fármacos , Cromakalim/farmacologia , Hemodinâmica/efeitos dos fármacos , Isoflurano/farmacologia , Canais de Potássio/agonistas , Vasodilatadores/farmacologia , Transportadores de Cassetes de Ligação de ATP , Anestesia , Animais , Pressão Sanguínea/efeitos dos fármacos , Cães , Relação Dose-Resposta a Droga , Feminino , Frequência Cardíaca/efeitos dos fármacos , Canais KATP , Masculino , Canais de Potássio Corretores do Fluxo de InternalizaçãoRESUMO
It has been empirically known that Ginkgo extract is useful for reducing many symptoms associated with cerebral blood flow (CBF) insufficiency, but its mechanisms have been uncertain. In the present study, therefore, we gave Ginkgo extract to rats with per os digestion, and investigated its effect on CBF and ischemic brain damage with middle cerebral artery occlusion (MCAO). The treatment with Ginkgo extract (10 mg 100 g-1 rat) increased CBF in the normal condition, but the degree of increase in CBF was lesser during and after MCAO. TTC staining showed that infarct volume was reduced with Ginkgo treatment. TUNEL and HSP72 immunostaining confirmed the protective effect of Ginkgo treatment reducing numbers of TUNEL and HSP72 positive cells. Immunohistochemical analysis showed that caspase-3 expression was less abundant in Ginkgo treated rats. The present results suggest that Ginkgo extract contains a substance which increases normal CBF and reduces ischemic brain damage.
Assuntos
Arteriopatias Oclusivas/patologia , Encéfalo/efeitos dos fármacos , Artérias Cerebrais , Ginkgo biloba/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais , Animais , Arteriopatias Oclusivas/genética , Arteriopatias Oclusivas/fisiopatologia , Encéfalo/patologia , Caspase 3 , Caspases/metabolismo , Infarto Cerebral/patologia , Circulação Cerebrovascular/efeitos dos fármacos , Fragmentação do DNA , Proteínas de Choque Térmico HSP72 , Proteínas de Choque Térmico/metabolismo , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Masculino , Ratos , Ratos Wistar , Sais de TetrazólioRESUMO
The human auditory cortex plays a special role in speech recognition. It is therefore necessary to clarify the functional roles of individual auditory areas. We applied functional magnetic resonance imaging (fMRI) to examine cortical responses to speech sounds, which were presented under the dichotic and diotic (binaural) listening conditions. We found two different response patterns in multiple auditory areas and language-related areas. In the auditory cortex, the medial portion of the secondary auditory area (A2), as well as a part of the planum temporale (PT) and the superior temporal gyrus and sulcus (ST), showed greater responses under the dichotic condition than under the diotic condition. This dichotic selectivity may reflect acoustic differences and attention-related factors such as spatial attention and selective attention to targets. In contrast, other parts of the auditory cortex showed comparable responses to the dichotic and diotic conditions. We found similar functional differentiation in the inferior frontal (IF) cortex. These results suggest that multiple auditory and language areas may play a pivotal role in integrating the functional differentiation for speech recognition.
Assuntos
Córtex Auditivo/fisiologia , Testes com Listas de Dissílabos , Idioma , Estimulação Acústica , Adulto , Mapeamento Encefálico , Lobo Frontal/fisiologia , Humanos , Imageamento por Ressonância Magnética , Magnetoencefalografia , Masculino , Desempenho Psicomotor/fisiologia , Percepção da Fala/fisiologia , Análise e Desempenho de Tarefas , Tomografia Computadorizada de EmissãoRESUMO
The acetone extract of Boehmeria nipononivea showed both potent 5alpha-reductase inhibitory activity and hair regrowth promotion effects on mice. 5alpha-Reductase inhibitory activity-guided fractionation led to six active fatty acids: alpha-linolenic, linoleic, palmitic, elaidic, oleic and stearic acids. The extract of B. nipononivea, and alphalinolenic, elaidic and stearic acids exhibited a hair regrowth effect.
Assuntos
Inibidores de 5-alfa Redutase , Alopecia/tratamento farmacológico , Ácidos Graxos/uso terapêutico , Cabelo/crescimento & desenvolvimento , Extratos Vegetais/farmacologia , Rosales/química , Acetona , Animais , Inibidores Enzimáticos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Recently, an alternative splicing variant of mouse protein kinase C delta (PKC deltaII, GenBank Accession No. AB011812) has been reported which has a 78 bp (26 amino acid) insertion at the caspase-3 recognition sequence in the V3 region of PKC delta (PKC deltaI). We isolated a cDNA encoding a new variant of PKC delta (PKC deltaIII, AF219629), which has a 83 bp insertion at the same site in the V3 region, by RT-PCR using rat testis RNA as a template. In rats, the 83 bp insertion causes inframe termination, and rat PKC deltaIII protein is expressed as a truncated form, having only the regulatory domain without a catalytic domain. Genomic DNA analysis revealed that the difference between mouse PKC deltaII and rat PKC deltaIII is derived from the different sequence at the 5'-splicing donor sites. To investigate the potential functions of the truncated form of PKC delta, rat PKC deltaIII fused to green fluorescent protein (GFP) was expressed in CHO-K1 cells. PKC deltaIII-GFP was localized in the cytoplasm with dot-like accumulation and highly expressed on the plasma membrane, whereas PKC deltaI-GFP is localized homogeneously throughout the cytoplasm, including the nucleoplasm. Stimulation by phorbol ester caused weak translocation of deltaIII-GFP from the cytosol to the plasma membrane. These results suggest that PKC deltaIII may show a dominant negative effect against PKC deltaI, and that the modulation of signal transduction by alternative splicing variant may play a crucial role in the physiological and/or pathological conditions, and the pathogenesis of disease.
Assuntos
Processamento Alternativo , Isoenzimas/genética , Proteína Quinase C/genética , Animais , Sequência de Bases , Transporte Biológico , Células CHO , Clonagem Molecular , Cricetinae , DNA Complementar , Proteínas de Fluorescência Verde , Humanos , Isoenzimas/metabolismo , Proteínas Luminescentes/genética , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Proteína Quinase C/metabolismo , Proteína Quinase C-delta , RNA Mensageiro/genética , Ratos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
Several flavonoids, stilbenes and related 4-substituted resorcinols, obtained from Artocarpus incisus and other plants or synthesized, were tested for their inhibitory activity against tyrosinase. The structure-activity relationships suggested that specific natural or synthesized compounds having the 4-substituted resorcinol skeleton have potent tyrosinase inhibitory ability. Kinetic studies have indicated that specific compounds having the 4-substituted resorcinol skeleton exhibit competitive inhibition of the oxidation of DL-beta-(3,4-dihydroxyphenyl)alanine (DL-DOPA) by mushroom tyrosinase. These findings could lead to the design and discovery of new tyrosinase inhibitors.
Assuntos
Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Resorcinóis/farmacologia , Estilbenos/farmacologia , Inibidores Enzimáticos/química , Flavonoides/química , Resorcinóis/química , Estilbenos/química , Relação Estrutura-AtividadeRESUMO
The methanol extract of heartwood of Artocarpus incisus showed potent 5 alpha-reductase inhibitory activity. We investigated the 5 alpha-reductase inhibitory effects of nine compounds isolated from A. incisus. Chlorophorin (IC50 = 37 microM) and artocarpin (IC50 = 85 microM) showed more potent inhibitory effects than did alpha-linolenic acid, which is known as a naturally occurring potent inhibitor. Structure-activity investigations suggested that the presence of an isoprene substituent (prenyl and geranyl) would enhance 5 alpha-reductase inhibitory effects.
Assuntos
Inibidores de 5-alfa Redutase , Inibidores Enzimáticos/farmacologia , Árvores/química , Animais , Inibidores Enzimáticos/química , Feminino , Ratos , Ratos Sprague-Dawley , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To study the effect of a loud auditory stimulus on the excitability of the human motor cortex. METHODS: Ten normal volunteers participated in this study. The size of responses to transcranial magnetic or electrical cortical stimulation (TMS or TES) given at different times (ISIs) after a loud sound were compared with those to TMS or TES alone (control response). Different intensities and durations of sound were used at several intertrial intervals (ITIs). In addition, we examined how the presence of a preceding click modulated the effect of a loud sound (prepulse inhibition). The incidence of startle response evoked by various stimuli was also studied. RESULTS: A loud auditory stimulus suppressed EMG responses to TMS when it preceded the magnetic stimulus by 30-60 ms, whereas it did not affect responses to TES. This suggests that the suppression occurred at a cortical level. Significant suppression was evoked only when the sound was louder than 80 dB and longer than 50 ms in duration. Such stimuli frequently elicited a startle response when given alone. The effect was not evoked if the ITI was 5 s, but was evoked when it was longer than 20 s. A preceding click reduced the suppression elicited by loud sounds. CONCLUSIONS: Auditory stimuli that produced the greatest effect on responses to TMS had the same characteristics as those which yielded the most consistent auditory startle. We suggest that modulation of cortical excitability occurs in parallel with the auditory startle and both may arise from the same region of the brain-stem.