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1.
Org Biomol Chem ; 16(25): 4619-4622, 2018 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-29872817

RESUMO

Three series of water-soluble anthracene-appended benzoxaboroles 1a-c were developed; their binding affinity toward cis-1,2-diols was explored by conventional fluorescence titrations to demonstrate the role of benzoxaborole as a general recognition motif of cis-1,2-diols for fluorescent probes. The complex structures of the tetra-coordinated boronate adducts between 1 and the cis-1,2-diols were revealed.

2.
Clin Exp Allergy ; 46(8): 1083-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26366720

RESUMO

BACKGROUND: Having an allergic disease may have health implications beyond those more commonly associated with allergy given that previous epidemiological studies have suggested that both atopy and allergy are linked to mortality. More viable immune functioning among the elderly, as indicated by the presence of an allergic disease, might therefore be associated with differences in all-cause mortality. OBJECTIVE: Using data from a Japanese cohort, this study examined whether having pollinosis (a form of allergic rhinitis) in a follow-up survey could predict all-cause and cause-specific mortality. METHODS: Data came from the Komo-Ise cohort, which at its 1993 baseline recruited residents aged 40-69 years from two areas in Gunma prefecture, Japan. The current study used information on pollinosis that was obtained from the follow-up survey in 2000. Mortality and migration data were obtained throughout the follow-up period up to December 2008. Proportional hazard models were used to examine the relation between pollinosis and mortality. RESULTS: At the 2000 follow-up survey, 12% (1088 of 8796) of respondents reported that they had pollinosis symptoms in the past 12 months. During the 76 186 person-years of follow-up, 748 died from all causes. Among these, there were 37 external, 208 cardiovascular, 74 respiratory, and 329 neoplasm deaths. After adjusting for potential confounders, pollinosis was associated with significantly lower all-cause [hazard ratio 0.57 (95% confidence interval = 0.38-0.87)] and neoplasms mortality [hazard ratio 0.48 (95% confidence interval = 0.26-0.92)]. CONCLUSIONS AND CLINICAL RELEVANCE: Having an allergic disease (pollinosis) at an older age may be indicative of more viable immune functioning and be protective against certain causes of death. Further research is needed to determine the possible mechanisms underlying the association between pollinosis and mortality.


Assuntos
Alérgenos/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/mortalidade , Adulto , Fatores Etários , Idoso , Causas de Morte , Comorbidade , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Vigilância da População , Modelos de Riscos Proporcionais , Rinite Alérgica Sazonal/epidemiologia , Fatores de Risco
3.
Anim Genet ; 45(4): 517-23, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24754898

RESUMO

We evaluated genetic introgression from domesticated pigs into the Ryukyu wild boar (RWB) population on Iriomote Island based on their genetic structure and diversity. We used a combination of mitochondrial DNA D-loop region (596 bp) polymorphisms and 23 microsatellite markers. RWBs (n = 130) were collected from 18 locations on Iriomote Island and compared with 66 reference samples of European and Asian domestic pigs. We identified six distinct haplotypes, involving 22 single nucleotide polymorphisms (including one insertion) in the RWB population. The phylogenetic tree had two branches: the RWB group and domestic lineage. Fourteen of 130 RWBs (10.8%) belonged to the European domestic lineage, including 11 RWBs from the Panari Islands, northwest of Iriomote Main Island (IMI). The heterozygosity values, total number of alleles, number of effective alleles and polymorphism information content of the RWB groups were lower than those of the European domestic groups. The RWB population on IMI had a lower heterozygous deficiency index (FIS = 0.059) than did the other populations, which indicates that this population was more inbred. There was a large genetic distance (FST = 0.560) between RWBs on IMI and the Meishan populations. Structure analysis using the 23 microsatellite markers revealed that 16 RWBs had an admixture pattern between RWB and domesticated pig breeds. These results suggest that gene flow may have occurred from domestic pigs to RWBs and demonstrate that there was low genetic variation in the IMI population.


Assuntos
DNA Mitocondrial/genética , Fluxo Gênico , Repetições de Microssatélites , Polimorfismo Genético , Sus scrofa/genética , Animais , Japão , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase/veterinária , Análise de Sequência de DNA/veterinária , Especificidade da Espécie , Sus scrofa/metabolismo
4.
Microsyst Nanoeng ; 9: 55, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37180456

RESUMO

Various soft actuators have been investigated to overcome the drawbacks of conventional solid machines and explore the applications of soft robotics. In particular, and because they are expected to be applicable in minimally invasive medicine because of their safety, soft inflatable microactuators using an actuation conversion mechanism from balloon inflation to bending motion have been proposed for high-output bending motion. These microactuators could be applied to create an operation space by safely moving organs and tissues; however, the conversion efficiency could be further improved. This study aimed to improve conversion efficiency by investigating the design of the conversion mechanism. The contact conditions between the inflated balloon and conversion film were examined to improve the contact area for force transmission, with the contact area dependent on the length of the contact arc between the balloon and force conversion mechanism and on the amount of balloon deformation. In addition, surface contact friction between the balloon and film, which affects actuator performance, was also investigated. The generated force of the improved device is 1.21 N at 80 kPa when it bends 10 mm, which is 2.2 times the generated force of the previous design. This improved soft inflatable microactuator is expected to assist in performing operations in a limited space, such as in endoscopic or laparoscopic operations.

5.
Scand J Surg ; 99(4): 201-7, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21159588

RESUMO

BACKGROUND AND AIMS: The serum pepsinogen (Pg) test is considered to be a high-risk marker for gastric cancer, so that it is intended that it will be gradually adopted for mass surveys in Japan. This manuscript examines the characteristics of the preoperative Pg test and the relationship between its results and the postoperative outcomes of gastric cancer cases in relation to the neutrophil/lymphocyte ratio (NLR) as a prognostic -marker. MATERIALS AND METHODS: Peripheral blood samples were taken within 1 week before gastrectomy for the Pg test and NLR. RESULTS: The Pg test identified 128 (+) cases (59.0%) and 89 (-) cases (41.0%). In three of all cases, cancer had not been detected by an upper gastrointestinal series (UGI) in the previous year (every case showed Pg (+)). Five-year survival was 80.5% in the Pg (+) group, 60.7% in the Pg (-) group, 85.6% in the NLR (<5.0) group, and 29.9% in the NLR (5.0) group, but 14.3% in the NLR (5.0) plus Pg (-) group, and 89.5% in the NLR (<5.0) plus Pg (+) group. The differences in the 5-year survivals were statistically significant. CONCLUSIONS: A mass survey using the Pg test alone is inadequate, but the Pg test may be an important adjunct to the conventional methods. Gastric cancer with Pg (-) may have a higher potential for malignancy than cancer with Pg (+).


Assuntos
Pepsinogênio A/sangue , Neoplasias Gástricas/sangue , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Resultado do Tratamento
6.
Epidemiol Psychiatr Sci ; 28(6): 662-669, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30103836

RESUMO

AIMS: Death ideation (thinking about/wishing for one's own death, thinking that one would be better off dead) is linked to an increased mortality risk. However, comparatively little is known about more general thoughts of death (GTOD) where no wish to die or life value is expressed. This study examined whether GTOD predicted mortality in a community-based cohort of older adults. METHODS: Data came from the Komo-Ise cohort study in Gunma prefecture, Japan. The analytic sample comprised 8208 individuals (average age 61.3 (range 47-77)) who were asked in wave 2 of the study in 2000 if they had 'Thought about death more than usual, either your own, someone else's or death in general?' in the past 2 weeks. Death data were obtained from the municipal resident registration file. Cox proportional hazards regression analysis was used to examine associations. RESULTS: During the follow-up period (2000-2008), there were 672 deaths. In a model adjusted for baseline covariates, GTOD were significantly associated with all-cause mortality (hazards ratio 1.66, 95% confidence interval 1.20-2.29). Stratified analyses showed an association between GTOD and mortality in men, older subjects (⩾70 years), married individuals and those with higher social support. CONCLUSIONS: GTOD are associated with an increased mortality risk among older citizens in Japan. Research is now needed to determine the factors underlying this association and assess the clinical relevance of screening for GTOD in older individuals.


Assuntos
Morte , Mortalidade , Suicídio , Distribuição por Idade , Idoso , Causas de Morte , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Distribuição por Sexo , Apoio Social , Inquéritos e Questionários
7.
Acta Neurol Belg ; 108(4): 167-9, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19239048

RESUMO

We report a rare case of lumbar disc prolapse with intradural schwannoma at the same level. A 33-year-old man had had moderate right leg pain for about four years, which had worsened suddenly when he lifted heavy baggage. MR imaging revealed lumbar disc prolapse at L4/5. An intradural tumor that was iso-intense on T1-weighted and slightly hyperintense on T2-weighted images was also recognized at the same level. The tumor was homogeneously enhanced on Gadolinium-MRI (Gd-MRI). Intractable back and leg pain necessitated surgical treatment, which yielded a definitive diagnosis of the intradural tumor as schwannoma on histological examination. The intractable pain disappeared immediately after surgery. The patient's intractable and prolonged pain appeared to be due to combined compression by the intradural tumor and disc prolapse. The findings of Gadolinium-MRI were helpful in making the diagnosis.


Assuntos
Cauda Equina , Deslocamento do Disco Intervertebral/diagnóstico , Vértebras Lombares , Neurilemoma/diagnóstico , Neoplasias do Sistema Nervoso Periférico/diagnóstico , Diagnóstico Diferencial , Humanos , Deslocamento do Disco Intervertebral/fisiopatologia , Deslocamento do Disco Intervertebral/cirurgia , Imageamento por Ressonância Magnética , Masculino , Neurilemoma/fisiopatologia , Neurilemoma/cirurgia , Neoplasias do Sistema Nervoso Periférico/fisiopatologia , Neoplasias do Sistema Nervoso Periférico/cirurgia , Tomografia Computadorizada por Raios X , Adulto Jovem
8.
Nat Neurosci ; 4(12): 1207-16, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11704764

RESUMO

Metabotropic gamma-aminobutyric acid type B (GABAB) and glutamate receptors (mGluRs) are postsynaptically co-expressed at cerebellar parallel fiber (PF)-Purkinje cell (PC) excitatory synapses, but their functional interactions are unclear. We found that mGluR1 agonist-induced currents and [Ca2+]i increases in PCs were enhanced following co-activation of GABAB receptors. A GABAB antagonist and a G-protein uncoupler suppressed these effects. Low-concentration baclofen, a GABAB agonist, augmented mGluR1-mediated excitatory synaptic current produced by stimulating PFs. These results indicate that postsynaptic GABAB receptors functionally interact with mGluR1 and enhance mGluR1-mediated excitatory transmission at PF-PC synapses. The interaction between the two types of metabotropic receptors provides a likely mechanism for regulating cerebellar synaptic plasticity.


Assuntos
Dendritos/metabolismo , Potenciais Pós-Sinápticos Excitadores/fisiologia , Terminações Pré-Sinápticas/metabolismo , Células de Purkinje/metabolismo , Receptores de GABA-B/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Transmissão Sináptica/fisiologia , Animais , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Dendritos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estimulação Elétrica , Inibidores Enzimáticos/farmacologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Agonistas GABAérgicos/farmacologia , Antagonistas GABAérgicos/farmacologia , Agonistas dos Receptores de GABA-B , Antagonistas de Receptores de GABA-B , Proteínas de Ligação ao GTP/antagonistas & inibidores , Proteínas de Ligação ao GTP/metabolismo , Ácido Glutâmico/metabolismo , Camundongos , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Terminações Pré-Sinápticas/efeitos dos fármacos , Células de Purkinje/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/farmacologia
9.
Nat Neurosci ; 3(6): 551-8, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10816310

RESUMO

A single neurotransmitter elicits diverse physiological responses through activation of multiple receptor subtypes and/or heterosynaptic interactions involving distinct synaptic targets. We found that a typical excitatory transmitter released from the climbing fiber (CF) in the cerebellar cortex not only excited Purkinje cells directly but also presynaptically inhibited GABAergic transmission from interneurons converging on the same Purkinje cells. Both homosynaptic and heterosynaptic actions of the CF transmitter (possibly glutamate) were mediated by activation of AMPA receptors. Dual AMPA receptor-mediated functions of excitation and disinhibition may ensure transmission of cerebellar CF signals controlling sensorimotor coordination.


Assuntos
Cerebelo/metabolismo , Interneurônios/metabolismo , Receptores de AMPA/metabolismo , Sinapses/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Membrana Celular/metabolismo , Cerebelo/citologia , Quelantes/farmacologia , Colforsina/farmacologia , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Estimulação Elétrica , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Técnicas In Vitro , Interneurônios/citologia , Microeletrodos , Fibras Nervosas/efeitos dos fármacos , Fibras Nervosas/metabolismo , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Técnicas de Patch-Clamp , Células de Purkinje/citologia , Células de Purkinje/efeitos dos fármacos , Células de Purkinje/metabolismo , Ratos , Ratos Wistar , Receptores de AMPA/antagonistas & inibidores , Ácido gama-Aminobutírico/farmacologia
10.
Nat Neurosci ; 1(1): 80-4, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-10195114

RESUMO

The Wisconsin Card Sorting Test, which probes the ability to shift attention from one category of stimulus attributes to another (shifting cognitive sets), is the most common paradigm used to detect human frontal lobe pathology. However, the exact relationship of this card test to prefrontal function and the precise anatomical localization of the cognitive shifts involved are controversial. By isolating shift-related signals using the temporal resolution of functional magnetic resonance imaging, we reproducibly found transient activation of the posterior part of the bilateral inferior frontal sulci. This activation was larger as the number of dimensions (relevant stimulus attributes that had to be recognized) were increased. These results suggest that the inferior frontal areas play an essential role in the flexible shifting of cognitive sets.


Assuntos
Atenção/fisiologia , Cognição/fisiologia , Córtex Pré-Frontal/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Córtex Pré-Frontal/anatomia & histologia , Reprodutibilidade dos Testes , Fatores de Tempo
11.
J Mol Biol ; 250(5): 659-71, 1995 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-7623383

RESUMO

The three-dimensional solution structure of omega-agatoxin IVA, which is a specific blocker of the P-type calcium channel isolated from funnel web spider venom and has a molecular mass of 5.2 kDa, was determined by two dimensional 1H NMR spectroscopy, combined with simulated annealing calculations. On the basis of 563 experimental constraints, including 516 distance constraints obtained from the nuclear Overhauser effect, 21 torsion angle (phi, chi 1) constraints, and 26 constraints associated with hydrogen bonds and disulfide bonds, a total of 14 converged structures were obtained. The atomic root mean square difference for the 14 converged structures with respect to the mean coordinates is 0.42 (+/- 0.07) A for the backbone atoms (N, C alpha, C) and 0.95 (+/- 0.15) A for all heavy atoms of the central part (residues 4 to 38) constrained by four disulfide bonds. The N- and C-terminal segments (residues 1 to 3 and 39 to 48, respectively) have a disordered structure in aqueous solution. The molecular structure of omega-agatoxin IVA is composed of a short triple-stranded antiparallel beta-sheet, three loops, and the disordered N- and C-terminal segments. The overall beta-sheet topology is +2x, -1, which is the same as that reported for omega-conotoxin GVIA, an N-type calcium channel blocker. Irrespective of differences in the number of disulfide bonds and low primary sequence homology, these two peptide toxins show a significant structural similarity in three dimensions. The whole-cell voltage-clamp recording using rat cerebellar slices suggests that the hydrophobic C-terminal segment of omega-agatoxin IVA, which does not exist in omega-conotoxin GVIA, plays a crucial role in the blocking action of omega-agatoxin IVA on the P-type calcium channel in rat cerebellar Purkinje cells. The present study provides a molecular basis for the toxin-channel interaction, and thereby provides insight into the discrimination of different subtypes of calcium channels.


Assuntos
Bloqueadores dos Canais de Cálcio/química , Venenos de Aranha/química , Sequência de Aminoácidos , Simulação por Computador , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Conformação Proteica , Dobramento de Proteína , Estrutura Secundária de Proteína , Soluções , Relação Estrutura-Atividade , ômega-Agatoxina IVA
12.
Aliment Pharmacol Ther ; 21 Suppl 2: 27-31, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15943843

RESUMO

BACKGROUND: Histamine 2-receptor antagonists were used as a first therapy against functional dyspepsia. However, few clinical studies with famotidine for functional dyspepsia have been reported. AIM: To evaluate the effectiveness of famotidine for functional dyspepsia patients. METHODS: A multicentre, randomized, double-blind, placebo-controlled crossover trail was conducted. Patients diagnosed with functional dyspepsia by the Roma II criteria were included. Subjects were randomized into two groups, and received either famotidine or placebo as the first 4 weeks medication. After a 1-week washout period, they were switched to the other regimen for another 4 weeks. Evaluation was made prior to the start of study, upon completion of the first drug cycle, and the second drug cycle, by Gastrointestinal Symptoms Rating Scale for the seriousness of abdominal symptoms, and by Short Form-36 for the level of quality of life. RESULTS: Nineteen of 21 enrolled patients successfully completed this study. Significant improvement in Gastrointestinal Symptoms Rating Scale scores was observed in abdominal pain (P = 0.007), indigestion and reflux syndrome after famotidine treatment. Also quality of life scores showed significant improvement in body pain, vitality and general health perceptions after famotidine treatment. There was no improvement of symptoms and quality of life scores after administration of placebo. CONCLUSIONS: Famotidine was effective for improving symptoms and quality of life in functional dyspepsia patients.


Assuntos
Antiulcerosos/uso terapêutico , Dispepsia/tratamento farmacológico , Famotidina/uso terapêutico , Adulto , Idoso , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento
13.
Cardiovasc Res ; 10(5): 599-604, 1976 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-971475

RESUMO

A protective effect of hyperbaric oxygen immediately after reopening of occluded coronary blood flow for the temporary ischaemic myocardial muscle was studied. Thirty dogs were used in this study, and 20 dogs were sacrificed after 4 h and 10 dogs were sacrificed after 5 d. Temporary occlusion of coronary artery (from 30 min to 2 h) was produced by ligation. One group were controls and the other group were a hyperbaric group in which dogs breathed 100% oxygen at an absolute pressure of 2 atmospheres before and after release of coronary ligation. The macroscopic extent of ischaemic area was studied by using nitroblue tetrazolium and microscopic and ECG findings were examined. By breathing oxygen at high pressure immediately after reopening of occluded coronary blood flow, the ischaemic area was markedly reduced. In such cases, some myocardial muscles around the arterioles and sinusoids, even when these vessels existed in the ischaemic area, were kept in a viable state. The repair of necrotic myocardial muscles was promoted histologically. Serious arrhythmia, especially ventricular fibrillation, was also well suppressed, and the stable haemodynamic conditions were obtained during operative procedures. No harmful side effects of hyperbaric oxygen were observed. One of the most effective treatments of acute myocardial infarction involves reconstruction of the occluded coronary artery as soon as possible after the onset of myocardial infarction by using these advantages of hyperbaric oxygen.


Assuntos
Doença das Coronárias/terapia , Oxigenoterapia Hiperbárica , Animais , Doença das Coronárias/patologia , Cães , Miocárdio/patologia , Tamanho do Órgão , Fatores de Tempo
14.
FEBS Lett ; 461(3): 315-8, 1999 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-10567718

RESUMO

Each amino acid in putative transmembrane helix VI and its flanking regions, from Ser-156 to Thr-185, of a Cys-free mutant of the Tn10-encoded metal-tetracycline/H(+) antiporter (TetA(B)) was individually replaced by Cys. All of the cysteine-scanning mutants showed a normal level of tetracycline resistance except for the S156C mutant, which showed moderate resistance, indicating that there is no essential residue located in this region. All 20 mutants from S159C to W178C showed no reactivity with N-ethylmaleimide (NEM), whereas the mutants of the flanking regions from S156C to H158C and F179C to T185C were highly or moderately reactive with NEM. These results indicate that like transmembrane helices III and IX, the transmembrane helix VI comprising residues Ser-159-Trp-178 is totally embedded in the hydrophobic environment.


Assuntos
Estrutura Secundária de Proteína , Sequência de Aminoácidos , Membrana Celular/química , Fenômenos Químicos , Físico-Química , Cisteína/química , Escherichia coli/efeitos dos fármacos , Etilmaleimida/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Conformação Proteica , Compostos de Sulfidrila/metabolismo , Resistência a Tetraciclina/genética
15.
Neuropharmacology ; 38(11): 1743-53, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10587090

RESUMO

The information processing at central synapses is mediated not only by homosynaptic transmission with direct synaptic connections but also by heterosynaptic interactions between distinct synaptic inputs. Using rat brain slices and whole-cell recordings this study aimed to examine the roles of GABA(B) receptors in synaptic interactions in the basolateral amygdala (BLA), a critical brain structure related to fear and anxiety. Stimulation in the BLA produced non-NMDA type glutamate receptor antagonist-sensitive excitatory postsynaptic currents (EPSCs) and bicuculline-sensitive inhibitory postsynaptic currents (IPSCs) in the BLA neurons. The GABA(B) receptor agonist baclofen markedly inhibited both EPSCs and IPSCs in a concentration-dependent manner, and the baclofen-induced inhibition was selectively abolished by the GABA(B) receptor antagonist CGP55845A. The paired-pulse ratio of EPSC and IPSC amplitude was increased by baclofen. The effect of baclofen was mimicked by lowering the external Ca2+ concentration but not by glutamate- and GABA(A)-receptor antagonists. The frequency but not the mean amplitude of miniature EPSCs and IPSCs was decreased by baclofen. The findings suggest that activation of GABA(B) receptors by baclofen reduces the strength of excitatory and inhibitory transmission in the BLA by a presynaptic mechanism. Repetitive conditioning stimulation applied to GABAergic synaptic inputs exerted an inhibitory action on glutamatergic excitatory transmission, and the stimulation-induced inhibition was abolished by CGP55845A. Furthermore, the paired-pulse ratio of EPSCs was increased during the stimulation-induced inhibition. The results in this study provide evidence that synaptic activation of GABA(B) heteroreceptors elicits presynaptic inhibition of glutamatergic excitatory transmission in the BLA.


Assuntos
Tonsila do Cerebelo/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Neurônios/fisiologia , Receptores de GABA-B/fisiologia , Receptores Pré-Sinápticos/fisiologia , Transmissão Sináptica/fisiologia , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Baclofeno/farmacologia , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Agonistas GABAérgicos/farmacologia , Antagonistas GABAérgicos/farmacologia , Neurônios/efeitos dos fármacos , Ácidos Fosfínicos/farmacologia , Propanolaminas/farmacologia , Ratos , Ratos Wistar , Receptores de GABA-B/efeitos dos fármacos , Receptores Pré-Sinápticos/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos
16.
Neuroscience ; 88(3): 871-83, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10363824

RESUMO

Long-term facilitation of neurotransmission by monoaminergic systems is implicated in the cellular mechanism of memory and learning-related processes at invertebrate synapses. Using whole-cell recording and rat cerebellar slices, we have examined whether mammalian monoamine-containing neurons play analogous roles in synaptic plasticity, and our results suggest that serotonin and noradrenaline are critically involved in short- and long-term modulation of GABAergic transmission in the cerebellar cortex. Exogenously applied serotonin and noradrenaline selectively induced a short-term enhancement of GABAergic transmission between cerebellar interneurons and Purkinje cells, their effect subsiding in 30 min. Successive amine applications converted this effect to long-term facilitation lasting more than 2 h. During the monoamine-induced short- and long-term facilitation, spontaneously occurring miniature inhibitory synaptic responses increased in frequency, without significant changes in their mean amplitude and amplitude distribution, as well as the GABA receptor sensitivity of Purkinje cells. The actions of the two amines on the inhibitory transmission were mimicked by forskolin and blocked by kinase inhibitors, H-7, H-89 and Rp-adenosine 3',5'-cyclic monophosphothioate. Thus, serotonin and noradrenaline are likely to activate cyclic-AMP- and protein kinase-dependent pathways in GABAergic interneurons, thereby reinforcing the inhibitory transmission on to Purkinje cells. Repetitive electrical stimulation within the molecular layer mimicked the facilitatory effect induced by exogenous monoamines: namely, neural stimulation selectively elicited long-lasting enhancement of GABAergic transmission in a manner sensitive to the monoamine receptor antagonists, methiothepin and propranolol, and an uptake inhibitor, imipramine. Synaptically released monoamines thus appear to induce cyclic-AMP- and protein kinase-dependent long-term facilitation of cerebellar GABAergic transmission, thereby providing a likely mechanism of synaptic plasticity associated with motor coordination within the mammalian cerebellar system.


Assuntos
Cerebelo/fisiologia , Potenciação de Longa Duração/fisiologia , Plasticidade Neuronal , Células de Purkinje/fisiologia , Receptores de GABA/fisiologia , Sulfonamidas , Sinapses/fisiologia , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/fisiologia , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Colforsina/farmacologia , AMP Cíclico/análogos & derivados , AMP Cíclico/farmacologia , Estimulação Elétrica , Inibidores Enzimáticos/farmacologia , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Técnicas In Vitro , Isoquinolinas/farmacologia , Potenciação de Longa Duração/efeitos dos fármacos , Metiotepina/farmacologia , Norepinefrina/farmacologia , Propranolol/farmacologia , Inibidores de Proteínas Quinases , Células de Purkinje/efeitos dos fármacos , Ratos , Ratos Wistar , Serotonina/farmacologia , Sinapses/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Tetrodotoxina/farmacologia , Tionucleotídeos/farmacologia , Ácido gama-Aminobutírico/farmacologia
17.
Neuroscience ; 7(9): 2025-37, 1982.
Artigo em Inglês | MEDLINE | ID: mdl-6183613

RESUMO

Electrophysiological and neurochemical experiments were carried out to examine a possible transmitter role substance P in the prevertebral ganglia of the guinea-pig. When potentials were recorded intracellularly from neurons of the isolated ganglia, stimulation of the pre- or postganglionic nerves elicited a non-cholinergic slow excitatory postsynaptic potential (EPSP). This synaptic potential was compared with the effects of substance P. Brief application of substance P caused a depolarization of the ganglion cells with a similar time course to that of the non-cholinergic slow EPSP. Changes in membrane resistance during the substance P-induced depolarization resembled those associated with the non-cholinergic slow EPSP. During the substance P-induced depolarization the non-cholinergic slow EPSP was markedly depressed. Attempts were made to determine the origin of the fibers eliciting the non-cholinergic slow EPSP. In the inferior mesenteric ganglia isolated together with preganglionic nerves that retained intact connections with spinal nerve roots, dorsal root stimulation evoked a non-cholinergic slow EPSP but not a cholinergic fast EPSP in the ganglion cells, whereas ventral root stimulation caused only cholinergic fast EPSPs. Following the prolonged treatment with capsaicin, the non-cholinergic slow EPSP was greatly depressed or abolished. Radioimmunoassay revealed that after ligation or section of pre- or postganglionic nerves an accumulation of substance P occurred in the proximal stumps of the interrupted nerves. Stimulation with high potassium medium evoked a release of immunoreactive substance P from the prevertebral ganglia and the release was calcium-dependent. The present findings suggests that axon collaterals of certain visceral primary efferents form synapses with principal cells in the prevertebral ganglia and release substance P as a transmitter for the non-cholinergic slow EPSP.


Assuntos
Gânglios Simpáticos/fisiologia , Substância P/fisiologia , Transmissão Sináptica , Fibras Adrenérgicas/fisiologia , Vias Aferentes/fisiologia , Animais , Fibras Autônomas Pré-Ganglionares/fisiologia , Transporte Axonal/efeitos dos fármacos , Capsaicina/farmacologia , Fibras Colinérgicas/fisiologia , Potenciais Evocados/efeitos dos fármacos , Gânglios Espinais/fisiologia , Cobaias , Masculino , Neurônios/fisiologia , Potássio/farmacologia , Radioimunoensaio , Substância P/administração & dosagem , Sinapses/fisiologia , Transmissão Sináptica/efeitos dos fármacos
18.
Neuroscience ; 74(3): 845-53, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8884780

RESUMO

Substance P is known to elicit diverse actions via activating multiple subtypes of tachykinin receptors, and these actions appear to be involved not only in synaptic transmission but also in synaptic plasticity during development of the mammalian central nervous system. The availability of sensitive quantitation of individual tachykinin receptor subtypes is crucial for elucidating the physiological function specifically mediated by activation of a particular receptor subtype. We thus attempted to develop an assay to determine the level of messenger RNA molecule encoding the neurokinin-1-type tachykinin receptor and apply it for assessment of developmental changes in the neurokinin-1 receptor gene expression in the rat brain to explore the role of tachykinin receptors during ontogeny. The assay was designed to use a competitive reverse transcription-polymerase chain reaction co-amplifying endogenous neurokinin-1 receptor messenger RNA and internal standard, which enabled specific quantification of the number of neurokinin-1 receptor transcripts, ranging from 3.1 x 10(3) to 1.3 x 10(5) molecules/microgram total RNA. The levels of neurokinin-1 receptor gene expression were examined in three different brain regions of the rat aged 0-56 days after birth. The order of neurokinin-1 receptor messenger RNA expression was hippocampus > cerebral cortex > > cerebellum at all ages examined except postnatal day 0, where its expression was more abundant in the cerebral cortex than in the hippocampus. From postnatal day 3 onward, the hippocampus contained 140-160% of the cortical levels. Although the tachykinin receptor expression in the cerebellum was too low to be accurately assessed by conventional techniques, our assay enabled us to determine the amount of cerebellar neurokinin-1 receptor messenger RNA that changed in the range 7-23% of the cortical level during postnatal development. A prominent feature revealed by this assay is that the neurokinin-1 receptor gene expression in the rat brain is developmentally regulated. The hippocampus displayed a transient peak of neurokinin-1 receptor messenger RNA at postnatal day 3 and a subsequent gradual decrease. In the cerebral cortex, the amount of the message was highest at birth, and was followed by a moderate decrease during postnatal development. At 56 days after birth, the expression levels in both brain regions were down-regulated to approximately 50% of their maximal levels. The transitory pattern of gene expression was also observed in the cerebellum. The results of this study demonstrate that the reverse transcription-polymerase chain reaction-based assay is useful to quantitate precisely the neurokinin-1 tachykinin receptor message in limited tissue samples derived from discrete brain regions. Together with previous findings, the increased level of neurokinin-1 receptor messenger RNA expression in immature rat brain shown by the present analysis suggests that the neurokinin-1-type tachykinin receptor may play a role in the synaptic plasticity associated with morphological and functional development of the mammalian CNS.


Assuntos
Envelhecimento/metabolismo , Encéfalo/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Receptores da Neurocinina-1/biossíntese , Transcrição Gênica , Animais , Animais Recém-Nascidos , Encéfalo/crescimento & desenvolvimento , Cerebelo/metabolismo , Córtex Cerebral/metabolismo , Primers do DNA , Hipocampo/metabolismo , Especificidade de Órgãos , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Receptores da Neurocinina-1/análise , Sensibilidade e Especificidade
19.
Neuroscience ; 93(4): 1475-82, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10501472

RESUMO

Subcellular localization of the 67,000 mol. wt isoform of glutamate decarboxylase and neurotransmitter function of GABA were investigated in the cerebellum of the mice lacking the 65,000 mol. wt isoform of glutamate decarboxylase. The GABA content decreased by 25% in the cerebellum. Putative GABA-releasing terminals from basket/stellate and Golgi cells were immunostained with glutamate decarboxylase-67 antibody. Basket cell-derived inhibitory postsynaptic currents in Purkinje cells and the high potassium-induced release of GABA were not significantly affected. Although previous investigations have suggested that glutamate decarboxylase-65 is mainly involved in transmitter synthesis and that glutamate decarboxylase-67 is transported to the nerve terminals only after association with glutamate decarboxylase-65, the present results indicate that glutamate decarboxylase-67 is independently concentrated in the nerve terminals and provides GABA for synaptic transmission in the absence of glutamate decarboxylase-65.


Assuntos
Glutamato Descarboxilase/análise , Isoenzimas/análise , Sinapses/enzimologia , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/fisiologia , Animais , Espaço Extracelular/química , Espaço Extracelular/efeitos dos fármacos , Glutamato Descarboxilase/química , Glutamato Descarboxilase/genética , Isoenzimas/química , Camundongos , Camundongos Mutantes , Microdiálise , Microscopia Confocal , Microscopia Imunoeletrônica , Peso Molecular , Técnicas de Patch-Clamp , Potássio/farmacologia , Células de Purkinje/química , Células de Purkinje/enzimologia , Células de Purkinje/ultraestrutura , Sinapses/ultraestrutura , Ácido gama-Aminobutírico/análise
20.
J Nucl Med ; 36(11): 1934-40, 1995 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7472578

RESUMO

UNLABELLED: Myocardial damage caused by vasospastic angina (VSA) may be detected by [123I]BMIPP, a beta-methyl-branched fatty acid. We investigated whether BMIPP could be used in the diagnosis and follow-up of patients with VSA. METHODS: Thirty-two patients with VSA were studied with resting BMIPP-SPECT in comparison to stress perfusion imaging with either 201Tl or 99mTc-MIBI. During coronary arteriography, spasm was induced by provocative testing with acetylcholine or ergonovine, and only total or subtotal occlusion was considered positive. Decreased BMIPP uptake was semiquantitatively evaluated segmentally aided by polar map display. RESULTS: Reduced BMIPP uptake was observed in 25 of 32 patients (78%), with complete or partial agreement between the BMIPP abnormality and coronary territory seen in 23 patients (72%). In contrast, a perfusion abnormality was seen in only 10 patients (31%). In the repeat BMIPP study (n = 23) during the follow-up period (average 206 days), 11 of 14 patients who showed BMIPP improvement also had improved angina attacks. Conversely, two of nine patients with nonimproved BMIPP showed improved symptoms (p < 0.05). CONCLUSION: BMIPP can detect myocardial injury associated with VSA and may be useful in monitoring response to treatment.


Assuntos
Angina Pectoris Variante/diagnóstico por imagem , Ácidos Decanoicos , Ácidos Graxos , Coração/diagnóstico por imagem , Radioisótopos do Iodo , Iodobenzenos , Tomografia Computadorizada de Emissão de Fóton Único , Acetilcolina , Angina Pectoris Variante/diagnóstico , Cateterismo Cardíaco , Angiografia Coronária , Ergonovina , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tecnécio Tc 99m Sestamibi , Radioisótopos de Tálio , Fatores de Tempo
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