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1.
Eur J Pain ; 19(8): 1186-96, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25808188

RESUMO

BACKGROUND: Although there is some evidence that massage therapy, especially compression at myofascial trigger points (MTrPs), is effective for sub-acute and chronic low back pain, the effectiveness of massage therapy with compression at MTrPs for acute low back pain has not been studied. METHODS: To evaluate the effectiveness of compression at MTrPs for acute low back pain, 63 patients with acute low back pain were randomly assigned to one of three groups: the MTrP group who received compression at MTrPs (N = 23), the non-MTrP group who received compression at non-trigger points (N = 21), and the effleurage massage group who received superficial massage (N = 19). The patients received the assigned treatment 3 times/week for 2 weeks. The subjective pain intensity in static and dynamic conditions and disability caused by low back pain were measured by the visual analogue scale (VAS) and Roland-Morris questionnaire (RMQ), respectively; along with the range of motion (ROM) at the lumbar region and pressure pain threshold (PPT) at trigger points before treatment (baseline), 1 week after the start of treatment, and 1 month after the end of treatment (follow-up). RESULTS: Static and dynamic VAS score, PPT and ROM were significantly improved in the MTrP group compared with those in the non-MTrP and effleurage groups. CONCLUSIONS: These results indicate that compression at MTrPs is effective to treat acute low back pain compared with compression at non-MTrPs and superficial massage. For this article, a commentary is available at the Wiley Online Library.


Assuntos
Dor Lombar/terapia , Massagem , Pontos-Gatilho , Doença Aguda , Adolescente , Adulto , Idoso , Povo Asiático , Determinação de Ponto Final , Feminino , Humanos , Masculino , Artes Marciais/lesões , Massagem/efeitos adversos , Pessoa de Meia-Idade , Medição da Dor , Limiar da Dor , Amplitude de Movimento Articular , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
2.
Neuroscience ; 119(2): 517-32, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12770565

RESUMO

To elucidate the brain mechanisms to encode sequential events, event-related potentials (ERPs) were recorded during a sound-sequence discrimination task using young and middle-aged adult subjects. In the task, a series of six or 12 kinds of natural sounds were sequentially presented; 70-80% of the stimuli were presented in a fixed order (Non-target), but the remaining stimuli, in a random order (Target). The subjects were instructed to detect the Targets and press a button at the end of each Target. In a control task, the same sounds were randomly presented (Control), and they were instructed to press the button at the end of each sound. Behavioral results indicated that the young subjects learned the task faster than did the middle-aged subjects. Positive ERP waves were evoked by Targets and Non-targets in the parieto-occipital area around 300-700 ms after stimulus onset. The mean amplitudes during this period in the young subjects were larger in Target than Control conditions, and those in Target condition were larger in the young than middle-aged subjects. Furthermore, the mean amplitudes in the Target condition were significantly correlated with behavioral performance. Equivalent dipoles for the ERPs evoked by Targets were estimated in the medial temporal lobe including the hippocampal formation and parahippocampal gyrus. The results suggest that the ERPs around 300-700 ms latency are involved in sound-sequence information processing. Furthermore, decrease in amplitudes of this positivity in the middle-aged subjects suggests that age-related memory decline is associated with deficits in encoding and retrieval of unfamiliar sequence.


Assuntos
Envelhecimento/fisiologia , Percepção Auditiva/fisiologia , Discriminação Psicológica/fisiologia , Som , Lobo Temporal/fisiologia , Estimulação Acústica , Adulto , Algoritmos , Análise de Variância , Mapeamento Encefálico , Eletroencefalografia , Potenciais Evocados Auditivos , Humanos , Pessoa de Meia-Idade , Lobo Occipital/fisiologia , Lobo Parietal/fisiologia
3.
Nihon Rinsho ; 59(9): 1733-7, 2001 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-11554044

RESUMO

Peripheral vascular pain consists of complex factors, and may be divided into three types, i.e., arterial pain, microvessel pain and venous pain. Among these, arterial pain requires intensive pain control because of severe ischemic pain due to arterial obstruction. Under ischemic condition, adenosine is generated, and activates unmyelinated afferents to produce pain. In addition to adenosine, acidic pH itself produces pain and sensitization to mechanical stimuli. Moreover bradykinin generated by kallikurein in acidic pH can produce pain. Nerve block is indicated to improve tissue circulation and to relieve pain. Endoscopic thoracic sympathectomy is indicated for upper extremities, and high frequency thermocoagulation is applied for lumbar sympathectomy. Spinal cord stimulation and the gene therapy with vascular endothelial growth factor have also been reported effective.


Assuntos
Dor , Doenças Vasculares/complicações , Terapia por Estimulação Elétrica , Terapia Genética , Humanos , Bloqueio Nervoso , Dor/etiologia , Manejo da Dor , Inibidores da Agregação Plaquetária/uso terapêutico , Medula Espinal , Doenças Vasculares/tratamento farmacológico , Vasodilatadores/uso terapêutico
4.
Biophys J ; 81(4): 1831-40, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11566758

RESUMO

Effects of adding monovalent alkali metal cations to Ca(2+)-depleted photosystem (PS)II membranes on the biochemical and spectroscopic properties of the oxygen-evolving complex were studied. The Ca(2+)-dependent oxygen evolution was competitively inhibited by K(+), Rb(+), and Cs(+), the ionic radii of which are larger than the radius of Ca(2+) but not inhibited significantly by Li(+) and Na(+), the ionic radii of which are smaller than that of Ca(2+). Ca(2+)-depleted membranes without metal cation supplementation showed normal S(2) multiline electron paramagnetic resonance (EPR) signal and an S(2)Q(A)(-) thermoluminescence (TL) band with a normal peak temperature after illumination under conditions for single turnover of PSII. Membranes supplemented with Li(+) or Na(+) showed properties similar to those of the Ca(2+)-depleted membranes, except for a small difference in the TL peak temperatures. The peak temperature of the TL band of membranes supplemented with K(+), Rb(+), or Cs(+) was elevated to approximately 38 degrees C which coincided with that of Y(D)(+)Q(A)(-) TL band, and no S(2) EPR signals were detected. The K(+)-induced high-temperature TL band and the S(2)Q(A)(-) TL band were interconvertible by the addition of K(+) or Ca(2+) in the dark. Both the Ca(2+)-depleted and the K(+)-substituted membranes showed the narrow EPR signal corresponding to the S(2)Y(Z)(+) state at g = 2 by illuminating the membranes under multiple turnover conditions. These results indicate that the ionic radii of the cations occupying Ca(2+)-binding site crucially affect the properties of the manganese cluster.


Assuntos
Cálcio/metabolismo , Manganês/metabolismo , Oxirredutases/metabolismo , Oxigênio/metabolismo , Potássio/metabolismo , Cátions/química , Cátions/metabolismo , Cátions/farmacologia , Espectroscopia de Ressonância de Spin Eletrônica , Luminescência , Metais Alcalinos/química , Metais Alcalinos/metabolismo , Metais Alcalinos/farmacologia , Oxirredução/efeitos dos fármacos , Oxirredutases/efeitos dos fármacos , Complexo de Proteínas do Centro de Reação Fotossintética/metabolismo , Complexo de Proteína do Fotossistema II , Potássio/farmacologia , Spinacia oleracea
5.
Nature ; 412(6846): 546-9, 2001 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-11484055

RESUMO

Reward is important for shaping goal-directed behaviour. After stimulus-reward associative learning, an organism can assess the motivational value of the incoming stimuli on the basis of past experience (retrospective processing), and predict forthcoming rewarding events (prospective processing). The traditional role of the sensory thalamus is to relay current sensory information to cortex. Here we find that non-primary thalamic neurons respond to reward-related events in two ways. The early, phasic responses occurred shortly after the onset of the stimuli and depended on the sensory modality. Their magnitudes resisted extinction and correlated with the learning experience. The late responses gradually increased during the cue and delay periods, and peaked just before delivery of the reward. These responses were independent of sensory modality and were modulated by the value and timing of the reward. These observations provide new evidence that single thalamic neurons can code for the acquired significance of sensory stimuli in the early responses (retrospective coding) and predict upcoming reward value in the late responses (prospective coding).


Assuntos
Neurônios/fisiologia , Recompensa , Tálamo/fisiologia , Animais , Eletrofisiologia , Aprendizagem/fisiologia , Masculino , Modelos Neurológicos , Vias Neurais , Neurônios Aferentes/fisiologia , Ratos , Ratos Wistar , Tálamo/anatomia & histologia
6.
Cancer ; 91(12): 2378-85, 2001 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-11413528

RESUMO

BACKGROUND: The goal of the current study was use metaanalysis to evaluate the effect of postoperative adjuvant chemotherapy after resection of hepatocellular carcinoma (HCC), especially in cirrhotic patients. METHODS: One hundred-eight patients with radical resection of HCC were included in 1 of 3 prospective randomized control studies that used different postoperative chemotherapy protocols. Fifty-one patients underwent resection alone, and 57 patients received postoperative adjuvant chemotherapy. The first protocol was intraarterial epirubicin (40 mg/m(2)) at 1 month after surgery followed by oral tegafur (300 mg/day) for 1 year. The second protocol was intraarterial epirubicin (40 mg/m(2)) at 1 month after resection followed by intravenous epirubicin (40 mg/m(2)) every 3 months for 2 years. Additionally, carmofur 300 mg/day was administered for 2 years. The third protocol was intravenous epirubicin (40 mg/m(2)) every 2 months starting 1 month after surgery for 1 year. RESULTS: There were no significant differences in clinicopathologic background in each of the three protocols between the groups with and without chemotherapy. Postoperative chemotherapy using the current protocols failed to improve patient outcome in all patients and failed to improve disease-free and overall survival in any patients who were included in individual protocols. In patients with cirrhosis, postoperative chemotherapy was associated with significantly worse disease-free (P = 0.0376) and overall survival rates (P = 0.0077). CONCLUSIONS: The current study indicated that cancer recurrence in the remnant liver is enhanced and the long-term outcome is deteriorated by postoperative chemotherapy after resection of HCC in cirrhotic patients.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Antibióticos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Quimioterapia Adjuvante/efeitos adversos , Terapia Combinada , Esquema de Medicação , Tolerância a Medicamentos , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Hepatectomia , Humanos , Cirrose Hepática/complicações , Masculino , Análise Multivariada , Recidiva Local de Neoplasia , Prognóstico , Taxa de Sobrevida , Tegafur/administração & dosagem , Resultado do Tratamento
7.
Gan To Kagaku Ryoho ; 28(5): 693-6, 2001 May.
Artigo em Japonês | MEDLINE | ID: mdl-11383220

RESUMO

A 69-year-old-man was referred to our hospital because of rectal cancer with multiple liver metastases. He was initially treated by hepatic arterial chemotherapy using an infusion reservoir (HACR) and radiotherapy for the rectal cancer. An abdomino-perineal resection and extended left lobectomy of the liver were performed and resulted in a reduction in size of the liver tumor. He was diagnosed as having a recurrent liver metastasis (S7) at 3 months after the operation, and was retreated by HACR in the outpatient clinic. A partial hepatectomy was reperformed at 6 months after the operation. Adjuvant hepatic arterial infusion chemotherapy (HAIC) was performed on an outpatient basis and the patient is doing well without recurrence or relapse. Preoperative arterial chemotherapy for metastatic liver tumor may be of some benefit for certain patients with far advanced colorectal carcinoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hepatectomia , Neoplasias Hepáticas/secundário , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Reto/cirurgia , Idoso , Cisplatino/administração & dosagem , Terapia Combinada , Esquema de Medicação , Fluoruracila/administração & dosagem , Hepatectomia/métodos , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Leucovorina/administração & dosagem , Neoplasias Hepáticas/cirurgia , Masculino , Prognóstico , Neoplasias Retais/patologia
8.
Hinyokika Kiyo ; 47(1): 11-4, 2001 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-11235214

RESUMO

From January 1993 to June 1998, 319 cases were histopathologically diagnosed as prostatic cancer. In 7 of the 319 cases (2.2%) transurethral resection of the prostate (TUR-P) had been performed and a diagnosis of benign prostatic hyperplasia had been made with the resected specimens. The interval between TUR-P and the diagnosis of prostatic cancer ranged from 22 months to 15 years. All the cases showed an elevation of the prostate specific antigen (PSA) value (6.4-399 ng/ml, Tandem-R: RIA) at the time of cancer diagnosis. In 2 cases, PSA was measured in cancer screening. The clinical stage was stage B1 in 2 cases, stage B2 in 2 and D2 in 3. Only one case had been regularly followed-up after TUR-P, in which cancer was diagnosed by needle biopsy 22 months after TUR-P, because of the sustained high PSA values. Since most of such patients have an advanced stage of prostate cancer, it is of importance to have periodical follow-up examinations after TUR-P. The measurement of PSA appears the most reliable means in this way.


Assuntos
Hiperplasia Prostática/cirurgia , Neoplasias da Próstata/diagnóstico , Ressecção Transuretral da Próstata , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Fatores de Tempo
9.
Planta Med ; 67(1): 24-8, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11270716

RESUMO

The leaves of Perilla frutescens (perilla) are a common herb used in Japan for garnishing raw seafood. Previously, we reported that a decoction of perilla leaves had suppressive effects on the progression of glomerulonephritis in an animal model of spontaneous IgA nephropathy. The objective of the present study was to isolate anti-nephritic constituents in the perilla decoction under the guidance of its in vitro anti-proliferative activity on cultured murine mesangial cells, and to measure the contents of the active constituents in decoctions prepared from various perilla chemotypes, which differ in their composition of essential oils and/or pigments. DNA synthesis of cultured mesangial cells induced by 1% fetal calf serum was significantly inhibited by the perilla decoction (IC50 values, 8.8 microg/ml). Caffeic acid, luteolin 7-O-[beta-glucuronosyl(1-->2)beta-glucuronide], apigenin 7-O-[beta-glucuronosyl(1-->2)beta-glucuronide], scutellarin, and rosmarinic acid were isolated as active constituents. The contents of these phenolic compounds were not significantly different among chemotypes of P. frutescens. Considering the relation between the contents in the perilla decoction and the activities of these compounds, rosmarinic acid represents the in vitro anti-proliferative effect of perilla decoction.


Assuntos
Divisão Celular/efeitos dos fármacos , Mesângio Glomerular/efeitos dos fármacos , Lamiaceae/química , Extratos Vegetais/farmacologia , Animais , Células Cultivadas , Mesângio Glomerular/citologia , Camundongos , Camundongos Endogâmicos BALB C , Óleos Voláteis/análise , Pigmentos Biológicos/análise , Extratos Vegetais/química
10.
Biol Pharm Bull ; 24(2): 172-5, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11217087

RESUMO

Leaves of Perilla frutescens var. crispa DECNE. (perilla, Labiatae) are used as a garnishing vegetable in East Asian countries as well as an herbal medicine prescribed in Kampo medicines such as Saiboku-to. A previous in vitro study revealed that a decoction of perilla leaves inhibits the proliferation of murine-cultured mesangial cells. In the present study, we evaluated the in vivo anti-proliferative effects of a perilla decoction using rat mesangio-proliferative glomerulonephritis induced by an intravenous injection of rabbit anti-rat thymocyte serum (ATS). Leaves of perilla were boiled, and the decoction was orally administered to the rats as drinking water at doses of 100 and 500 mg/kg/d from the day of ATS-injection (day 0) to day 8, when rats were sacrificed. In the histological evaluation, the total number of glomerular cells, proliferating cell nuclear antigen (PCNA) positive cells, and macrophage/monocyte antigen-positive cells in the glomerulus, was significantly decreased in perilla-treated rats. A significantly lower level of proliferation was induced by the serum of the perilla-treated rats than by that of the controls. These results suggest that the perilla decoction suppresses the proliferation of mesangial cells in vivo by an inhibition of the glomerular infiltration of macrophage/monocytes and of the production of circulating growth factors.


Assuntos
Divisão Celular/efeitos dos fármacos , Mesângio Glomerular/efeitos dos fármacos , Glomerulonefrite/patologia , Magnoliopsida/química , Extratos Vegetais/farmacologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Mesângio Glomerular/patologia , Masculino , Ratos , Ratos Wistar
11.
J Neurophysiol ; 84(6): 2844-58, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11110814

RESUMO

The present study investigated the effects of repeated cold stress on single neuron activity in the lateral hypothalamic area (LHA) and medial hypothalamic area (MHA) of behaving rats. The rats were trained to lick a protruding spout in response to one of several cue-tone stimuli (CTSs) to ingest water, or amino acid, NaCl or glucose solution. Following this training, the rats were raised under either stressed (repeated temperature changes between -3 and 24 degrees C) or control (24 degrees C) condition for 2 mo. During this period, neuronal activity was recorded in the LHA and MHA. For rats raised under the stressed condition, mean spontaneous firing rate of LHA neurons was significantly greater than for rats under the control condition. More LHA neurons in the stressed rats responded, with an accompanying decrease in activity (inhibitory response), to CTSs than in the control rats. During extinction learning, some LHA neurons enhanced or reversed the responses to CTSs in the stressed rats, whereas no LHA neurons showed such response changes in the control rats. In contrast to the effects of the stressed condition on LHA neuron activity, mean spontaneous firing rate of MHA neurons in the stressed rats was significantly smaller than in the control rats. Fewer MHA neurons in the stressed rats responded to CTSs and/or ingestion of sapid solutions. The preceding results suggested that repeated cold stress produces a specific pattern of changes in spontaneous activity and responses to sensory stimuli in LHA and MHA neurons; this could underlie the behavioral changes induced by repeated cold stress such as hyperphagia and hyper-reactivity to sensory stimuli.


Assuntos
Temperatura Baixa , Condicionamento Operante/fisiologia , Hipotálamo/fisiologia , Neurônios/fisiologia , Estresse Fisiológico , Estimulação Acústica , Potenciais de Ação/fisiologia , Aminoácidos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Condicionamento Operante/efeitos dos fármacos , Sinais (Psicologia) , Aprendizagem por Discriminação/efeitos dos fármacos , Aprendizagem por Discriminação/fisiologia , Eletrodos Implantados , Hipotálamo/citologia , Masculino , Plasticidade Neuronal/fisiologia , Neurônios/citologia , Ratos , Ratos Wistar , Cloreto de Sódio/farmacologia , Glutamato de Sódio/farmacologia , Hábitos Linguais
12.
Physiol Behav ; 69(4-5): 511-25, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10913791

RESUMO

Effects of hippocampal lesions and aging on spatial learning and memory and ameliorating effects of red ginseng on learning deficits were investigated in the following two experiments: performance of young rats with selective hippocampal lesions with red ginseng by mouth (p.o.; Experiment 1) and aged rats with red ginseng (p.o.; Experiment 2) in the spatial tasks was compared with that of sham-operated or intact young rats. Each rat in these two behavioral experiments was tested with the three types of spatial-learning tasks (distance movement task, DMT; random-reward place search task, RRPST; and place-learning task, PLT) in a circular open field using intracranial self-stimulation as reward. The results in the DMT and RRPST tasks indicated that motivational and motor activity of young rats with hippocampal lesions with and without ginseng were not significantly different from that of sham-operated young rats in Experiment 1. However, young rats with hippocampal lesions displayed significant deficits in the PLT task. Treatment with red ginseng significantly ameliorated place-navigation deficits in young rats with hippocampal lesions on the PLT task. Similarly, red ginseng improved performance of aged rats on the PLT task in Experiment 2. The results, along with previous studies showing significant effects of red ginseng on the central nervous system, suggest that red ginseng ameliorates learning and memory deficits through effects on the central nervous system, partly through effects on the hippocampal formation.


Assuntos
Envelhecimento/fisiologia , Medicamentos de Ervas Chinesas/farmacologia , Hipocampo/efeitos dos fármacos , Orientação/fisiologia , Panax , Plantas Medicinais , Comportamento Espacial/efeitos dos fármacos , Análise de Variância , Animais , Aprendizagem por Associação/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Estimulação Elétrica , Eletrodos Implantados , Hipocampo/irrigação sanguínea , Hipocampo/patologia , Hipocampo/fisiologia , Ataque Isquêmico Transitório , Masculino , Memória/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Autoestimulação/efeitos dos fármacos
13.
J Biol Chem ; 275(40): 31145-54, 2000 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-10878006

RESUMO

A p21(Cip1/Waf1/Sdi1) is known to act as a negative cell-cycle regulator by inhibiting kinase activity of a variety of cyclin-dependent kinases. In addition to binding of the cyclin-dependent kinase to the N-terminal region of p21, p21 is also bound at its C-terminal region by proliferating cell nuclear antigen (PCNA), SET/TAF1, and calmodulin, indicating the versatile function of p21. In this study, we cloned cDNA encoding a novel protein named TOK-1 as a p21 C-terminal-binding protein by a two-hybrid system. Two splicing isoforms of TOK-1, TOK-1alpha and TOK-1beta, comprising 322 and 314 amino acids, respectively, were co-localized with p21 in nuclei and showed a similar expression profile to that of p21 in human tissues. TOK-1alpha, but not TOK-1beta, directly bound to the C-terminal proximal region of p21, and both were expressed at the G(1)/S boundary of the cell cycle. TOK-1alpha also preferentially bound to an active form of cyclin-dependent kinase 2 (CDK2) via p21, and these made a ternary complex in human cells. Furthermore, the results of three different types of experiments showed that TOK-1alpha enhanced the inhibitory activity of p21 toward histone H1 kinase activity of CDK2. TOK-1alpha is thus thought to be a new type of CDK2 modulator.


Assuntos
Quinases relacionadas a CDC2 e CDC28 , Proteínas de Ligação ao Cálcio , Proteínas de Transporte/genética , Proteínas de Ciclo Celular , Quinases Ciclina-Dependentes/metabolismo , Ciclinas/metabolismo , Proteínas Nucleares , Proteínas Serina-Treonina Quinases/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Células COS , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Ciclo Celular , Linhagem Celular , Núcleo Celular/metabolismo , Clonagem Molecular , Códon de Terminação , Quinase 2 Dependente de Ciclina , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/química , DNA Complementar/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Glutationa Transferase/metabolismo , Células HeLa , Humanos , Modelos Genéticos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Fosfotransferases/metabolismo , Plasmídeos/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ligação Proteica , Isoformas de Proteínas , Estrutura Terciária de Proteína , Proteínas Recombinantes/metabolismo , Fatores de Tempo , Distribuição Tecidual , Técnicas do Sistema de Duplo-Híbrido
14.
J Med Chem ; 43(10): 2040-8, 2000 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-10821716

RESUMO

Various 1,2-isothiazolidine-1,1-dioxide (gamma-sultam) derivatives containing an antioxidant moiety, 2,6-di-tert-butylphenol substituent, were prepared. Some compounds, which have a lower alkyl group at the 2-position of the gamma-sultam skeleton, showed potent inhibitory effects on both cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO), as well as production of interleukin (IL)-1 in in vitro assays. They also proved to be effective in several animal arthritic models without any ulcerogenic activities. Among these compounds, (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1, 2-isothiazolidine-1,1-dioxide (S-2474) was selected as an antiarthritic drug candidate and is now under clinical trials. The structure-activity relationships (SAR) examined and some pharmacological evaluations are described.


Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Artrite/tratamento farmacológico , Óxidos S-Cíclicos/síntese química , Isoenzimas/farmacologia , Inibidores de Lipoxigenase , Prostaglandina-Endoperóxido Sintases/farmacologia , Tiazóis/síntese química , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Experimental/tratamento farmacológico , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Óxidos S-Cíclicos/efeitos adversos , Óxidos S-Cíclicos/uso terapêutico , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/uso terapêutico , Dinoprostona/antagonistas & inibidores , Dinoprostona/biossíntese , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Mucosa Gástrica/efeitos dos fármacos , Humanos , Interleucina-1/antagonistas & inibidores , Interleucina-1/farmacologia , Leucotrieno B4/antagonistas & inibidores , Leucotrieno B4/biossíntese , Inibidores de Lipoxigenase/síntese química , Inibidores de Lipoxigenase/uso terapêutico , Masculino , Proteínas de Membrana , Ratos , Ratos Endogâmicos Lew , Relação Estrutura-Atividade , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Tiazóis/efeitos adversos , Tiazóis/uso terapêutico
15.
J Nutr ; 130(4S Suppl): 954S-9S, 2000 04.
Artigo em Inglês | MEDLINE | ID: mdl-10736360

RESUMO

The forebrain, including the amygdala (AM) and hypothalamus, may be a higher brain center that modulates the activity of a brainstem neural system that influences ingestive behavior via descending projections. In this study, to elucidate the characteristics of sensory information processing in the forebrain in relation to this putative connection, we recorded neuronal activity in the AM and hypothalamus [lateral hypothalamic area (LHA), medial hypothalamic area (MHA)] of rats during discrimination of conditioned sensory stimuli and the ingestion of various tastant solutions. Of 420 responsive AM neurons identified, 24 were taste responsive and located mainly in the central nucleus of the AM. Multivariate analyses of these taste neurons suggested that in the AM, taste quality is processed on the basis of palatability. In the hypothalamus, of 282 LHA and MHA neurons recorded, 144 responded to one or more conditioned auditory stimuli and/or licking of one or more solutions. Stress, which is known to influence feeding behavior, increased the mean spontaneous activity of LHA neurons but decreased the mean spontaneous neuronal activity of MHA neurons. This pattern of changes in spontaneous neuronal activity correlated with alterations in feeding behavior during stress. Furthermore, the activity of both AM and LHA neurons was modulated flexibly during conditioned associative learning. Together, the data suggest that the activity of the AM and hypothalamic neurons is altered when animals must modulate ingestive behavior by learning a new stimulus associated with food and by being exposed to stress, suggesting that these forebrain areas are important modulators of the activity of a basic neural system in the brainstem that influences ingestive behavior.


Assuntos
Tonsila do Cerebelo/fisiologia , Ingestão de Líquidos/fisiologia , Hipotálamo/fisiologia , Paladar/fisiologia , Estimulação Acústica , Tonsila do Cerebelo/citologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiopatologia , Animais , Condicionamento Psicológico/fisiologia , Discriminação Psicológica/fisiologia , Eletrofisiologia , Hipotálamo/citologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/fisiopatologia , Masculino , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Ratos , Ratos Wistar , Soluções/farmacologia , Estimulação Química , Estresse Fisiológico/fisiopatologia
16.
J Biol Chem ; 275(8): 5785-93, 2000 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-10681567

RESUMO

Mammalian secretory phospholipase A(2)s (sPLA(2)s) form a family of structurally related enzymes that are involved in a variety of physiological and pathological processes via the release of arachidonic acid from membrane phospholipids or the binding to specific membrane receptors. Here, we report the cloning and characterization of a novel sPLA(2) that is the sixth isoform of the sPLA(2) family found in humans. The novel human mature sPLA(2) consists of 123 amino acids (M(r) = 14,000) and is most similar to group IIA sPLA(2) (sPLA(2)-IIA) with respect to the number and positions of cysteine residues as well as overall identity (51%). Therefore, this novel sPLA(2) should be categorized into group II and called group IIE (sPLA(2)-IIE) following the recently identified group IID sPLA(2) (sPLA(2)-IID). The enzymatic properties of recombinant human sPLA(2)-IIE were almost identical to those of sPLA(2)-IIA and IID in terms of Ca(2+) requirement, optimal pH, substrate specificity, as well as high susceptibility to the sPLA(2) inhibitor indoxam. Along with the biochemical properties of proteins, genetic and evolutional similarities were also observed among these three types of group II sPLA(2)s as to the chromosomal location of the human gene (1p36) and the exon/intron organization. The expression of sPLA(2)-IIE transcripts in humans was restricted to the brain, heart, lung, and placenta in contrast to broad expression profiles for sPLA(2)-IIA and -IID. In sPLA(2)-IIA-deficient mice, the expression of sPLA(2)-IIE was markedly enhanced in the lung and small intestine upon endotoxin challenge, which contrasted with the reduced expression of sPLA(2)-IID mRNA. In situ hybridization analysis revealed elevation of sPLA(2)-IIE mRNA at alveolar macrophage-like cells in the lung of endotoxin-treated mice. These findings suggest a distinct functional role of novel sPLA(2)-IIE in the progression of inflammatory processes.


Assuntos
Fosfolipases A/química , Fosfolipases A/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Cloreto de Cálcio/farmacologia , Carbamatos/farmacologia , Cromossomos , Clonagem Molecular , DNA Complementar/metabolismo , Bases de Dados Factuais , Inibidores Enzimáticos/farmacologia , Etiquetas de Sequências Expressas , Fosfolipases A2 do Grupo II , Humanos , Concentração de Íons de Hidrogênio , Hibridização In Situ , Indolizinas/farmacologia , Pulmão/citologia , Pulmão/enzimologia , Camundongos , Dados de Sequência Molecular , Fosfolipases A/genética , Isoformas de Proteínas , Proteínas Recombinantes/química , Homologia de Sequência de Aminoácidos , Especificidade por Substrato , Distribuição Tecidual
17.
J Neuroendocrinol ; 12(1): 13-21, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10692139

RESUMO

The influence of chronic stress on the expression of interleukin (IL)-1beta and IL-2 mRNAs in ovariectomized rat brains, and the physiological consequences of the expression of these cytokines on hypothalamic-pituitary-gonadal (HPG) activity were investigated. Using polymerase chain reaction (PCR)-assisted semiquantitative analysis, we demonstrated alterated expression of IL-1beta and IL-2 mRNA during repeated cold stress; the expression of both IL-beta and IL-2 mRNA increased in the medial preoptic area and ventromedial hypothalamus, and decreased in the lateral hypothalamic area. In the arcuate nucleus/median eminence, IL-2 mRNA expression was dramatically decreased, in contrast to the increase in IL-1beta mRNA expression. Concomitant analysis of GnRH mRNA expression indicated significant suppression of GnRH synthesis in the chronic phase, and a strong negative correlation with cytokine expression in the medial preoptic area. Similar results were obtained in intact females exposed to this stress. These results, together with previous pharmacological studies, suggest that chronic stress may induce reproductive dysfunction through the effects of stress-induced expression of endogenous cytokines.


Assuntos
Regulação da Expressão Gênica , Hormônio Liberador de Gonadotropina/genética , Hipotálamo/metabolismo , Interleucina-1/genética , Interleucina-2/genética , Estresse Fisiológico/fisiopatologia , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Temperatura Baixa , Feminino , Região Hipotalâmica Lateral/metabolismo , Eminência Mediana/metabolismo , Ovariectomia , Área Pré-Óptica/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Wistar , Transcrição Gênica , Núcleo Hipotalâmico Ventromedial/metabolismo
18.
Biochem Biophys Res Commun ; 268(3): 767-71, 2000 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-10679280

RESUMO

The green tea gallocatechins, (-)-epigallocatechin-3-O-gallate (EGCG) (IC(50) = 0.69 microM), (-)-gallocatechin-3-O-gallate (GCG) (IC(50) = 0.67 microM), (-)-epicatechin-3-O-gallate (ECG) (IC(50) = 1.3 microM), and theasinensin A (IC(50) = 0.13 microM), were found to be potent and selective inhibitors of rat squalene epoxidase (SE), a rate-limiting enzyme of cholesterol biogenesis. On the other hand, flavan-3-ols without galloyl group at C-3 did not show significant enzyme inhibition. It was demonstrated for the first time that the cholesterol lowering effect of green tea may be attributed to their potent SE inhibition activities. Inhibition kinetics revealed that EGCG inhibited SE in noncompetitive (K(I) = 0.74 microM), and non-time-dependent manner. The potent enzyme inhibition would be caused by specific binding to the enzyme, and by scavenging reactive oxygen species required for the monooxygenase reaction.


Assuntos
Catequina/análogos & derivados , Inibidores Enzimáticos/farmacologia , Oxigenases/antagonistas & inibidores , Fenóis/farmacologia , Polímeros/farmacologia , Chá/química , Animais , Anticolesterolemiantes/química , Anticolesterolemiantes/farmacologia , Inibidores Enzimáticos/química , Flavonoides/química , Flavonoides/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Técnicas In Vitro , Cinética , Oxigenases/genética , Fenóis/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polímeros/química , Ratos , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/genética , Esqualeno Mono-Oxigenase
19.
J Biol Chem ; 274(42): 29749-54, 1999 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-10514450

RESUMO

Intestinal bile acid-binding protein (I-BABP) is a cytosolic protein that binds bile acids (BAs) with a high affinity. In the small intestine, its expression is restricted to the ileum where it is involved in the enterohepatic circulation of BAs. Using the human enterocyte-like Caco-2 cell line, we have recently shown that BAs increased I-BABP gene expression. To determine whether this regulation occurs in vivo, the effect of BA depletion or supplementation was studied in mice. A dramatic drop in I-BABP mRNA levels was observed in mice treated with the BA-binding resin cholestyramine, whereas an increase was found in animals fed with taurocholic acid. BAs are physiological ligands for the nuclear farnesoid X receptor (FXR). Both FXR and I-BABP are co-expressed along the small intestine and in Caco-2 cells. To determine the role of FXR in the regulation of I-BABP expression, the promoter of the human I-BABP gene was cloned. In Caco-2 cells, cotransfection of FXR and RXRalpha is required to obtain the full transactivation of the I-BABP promoter by BAs. Deletion and mutation analyses demonstrate that the FXR/RXRalpha heterodimer activates transcription through an inverted repeat bile acid responsive element located in position -160/-148 of the human I-BABP promoter. In conclusion, we show that FXR is a physiological BA sensor that is likely to play an essential role in BA homeostasis through the regulation of genes involved in their enterohepatic circulation.


Assuntos
Ácidos e Sais Biliares/metabolismo , Proteínas de Transporte/genética , Proteínas de Ligação a DNA/metabolismo , Hidroxiesteroide Desidrogenases , Íleo/metabolismo , Glicoproteínas de Membrana , Receptores do Ácido Retinoico/metabolismo , Fatores de Transcrição/metabolismo , Animais , Sequência de Bases , Primers do DNA , Proteínas de Ligação a DNA/genética , Dimerização , Humanos , Camundongos , Regiões Promotoras Genéticas , Receptores Citoplasmáticos e Nucleares , Receptores do Ácido Retinoico/genética , Homologia de Sequência do Ácido Nucleico , Fatores de Transcrição/genética
20.
Nephron ; 83(1): 40-6, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10461034

RESUMO

Perilla frutescens (perilla) is a common herb used in Japan for garnishing raw seafood to protect the alimentary tract from inflammatory diseases. The present study was performed to investigate whether or not perilla prevents the development of lesions of IgA nephropathy in ddY mice which spontaneously develop this disease. After orally administering perilla extract to ddY mice from 8 to 42 weeks of age, the changes in urine, serum, and kidneys were evaluated. Perilla extract significantly suppressed proteinuria and glomerular IgA deposition (p < 0.01 and p < 0.05, respectively). The decreased serum IgA concentration in perilla-treated mice showed a significant correlation with glomerular IgA deposition. Such findings suggest that perilla reduced glomerular IgA deposition via suppression of IgA production in the serum. On the other hand, the nitric oxide concentration in the serum of perilla-treated mice was significantly higher than that observed in the controls. The addition of the sera of perilla-treated mice to quiescent cultured murine mesangial cells resulted in a cell proliferation which was less than in controls, suggesting that perilla might either directly prevent mesangial cell proliferation or prevent proliferation by regulating circulating cytokines. Such results indicate that perilla should prevent IgA nephropathy, thus representing a promising herbal medicine for glomerulonephritis.


Assuntos
Glomerulonefrite por IGA/tratamento farmacológico , Lamiaceae/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Administração Oral , Animais , Proteínas Sanguíneas/farmacologia , Divisão Celular/efeitos dos fármacos , Células Cultivadas , DNA/biossíntese , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Mesângio Glomerular/citologia , Mesângio Glomerular/efeitos dos fármacos , Mesângio Glomerular/metabolismo , Mesângio Glomerular/patologia , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/patologia , Imunoglobulina A/sangue , Imunoglobulina A/metabolismo , Camundongos , Óxido Nítrico/sangue , Tamanho do Órgão/efeitos dos fármacos , Proteinúria/tratamento farmacológico
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