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1.
Epidemiol Infect ; 147: e38, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30409242

RESUMO

Japan is still a medium-burden tuberculosis (TB) country. We aimed to examine trends in newly notified active TB incidence and TB-related mortality in the last two decades in Japan. This is a population-based study using Japanese Vital Statistics and Japan Tuberculosis Surveillance from 1997 to 2016. We determined active TB incidence and mortality rates (per 100 000 population) by sex, age and disease categories. Joinpoint regression was applied to calculate the annual percentage change (APC) in age-adjusted mortality rates and to identify the years showing significant trend changes. Crude and age-adjusted incidence rates reduced from 33.9 to 13.9 and 37.3 to 11.3 per 100 000 population, respectively. Also, crude and age-adjusted mortality rates reduced from 2.2 to 1.5 and 2.8 to 1.0 per 100 000 population, respectively. Average APC in the incidence and mortality rates showed significant decline both in men (-6.2% and -5.4%, respectively) and women (-5.7% and -4.6%, respectively). Age-specific analysis demonstrated decreases in incidence and mortality rates for every age category, except for the incidence trend in the younger population. Although trends in active TB incidence and mortality rates in Japan have favourably decreased, the rate of decline is far from achieving TB elimination by 2035.

2.
Br J Dermatol ; 176(2): 395-402, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27452897

RESUMO

BACKGROUND: Antimelanoma differentiation-associated protein (anti-MDA)5 antibodies are associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis (CADM) or dermatomyositis (DM). OBJECTIVES: We aimed to evaluate the relevance of monitoring anti-MDA5 antibody levels for the management of RP-ILD in patients with CADM or DM. METHODS: Twelve patients with CADM (n = 10) or DM (n = 2) accompanied by RP-ILD were included. Baseline characteristics and outcomes were recorded. Serial measurements of anti-MDA5 antibody levels were measured. All patients were treated with corticosteroids, tacrolimus and intravenous cyclophosphamide. RESULTS: All patients achieved RP-ILD remission after combined immunosuppressive therapy for a mean of 6·8 months, with significant decreases noted in the mean anti-MDA5 antibody levels at remission. Six (50%) patients became anti-MDA5 antibody negative after therapy. After a mean follow-up of 31 months, RP-ILD relapse was observed in four (33%) patients in both the anti-MDA5 antibody sustained positive group and the negative conversion group. However, relapsed patients in the sustained positive group relapsed earlier than those in the negative conversion group. Thus, a decrease in anti-MDA5 antibody levels during remission was associated with longer remission. Relapses were associated with a reincrease of anti-MDA5 antibody levels in four of four (100%) patients. In contrast, none of the patients without reincrease in anti-MDA5 antibody exhibited symptoms of relapse during follow-up. Therefore, reincrease in anti-MDA5 antibody levels was associated with relapse. CONCLUSIONS: The anti-MDA5 antibody level is a novel parameter for monitoring and a good predictor of RP-ILD relapse in patients with CADM or DM.


Assuntos
Dermatomiosite/imunologia , Doenças Pulmonares Intersticiais/imunologia , Corticosteroides/uso terapêutico , Autoanticorpos/metabolismo , Ciclofosfamida/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Dermatomiosite/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento
3.
Dis Esophagus ; 30(7): 1-7, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30052898

RESUMO

Esophageal squamous cell carcinoma is a highly aggressive neoplasm and the sixth leading cause of global cancer-related death; the 5-year survival rate for esophageal cancer is only about 20%-25% for all stages. Therefore, improving the therapeutic effect is important. This study assessed whether low-dose hyperthermia (LDH) enhances the antitumor effects of chemotherapy. The antitumor effect of chemotherapy with/without LDH in the squamous cell carcinoma cell line SCCVII was evaluated. A comprehensive analysis was performed with real-time polymerase chain reaction (PCR) to study the hyperthermia-induced changes in the gene expression of SCCVII cell lines. In addition, the cytotoxic and apoptotic changes in the cells treated with LDH combined with/without 5-fluorouracil (5-FU) were measured. LDH combined with 5-FU (10 nM) strongly inhibited the cell growth of SCCVII, with flow cytometry showing an increased population of apoptotic cells. PCR showed that LDH promoted a 25.22-fold increase of p53 mRNA and 18.08-fold increase of Bax mRNA in vitro. MDR1 expression was decreased to 28.7% after LDH. This treatment can result in much higher efficacy of antitumor drugs. After LDH, the expressions of TS decreased to 12.06%, OPRT increased by 4.17-fold, and DPD did not change (1.03-fold). This transformations will induce susceptibility to 5-FU. LDH may be a useful enhancer of chemotherapy drugs for squamous cell carcinoma.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Fluoruracila/farmacologia , Expressão Gênica , Hipertermia Induzida , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Di-Hidrouracila Desidrogenase (NADP)/genética , Expressão Gênica/efeitos dos fármacos , Humanos , Orotato Fosforribosiltransferase/genética , RNA Mensageiro/metabolismo , Timidilato Sintase/genética , Proteína Supressora de Tumor p53/genética , Proteína X Associada a bcl-2/genética
4.
Gene Ther ; 23(1): 50-6, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26241176

RESUMO

Combination therapy of carbon-ion beam with the far upstream element-binding protein (FBP)-interacting repressor, FIR, which interferes with DNA damage repair proteins, was proposed as an approach for esophageal cancer treatment with low side effects regardless of TP53 status. In vivo therapeutic antitumor efficacy of replication-defective adenovirus (E1 and E3 deleted adenovirus serotype 5) encoding human FIR cDNA (Ad-FIR) was demonstrated in the tumor xenograft model of human esophageal squamous cancer cells, TE-2. Bleomycin (BLM) is an anticancer agent that introduces DNA breaks. The authors reported that Ad-FIR involved in the BLM-induced DNA damage repair response and thus applicable for other DNA damaging agents. To examine the effect of Ad-FIR on DNA damage repair, BLM, X-ray and carbon-ion irradiation were used as DNA damaging agents. The biological effects of high linear energy transfer (LET) radiotherapy used with carbon-ion irradiation are more expansive than low-LET conventional radiotherapy, such as X-rays or γ rays. High LET radiotherapy is suitable for the local control of tumors because of its high relative biological effectiveness. Ad-FIR enhanced BLM-induced DNA damage indicated by γH2AX in vitro. BLM treatment increased endogenous nuclear FIR expression in TE-2 cells, and P27Kip1 expression was suppressed by TP53 siRNA and BLM treatment. Further, Ad-FIRΔexon2, a dominant-negative form of FIR that lacks exon2 transcriptional repression domain, decreased Ku86 expression. The combination of Ad-FIR and BLM in TP53 siRNA increased DNA damage. Additionally, Ad-FIR showed synergistic cell toxicity with X-ray in vitro and significantly increased the antitumor efficacy of carbon-ion irradiation in the xenograft mouse model of TE-2 cells (P=0.03, Mann-Whitney's U-test) and was synergistic with the sensitization enhancement ratio (SER) value of 1.15. Therefore, Ad-FIR increased the cell-killing activity of the carbon-ion beam that avoids late-phase severe adverse effects independently of the TP53 status in vitro. Our findings indicated the feasibility of the combination of Ad-FIR with DNA damaging agents for future esophageal cancer treatment.


Assuntos
Adenoviridae/genética , Neoplasias Esofágicas/tratamento farmacológico , Radioterapia com Íons Pesados/métodos , Proteínas de Ligação a RNA/metabolismo , Proteínas Repressoras/metabolismo , Proteína Supressora de Tumor p53/genética , Animais , Bleomicina/farmacologia , Linhagem Celular Tumoral , Terapia Combinada , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Técnicas de Silenciamento de Genes , Vetores Genéticos , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Fatores de Processamento de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas Repressoras/genética , Proteína Supressora de Tumor p53/metabolismo , Raios X , Ensaios Antitumorais Modelo de Xenoenxerto
5.
J Urban Health ; 91(1): 1-16, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23974945

RESUMO

Detailed information on health linked to geographic, sociodemographic, and environmental data are required by city governments to monitor health and the determinants of health. These data are critical for guiding local interventions, resource allocation, and planning decisions, yet they are too often non-existent or scattered. This study aimed to develop a conceptual framework of Urban Health Observatories (UHOs) as an institutional mechanism which can help synthesize evidence and incorporate it into urban policy-making for health and health equity. A survey of a select group of existent UHOs was conducted using an instrument based on an a priori conceptual framework of key structural and functional characteristics of UHOs. A purposive sample of seven UHOs was surveyed, including four governmental, two non-governmental, and one university-based observatory, each from a different country. Descriptive and framework analysis methods were used to analyze the data and to refine the conceptual framework in light of the empirical data. The UHOs were often a product of unique historical circumstances. They were relatively autonomous and capable of developing their own locally sensitive agenda. They often had strong networks for accessing data and were able to synthesize them at the urban level as well as disaggregate them into smaller units. Some UHOs were identified as not only assessing but also responding to local needs. The findings from this study were integrated into a conceptual framework which illustrates how UHOs can play a vital role in monitoring trends in health determinants, outcomes, and equity; optimizing an intersectoral urban information system; incorporating research on health into urban policies and systems; and providing technical guidance on research and evidence-based policy making. In order to be most effective, UHOs should be an integral part of the urban governance system, where multiple sectors of government, the civil society, and businesses can participate in taking the right actions to promote health equity.


Assuntos
Prestação Integrada de Cuidados de Saúde/organização & administração , Política de Saúde , Disparidades nos Níveis de Saúde , Formulação de Políticas , Serviços Urbanos de Saúde/organização & administração , Pesquisa Biomédica , Inquéritos Epidemiológicos , Humanos , Governo Local , Inquéritos e Questionários , População Urbana
6.
J Dairy Sci ; 96(2): 832-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23200466

RESUMO

Homeostasis in the stomach environment is maintained by the balance of protective factors such as gastric mucus and aggressive factors such as gastric acid, stress, alcohol, and drugs. An overload of aggressive factors that upsets this balance can induce gastric injury. Fermented milk that contains Bifidobacterium bifidum BF-1 (BF-1), a probiotic strain, and Streptococcus thermophilus YIT 2021 (ST) is known to improve Helicobacter pylori-associated gastritis in humans. Here, we investigated the gastroprotective potential of BF-1 in a rat model of acid-ethanol-induced acute gastric injury to fully elucidate its potential compared with ST. Living BF-1, ST, or vehicle was orally administrated to rats, and acid-ethanol gastric injury was induced 2h later. The gastric injury rate was determined and shown to be significantly lower in the BF-1 group than in the vehicle group, which showed a similar level to the ST group. The production of gastric mucin and the expression of several target genes associated with protection and inflammation were examined before and after induction of gastric injury. Interestingly, mucin 5ac (muc5ac) gene expression in gastric corpus samples and gastric mucin production in stomach samples from the BF-1 group, but not the ST group, were significantly higher than those in the respective samples from the vehicle group. These findings indicate that BF-1 has the potential to provide gastroprotection, alleviating acute gastric injury by enhancing the production of gastric mucin in a rat model.


Assuntos
Bifidobacterium/metabolismo , Mucinas/biossíntese , Gastropatias/prevenção & controle , Estômago/microbiologia , Animais , Produtos Fermentados do Leite/microbiologia , Modelos Animais de Doenças , Etanol/farmacologia , Mucosa Gástrica/metabolismo , Masculino , Mucina-5AC/biossíntese , Probióticos/farmacologia , Ratos , Ratos Sprague-Dawley , Estômago/efeitos dos fármacos
7.
J Viral Hepat ; 19(2): e112-9, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22239508

RESUMO

BACKGROUND: Telaprevir in combination with peginterferon and ribavirin is a promising advancement in chronic hepatitis C treatment. However, the safety, tolerability, pharmacokinetics and antiviral profiles of telaprevir alone beyond 2 weeks have not been studied. METHODS: In a phase 1b study in Japan, 10 treatment-naïve patients infected with hepatitis C virus genotype 1b with high viral load (>5 log(10) IU/mL) received telaprevir 750 mg every 8 h (q8h) for 12 weeks. We examined the safety, tolerability, pharmacokinetics, hepatitis C virus (HCV) RNA levels and resistant variants of telaprevir. RESULTS: Neither serious adverse events nor discontinuations of study drug owing to an adverse event occurred. The most common adverse drug reactions were rash (80%) and anaemia (70%). Telaprevir concentration reached its steady state within 2 days after the first administration without abnormal accumulation. Telaprevir alone provided potent antiviral activity: a median log(10) decrease of 2.325 at 16 h and 5.175 on Day 14. During the treatment, HCV RNA levels at the nadir were below the limit of the quantification in seven patients and undetectable in three of 10 patients. Viral breakthrough associated with mainly Ala(156) -substituted variants occurred in eight patients, and only one patient showed end-of-treatment response. The selected variants reverted to the wild-type during the 24-week follow-up period. CONCLUSION: Telaprevir alone was well tolerated at 750 mg q8h for up to 12 weeks. The safety profile and emergence of resistant variants of genotype 1b under telaprevir monotherapy for 12 weeks will become increasingly important in evaluating an oral combination of telaprevir with other direct-acting antiviral agents.


Assuntos
Antivirais/efeitos adversos , Antivirais/farmacocinética , Farmacorresistência Viral , Hepacivirus/isolamento & purificação , Hepatite C/tratamento farmacológico , Oligopeptídeos/efeitos adversos , Oligopeptídeos/farmacocinética , Adulto , Antivirais/administração & dosagem , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C/virologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/administração & dosagem , RNA Viral/sangue , Fatores de Tempo , Carga Viral
8.
Int J Oral Maxillofac Surg ; 49(8): 984-992, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32070653

RESUMO

The objectives of this study were to evaluate survival in 141 patients with stage II-IV oral squamous cell carcinoma (OSCC) treated with preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil (IADCPIVF) via the superficial temporal artery, and to clarify the prognostic factors. The study population included 59 patients with stage II OSCC, 34 with stage III, and 48 with stage IV. After IADCPIVF, 139 patients underwent surgery; minimally invasive surgeries (MIS) including excisional biopsy were performed on 96 patients with a remarkably good response to IADCPIVF. The primary tumour response rate was 99.3% (complete response rate 56.7%, good partial response rate 17.0%, fair partial response rate 25.5%). Additionally, there were no serious adverse events associated with IADCPIVF. The 5-year overall survival rate was 74.6% (stage II 83.6%, stage III 72.7%, stage IV 64.8%). In the multivariate analysis of survival, T classification and clinical tumour response were significant prognostic factors. Eight (8.3%) of the patients who received MIS had primary recurrence and six were salvaged. In conclusion, IADCPIVF is safe and efficacious for treating OSCC, and MIS could reduce the extent of primary tumour resection in the case of a remarkably good response.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino/uso terapêutico , Docetaxel , Fluoruracila , Humanos , Recidiva Local de Neoplasia , Peplomicina/uso terapêutico , Taxoides/uso terapêutico
9.
Neuroimage ; 47(3): 946-51, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19426812

RESUMO

BACKGROUND AND AIMS: Determining the gene that plays a key role in brain-gut interactions is a crucial step for clarifying the pathophysiology of irritable bowel syndrome (IBS). We previously reported that the 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is related to anxiety in subjects with IBS. The amygdala is more activated during fearful face recognition in individuals with the s allele of 5-HTTLPR. Here, we tested our hypothesis that 5-HTTLPR differentially activates brain regions with colorectal distention in humans. METHODS: We enrolled 28 subjects without any organic disease. The study was approved by the Ethics Committee and all subjects gave written informed consent. DNA was extracted from the peripheral blood. The genotype of 5-HTTLPR was determined using polymerase chain reaction. Age, sex, diagnosis-matched individuals with the s/s genotype (n=14) and individuals with the l allele (genotypes l/s, l/l, l/extra-l, n=14) were compared. A barostat bag was inserted to the colorectum and was intermittently inflated with no (0 mm Hg), mild (20 mm Hg), or intense (40 mm Hg) stimulation on a random order. Radioactive H2[(15-)O] saline was injected at bag inflation and then positron emission tomography was performed. Changes in rCBF were analyzed using statistical parametric mapping. RESULTS: Individuals with the s/s genotype showed a significantly larger increase in rCBF by colorectal distention from 0 mm Hg to 40 mm Hg than individuals with the l allele. The significantly more activated brain regions in individuals with the s/s genotype were the left anterior cingulate cortex and right parahippocampal gyrus (p<0.0001). The increase in rCBF by colorectal distention of 20 mm Hg compared with 0 mm Hg was significantly larger in the left orbitofrontal cortex of individuals with the s/s genotype than that of individuals with the l allele (p<0.0001). CONCLUSION: These data suggest that individuals with a weak function of serotonin transporter respond to gut signals more in emotion-regulating brain regions. Functional gene polymorphism may partially predict the individual effect of a selective serotonin reuptake inhibitor on visceral pain.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Colo/inervação , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adulto , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Feminino , Predisposição Genética para Doença , Humanos , Síndrome do Intestino Irritável/diagnóstico por imagem , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Manometria , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Tomografia por Emissão de Pósitrons , Adulto Jovem
10.
Br J Cancer ; 101(8): 1425-32, 2009 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-19826427

RESUMO

BACKGROUND: Several human cancers have been found to contain cancer stem-like cells (CSCs) having cancer-initiating ability. However, only a few reports have shown the existence of CSCs in bone and soft tissue sarcomas. In this study, we identified and characterised side population (SP) cells that showed drug-resistant features in human bone sarcoma cell lines. METHODS: In seven osteosarcoma cell lines (OS2000, KIKU, NY, Huo9, HOS, U2OS and Saos2) and in one bone malignant fibrous histiocytoma (MFH) cell line (MFH2003), the frequency of SP cells was analysed. Tumourigenicity of SP cells was assessed in vitro and in vivo. Gene profiles of SP cells and other populations (main population; MP) of cells were characterised using cDNA microarrays. RESULTS: SP cells were found in NY (0.31%) and MFH2003 (5.28%). SP cells of MFH2003 formed spherical colonies and re-populated into SP and MP cells. In an NOD/SCID mice xenograft model, 1 x 10(3) sorted SP cell-induced tumourigenesis. cDNA microarray analysis showed that 23 genes were upregulated in SP cells. CONCLUSIONS: We showed that SP cells existed in bone sarcoma cell lines. SP cells of MFH2003 had cancer-initiating ability in vitro and in vivo. The gene profiles of SP cells could serve as candidate markers for CSCs in bone sarcomas.


Assuntos
Neoplasias Ósseas/patologia , Células-Tronco Neoplásicas/patologia , Osteossarcoma/patologia , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos SCID
11.
Science ; 164(3879): 571-2, 1969 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-4388476

RESUMO

In cats, significant loss of glycine occurred in spinal grey matter on the side of local tetanus, whereas the gamma-aminobutyric acid concentration remained unaltered. These findings suggest that tetanus rigidity is due to the blocking of the spinal inhibitory transmission by decrease of inhibitory transmitter and that glycine is an effective inhibitory transmitter in cat spinal cord.


Assuntos
Aminobutiratos/metabolismo , Glicina/metabolismo , Neurotransmissores/metabolismo , Medula Espinal/fisiopatologia , Tétano/fisiopatologia , Aminoácidos/análise , Aminobutiratos/análise , Animais , Gatos , Depressão Química , Glicina/análise , Região Lombossacral , Medula Espinal/análise , Transmissão Sináptica/efeitos dos fármacos , Toxina Tetânica/farmacologia
12.
Science ; 288(5472): 1832-5, 2000 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-10846166

RESUMO

Targeted deletion of metabotropic glutamate receptor-subtype 1 (mGluR1) gene can cause defects in development and function in the cerebellum. We introduced the mGluR1alpha transgene into mGluR1-null mutant [mGluR1 (-/-)] mice with a Purkinje cell (PC)-specific promoter. mGluR1-rescue mice showed normal cerebellar long-term depression and regression of multiple climbing fiber innervation, events significantly impaired in mGluR1 (-/-) mice. The impaired motor coordination was rescued by this transgene, in a dose-dependent manner. We propose that mGluR1 in PCs is a key molecule for normal synapse formation, synaptic plasticity, and motor control in the cerebellum.


Assuntos
Atividade Motora/fisiologia , Plasticidade Neuronal/fisiologia , Desempenho Psicomotor/fisiologia , Células de Purkinje/fisiologia , Receptores de Glutamato Metabotrópico/fisiologia , Sinapses/fisiologia , Animais , Potenciais Pós-Sinápticos Excitadores , Marcação de Genes , Locomoção , Camundongos , Camundongos Transgênicos , Fibras Nervosas/fisiologia , Receptores de Glutamato Metabotrópico/genética , Transgenes
13.
Acta Radiol ; 50(1): 61-4, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19160082

RESUMO

BACKGROUND: Vaporization around the radiofrequency (RF) electrode after RF application (RFA) limits the RF ablation area. PURPOSE: To determine whether saturated saline injected into the area of vaporization after initial RFA extends ablation area after further RFA. MATERIAL AND METHODS: RFA was performed in 18 ex vivo porcine livers and four in vivo rabbit erector spinae muscles. An RF electrode was used to ablate an area with 40W of parallel current for 15 min. The ablation margin was determined using a thermocouple, and the radius of the ablated area was measured. After RF electrode removal, saturated saline was infused through a percutaneous ethanol injection needle into the site of the original RFA in 11 liver samples and two erector spinae muscles. Three minutes later, RFA was resumed for 15 min. The remaining seven control liver samples and two spinae muscles received RFA without saline injection. The radius of the final ablated area was then measured. RESULTS: In the ex vivo study, injection of saturated saline significantly decreased tissue impedance (87.7+/-9.4 to 51.1+/-9.7 Omega, P<0.0001), and increased the mean radius of the ablated area (15.9+/-3.0 to 25.0+/-3.6 mm, P<0.0001). These significant changes were not observed without injection of saturated saline. Similar trends were found in the in vivo study. CONCLUSION: Injection of saturated saline into the area of vaporization around the RF electrode, followed by additional RFA, caused concentric expansion of the final ablation area, facilitating more efficient tumor ablation.


Assuntos
Ablação por Cateter/métodos , Fígado/cirurgia , Músculo Esquelético/cirurgia , Cloreto de Sódio/administração & dosagem , Animais , Injeções , Coelhos , Suínos , Volatilização
14.
Neuron ; 29(3): 729-38, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11301031

RESUMO

Endogenous cannabinoids are considered to function as diffusible and short-lived modulators that may transmit signals retrogradely from postsynaptic to presynaptic neurons. To evaluate this possibility, we have made a paired whole-cell recording from cultured hippocampal neurons with inhibitory synaptic connections. In about 60% of pairs, a cannabinoid agonist greatly reduced the release of the inhibitory neurotransmitter GABA from presynaptic terminals. In most of such pairs but not in those insensitive to the agonist, depolarization of postsynaptic neurons and the resultant elevation of intracellular Ca2+ concentration caused transient suppression of inhibitory synaptic currents, which is mainly due to reduction of GABA release. This depolarization-induced suppression was completely blocked by selective cannabinoid antagonists. Our results reveal that endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals to cause the reduction of transmitter release.


Assuntos
Canabinoides/metabolismo , Terminações Nervosas/fisiologia , Neurônios/fisiologia , Transdução de Sinais , Sinapses/fisiologia , Potenciais de Ação , Animais , Animais Recém-Nascidos , Transporte Axonal , Benzoxazinas , Bicuculina/farmacologia , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio , Canabinoides/agonistas , Canabinoides/antagonistas & inibidores , Células Cultivadas , Condutividade Elétrica , Antagonistas GABAérgicos/farmacologia , Hipocampo/fisiologia , Morfolinas/farmacologia , Naftalenos/farmacologia , Neurotransmissores/metabolismo , Ratos , Receptores de GABA-B/fisiologia , Receptores de Glutamato Metabotrópico/fisiologia , Transmissão Sináptica/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo
15.
Neuron ; 31(3): 463-75, 2001 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-11516402

RESUMO

We report a type of synaptic modulation that involves retrograde signaling from postsynaptic metabotropic glutamate receptors (mGluRs) to presynaptic cannabinoid receptors. Activation of mGluR subtype 1 (mGluR1) expressed in cerebellar Purkinje cells (PCs) reduced neurotransmitter release from excitatory climbing fibers. This required activation of G proteins but not Ca2+ elevation in postsynaptic PCs. This effect was occluded by a cannabinoid agonist and totally abolished by cannabinoid antagonists. Depolarization-induced Ca2+ transients in PCs also caused cannabinoid receptor-mediated presynaptic inhibition. Thus, endocannabinoid production in PCs can be initiated by two distinct stimuli. Activation of mGluR1 by repetitive stimulation of parallel fibers, the other excitatory input to PCs, caused transient cannabinoid receptor-mediated depression of climbing fiber input. Our data highlight a signaling mechanism whereby activation of postsynaptic mGluR retrogradely influences presynaptic functions via endocannabinoid system.


Assuntos
Canabinoides/metabolismo , Cerebelo/fisiologia , Potenciais Evocados/fisiologia , Metoxi-Hidroxifenilglicol/análogos & derivados , Terminações Pré-Sinápticas/fisiologia , Células de Purkinje/fisiologia , Receptores de Droga/fisiologia , Receptores de Glutamato Metabotrópico/fisiologia , Animais , Cálcio/metabolismo , Moduladores de Receptores de Canabinoides , Potenciais Evocados/efeitos dos fármacos , Técnicas In Vitro , Metoxi-Hidroxifenilglicol/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Terminações Pré-Sinápticas/efeitos dos fármacos , Regiões Promotoras Genéticas , Células de Purkinje/efeitos dos fármacos , Ratos , Receptores de Canabinoides , Receptores de Droga/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/deficiência , Receptores de Glutamato Metabotrópico/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
16.
Neuron ; 7(4): 577-83, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1681831

RESUMO

The ability of excitatory amino acids to induce increases in the intracellular Ca2+ concentration ([Ca2+]i) of cerebellar Purkinje cells was examined by digital fluorescence ratio imaging of voltage-clamped Purkinje cells dialyzed with the Ca2+ indicator fura-2. Purkinje cells responded with large inward currents accompanied by increases in dendritic [Ca2+]i when challenged with the excitatory amino acid agonists glutamate and quisqualate. The rise in [Ca2+]i was transient and reached peak values of several hundred nanomolar. The response subsisted in the absence of extracellular Ca2+, a condition that eliminates Ca2+ entry through voltage-gated Ca2+ channels, indicating that Ca2+ arose in large part from an intracellular compartment. In support of this hypothesis, only the first agonist application elicited a [Ca2+]i increase in slices maintained in Ca(2+)-free medium, as expected if the intracellular stores become depleted. These results indicate that metabotropic glutamate receptors are functional in Purkinje cells and point to glutamate as a possible modulator of [Ca2+]i in these neurons.


Assuntos
Cálcio/metabolismo , Dendritos/metabolismo , Glutamatos/farmacologia , Células de Purkinje/metabolismo , Animais , Ácido Egtázico/farmacologia , Eletrofisiologia , Fura-2 , Ácido Glutâmico , Técnicas In Vitro , Concentração Osmolar , Células de Purkinje/efeitos dos fármacos , Células de Purkinje/fisiologia , Ácido Quisquálico/farmacologia , Sinapses/fisiologia
17.
Neuron ; 22(4): 763-75, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10230796

RESUMO

This study of rat cerebellar slices yielded two lines of evidence indicating that the corticotropin-releasing factor (CRF) found in climbing fibers (CFs) is critical for the induction of long-term depression (LTD) at the parallel fiber (PF) synapses of Purkinje cells (PCs) by their conjunctive activation with either stimulation of CFs or depolarization of PCs. First, LTD induction was effectively blocked by specific CRF receptor antagonists, alpha-helical CRF-(9-41) (alpha-h CRF) and astressin; and second, LTD was no longer observed in CF-deprived cerebella but was restored by CRF replenishment. The data obtained in this study suggest that these effects are mediated by protein kinase C (PKC) and not by Ca2+ signaling or cyclic GMP (cGMP) production.


Assuntos
Cerebelo/fisiologia , Hormônio Liberador da Corticotropina/fisiologia , Plasticidade Neuronal/fisiologia , Animais , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores , Técnicas In Vitro , Masculino , Potenciais da Membrana/fisiologia , Técnicas de Patch-Clamp , Células de Purkinje/fisiologia , Ratos , Ratos Wistar
18.
Neuron ; 18(1): 71-9, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9010206

RESUMO

Most of the cerebellar Purkinje cells (PCs) of an adult animal are innervated individually by a single climbing fiber (CF) that forms strong excitatory synapses with the PCs. This one-to-one relationship between a PC and a CF is a consequence of a developmentally regulated regression of the innervation of PCs by CFs. We found that, in mice deficient in the type 1 metabotropic glutamate receptor (mGluR1), the regression of supernumerary CFs ceases by the end of the second postnatal week, which is about one week earlier than in normal mice. Consequently, about one third of PCs in the mGluR1 mutant mice are innervated by multiple CFs in adulthood. We conclude that the regression of CFs normally occurs in two developmental phases and that mGluR1 plays a crucial role in the second phase.


Assuntos
Envelhecimento/fisiologia , Cerebelo/fisiologia , Fibras Nervosas/fisiologia , Células de Purkinje/fisiologia , Receptores de Glutamato Metabotrópico/efeitos dos fármacos , Sinapses/fisiologia , Animais , Cerebelo/crescimento & desenvolvimento , Eletrofisiologia/métodos , Potenciais Evocados , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Knockout , Camundongos Mutantes Neurológicos , Plasticidade Neuronal , Receptores de Glutamato Metabotrópico/genética , Transmissão Sináptica
19.
Neuron ; 28(1): 233-44, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11086997

RESUMO

We have used rats and mice with mutations in myosin-Va to evaluate the range and function of IP3-mediated Ca2+ signaling in dendritic spines. In these mutants, the endoplasmic reticulum and its attendant IP3 receptors do not enter the postsynaptic spines of parallel fiber synapses on cerebellar Purkinje cells. Long-term synaptic depression (LTD) is absent at the parallel fiber synapses of the mutants, even though the structure and function of these synapses otherwise appear normal. This loss of LTD is associated with selective changes in IP3-mediated Ca2+ signaling in spines and can be rescued by photolysis of a caged Ca2+ compound. Our results reveal that IP3 must release Ca2+ locally in the dendritic spines to produce LTD and indicate that one function of dendritic spines is to target IP3-mediated Ca2+ release to the proper subcellular domain.


Assuntos
Sinalização do Cálcio/fisiologia , Dendritos/metabolismo , Cadeias Pesadas de Miosina , Miosina Tipo V , Inibição Neural/fisiologia , 2-Amino-5-fosfonovalerato/farmacologia , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Animais , Benzoatos/farmacologia , Canais de Cálcio/deficiência , Canais de Cálcio/metabolismo , Cerebelo/citologia , Cerebelo/metabolismo , Dendritos/ultraestrutura , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Glicina/análogos & derivados , Glicina/farmacologia , Técnicas In Vitro , Receptores de Inositol 1,4,5-Trifosfato , Proteínas de Filamentos Intermediários/deficiência , Proteínas de Filamentos Intermediários/genética , Camundongos , Camundongos Mutantes Neurológicos , Inibição Neural/efeitos dos fármacos , Técnicas de Patch-Clamp , Células de Purkinje/metabolismo , Células de Purkinje/ultraestrutura , Ratos , Ratos Mutantes , Receptores Citoplasmáticos e Nucleares/deficiência , Receptores Citoplasmáticos e Nucleares/metabolismo , Transmissão Sináptica/genética , Tempo
20.
Int J Oral Maxillofac Surg ; 37(1): 82-5, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17611076

RESUMO

Catheter placement for continuous intra-arterial chemotherapy in head and neck cancer is generally performed via the superficial temporal artery. If placement via this artery is impossible, other arteries, such as the occipital artery, are chosen. A surgical method has been developed for catheter placement in the occipital artery by approaching from the posterior of the mastoid process. Catheter placement was performed by this method in 15 patients with oral squamous cell carcinoma. Target arteries were the lingual artery in seven cases, facial artery in three cases, maxillary artery in three cases, superior thyroid artery in one case, and the occipital artery itself in one case. The occipital artery was exposed without fail and catheter placement was completed in all patients. The wound healed without complication after treatment. This approach via the occipital artery is a useful technique to achieve continuous intra-arterial chemotherapy in head and neck cancer, especially for cases in which catheter placement is impossible via the superficial temporal artery.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Artéria Carótida Externa/cirurgia , Cateteres de Demora , Infusões Intra-Arteriais/métodos , Neoplasias Bucais/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Artéria Carótida Externa/diagnóstico por imagem , Feminino , Humanos , Masculino , Processo Mastoide , Pessoa de Meia-Idade , Radiografia
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