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1.
J Intellect Disabil Res ; 62(11): 931-940, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29968366

RESUMO

BACKGROUND: People with intellectual disabilities are more likely than people in the general population to experience life events associated with an increased risk of mental health problems. However, there has been little research in Japan on the prevalence of mental health problems in adults with intellectual disability (ID) or on associated factors and access to relevant services. METHODS: Informants completed the Japanese version of the Psychiatric Assessment Schedule for Adults with Developmental Disabilities Checklist, and questions on the use of mental health services, for 126 adults with ID living in Tokyo. RESULTS: A total of 23.8% of adults with ID had scores above the Psychiatric Assessment Schedule for Adults with Developmental Disabilities Checklist threshold score. Mental health problems were associated with age, gender and life events and not associated with the level of ID or living environment. Approximately 60% of participants with mental health problems were treated by psychiatrists and 6% of them received psychotherapy. CONCLUSION: In the present study, mental health problems occurred in adults with ID at similar frequencies as in previous studies. Adults with ID who experienced mental health problems tended to receive less psychological therapy than the general Japanese population experiencing such problems. This result may indicate poor provision of psychological services for people with intellectual disabilities in Japan.


Assuntos
Utilização de Instalações e Serviços/estatística & dados numéricos , Deficiência Intelectual/epidemiologia , Transtornos Mentais/epidemiologia , Serviços de Saúde Mental/estatística & dados numéricos , Psicoterapia/estatística & dados numéricos , Adolescente , Adulto , Comorbidade , Feminino , Humanos , Deficiência Intelectual/terapia , Masculino , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Prevalência , Tóquio/epidemiologia , Adulto Jovem
2.
BMC Anesthesiol ; 15: 180, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26667409

RESUMO

BACKGROUND: It is unknown whether cerebral oxygenation in patients with carotid artery stenosis (CAS) undergoing off-pump coronary artery bypass grafting (CABG) differs from that in patients without CAS. Thus, the effect of the presence of CAS ≥ 50 % on cerebral oxygenation during off-pump CABG in adult patients was evaluated retrospectively. METHODS: Eleven patients with CAS ≥ 50% and 14 patients without CAS ≥ 50% were enrolled. Regional cerebral tissue oxygen saturation (rSO2) was quantified using near-infrared spectroscopy. Mean arterial pressure, cardiac index, central venous pressure (CVP), and rSO2 at specific points were collected, and significant changes in each parameter were detected using repeated analysis of variance. Mean rSO2 and minimum rSO2 during anastomosis were analyzed by one-way analysis of variance. Multiple logistic regression analysis was used to estimate the odds ratio (OR) with 95% confidence interval (CI) for cerebral desaturation (a decrease in rSO2 ≥ 10% from preoperative value). RESULTS: Two patients with CAS ≥ 50% who received complete carotid artery stenting preoperatively were excluded from the analyses. In both patients with and without CAS, a decrease in rSO2 and cardiac index and an increase in CVP were observed during anastomosis. Mean (SD) maximum decrease in rSO2 from preoperative value was 9.2 (12.7) % on the left side and 8.1 (11.7) % on the right side in patients with CAS ≥ 50%, and 13.5 (11.3) % on the left side and 16.1 (9.8) % on the right side in patients without CAS ≥ 50% (p = 0.316). Neurological complications were not identified in both patients with and without CAS ≥ 50%. In multiple logistic regression analysis, CAS ≥ 50% was not associated with an increased risk of cerebral desaturation (OR 0.160, 95% CI 0.036-0.707, p = 0.016), and rSO2 decreased with decreasing cardiac index < 2.0 l/min/m(2) (OR 3.287, 95 % CI 2.218-5.076, p < 0.001). CONCLUSIONS: CAS ≥ 50% was not an independent risk factor of cerebral desaturation during off-pump CABG. Our results suggest that maintaining cardiac output can prevent a decrease in cerebral oxygenation in both patients with and without CAS ≥ 50%.


Assuntos
Encéfalo/metabolismo , Estenose das Carótidas/complicações , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Vasos Coronários/cirurgia , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica/efeitos adversos , Estudos de Casos e Controles , Ponte de Artéria Coronária sem Circulação Extracorpórea/métodos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Resultado do Tratamento
3.
Br J Anaesth ; 111(2): 235-41, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23518802

RESUMO

BACKGROUND: Hypotension during spinal anaesthesia for Caesarean delivery is a result of decreased vascular resistance due to sympathetic blockade and decreased cardiac output due to blood pooling in blocked areas of the body. Change in baseline peripheral vascular tone due to pregnancy may affect the degree of such hypotension. The perfusion index (PI) derived from a pulse oximeter has been used for assessing peripheral perfusion dynamics due to changes in peripheral vascular tone. The aim of this study was to examine whether baseline PI could predict the incidence of spinal anaesthesia-induced hypotension during Caesarean delivery. METHODS: Parturients undergoing elective Caesarean delivery under spinal anaesthesia with hyperbaric bupivacaine 10 mg and fentanyl 20 µg were enrolled in this prospective study. The correlation between baseline PI and the degree of hypotension during spinal anaesthesia and also the predictability of spinal anaesthesia-induced hypotension during Caesarean delivery by PI were investigated. RESULTS: Baseline PI correlated with the degree of decreases in systolic and mean arterial pressure (r=0.664, P<0.0001 and r=0.491, P=0.0029, respectively). The cut-off PI value of 3.5 identified parturients at risk for spinal anaesthesia-induced hypotension with a sensitivity of 81% and a specificity of 86% (P<0.001). The change of PI in parturients with baseline PI ≤ 3.5 was not significant during the observational period, while PI in parturients with baseline PI>3.5 demonstrated marked decreases after spinal injection. CONCLUSIONS: We demonstrated that higher baseline PI was associated with profound hypotension and that baseline PI could predict the incidence of spinal anaesthesia-induced hypotension during Caesarean delivery.


Assuntos
Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Cesárea , Hipotensão/diagnóstico , Hipotensão/epidemiologia , Oximetria/métodos , Adulto , Anestésicos Intravenosos , Anestésicos Locais , Pressão Sanguínea/efeitos dos fármacos , Bupivacaína , Feminino , Fentanila , Frequência Cardíaca/efeitos dos fármacos , Humanos , Incidência , Japão/epidemiologia , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Adulto Jovem
5.
Acta Anaesthesiol Scand ; 56(2): 256-9, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22103631

RESUMO

We report an unusual case of massive macroglossia that developed very rapidly after neurosurgery in the park bench position with neck flexion. A few minutes after endotracheal extubation, massive macroglossia was noticed with marked protrusion of the tongue from the oral cavity. The patient's hospital stay was prolonged due to difficulty in speaking and eating. Macroglossia is a rare complication; however, it may cause life-threatening airway obstruction. It is important to be prepared for managing post-operative macroglossia and keep in mind that it may develop rapidly, especially after prolonged surgery performed with sustained neck flexion. The patient should be informed of the risk of macroglossia and the associated problems prior to the operation.


Assuntos
Extubação/efeitos adversos , Complicações Intraoperatórias/etiologia , Macroglossia/etiologia , Adulto , Manuseio das Vias Aéreas/métodos , Obstrução das Vias Respiratórias/etiologia , Anestesia Geral , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroma Acústico/complicações , Neuroma Acústico/cirurgia , Vertigem/etiologia , Vertigem/cirurgia
6.
Rev Sci Instrum ; 82(7): 074501, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21806205

RESUMO

It is commonly believed that an energy transfer from thermal to suprathermal electrons (

7.
Ann Oncol ; 22(6): 1382-1391, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21196441

RESUMO

BACKGROUND: CHOP-21 has remained the standard chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), and dose intensification is a potential strategy for improving therapeutic results. We conducted a phase III trial to determine whether dose-dense strategy involving interval shortening of CHOP (CHOP-14) is superior to CHOP-21. PATIENTS AND METHODS: A total of 323 previously untreated patients (aged 15-69 years) with stages II-IV aggressive NHL were randomized. The primary end point was progression-free survival (PFS). RESULTS: Treatment compliance was comparable in both study arms. At 7-year follow-up, no substantial differences were observed in PFS and overall survival (OS) between CHOP-21 (n = 161) and CHOP-14 (n = 162) arms. Median PFS was 2.8 and 2.6 years with CHOP-21 and CHOP-14, respectively (one-sided log-rank P = 0.79). Eight-year OS and PFS rates were 56% and 42% [95% confidence interval (CI) 47% to 64% and 34% to 49%], respectively, with CHOP-21 and 55% and 38% (95% CI 47% to 63% and 31% to 46%), respectively, with CHOP-14. Subgroup analyses showed no remarkable differences in PFS or OS for patients stratified as per the International Prognostic Index or by age. CONCLUSION: Dose-intensification strategy involving interval shortening of CHOP did not prolong PFS in advanced, aggressive NHL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Japão , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Vincristina/uso terapêutico
9.
J Plast Reconstr Aesthet Surg ; 63(4): 693-9, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19272851

RESUMO

BACKGROUND: Burns to the dorsum of the fingers and hands require debridement and immediate coverage by skin flap at the earliest opportunity. In such situations, the conventional abdominal wall flap is still commonly used as it is a convenient and safe technique, but the foremost problem with this flap is that it is thick and therefore cosmetically unacceptable; it is also functionally not very suitable as the bulkiness of the digits prevents full range of motion. We have developed a modified thin abdominal flap (glove flap) which attains good results. METHODS: Incisions are made in the skin of the abdominal wall only where the hand is to be inserted and where each of the finger tips will be pulled through. The flap is undermined just under the skin to the depth that preserves the subcutaneous vascular networks to create a thin flap. The interdigital area of the flaps should not be undermined so as to create a glove-type pocket. The hand is then inserted in this subcutaneous pocket. After insertion of the injured hand for 10 to 14 days, the flap is resected and attached to the hand. RESULTS: Seven hands of 5 patients were treated by this technique and all the flaps survived safely. The function of the hands and fingers, including range of motion (ROM) in each joint, was successfully salvaged. The reconstructed hands and fingers were aesthetically pleasing. CONCLUSIONS: Although the abdominal wall flap is not a new technique, our modifications to this flap make it possible to acquire functionally and aesthetically better results. Although many excellent techniques such as perforator flaps have been reported recently, we conclude that the abdominal wall flap is still a very useful technique because it can be performed easily, safely and within a short time.


Assuntos
Parede Abdominal/cirurgia , Queimaduras/cirurgia , Traumatismos dos Dedos/cirurgia , Traumatismos da Mão/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos , Doença Aguda , Adulto , Idoso , Queimaduras/diagnóstico , Traumatismos dos Dedos/diagnóstico , Seguimentos , Traumatismos da Mão/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Transplant Proc ; 41(9): 3873-6, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19917404

RESUMO

To prevent acute graft-versus-host disease (GVHD), mycophenolate mofetil (MMF) combined with calcineurin inhibitors have been used in allogeneic hematopoietic stem cell transplantation (allo-SCT). Previous studies commonly utilize MMF treatment until day 30 after allo-SCT. However, the feasibility of continuous administration after day 30 has not been well evaluated. We retrospectively assessed the safety and efficacy of extended drug administration. Twenty-five patients ceased MMF at day 30 (group A); whereas, 16 patients (group B) received extended regimens depending on individual risk factors for GVHD. No severe adverse events were observed in either group. Although the cumulative incidence (CI) of grade I to IV GVHD at day 100 was comparable between the 2 groups, the CI of grade II to IV GVHD was less among group B (12.5%) compared with group A (42.3%). Extended MMF administration may be safe and beneficial as preemptive therapy to reduce the development of moderate-to-severe acute GVHD.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Ácido Micofenólico/análogos & derivados , Adulto , Idoso , Ciclosporina/uso terapêutico , Esquema de Medicação , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Leucemia/tratamento farmacológico , Leucemia/cirurgia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/cirurgia , Segurança , Tacrolimo/uso terapêutico , Fatores de Tempo , Transplante Homólogo , Adulto Jovem
11.
Kyobu Geka ; 58(11): 1010-2, 2005 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-16235853

RESUMO

An 81-year-old man was referred to our hospital for the treatment for left spontaneous pneumothorax. A chest X-ray revealed a left-sided total pneumothorax and complete collapse of the lung. After intravenous administration of methylprednisolone, a 16 Fr chest tube was inserted, and drainage was started without negative pressure suction. Four hours after chest tube insertion, the patient's condition deteriorated. He complained severe cough and dyspnea, and pulse oximetry reading was 70%. A repeat chest X-ray demonstrated diffuse reexpansion pulmonary edema (RPE) on the left. After mechanical ventilation and intravenous infusion therapy with sivelestat sodium hydrate, methylprednisolone and ulinastatin were started, P(O2)/ Fi(O2) ratio improved rapidly. He was extubated on hospital day 6 and was discharged after pleurodesis for the pneumothorax. This case suggests that sivelestat sodium hydrate may be useful for the treatment for RPE.


Assuntos
Glicina/análogos & derivados , Pneumotórax/terapia , Edema Pulmonar/tratamento farmacológico , Inibidores de Serina Proteinase/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Drenagem , Glicina/uso terapêutico , Humanos , Masculino , Metilprednisolona/administração & dosagem , Edema Pulmonar/patologia , Edema Pulmonar/terapia , Pulsoterapia , Respiração Artificial
12.
Neuroscience ; 130(2): 349-58, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15664691

RESUMO

Endothelin-1 (ET-1) exists in endothelial cells as well as a variety of other cell types. The presence of ET-1 and its receptors in neurons suggests its possible role as a neurotransmitter and/or neuromodulator. Studies utilizing exogenous ET-1 have suggested that ET-1 affects pain transmission. This study was designed to examine the possible role(s) of neuronal ET-1 in pain processing. We produced neuron-specific ET-1 knockout mice using the Cre/loxP system with a synapsin I promoter and examined the effects produced by the lack of neuronal ET-1 on pain behavior using common pain models and a model of stress-induced analgesia. In acute nociceptive pain models, paw withdrawal thresholds to radiant heat and mechanical stimuli applied with von Frey hairs were significantly lower in the knockout mice compared with control. This indicated that the absence of neuronal ET-1 leads to greater sensitivity to acute nociceptive stimuli. After inflammation was produced by intraplantar injection of carrageenan, there was a significantly greater degree of thermal hyperalgesia and mechanical allodynia in the knockout mice even after the difference in baseline values was compensated. Furthermore, in a neuropathic pain model produced by spinal nerve ligation, there was also a greater degree of mechanical allodynia in the knockout mice. Finally, in a swim-stress model, the magnitude of stress-induced analgesia was less in the knockout mice, indicating the involvement of neuronal ET-1 in stress-induced analgesia. The results suggest that there is a basal release of ET-1 from neurons that affect baseline pain thresholds as well as an additional release during persistent pain states that acts to suppress the pain. The involvement of neuronal ET-1 in stress-induced analgesia further suggests its role in endogenous pain inhibitory systems. To confirm that ET-1 is released in persistent pain states and to determine which part of the CNS is involved, we measured the concentrations of ET-1 before and after inducing peripheral inflammation in different parts of the CNS involved in endogenous pain inhibitory systems in normal mice. We found that ET-1 was increased in the hypothalamus while no significant increase was observed in the midbrain, medulla and spinal cord. The results of the present study suggest that neuronal ET-1 is involved in endogenous pain inhibitory control likely via pathways through the hypothalamus.


Assuntos
Endotelina-1/genética , Hiperalgesia/genética , Hipotálamo/metabolismo , Vias Neurais/metabolismo , Limiar da Dor/fisiologia , Dor/genética , Doença Aguda , Animais , Modelos Animais de Doenças , Endotelina-1/deficiência , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Camundongos , Camundongos Knockout , Inibição Neural/fisiologia , Neurônios/metabolismo , Dor/metabolismo , Dor/fisiopatologia , Medição da Dor , Dor Intratável/genética , Dor Intratável/metabolismo , Dor Intratável/fisiopatologia , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/fisiopatologia , Estimulação Física , Regiões Promotoras Genéticas/genética , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Estresse Fisiológico/fisiopatologia , Sinapsinas/genética
13.
Gene ; 335: 47-56, 2004 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-15194189

RESUMO

Eight novel small RNAs that were encoded in the regions corresponding to the introns of protein-coding genes were isolated from Caenorhabditis elegans. Seven of them showed a typical snoRNA secondary structure: one C/D snoRNA and six H/ACA snoRNAs. The remaining one RNA did not show any homology to other RNAs in a database. Four of the seven isolated snoRNAs could form base pairings with parts of rRNAs, suggesting that they are potential pseudouridilation sites and methylation sites. The results of our study suggest that there are more as-yet-unidentified small ncRNAs of which genes are located in the intron regions of protein-coding genes in C. elegans.


Assuntos
Caenorhabditis elegans/genética , RNA de Helmintos/genética , Animais , Sequência de Bases , Caenorhabditis/genética , DNA Complementar/química , DNA Complementar/genética , Genes de Helmintos/genética , Dados de Sequência Molecular , Conformação de Ácido Nucleico , RNA de Helmintos/química , RNA de Helmintos/isolamento & purificação , RNA Nucleolar Pequeno/química , RNA Nucleolar Pequeno/genética , RNA Nucleolar Pequeno/isolamento & purificação , Alinhamento de Sequência , Análise de Sequência de DNA , Especificidade da Espécie
17.
Ann Oncol ; 13(9): 1347-55, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12196359

RESUMO

BACKGROUND: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) is accepted as the best available standard treatment for first-line chemotherapy in aggressive non-Hodgkin's lymphoma (NHL). However, the therapeutic efficacy of CHOP remains unsatisfactory, particularly in high-intermediate risk and high risk patients, and a new strategy is warranted in this patient population. The aim of the present study was to explore a suitable therapeutic-intensified regimen for the treatment of aggressive NHL. PATIENTS AND METHODS: Between May 1995 and July 1998, a total of 70 patients with high-intermediate risk or high risk aggressive NHL, according to the International Prognostic Index, were enrolled and randomly assigned to receive either eight cycles of standard CHOP (cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.4 mg/m(2) and prednisolone 100 mg for 5 days) every 2 weeks, or six cycles of dose-escalated CHOP (cyclophosphamide 1500 mg/m(2), doxorubicin 70 mg/m(2), vincristine 1.4 mg/m(2) and prednisolone 100 mg for 5 days) every 3 weeks. Lenograstim (glycosylated rHuG-CSF), at a dose of 2 micro g/kg/day s.c., was administered daily from day 3 until day 13 with biweekly CHOP and until day 20 with the dose-escalated CHOP. The primary endpoint was complete response rate. RESULTS: The complete response rate was 60% [21 of 35; 95% confidence interval (CI) 42% to 76%] with biweekly CHOP and 51% (18 of 35; 95% CI 34% to 69%) with dose-escalated CHOP. The major toxicity was grade 4 neutropenia and was more frequent in the dose-escalated CHOP arm (86%) than in the biweekly CHOP arm (50%). Grade 4 thrombocytopenia was also more frequent in the dose-escalated CHOP arm (20%) than the biweekly CHOP arm (3%). Non-hematological toxicities were acceptable in both arms. One treatment-related death (due to cardiac arrhythmia) was observed in a dose-escalated CHOP patient. Progression-free survival at 3 years was 43% (95% CI 27% to 59%) in the biweekly CHOP arm and 31% (95% CI 16% to 47%) in the dose-escalated CHOP arm. Although seven patients were deemed ineligible by central review of the pathological diagnosis, the results for both eligible and all enrolled patients were similar. CONCLUSIONS: Similar complete response rates and progression-free survival rates, but lower toxicity, indicated that biweekly CHOP was superior to dose-escalated CHOP in the treatment of aggressive NHL. Based on these results, the Lymphoma Study Group of the Japan Clinical Oncology Group is conducting a randomized phase III study comparing biweekly CHOP with standard CHOP in newly diagnosed patients with advanced-stage aggressive NHL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Linfoma não Hodgkin/tratamento farmacológico , Dose Máxima Tolerável , Neutropenia/prevenção & controle , Prednisolona/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Vincristina/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalos de Confiança , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Japão , Lenograstim , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisolona/efeitos adversos , Probabilidade , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Vincristina/efeitos adversos
19.
Calcif Tissue Int ; 69(2): 88-93, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11683429

RESUMO

Different regions within the parathyroid hormone (PTH) molecule are known to have different biological activities. In the heart, the physiological actions of the intact PTH molecule are known as positive chronotropy and coronary vasodilatation. However, it is unclear which region of the PTH exerts which physiological action in the heart. Therefore, to clarify this point, we examined the hemodynamic effect of intact PTH(1-84) and selected PTH analogs, namely, PTH(1-34), PTH(2-34), [Nle8, 18Tyr34]PTH(3-34), PTH(4-34), [Tyr34]PTH(7-34), and PTH(13-34) in isolated perfused rat hearts. Both PTH(1-84) and PTH(1-34) significantly increased heart rate and decreased coronary perfusion pressure. In contrast, neither PTH(2-34) nor [Nle8,18Tyr34]PTH(3-34) increased heart rate, but they did decrease coronary perfusion pressure. Peptides further truncated at the amino terminus, PTH(4-34), [Tyr34]PTH(7-34), and PTH(13-34), had no effect on hemodynamics. Furthermore, the protein kinase A inhibitor H89, but not the protein kinase C inhibitor H7, attenuated the hemodynamic effects of PTH(1-34) or PTH(2-34), while it prevented those of [Nle8,18Tyr34]PTH(3-34). These results clearly demonstrate that the first amino acid of PTH is essential for its chronotropic property whereas the first 3 amino acids of PTH are involved in its coronary vasodilatory action. Furthermore, protein kinase A, but not protein kinase C, appears to be involved in the chronotropic and coronary vasodilatory actions of PTH.


Assuntos
Coração/efeitos dos fármacos , Hormônio Paratireóideo/farmacologia , Animais , Relação Dose-Resposta a Droga , Frequência Cardíaca/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Perfusão , Ratos , Ratos Wistar , Fatores de Tempo , Vasodilatação/efeitos dos fármacos
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