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1.
Eur J Pharmacol ; 865: 172759, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31676305

RESUMO

The inducible endothelium-dependent hyperpolarizing factor (iEDHF) pathway is activated as a compensatory response to adverse changes in the body. It causes vasorelaxation and maintains circulatory homeostasis in the organs. Small to moderate quantities of ethanol enhance vascular relaxation. However, its mechanism and the involvement of the iEDHF pathway in this process are unknown. Therefore, we studied iEDHF-mediated, acetylcholine-induced, endothelium-dependent relaxation in the superior mesenteric arteries (SMAs) of rats chronically fed ethanol. Rats were administered a standard diet (S-Control group), Lieber's control diet (L-Control group), or Lieber's ethanol diet (EtOH group). SMA relaxation was assessed by isometric tension measurements. Arachidonate 15-lipoxygenase (ALOX15) and soluble epoxide hydrolase (sEH) were determined by immunoblot. Acetylcholine-induced, endothelium-dependent relaxation was significantly greater in the EtOH than the control groups. These differences persisted after PGI2 and NO blockade. Thus, the increase in acetylcholine-induced relaxation was EDHF-mediated. In the EtOH group, however, it was prevented by iEDHF inhibitors. ALOX15 and sEH protein expression levels were higher in the EtOH than the L-Control group. The increase in acetylcholine-induced relaxation by chronic ethanol consumption was mediated by the iEDHF pathway. This mechanism may compensate for the blood pressure elevation induced by ethanol. This study suggests that iEDHF is induced during proper drinking and may help prevent the onset of cardiovascular conditions.

2.
Int Arch Allergy Immunol ; 179(2): 158-164, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30893690

RESUMO

BACKGROUND: We have previously shown that human monocyte-derived dendritic cells (moDCs) may participate in immune system-mediated hypercoagulable state through enhanced tissue factor (TF) expression and that the complement system may be involved in this process. OBJECTIVES: The aim of this study was to explore the role of pentraxin 3 (PTX3) and the complement system in enhanced TF expression in moDCs. METHODS: moDCs were generated from isolated human monocytes. PTX3 levels in whole human blood supplemented with moDCs were determined after lipopolysaccharide (LPS) stimulation. PTX3 release by the generated moDCs upon LPS stimulation was also assessed. The effect of PTX3 on whole blood coagulation was investigated using thromboelastometric analysis. TF expression in stationary moDCs treated with LPS and/or PTX3 was determined by measuring TF activity. The effect of complement inhibitors on TF activity in moDCs treated with LPS and/or PTX3 under low-shear conditions was evaluated. RESULTS: PTX3 levels were higher in whole blood supplemented with moDCs than in the presence of monocytes and were further elevated by LPS stimulation. PTX3 release from generated moDCs was also increased by LPS stimulation. PTX3 reduced whole blood coagulation time in a dose-dependent manner. However, PTX3 did not increase TF expression in stationary moDCs. Under low-shear conditions, PTX3 increased TF expression in moDCs. C1 esterase inhibitor (C1-inh) suppressed this effect. CONCLUSIONS: PTX3 might have a thrombophilic activity and enhance TF expression in moDCs under low-shear conditions. Furthermore, suppression of moDC-associated hypercoagulability by C1-inh might be partly ascribed to its inhibitory effect on PTX3.


Assuntos
Proteína C-Reativa/metabolismo , Proteína Inibidora do Complemento C1/farmacologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Componente Amiloide P Sérico/metabolismo , Tromboplastina/genética , Adulto , Coagulação Sanguínea , Ativação Enzimática , Feminino , Humanos , Lipopolissacarídeos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Resistência ao Cisalhamento , Tromboelastografia
3.
J Infect Dis ; 219(3): 382-390, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30299519

RESUMO

Background: Proactive recommendations for human papillomavirus (HPV) vaccines in Japan have been suspended for 5 years because of safety concerns. While no scientific evidence exists to substantiate these concerns, one reason given for not reinstating recommendations is the lack of reliable vaccine effectiveness (VE) data in a Japanese population. This study reports the VE of the bivalent HPV vaccine in Japanese women aged 20-22 years. Methods: During cervical screening between 2014 and 2016, women had Papanicolaou smears and HPV tests performed and provided data about their sexual history. Estimates of VE for vaccine-targeted HPV type 16 (HPV16) and 18 and cross-protection against other types were calculated. Results: Overall, 2197 women were tested, and 1814 were included in the analysis. Of these, 1355 (74.6%) were vaccinated, and 1295 (95.5%) completed the 3-dose schedule. In women sexually naive at vaccination, the pooled VEs against HPV16 and 18 and for HPV31, 45, and 52 were 95.5% (P < .01) and 71.9% (P < .01), respectively. When adjusted for number of sex partners and birth year, pooled VEs were 93.9% (P = .01) and 67.7% (P = .01) for HPV16 and 18 and HPV31, 45, and 52, respectively. Conclusions: The bivalent HPV vaccine is highly effective against HPV16 and 18. Furthermore, significant cross-protection against HPV31, 45, and 52 was demonstrated and sustained up to 6 years after vaccination. These findings should reassure politicians about the VE of bivalent HPV vaccine in a Japanese population.


Assuntos
Proteção Cruzada/imunologia , Papillomaviridae/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Adulto , Colo do Útero/imunologia , Detecção Precoce de Câncer , Feminino , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Papillomavirus Humano 31/imunologia , Humanos , Imunização , Programas de Imunização , Japão , Infecções por Papillomavirus/diagnóstico , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinação , Adulto Jovem
4.
Forensic Sci Med Pathol ; 15(2): 300-303, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30554350

RESUMO

Ventricular septal defect (VSD) generally has a good prognosis unless complicated by heart failure (HF). We report a case of sudden infant death because of clinically undiagnosed VSD in a seemingly healthy 16-day-old boy. Although a cardiac murmur was auscultated at birth, detailed clinical examination was not performed. Medicolegal autopsy revealed a perimembranous large VSD with a single coronary artery. The infant was diagnosed to have had HF based on the increased weight of the heart and extremely high serum brain natriuretic peptide levels. Histological examination revealed the degeneration of cardiomyocytes. The large VSD was thought to be the major cause of HF, although single coronary artery-associated cardiomyopathy might have also partially contributed to it. The decline in the physiological neonatal pulmonary resistance, which occurs over the first 1 or 2 weeks following birth, led to the acute progression of HF, resulting in circulatory collapse and sudden death. Detailed clinical examination should be performed for neonates with cardiac murmur to prevent avoidable death.


Assuntos
Anomalias dos Vasos Coronários/patologia , Morte Súbita Cardíaca/etiologia , Insuficiência Cardíaca/etiologia , Comunicação Interventricular/patologia , Humanos , Recém-Nascido , Masculino , Peptídeo Natriurético Encefálico/sangue
5.
J Thromb Thrombolysis ; 46(2): 219-226, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29860607

RESUMO

The crosstalk between immune and coagulation systems plays pivotal roles in host defense, which may involve monocyte-derived dendritic cells (moDCs). Our objectives were to elucidate the role of moDCs in coagulation under inflammatory conditions and the involvement of the complement system. We assessed the effects of lipopolysaccharide (LPS)-stimulated moDCs on coagulation using whole blood thromboelastometry in the presence of complement inhibitors. The sum of clotting time and clot formation time (CT plus CFT) in whole blood thromboelastometry was significantly more reduced in the presence of moDCs than in the absence of monocytes or moDCs and in the presence of monocytes, indicating a more potent coagulability of moDCs. The mRNA expression of coagulation-related proteins in moDCs was analyzed by quantitative PCR, which showed an increase only in the mRNA levels of tissue factor (TF). TF protein expression was assessed by western blot analysis and an activity assay, revealing higher TF expression in moDCs than that in monocytes. The in vitro moDC-associated hypercoagulable state was suppressed by a TF-neutralizing antibody, whereas LPS enhanced the in vitro hypercoagulation further. C1 inhibitor suppressed the in vitro LPS-enhanced whole blood hypercoagulability in the presence of moDCs and the increased TF expression in moDCs. These results suggest a significant role of moDCs and the complement system through TF expression in a hypercoagulable state under inflammatory conditions and demonstrate the suppressive effects of C1 inhibitor on moDC-associated hypercoagulation.


Assuntos
Células Dendríticas/metabolismo , Trombofilia/etiologia , Tromboplastina/metabolismo , Coagulação Sanguínea , Proteína Inibidora do Complemento C1/farmacologia , Proteínas do Sistema Complemento , Células Dendríticas/efeitos dos fármacos , Humanos , Inflamação , Lipopolissacarídeos , Monócitos , RNA Mensageiro/sangue , Tromboelastografia , Trombofilia/genética , Tromboplastina/genética
6.
Papillomavirus Res ; 6: 6-10, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29807210

RESUMO

Japan has no national vaccine registry and approximately 1700 municipalities manage the immunization records independently. In June 2013, proactive recommendations for the human papillomavirus (HPV) vaccine were suspended after unconfirmed reports of adverse events following immunization in the media, despite no vaccine safety signal having been raised. Furthermore, studies assessing HPV vaccine safety and effectiveness published post suspension are predominantly based on self-reported information. Our aim was to examine the accuracy of self-reported vaccination status compared with official municipal records. Participants were women aged 20-22 yrs, who were attending for cervical screening in Niigata city. Among the 1230 eligible registrants, vaccine uptake, defined as any dose, was 75.0% and 77.2% according to a self-reported questionnaire and municipal records, respectively. The accuracy rate of self-reported information was as follows: positive predictive value (PPV) was 87.7%; negative predictive value (NPV) was 54.5%; sensitivity was 85.2%; and specificity was 59.8%. The validity of self-reported information was only moderate (Kappa statistic = 0.44, 95% confidence interval 0.37-0.50). This combined with the low NPV may lead to reduced estimation of effectiveness and safety. A more reliable method, such as a national HPV vaccine registry, needs to be established for assessing HPV immunization status in Japan.


Assuntos
Registros Médicos , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/efeitos adversos , Autorrelato , Cobertura Vacinal , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Métodos Epidemiológicos , Feminino , Humanos , Japão , Sistema de Registros , Sensibilidade e Especificidade , Adulto Jovem
7.
Alcohol ; 64: 1-9, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28965650

RESUMO

Acute ethanol intoxication impairs immunological reactions and increases the risk of sepsis; however, the underlying mechanism remains unclear. Pentraxin (PTX) 3 is a humoral pattern recognition receptor whose levels rapidly increase in response to inflammation. PTX3 production is triggered by tumor necrosis factor (TNF)-α and is mediated by c-Jun N-terminal kinase (JNK). As PTX3 exerts protective effects against sepsis as well as acute lung injury, we investigated whether acute ethanol exposure exacerbates sepsis by altering PTX3 expression. Sepsis was induced in C57/BL6 mice by cecal ligation and puncture (CLP) after ethanol/saline administration. Survival rates were significantly lower in ethanol-treated than in saline-treated mice. Increased vascular permeability and attenuation of PTX3 expression were observed in the lungs of ethanol-treated mice 4 h after CLP. Concomitant with a delayed increase of plasma TNF-α in ethanol-treated mice, plasma PTX3 was also suppressed in the early phase of sepsis. Although TNF-α level in ethanol-treated mice exceeded that in saline-treated mice 16 h after CLP, PTX3 levels were still suppressed in the former group. JNK phosphorylation in lung tissue was suppressed in both groups 4 and 16 h after CLP. Furthermore, JNK phosphorylation in ethanol-treated human umbilical vein endothelial cells was suppressed even in the presence of exogenous TNF-α, resulting in inhibition of PTX3 mRNA and protein expression. Our results suggest that ethanol suppresses de novo PTX3 synthesis via two mechanisms - i.e., suppression of TNF-α production and inhibition of JNK phosphorylation. PTX3 suppression may therefore contribute to exacerbation of sepsis in acute ethanol intoxication.


Assuntos
Intoxicação Alcoólica/sangue , Modelos Animais de Doenças , Etanol/administração & dosagem , Proteínas do Tecido Nervoso/sangue , Sepse/sangue , Intoxicação Alcoólica/complicações , Intoxicação Alcoólica/patologia , Animais , Biomarcadores/sangue , Proteína C-Reativa/genética , Ceco/cirurgia , Relação Dose-Resposta a Droga , Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/sangue , Ligadura/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/genética , Punções/efeitos adversos , Sepse/etiologia , Sepse/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/sangue
8.
Leg Med (Tokyo) ; 25: 83-88, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28457516

RESUMO

The fluidity of cadaveric blood is an important characteristic in the post-mortem examination of cases of asphyxial death. Although it is empirically known that soft blood clots are present in cadaveric blood containing alcohol, the relationship between such clots and blood alcohol is unclear. We addressed this issue through in vitro studies using blood collected from healthy volunteers. Assessment of global hemostasis by rotational thromboelastometry revealed that ethanol treatment enhanced the procoagulant activity of whole blood. However, ethanol inhibited epinephrine-induced platelet aggregation, whereas plasma levels of von Willebrand factor and the activity of coagulation factors VIII and IX were unaffected. In contrast, tissue factor (TF) activity was higher in plasma obtained from ethanol-treated whole blood than that in plasma from untreated blood. Ethanol induced hemolysis of red blood cells, and the consequent hemoglobin (Hb) release promoted de novo synthesis of TF in isolated monocytes, as determined by real-time reverse transcription PCR, western blotting, and flow cytometry. However, ethanol itself did not induce TF expression in monocytes. Given that TF activates the extrinsic coagulation pathway and amplifies hemostatic reactions, Hb-induced TF expression in monocytes might contribute to soft blood clot formation.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Etanol/sangue , Hemólise , Monócitos/efeitos dos fármacos , Tromboplastina/efeitos dos fármacos , Autopsia , Cadáver , Citometria de Fluxo , Medicina Legal , Humanos
9.
Hum Vaccin Immunother ; 13(7): 1700-1704, 2017 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-28272968

RESUMO

OBJECTIVE: In Japan, the possible adverse events upon HPV vaccination was widely reported in the media. MHLW announced the suspension of aggressively encouraging HPV vaccination in 2013, and inoculation rate has sharply declined. The aim of the present study was estimation of future cervical cancer risk. METHODS: The latest data on vaccination rate at each age in Sakai City were first investigated. The rate of experiencing sexual intercourse at the age of 12, 13, 14, 15, 16, 17 and throughout lifetime is assumed to be 0%, 1%, 2%, 5%, 15%, 25%, and 85% respectively. The cervical cancer risk was regarded to be proportional to the relative risk of HPV infection over the lifetime. The risk in those born in 1993 whom HPV vaccination was not available yet for was defined to be 1.0000. RESULTS: The cumulative vaccination rates were 65.8% in those born in 1994, 72.7% in 1995, 72.8% in 1996, 75.7% in 1997, 75.0% in 1998, 66.8% in 1999, 4.1% in 2000, 1.5% in 2001, 0.1% in 2002, and 0.1% in 2003. The relative cervical cancer risk in those born in 1994-1999 was reduced to 0.56-0.70, however, the rate in those born in 2000-2003 was 0.98-1.0, almost the same risk as before introduction of the vaccine. DISCUSSION: The cumulative initial vaccination rates were different by the year of birth. It is confirmed that the risk of future cervical cancer differs in accordance with the year of birth. For these females, cervical cancer screening should be recommended more strongly.


Assuntos
Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adolescente , Fatores Etários , Criança , Medo , Feminino , Humanos , Japão , Medição de Risco , Neoplasias do Colo do Útero/psicologia , Cobertura Vacinal
10.
Soud Lek ; 61(4): 42-43, 2016.
Artigo em Tcheco | MEDLINE | ID: mdl-27869442

RESUMO

The positive identification of decomposed corpses is often difficult. We describe two autopsy cases in which medical materials, which had been implanted during previous surgical treatments, facilitated positive identification. The discovery of decomposed corpses is increasingly common in Japan, due to the increasing number of lonely deaths. Implanted medical materials and devices may be a useful tool for personal identification in the near future.


Assuntos
Autopsia , Restos Mortais , Patologia Legal , Aneurisma Aórtico/cirurgia , Fraturas do Fêmur/cirurgia , Humanos , Japão , Mudanças Depois da Morte
11.
J Obstet Gynaecol Res ; 42(12): 1802-1807, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27641631

RESUMO

AIM: In Japan, the rate of routine cervical cancer screening is quite low, and the incidence of cervical cancer has recently been increasing. Our objective was to investigate ways to effectively influence parental willingness to recommend that their 20-year-old daughters undergo cervical cancer screening. METHODS: We targeted parents whose 20-year-old daughters were living with them. In fiscal year 2013, as usual, the daughter received a reminder postcard several months after they had received a free coupon for cervical cancer screening. In fiscal year 2014, the targeted parents received a cervical cancer information leaflet, as well as a cartoon about cervical cancer to show to their daughters, with a request that they recommend to their daughter that she undergo cervical cancer screening. The subsequent screening rates for fiscal years 2013 and 2014 were compared. RESULTS: The cervical cancer screening rate of 20-year-old women whose parents received the information packet in fiscal year 2014 was significantly higher than for the women who, in fiscal year 2013, received only a simple reminder postcard (P < 0.001). As a result, the total screening rate for 20-year-old women for the whole of the 2014 fiscal year was significantly increased over 2013 (P < 0.001). CONCLUSION: For the first time, we have shown that the parents of 20-year-old daughters can be motivated to recommend that their daughters receive their first cervical cancer screening. This was achieved by sending a cervical cancer information leaflet and a cartoon about cervical cancer for these parents to show to their daughters. This method was significantly effective for improving cervical cancer screening rates.


Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Marketing de Serviços de Saúde , Pais , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Feminino , Humanos , Japão , Núcleo Familiar , Adulto Jovem
12.
Am J Forensic Med Pathol ; 37(3): 198-200, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27356014

RESUMO

Cases of sudden death due to pulmonary thromboembolism (PTE) following laparoscopic surgery are very rare. The risk factors for PTE include sex, operation duration, age, obesity, and underlying diseases. The development of thromboprophylaxis according to specific risk factors has contributed to the decrease in postoperative mortality. Here, we describe the case of a 50-year-old patient with sudden death due to PTE at 24 hours after laparoscopic cholecystectomy. The origin of the thrombi were bilateral deep vein thromboses in both the lower extremities. No severe risk factors for PTE were detected in the patient, and pneumatic compression devices were used during the surgery for thromboprophylaxis. We believe that the accumulation of minor risk factors may have contributed to the onset of PTE. Hence, a more cautious assessment of the risk factors for PTE prior to surgery is required in such cases.


Assuntos
Colecistectomia Laparoscópica/efeitos adversos , Morte Súbita/etiologia , Embolia Pulmonar/etiologia , Feminino , Humanos , Dispositivos de Compressão Pneumática Intermitente , Cuidados Intraoperatórios , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Trombose Venosa/complicações
13.
Int J Clin Oncol ; 21(5): 962-968, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26968588

RESUMO

BACKGROUND: Cervical cancer and its precancerous lesions caused by human papilloma virus (HPV) are steadily increasing in women in Japan. In comparison with women in other resource-rich countries, young women in Japan have a dismally low screening rate for cervical cancer. Our preliminary research has shown that 20-year-old women in Japan usually ask their mothers for advice regarding their initial cervical cancer screening. The objective of our current research is to determine the social factors among mothers in Japan that are causing them to give advice to their daughters regarding the HPV vaccine and cervical cancer screening. METHODS: The survey's targets were mothers who had 20-year-old daughters. We recruited respondents from the roster of a commercial internet survey panel. We analyzed for correlations between a mother's knowledge concerning cervical cancer, her recent cancer screening history, and the advice she gave to her daughter regarding cervical cancer screening. RESULTS: We obtained 618 valid answers to the survey. Compared with mothers who did not get screening, mothers who had cervical cancer screening had significantly more knowledge about cervical cancer and its screening (p < 0.05). The daughters of mothers with recent screening had received HPV vaccination more often than those of mothers without recent screening (p = 0.018). Mothers with recent screening histories tended more often to encourage their daughters to have cervical cancer screening (p < 0.05). When mothers were properly educated concerning cervical cancer and its screening, they were significantly more likely than before to recommend that their daughters have it (p < 0.0001). CONCLUSIONS: In young Japanese women, given the important role their mothers have in their lives, it is probable that we could improve their cervical cancer screening rate significantly by giving their mothers better medical information, and a chance to experience cervical cancer screening for themselves.


Assuntos
Detecção Precoce de Câncer , Conhecimentos, Atitudes e Prática em Saúde , Relações Mãe-Filho , Mães/psicologia , Infecções por Papillomavirus/prevenção & controle , Neoplasias do Colo do Útero/diagnóstico , Vacinação , Adulto , Feminino , Humanos , Intenção , Japão , Pessoa de Meia-Idade , Núcleo Familiar , Vacinas contra Papillomavirus , Inquéritos e Questionários , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Adulto Jovem
14.
Leg Med (Tokyo) ; 18: 49-51, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26832376

RESUMO

A car containing a male corpse with complete adipocere formation was found at the bottom of a lake. The deceased had presumably driven into the lake 7 years earlier. The surface of the deceased was unusually hard and firm like a gypsum board, and the entire internal viscera had turned into adipocere. Since the time required for adipocerous changes depends largely on environmental conditions, we considered the key conditions, namely, water temperature, pH, and oxygen content. In our case, cold, acidic water may have delayed adipocere formation, thus necessitating a long period of time for completeness. On the other hand, anoxic conditions and the peculiar environment of a lake bottom presumably contributed to complete adipocere formation.


Assuntos
Meio Ambiente , Patologia Legal/métodos , Mudanças Depois da Morte , Animais , Autopsia , Água Doce/química , Humanos , Masculino , Temperatura Ambiente , Fatores de Tempo
15.
Nihon Arukoru Yakubutsu Igakkai Zasshi ; 50(3): 123-34, 2015 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-26502571

RESUMO

Vascular function is regulated by a balance of vasoconstriction and vasorelaxation. Disorder in this balance due to alcohol consumption causes various clinical conditions. In this review, we discuss the effects of acute and chronic ethanol consumption on vascular responses, including vasoconstriction, endothelium-dependent vasorelaxation, and nerve-mediated vasorelaxation. Acute ethanol administration induces vasoconstriction in ethanol-naive animals in vitro. Furthermore, ethanol can both potentiate and suppress agonist-induced Ca(2+)-dependent vasoconstriction. Moreover, ethanol augments Ca(2+)-independent vasoconstriction by increasing Ca2+ sensitivity. Endothelium-dependent relaxation is mediated by the nitric oxide (NO) pathway and the endothelium-derived hyperpolarizing factor (EDHF) pathway. Acute ethanol treatment inhibits both NO- and EDHF-mediated relaxation. Furthermore, acute ethanol ingestion can also potentiate and suppress calcitonin gene-related peptide (CGRP)-induced nerve-mediated relaxation. These opposing effects may be due to differences in species or vascular beds. Thus, acute ethanol treatment decreases vasorelaxation, thereby shifting the contraction-relaxation balance towards contraction. Combined, these effects are one mechanism by which acute heavy alcohol consumption causes circulatory disturbances such as vasospasms or ischemic heart disease. In contrast, chronic low-dose ethanol has no effect on vasoconstriction, whereas chronic high-dose ethanol increases vasoconstriction. Additionally, chronic ethanol intake has diminished, unchanged, and even increased effects on nerve-mediated relaxation; therefore, conclusions on these effects are not possible at present. Interestingly, chronic low-dose ethanol administration enhanced endothelium-dependent relaxation; however, higher doses inhibited these responses. Therefore, regular or light-to-moderate alcohol intake increases vasorelaxation and may suppress elevated blood pressure, whereas chronic heavy alcohol consumption may raise blood pressure, causing various clinical conditions.


Assuntos
Etanol/farmacologia , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Animais , Pressão Sanguínea , Humanos , Fatores de Tempo
16.
Nihon Arukoru Yakubutsu Igakkai Zasshi ; 50(3): 158-66, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26502574

RESUMO

Interleukin (IL)-1 ß is a cytokine that is upregulated by the pro-inflammatory bacterial endotoxin lipopolysaccharide. This study examined the effect of ethanol on IL-1 ß-mediated suppression of phenylephrine-induced contractility and inducible nitric oxide synthase (iNOS) expression in the rat superior mesenteric artery (SMA). IL-1 ß suppressed the phenylephrine-induced contractile response, and this effect was inhibited by ethanol. The IL-1 ß-mediated effects were also blocked by cycloheximide, an inhibitor of protein synthesis, as well as AMT and 1400W, which are iNOS inhibitors, and PTIO, an NO scavenger. However, indomethacin, a cyclooxygenase (COX) inhibitor that promotes NO-independent vasodilation, did not affect IL-1 ß-mediated suppression of the contractile response. Western blot analysis revealed that iNOS levels in SMA were upregulated by IL-1 ß and inhibited by ethanol (50 and 100 mM). These results indicate that the suppression of the SMA contractile response by IL-1 ß requires iNOS activity, but not COX-2. Furthermore, these data suggest that ethanol inhibits the effects of IL-1 ß on the contractile response via inhibition of iNOS, rather than COX-2.


Assuntos
Etanol/farmacologia , Interleucina-1beta/farmacologia , Artéria Mesentérica Superior/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Animais , Endotélio/efeitos dos fármacos , Endotélio/metabolismo , Masculino , Ratos Wistar
17.
Forensic Sci Int ; 228(1-3): e47-9, 2013 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-23537717

RESUMO

We here report an autopsy case of a man in his seventies who died from asphyxia due to compression of the trachea caused by postextraction bleeding after extraction of his left mandibular third molar by a dentist in private practice. On the morning after the tooth extraction, he had complained of dyspnea and became unconscious at home. Although he was brought to the emergency room by ambulance, he died 7 days later without regaining consciousness. Autopsy examination revealed that the lingual side of the alveolar bone was fractured at the extraction socket. Moreover, subcutaneous bleeding that extended from the extraction socket to the thyrohyoid ligament in the cervical region and deviation of the epiglottis due to the bleeding were observed. Histological findings revealed liver cirrhosis; there were no significant findings in other organs. On the basis of these findings, we concluded that alveolar bone fracture occurred during the extraction and that the bleeding spread to the cervical region. Thus, the patient had died from asphyxia resulting from airway obstruction caused by cervical subcutaneous bleeding derived from postextraction bleeding. We emphasize that tooth extraction may cause fatal complications in patients with bleeding tendencies, particularly in the elderly.


Assuntos
Asfixia/etiologia , Hemorragia Bucal/complicações , Extração Dentária/efeitos adversos , Idoso , Processo Alveolar/lesões , Processo Alveolar/patologia , Patologia Legal , Humanos , Fraturas Maxilomandibulares/etiologia , Fraturas Maxilomandibulares/patologia , Masculino , Dente Serotino , Hemorragia Bucal/etiologia , Hemorragia Bucal/patologia
18.
Leg Med (Tokyo) ; 15(1): 23-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22940417

RESUMO

We describe a case of Ehlers-Danlos syndrome (EDS) type IV in a male in early half in his twenties, who experienced recurrent and eventually fatal pulmonary hemorrhage. EDS type IV is a rare disorder of type III collagen synthesis that is characterized by unusual facies, thin translucent skin with a venous vascular pattern, easy bruising, and hypermobility of the small joints. Autopsy findings showed hypermobility of the joints and distensibility of the skin. Microscopically, the abdominal skin showed substantially decreased dermal thickness. Moreover, the reticular dermis showed fine collagen bundles and large interstitial spaces compared with the skin from a normal control that showed large collagen bundles. Individual elastic fibers were also thicker than those observed in the skin of a normal control. The thoracic aorta showed thin adventitia and a relative increase in elastic fibers. The parenchyma of both the lungs showed markedly diffuse hemorrhage with hemosiderin-laden alveolar macrophages or old thrombi and organized thrombi in the small bronchi. Furthermore, both sections of the lung showed multiple fibrous nodules containing benign metaplastic bone. Vascular wall disruption and tearing of the vessel walls in the lung parenchyma were also observed. We concluded that EDS type IV led to the patient's death because of pulmonary hemorrhage. Because this syndrome resulted in the patient's death from arterial and bowel rupture, it is important to consider EDS as a potential cause of sudden death.


Assuntos
Síndrome de Ehlers-Danlos/complicações , Parada Cardíaca/etiologia , Hemorragia/etiologia , Pneumopatias/etiologia , Adolescente , Adulto , Autopsia , Síndrome de Ehlers-Danlos/classificação , Síndrome de Ehlers-Danlos/patologia , Evolução Fatal , Feminino , Hemorragia/complicações , Humanos , Pneumopatias/complicações , Pneumopatias/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Artigo em Japonês | MEDLINE | ID: mdl-21706814

RESUMO

Vascular tone is controlled by endothelium and nerves innervating blood vessels. Endothelium releases various substances such as PGI2 (Prostacyclin), NO (nitric oxide), TXA2 (thromboxane A2) and ET-1 (endothelin-1). It is well documented that ethanol affects vascular responses mediated by these substances. On the other hand, peripheral vascular tone is also regulated not only by sympathetic adrenergic nerves but also by nonadrenergic noncholinergic (NANC) nerves. NANC nerves include NO nerves and sensory nerves which release calcitonin gene-related peptide (CGRP) and nerve-mediated hyperpolarizing factor (NDHF). However, effect of ethanol on nerve-mediated vascular responses remains poorly understood. Therefore, this review summarizes the effect of ethanol on the sympathetic adrenergic nerve-mediated vasoconstriction and the sensory nerve-mediated vasorelaxation.


Assuntos
Etanol/farmacologia , Sistema Vasomotor/efeitos dos fármacos , Animais , Ratos , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Sistema Vasomotor/fisiologia
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