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2.
J Cardiol Cases ; 29(3): 124-127, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38481644

RESUMO

The patient, a 68-year-old man, presented to our emergency room with chest pain, prompting an emergency cardiac catheterization due to elevated cardiac troponin-I levels. While no obvious coronary artery stenosis was found, there was evidence of apical ballooning wall motion in the left ventricle, leading to a diagnosis of takotsubo syndrome. Three months later, he occasionally experienced chest pain at rest, prompting us to conduct another cardiac catheterization. Left ventriculography showed normal contraction. Suddenly, he experienced chest pain accompanied by ST elevation, which occurred spontaneously. Subsequently, slow-flow phenomenon was observed in the intermediate part of left anterior descending artery (LAD). We promptly administered nitroglycerin to alleviate the symptoms. Following the diagnosis of coronary microvascular dysfunction (CMD), he started calcium-channel blocker therapy and remained asymptomatic. One year later, we re-performed cardiac catheterization to further explore his condition. Acetylcholine provocation test was performed, which showed no epicardial coronary spasm. However, lactic acid elevation was observed in the coronary sinus blood sample. Additionally, a coronary physiological measurement in the LAD revealed a high index of microcirculatory resistance and low coronary flow reserve. Based on this series of clinical events, we inferred a significant contribution of CMD to the patient's condition. Learning objective: Coronary microvascular dysfunction (CMD) is increasingly recognized as an important cardiovascular disease, leading to myocardial ischemia, which is occasionally associated with takotsubo syndrome (TTS). In this report, we present a case of spontaneous CMD associated with TTS. This case emphasizes the significance of accurate diagnosis and appropriate treatment, highlighting the importance of recognizing CMD in patients with TTS.

3.
Am Heart J Plus ; 35: 100331, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38511182

RESUMO

Objective: Oncostatin M (OSM) is an inflammatory cytokine belonging to the interleukin-6 family member, which plays an important role in various cardiovascular diseases. We recently reported increased serum OSM levels in patients with coronary artery disease. However, the specific role in HF with ischemic heart disease (IHD) remains unclear. Methods and results: A total of 120 patients with HF and 48 control subjects were enrolled in this study. Serum OSM levels were measured using a sandwich technique immunoassay during the compensated state. The results revealed significantly higher serum OSM levels in HF patients compared to controls. Importantly, HF patients with IHD had higher OSM levels, and those with collateral flow showed the even higher levels, indicating a potential involvement in angiogenesis. Furthermore, a positive correlation was found between serum OSM levels and levels of vascular endothelial growth factor (VEGF). In vitro experiments demonstrated that recombinant OSM upregulated VEGF production in cultured human coronary artery endothelial cells. We additionally observed that endogenous OSM levels were enhanced through exercise. Lastly, we identified the potential of SGLT2 inhibitors to enhance OSM production. Conclusions: Serum OSM levels were elevated in HF patients, particularly in those with IHD Our data indicated that endogenous OSM induces VEGF production in the heart, suggesting the activation of angiogenesis, which can be further enhanced by exercise or SGLT2 inhibitors.

4.
Pacing Clin Electrophysiol ; 45(5): 598-604, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35353402

RESUMO

BACKGROUND: A left common pulmonary vein (LCPV) is the most common anatomical variation in the pulmonary vein (PV) and often influences strategies of PV isolation for atrial fibrillation (AF). Our objective was to elucidate the electrical properties of the specific shape of LCPV and to apply it to an ablation procedure. METHODS AND RESULTS: We investigated consecutive 12 out of 204 paroxysmal AF patients who had the shape of a straight common trunk in LCPV defined by the formation of a single conduit with parallel cranial and caudal walls after the coalescence of superior and inferior PVs on the distal side. The distance between the top of the bifurcation of LPVs and the level coinciding with the middle of the anterior wall of LCPV (left lateral ridge: LLR) was more than 10 mm in all the patients. The activation pattern of the LLR showed longitudinal conduction without outside connections. All the LCPV except one were successfully isolated without ablating the LLR (C-shape ablation). Only one patient had AF recurrence during the follow-up period. CONCLUSION: The LLR in LCPV with a straight common trunk has longitudinal conduction without outside connections, which permits the isolation of LCPV without ablating LLR.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Fibrilação Atrial/cirurgia , Humanos , Veias Pulmonares/cirurgia , Recidiva , Resultado do Tratamento
5.
Int J Cardiol Heart Vasc ; 35: 100829, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34235245

RESUMO

OBJECTIVE: Oncostatin M (OSM) is an inflammatory cytokine of the interleukin-6 family which plays a crucial role in the pathogenesis of atherosclerosis. Therefore, we tested our hypothesis that serum OSM levels are increased in patients with coronary artery diseases (CAD). METHODS AND RESULTS: Serum OSM level was measured by sandwich technique immunoassay in 315 consecutive patients and who underwent coronary angiography at the International University of Health and Welfare Hospital from April 2019 to March 2021. A diagnosis of CAD was made in 169 patients. Serum OSM levels were significantly higher in patients with significant coronary stenosis compared to those without it. [123.0 ± 46.7 pg/mL (n = 169) vs. 98.3 ± 47.9 pg/mL (n = 146), p < 0.001]. A positive correlation was noted between serum OSM levels and severity and complexity of coronary stenosis. Importantly, the coronary revascularization significantly decreased the serum OSM levels. We furthermore detected a positive correlation between serum OSM levels and HbA1c levels. Finally, our data suggested that 120 pg/mL of serum OSM was the potential cutoff value for screening of silent myocardial ischemia related with diabetic mellitus (DM). CONCLUSION: Serum OSM can be a novel biomarker for CAD and may be useful for the screening of asymptomatic CAD in patients with DM.

6.
J Interv Card Electrophysiol ; 61(1): 105-113, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32488748

RESUMO

BACKGROUND: It has been recently reported that sinus rhythm (SR) maintenance with catheter ablation therapy improves exercise tolerance (ET) in patients with persistent atrial fibrillation (AF). However, it remains to be elucidated whether this is also the case for patients with paroxysmal AF (PAF). METHODS: We enrolled consecutive 54 patients with PAF (age; 63 ± 10 [SD] years old, male/female 46/8) and 26 patients with persistent AF (non-PAF) (age; 57 ± 12 [SD] years old, male/female 23/3) who underwent AF ablation without recurrence. ET and cardiac function were evaluated by cardio-pulmonary exercise test and ultrasound echocardiography before and 6 months after ablation. RESULTS: The parameters of cardiopulmonary exercise test were comparable between the 2 groups. When PAF group was divided into 2 groups according to the time since diagnosis, peak oxygen uptake (peak VO2) before ablation was significantly lower in patients with PAF duration of more than 1 year (n = 26), compared with those with less than 1 year (n = 28) (18.1 ± 3.7 vs 21.3 ± 5.8 ml/kg/min, P = 0.022). At 6 months after SR maintenance without AF burden, peak VO2 significantly improved in both PAF (19.8 ± 5.1 to 22.0 ± 4.8 ml/kg/min, P = 0.0001) and non-PAF (20.6 ± 3.9 to 23.4 ± 5.0 ml/kg/min, P < 0.01). Furthermore, the improvement rate of peak VO2 after successful ablation had a highly significant inverse relationship with peak VO2 at baseline in patients with PAF (r = - 0.48, P = 0.0003). CONCLUSIONS: These results indicate that SR maintenance with ablation improves ET in patients with PAF, especially in those with reduced ET.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Criança , Teste de Esforço , Tolerância ao Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento
7.
J Cardiol Cases ; 24(4): 199-202, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35059057

RESUMO

We herein report a case of a 56-year-old woman with angina pectoris. She visited our emergency room because of chest pain. She finally underwent emergency percutaneous coronary intervention in right coronary artery due to acute coronary syndrome. Several months later, she complained of exertional chest pain again. Exercise-stress electrocardiogram showed ST-segment depression in V2-V6. However, coronary angiography showed no organic stenosis and we conducted acetylcholine provocation test. We finally detected severe coronary artery spasm and diagnosed exercise-induced vasospastic angina (VSA). This case highlights the importance of the recognition of exercise-induced VSA. Exercise-induced VSA needs the definite diagnosis and appropriate treatment. Learning objective Many patients felt chest pain even if they have undergone percutaneous coronary intervention (PCI). This case highlights the importance of the recognition of exercise-induced vasospastic angina (VSA). Exercise-induced VSA needs definite diagnosis and appropriate treatment. This case report describes the importance of precise diagnosis and highlights the recognition of exercise-induced VSA. We recommend the acetylcholine provocation test after PCI in order to determine the diagnosis of exercise-induced VSA.

8.
J Cardiol ; 75(1): 34-41, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31277963

RESUMO

BACKGROUND: Although recent reports showed that left ventricular ejection fraction (LVEF) is a prognostic factor in patients with cardiac sarcoidosis (CS), advances in diagnostic imaging have enabled us to detect CS patients with preserved LVEF in the early stage of the disorder. In the present study, we examined the prognosis and risk stratification in CS patients with preserved LVEF. METHODS AND RESULTS: We retrospectively examined 91 consecutive CS patients at our hospital from October 1998 to December 2015 (age, 57±11 years; male/female, 25/66) for the relationship between LVEF and major adverse cardiac events (MACE), including ventricular tachycardia and fibrillation (VT/VF), heart failure (HF) admission, complete atrioventricular block, and all-cause death. CS patients with preserved LVEF (≥50%), as compared with those with reduced LVEF (<50%), showed significantly higher survival free from total MACE or VT/VF (log-rank p<0.001) and significantly smaller LV myocardial damaged area as evaluated by magnetic resonance imaging (MRI) (p<0.001). Although CS patients with preserved LVEF had a good prognosis in general, persistent right ventricular (RV) pacing and reduced EF were significant predictors for MACE after 1 year from introduction of steroid therapy (hazard ratio, 5.25; 95% confidence interval, 1.31-22.50, p=0.020, hazard ratio, 9.01; 95% confidence interval, 2.45-72.09; p=0.001). Patients with the 2 factors (LVEF reduction rate >13.9% per year and persistent RV pacing) had significantly higher risk for MACE, compared with those without them (log-rank p<0.001). CONCLUSION: The present study demonstrates that CS patients with preserved LVEF have better long-term prognosis than those with reduced LVEF in general. However, we should carefully follow them up, since chronological reduction in LVEF and persistent RV pacing could predict worse prognosis in those patients.


Assuntos
Cardiomiopatias/fisiopatologia , Sarcoidose/fisiopatologia , Função Ventricular Esquerda , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Risco , Volume Sistólico , Função Ventricular Direita
9.
Heart Rhythm ; 16(9): 1305-1313, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30898584

RESUMO

BACKGROUND: It is important to identify the risk factors and localization of silent cerebral infarction (SCI), especially in younger patients with atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to examine the characteristics and risk factors for SCI in AF patients, with particular attention to localization of SCI. METHODS: The study enrolled 286 consecutive neurologically asymptomatic patients who underwent AF ablation from January 2014 to July 2017 (age 61.7 ± 10.2 [SD] years; 208 male and 78 female). All patients underwent magnetic resonance imaging (MRI) before ablation. RESULTS: SCIs were classified independently by 2 radiologists as follows: cardiogenic SCI in 19 (10.6%), lacunar SCI in 13 (8.9%), undetermined causes in 6 (1.6%), and no SCI in 248 (controls, 78.7%). Importantly, no patients with CHA2DS2-VASc score 0 had SCI on MRI. In univariable analysis, significant risk factors for lacunar SCI included age (P = .007), hypertension (P = .037), congestive heart failure (P = .040), left atrial (LA) diameter (P = .013), and cardio-ankle vascular index (P = .004). In multivariable analysis, significant risk factors for cardiogenic SCI were AF duration (odds ratio [OR] 1.01; 95% confidence interval [CI] 1.00-1.02; P = .038), ankle-brachial pressure index (OR 0.002; 95% CI 0-0.68; P = .030), and LA abnormality (OR 8.99; 95% CI 2.78-31.00; P <.001), defined by the presence of spontaneous echo contrast and/or decreased LA appendage emptying velocity. CONCLUSION: The study results indicate that among AF patients, SCIs localized in the cerebral cortex and cerebellum are frequently noted, for which cardiogenic mechanisms may be mainly involved; CHA2DS2-VASc score could be useful for screening SCI; and LA abnormality is the specific marker for cardiogenic SCI, providing useful information for risk stratification of SCI.


Assuntos
Fibrilação Atrial , Ablação por Cateter/estatística & dados numéricos , Infarto Cerebral , Imageamento por Ressonância Magnética , Doenças Assintomáticas/epidemiologia , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/epidemiologia , Infarto Cerebral/etiologia , Feminino , Humanos , Japão/epidemiologia , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Medição de Risco , Fatores de Risco
10.
Circ Arrhythm Electrophysiol ; 11(11): e006234, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30571179

RESUMO

BACKGROUND: Several studies have demonstrated the importance of mechanoelectrical interaction in patients with surgically corrected tetralogy of Fallot. However, the significance of atrioventricular conduction disturbance, that is PR interval prolongation, on adverse cardiac events in those patients remains to be elucidated. METHODS: We examined electrocardiograms at baseline and their temporal change in a total of 176 patients with repaired tetralogy of Fallot (49% men; median age, 17.4 years). Then, we evaluated their correlation with right ventricular volume and function measured by cardiac magnetic resonance and the significance as a risk factor of adverse cardiac events: lethal ventricular arrhythmias, atrial arrhythmias, heart failure hospitalization, complete atrioventricular block (AVB), and all-cause death. RESULTS: First-degree AVB was noted in 25 patients (14%). During a median follow-up of 10.0 (5.0-14.2) years, there was a progressive prolongation of PR interval (2.00±3.99 ms/y). Importantly, there were significant correlations between PR interval prolongation and right ventricular enlargement or right ventricular dysfunction. In contrast, in patients who underwent pulmonary valve replacement (n=23), significant shortening of PR interval by pulmonary valve replacement was noted (204±32 versus 176±34 ms; P=0.007). Cox regression analysis showed that first-degree AVB was an independent risk factor for lethal ventricular arrhythmias (hazard ratio, 5.479; 95% CI, 1.181-25.42; P=0.030) and complete AVB (hazard ratio, 27.67; 95% CI, 4.152-184.3; P<0.001) and had a tendency for heart failure hospitalization (hazard ratio, 3.301; 95% CI, 0.864-11.80; P=0.069). In addition, PR interval prolongation >2 ms/y was also a significant risk factor for lethal ventricular arrhythmias, regardless of the presence or absence of first-degree AVB at enrollment (hazard ratio, 24.18; 95% CI, 2.080-281.1; P=0.011). CONCLUSIONS: These results indicate that progressive atrioventricular conduction disturbance is correlated with right ventricular enlargement and could be a useful predictor for increased risk of lethal ventricular arrhythmias in patients with repaired tetralogy of Fallot.


Assuntos
Bloqueio Atrioventricular/etiologia , Bloqueio Atrioventricular/fisiopatologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Sistema de Condução Cardíaco/fisiopatologia , Tetralogia de Fallot/cirurgia , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologia , Adolescente , Adulto , Eletrocardiografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Fatores de Risco
11.
Tohoku J Exp Med ; 240(3): 191-198, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27803433

RESUMO

Brugada syndrome is characterized by distinguishing electrocardiogram (ECG) patterns (coved and saddle-back types with day-to-day variation) and occurrence of lethal tachy-arrhythmias. The appearance of coved type ECG (type 1) is required for the diagnosis of Brugada syndrome, whereas the significance of saddle-back type ECG (type 2), which is inadequate for the diagnosis, has not been fully established. We enrolled 34 consecutive patients with type 2 ECG on outpatient-clinic. Among them, 7 patients were ventricular fibrillation (VF) survivors who were diagnosed as Brugada syndrome with transient appearance of type 1 ECG, and showed type 2 ECG on their first outpatient-clinic visit after the VF event (VF group). The remaining 27 were asymptomatic and never showed type 1 ECG on repeated ECG examinations (control group). The VF group showed significantly longer RJ intervals in leads V1 and V2 and QTc intervals in lead V2 compared with the control group (P < 0.030, P < 0.017, and P < 0.030, respectively). Late potentials, detected on the signal-averaged ECG (SA-ECG), reflect conduction abnormalities and are known as one of the risk markers of arrhythmic events. Among the 34 patients, late potentials were negative in 12 patients belonging to the control group. In conclusion, the SA-ECG could be helpful to identify high-risk patients for its high negative predictive value as the first step, and ECG parameters, including RJ intervals in leads V1 and V2 and QTc interval in lead V2, could be useful for further risk stratification in patients with type 2 Brugada ECG.


Assuntos
Síndrome de Brugada/diagnóstico por imagem , Síndrome de Brugada/fisiopatologia , Eletrocardiografia , Potenciais da Membrana , Pacientes Ambulatoriais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Análise de Regressão , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador
12.
Surg Today ; 42(5): 470-4, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22037939

RESUMO

This report presents the case of an 84-year-old woman who developed tetanus 3 days after the resection of a gangrenous small intestine caused by obturator hernia incarceration. The diagnosis of tetanus was clinically made after the appearance of generalized spastic contractions with opisthotonus. Clostridium tetani organisms residing in the gastrointestinal tract were presumed to have been endogenously inoculated into the strangulated intestine, where it produced tetanospasmin, causing tetanus. The patient successfully recovered after aggressive intensive care. There have been 16 case reports of tetanus occurring after gastrointestinal surgical procedures. Primary care physicians should thus be aware of the fact that, although extremely rare, C. tetani residing in the gastrointestinal tract can provide a possible endogenous source of tetanus infection.


Assuntos
Hérnia do Obturador/cirurgia , Íleo/cirurgia , Íleus/cirurgia , Laparoscopia/efeitos adversos , Tétano/microbiologia , Idoso de 80 Anos ou mais , Clostridium tetani/isolamento & purificação , Feminino , Gangrena/complicações , Gangrena/cirurgia , Hérnia do Obturador/complicações , Humanos , Íleo/diagnóstico por imagem , Íleus/complicações , Radiografia
13.
Am J Physiol Gastrointest Liver Physiol ; 297(4): G840-8, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19713467

RESUMO

Liver dysfunction secondary to severe inflammation is associated with the release of enzymes normally sequestered within hepatocytes. The purpose of these studies was to test the hypothesis that these enzymes are released, at least in part, to modulate potentially deleterious inflammatory processes in distant tissues like the gut. Human Caco-2(BBe) enterocyte-like cells were exposed to cytomix (IFN-gamma, TNF-alpha, and IL-1beta) in the absence or presence of human liver cytosol (LC). Nitric oxide (NO(*)) and inducible nitric oxide synthase (iNOS) protein production were measured by the Griess assay and Western analysis, respectively. Cytomix induced the expression of iNOS and release of NO(*). LC protein (400 microg/ml) added to the basal compartment but not apical compartment completely blocked the release of NO(*) but only slightly decreased the magnitude of iNOS protein induction. Ultrafiltration and ultracentrifugation studies demonstrated that microsome-associated arginase-1 activity was the iNOS-suppressing activity in LC. Liver arginase required activation by a <10-kDa factor that was present in supernatants of cytomix-stimulated cells. The selective iNOS inhibitor l-N(6)-(1-iminoethyl)-lysine.2HCl prevented production of this factor. The biotin switch assay detected increased S-nitrosylation of arginase-1 after incubation with supernatants from immunostimulated Caco-2 cells. Serum from endotoxemic mice contained significantly greater arginase activity compared with serum from control mice. Furthermore, the ratio of mucosal monomeric to dimeric iNOS increased in endotoxemic mice compared with controls. Thus reciprocal activation of arginase-1 and modulation of mucosal iNOS activity may be protective because it would be expected to decrease NO(*)-dependent intestinal barrier dysfunction on that basis.


Assuntos
Arginase/metabolismo , Enterócitos/enzimologia , Inflamação/enzimologia , Fígado/enzimologia , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Animais , Western Blotting , Células CACO-2 , Modelos Animais de Doenças , Regulação para Baixo , Enterócitos/efeitos dos fármacos , Enterócitos/imunologia , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Humanos , Inflamação/induzido quimicamente , Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Interferon gama/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos , Fígado/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Multimerização Proteica , Processamento de Proteína Pós-Traducional , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismo
14.
Am J Physiol Regul Integr Comp Physiol ; 297(2): R362-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19494177

RESUMO

Lipopolysaccharide (LPS) is an important factor in sepsis. LPS given by intraperitoneal injection induces intestinal hyperpermeability and bacterial translocation in animals and stimulates hepatic Kupffer cells to release TNF-alpha into the bile. This study aims to test the hypothesis that in response to LPS stimulation, hepatic Kupffer cells and extrahepatic macrophages release a large amount of the inflammatory cytokine high-mobility group box 1 (HMGB1) into the bile and that bile containing HMGB1 contributes to gut barrier dysfunction in experimental endotoxemia. To test this, rat common bile ducts were catheterized and bile flow rate was monitored before and during the LPS administration. Eight hours after LPS challenge, anti-HMGB1 neutralizing antibody or nonimmune (sham) IgG was injected into the duodenal lumen of endotoxemic rats; normal mice were also gavaged with normal or endotoxemic rat bile (bile collected from LPS-treated rats). We found that after LPS challenge, the bile flow rate in rats was significantly decreased at the 4- to 12-h time points, TNF-alpha concentration in the bile was markedly elevated at the 3- to 4-h time points, and bile HMGB1 levels were significantly increased at the 8- to 12-h time points. Duodenal injection with anti-HMGB1 antibody reversed LPS-induced gut barrier dysfunction in rats. In addition, feeding endotoxemic rat bile to normal mice significantly increased both mucosal permeability and bacterial translocation. The increase in permeability and bacterial translocation was reversible following removal of HMGB1 from the endotoxemic rat bile. These findings document that bile HMGB1 mediates gut barrier dysfunction in experimental endotoxemia.


Assuntos
Bile/metabolismo , Endotoxemia/fisiopatologia , Proteína HMGB1/metabolismo , Mucosa Intestinal/fisiopatologia , Animais , Anticorpos/imunologia , Anticorpos/farmacologia , Claudina-1 , Dextranos/metabolismo , Endotoxemia/induzido quimicamente , Endotoxemia/metabolismo , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Proteína HMGB1/sangue , Proteína HMGB1/imunologia , Íleo/efeitos dos fármacos , Íleo/metabolismo , Íleo/microbiologia , Íleo/fisiopatologia , Interleucina-6/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ocludina , Permeabilidade/efeitos dos fármacos , Fosfoproteínas/metabolismo , Ratos , Ratos Sprague-Dawley , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína da Zônula de Oclusão-1
15.
Crit Care ; 13(2): R55, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19358737

RESUMO

INTRODUCTION: Acetaminophen (APAP) toxicity is the most common cause of acute liver failure in the US and Europe. Massive hepatocyte necrosis is the predominant feature of APAP-induced acute liver injury (ALI). Liver regeneration is a vital process for survival after a toxic insult, it occurs at a relative late time point after the injurious phase. Currently, N-acetylcysteine (NAC), a glutathione precursor, is the antidote for acetaminophen overdose. However, NAC is effective only for patients who present within hours of an acute overdose, and is less effective for late-presenting patients. It is possible that in delayed patients, previously reduced endogenous glutathione (GSH) level has restored and prolonged treatment with NAC might be toxic and impair liver regeneration. Therefore, we hypothesize that prolonged treatment with NAC impairs liver regeneration in ALI induced by APAP. METHODS: ALI was induced in C57BL/6 male mice by a single dose of APAP (350 mg/kg) by intraperitoneal injection. After two hours of APAP challenge, the mice were given 100 mg/kg NAC dissolved in 0.6 mL saline, or saline treatment every 12 hours for a total of 72 hours. RESULTS: Seventy-two hours after APAP challenge, compared with saline treatment, NAC treatment significantly increased serum transaminases (alanine transaminase/aspartate aminotransferase), induced evident hepatocyte vacuolation in the periportal area and delayed liver regeneration seen in histopathology. This detrimental effect was associated with reduced hepatic nuclear factor (NF)-kappaB DNA binding and decreased expression of cell cycle protein cyclin D1, two important factors in liver regeneration. CONCLUSIONS: Prolonged treatment with NAC impairs liver regeneration in ALI induced by APAP.


Assuntos
Acetaminofen/intoxicação , Analgésicos não Narcóticos/intoxicação , Antídotos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Cistina/análogos & derivados , Overdose de Drogas/tratamento farmacológico , Alanina Transaminase/sangue , Animais , Antídotos/administração & dosagem , Antídotos/farmacologia , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Cistina/administração & dosagem , Cistina/farmacologia , Cistina/uso terapêutico , Modelos Animais de Doenças , Glutationa/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Tempo , Resultado do Tratamento
16.
Shock ; 22(5): 446-52, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15489637

RESUMO

Interaction between the products of intestinal bacteria and the intestinal epithelial cells is a key event in understanding the biological, physiological, and pathological functions of the intestinal epithelium. Here, we examined the effect of butyrate, one of the major intestinal bacterial products, on hypoxia-inducible factor-1 (HIF-1) activity under hypoxic conditions in intestinal epithelial cells. HIF-1 activity was assessed by luciferase assay using cytoplasmic extracts of intestinal epithelial cells, Caco-2, and IEC-6 cells. These cells were transiently transfected with hypoxia response element (HRE)-luciferase reporter plasmids and cultured under hypoxic conditions in the presence or absence of sodium butyrate (NaB). The effect of NaB on HRE DNA binding activity in Caco-2 cells under hypoxic conditions was assessed by electrophoretic mobility shift assay. Expression of a hypoxia-responsive gene encoding intestinal trefoil factor (ITF) in Caco-2 cells after NaB treatment was assessed using reverse-transcription PCR. The barrier function of Caco-2 cells under hypoxic conditions was also evaluated by transepithelial electrical resistance measurement. NaB suppressed up-regulation of HIF-1 transcriptional activity under hypoxic conditions in Caco-2 and IEC-6 cells. In parallel, NaB reduced HRE DNA binding activity under the same conditions. Furthermore, NaB down-regulated enhanced transcription of ITF gene. Addition of NaB under hypoxic conditions delayed recovery of transepithelial electrical resistance of the monolayers after hypoxia-reoxygenation treatment. These findings indicate that NaB suppresses HIF-1 transcriptional activity on hypoxia-responsive genes by reducing the HRE DNA binding activity under hypoxic conditions in intestinal epithelial cells.


Assuntos
Butiratos/farmacologia , Células Epiteliais/metabolismo , Hipóxia , Mucosa Intestinal/metabolismo , Fatores de Transcrição/metabolismo , Animais , Células CACO-2 , Linhagem Celular , Linhagem Celular Tumoral , Células Cultivadas , Regulação para Baixo , Eletrofisiologia , Células Epiteliais/efeitos dos fármacos , Ácidos Graxos/química , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Intestinos/efeitos dos fármacos , Luciferases/metabolismo , Mucinas/metabolismo , Proteínas Musculares/metabolismo , Peptídeos/metabolismo , Plasmídeos/metabolismo , Ratos , Elementos de Resposta , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Oxibato de Sódio/farmacologia , Fatores de Tempo , Transfecção , Fator Trefoil-2 , Regulação para Cima
17.
Infect Immun ; 72(4): 2014-21, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15039321

RESUMO

We report here the induction of specific protective cellular immunity against Mycobacterium tuberculosis by the employment of vaccination with recombinant attenuated Listeria monocytogenes strains. We constructed self-destructing attenuated L. monocytogenes Delta 2 strains carrying eukaryotic expression plasmids for the antigen 85 complex (Ag85A and Ag85B) and for MPB/MPT51 (mycobacterial protein secreted by M. bovis BCG/mycobacterial protein secreted by M. tuberculosis) molecules. Infection of these recombinant bacteria allowed expression of the genes in the J774A.1 murine macrophage cell line. Intraperitoneal vaccination of C57BL/6 mice with these recombinant bacteria was capable of inducing purified protein derivative-specific cellular immune responses, such as foot pad reactions, proliferative responses of splenocytes, and gamma interferon production from splenocytes, suggesting the efficacy of vaccination against mycobacterial infection by use of these recombinant L. monocytogenes strains. Furthermore, intravenous vaccination with recombinant bacteria carrying expression plasmids for Ag85A, Ag85B, or MPB/MPT51 in BALB/c mice elicited significant protective responses, comparable to those evoked by a live Mycobacterium bovis BCG vaccine. Notably, this is the first report to show that MPB/MPT51 is a major protective antigen in addition to Ag85A and Ag85B, which have been reported to be major mycobacterial protective antigens.


Assuntos
Imunidade Celular , Listeria monocytogenes/genética , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia , Vacinas Atenuadas/imunologia , Vacinas de DNA/imunologia , Aciltransferases/genética , Animais , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Bovinos , Linhagem Celular , Imunização , Macrófagos , Camundongos , Camundongos Endogâmicos BALB C , Plasmídeos/genética , Vacinas contra a Tuberculose/administração & dosagem , Vacinas contra a Tuberculose/genética , Vacinas contra a Tuberculose/imunologia , Tuberculose Pulmonar/prevenção & controle , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/genética , Vacinas de DNA/administração & dosagem
18.
J Vasc Surg ; 38(2): 340-5, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12891118

RESUMO

OBJECTIVE: We investigated the relation between flow pattern in abdominal aortic aneurysm (AAA) and intravascular coagulopathy characterized by increased fibrin degradation product d-dimer (FDP-DD) or thrombin-antithrombin complex (TAT). Materials and methods The ratio of AAA maximum endoluminal diameter (diameter of flow channel) (n = 23) to diameter of the aorta between the superior mesenteric and renal arteries (R ratio) was measured with three-dimensional computed tomography angiography. Digital subtraction angiography was performed with 20 mL (10 mL/s) of contrast agent injected from the suprarenal portion of the abdominal aorta. The duration between the time when average gray scale in the AAA reached maximum and average region of interest gray scale decreased to half-maximum (bolus transit time in AAA [BTT(AAA)]) was calculated. RESULTS: Single correlation coefficient with statistic significance was detected between R ratio and BTT(AAA) (BTT(AAA) = 2.54 x R ratio + 3.65; r(2) =.30; P =.042). Among the three-dimensional morphologic and videodensitometric variants, BTT(AAA) was the most determinant factor associated with FDP-DD (FDP-DD = - 8.647 + 2.029 x BTT(AAA); r(2) =.448; P =.005). The most efficient predictors for TAT were maximum AAA endoluminal diameter (R(endomax)) and BTT(AAA) (TAT = - 14.007 + 2.102 x BTT(AAA) + 0.296 x R(endomax), r(2) =.360; P =.0069). CONCLUSIONS: Our findings suggest a close link between abnormal flow pattern in AAA and activation of the coagulation-fibrinolysis system. Videodensitometric blood flow analysis can be useful in investigation of the pathophysiology of phenomena related to abnormal flow field in AAA.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/fisiopatologia , Coagulação Intravascular Disseminada/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Idoso , Angiografia Digital , Antitrombina III/metabolismo , Aneurisma da Aorta Abdominal/complicações , Velocidade do Fluxo Sanguíneo/fisiologia , Coagulação Intravascular Disseminada/complicações , Coagulação Intravascular Disseminada/fisiopatologia , Feminino , Humanos , Imageamento Tridimensional , Masculino , Peptídeo Hidrolases/metabolismo , Fluxo Sanguíneo Regional/fisiologia , Tomografia Computadorizada Espiral
19.
J Vasc Surg ; 36(6): 1225-30, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12469055

RESUMO

OBJECTIVE: Interruption of incompetent perforating veins (PVs) is important for varicose vein surgery. The purpose of this study was to evaluate the preoperative and intraoperative diameter-reflux relationship of PVs and to evaluate the accuracy of preoperative duplex scanning in patients with varicose vein. METHODS: Patients with primary varicose veins were retrospectively investigated. Diameters and reflux of PVs were evaluated before surgery with color flow duplex ultrasound scan (US). During operation, the incompetent PVs were defined as those that showed an outward spurt of blood flow from the stump of the PVs. The sensitivity and specificity of US in the detection of reflux of PVs were calculated. Competent versus incompetent vein diameters were compared with the Student t test and one-way analysis of variance. RESULTS: Three hundred twenty-four calf PVs were detected in 304 legs of 175 patients with varicose vein. Diameters of competent and incompetent PVs confirmed with intraoperative finding averaged 2.67 +/- 1.10 mm (n = 28) and 3.28 +/- 1.01 mm (n = 58), respectively, at the upper calf (P =.012), 2.85 +/- 0.85 mm (n = 53) and 3.68 +/- 0.94 mm (n = 137), respectively, at the lower calf (p <.001), and 2.67 +/- 0.99 mm (n = 14) and 3.27 +/- 0.66 mm (n = 22), respectively, at the posterior calf (P =.036). The overall sensitivity of detection of reflux with US was 87.7%, and the specificity was 75.3%. Diameters of true-incompetent PVs and false-incompetent PVs were 3.59 +/- 0.94 mm (n = 199) and 3.31 +/- 0.84 mm (n = 24), respectively (P =.157). Diameters of true-competent PVs and false-competent PVs were 2.61 +/- 0.91 mm (n = 73) and 2.89 +/- 0.82 mm (n = 28), respectively (P =.158). CONCLUSION: Although the diameter of incompetent PVs was larger than that of competent PVs in both US and intraoperative findings, diameter measurement alone can not completely distinguish competent and incompetent PVs. The sensitivity and specificity of reflux obtained with US showed that the accuracy of preoperative duplex scanning to evaluate PV competency was not sufficient.


Assuntos
Cuidados Intraoperatórios , Perna (Membro)/diagnóstico por imagem , Perna (Membro)/cirurgia , Cuidados Pré-Operatórios , Ultrassonografia Doppler em Cores , Varizes/diagnóstico por imagem , Varizes/cirurgia , Insuficiência Venosa/diagnóstico por imagem , Insuficiência Venosa/cirurgia , Adulto , Idoso , Feminino , Humanos , Perna (Membro)/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Varizes/complicações , Insuficiência Venosa/complicações
20.
Surgery ; 132(1): 66-71, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12110797

RESUMO

BACKGROUND: Plasma platelet-activating factor-acetylhydrolase (PAF-AH) is known to catalyze platelet-activating factor (PAF). The single nucleotide polymorphism (SNP) of plasma PAF-AH gene (G994 -->T in exon 9) is associated with a decreased level of plasma PAF-AH activity. This study analyzed the risk of the SNP on graft occlusion of femoropopliteal bypass in patients with atherosclerotic occlusive disease. METHODS: We retrospectively assessed the patency of 50 above-knee femoropopliteal bypass grafting in 50 patients. Genomic DNA was analyzed for the mutant allele. Plasma PAF-AH activity was measured by radioimmunoassay. RESULTS: The 10-year cumulative primary patency of the bypass was 78.5% in GG (normal genotype) and 50.0% in GT (heterozygous) or TT (homozygous deficient) (P <.05, Kaplan-Meier method). The relative risk of graft failure in GT or TT genotypes was 1.68 (P =.08, Cox proportional hazards model). PAF-AH activity (nmol/min/50 microL) was 1.92 +/- 0.82 in patients with patent grafts and 1.42 +/- 0.47 in those with occluded grafts (mean +/- standard deviation; P <.05, unpaired t test). CONCLUSIONS: The SNP of plasma PAF-AH was associated with a decreased primary graft patency of above-knee femoropopliteal bypass. The risk of graft failure may increase when patients have the SNP. To confirm the independent risk of graft failure by the SNP, further study is necessary and prospective study should be performed.


Assuntos
Implante de Prótese Vascular , Artéria Femoral/cirurgia , Fosfolipases A/genética , Fator de Ativação de Plaquetas/genética , Polimorfismo de Nucleotídeo Único , Artéria Poplítea/cirurgia , Grau de Desobstrução Vascular/genética , 1-Alquil-2-acetilglicerofosfocolina Esterase , Idoso , Arteriopatias Oclusivas/genética , Arteriopatias Oclusivas/cirurgia , Feminino , Genótipo , Oclusão de Enxerto Vascular/genética , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco
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