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1.
Int J Mol Sci ; 23(22)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36430717

RESUMO

Maternal high-fat (HF) diet exposure in utero may affect fetal development and cause metabolic problems throughout life due to lipid dysmetabolism and oxidative damage. Metformin has been suggested as a potential treatment for body weight reduction and nonalcoholic fatty liver disease, but its reprogramming effect on offspring is undetermined. This study assesses the effects of maternal metformin treatment on hepatic steatosis in offspring caused by maternal HF diet. Female rats were fed either a control or an HF diet before conception, with or without metformin treatment during gestation, and placenta and fetal liver tissues were collected. In another experiment, the offspring were fed a control diet until 120 d (adult stage). Metformin treatment during pregnancy ameliorates placental oxidative stress and enhances placental glucose transporter 1 (GLUT1), GLUT3, and GLUT4 expression levels through 5' adenosine monophosphate-activated protein kinase (AMPK) activation. Maternal metformin treatment was shown to reprogram maternal HF diet-induced changes in offspring fatty liver with the effects observed in adulthood as well. Further validation is required to develop maternal metformin therapy for clinical applications.


Assuntos
Metformina , Hepatopatia Gordurosa não Alcoólica , Feminino , Ratos , Gravidez , Animais , Dieta Hiperlipídica/efeitos adversos , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Placenta/metabolismo , Metformina/farmacologia , Metformina/uso terapêutico , Metformina/metabolismo , Gorduras na Dieta/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo
2.
Front Pediatr ; 9: 687276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336741

RESUMO

Background: The objective of this research was to evaluate the fertility of Taiwanese women with diagnoses of congenital heart diseases (CHDs). The study also investigated how different forms of CHDs may have variously influenced fertility. Methods: We directed this nationwide, population-based and retrospective matched-cohort research by using data from the Taiwan National Health Insurance Research Database. The CHD group (n = 6602) included women with congenital structural heart diseases, aged 16-45 years in 2000. The non-CHD group (n = 6602) was matched according to urbanization and income. The outcomes, involving live birth, abortion, and fertility rates, were followed until the end of 2013. Poisson regression was used to evaluate the incidence rate ratios (IRRs). Results: The CHDs had an inferior rate of live births (IRR 0.74 [95% CI 0.71-0.78]) than the non-CHD group. There was also a lower fertility rate in the CHD group (IRR 0.81 [95% CI 0.78-0.84]) than the non-CHD group. Abortion rates between the two groups were similar. Conclusion: Congenital structural heart disease compromises female fertility, even among patients with simple forms of CHDs. It is suggested that pregnant patients with CHDs are early appeared to and advised personally with multidisciplinary care to improve their outcomes.

3.
Acta Cardiol Sin ; 37(1): 58-64, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33488028

RESUMO

BACKGROUND: Coronary cameral fistula (CCF), a rare abnormal coronary communication to cardiac chambers, may lead to coronary steal phenomenon and increase cardiac overload. We investigated the clinical and cardiovascular characteristics in children before and after transcatheter closure. METHODS: We retrospectively reviewed pediatric patients with CCFs diagnosed by echocardiography in a tertiary medical center between 1998 and 2019. Basic information, echocardiogram, catheterization and interventional procedures were obtained from medical charts. RESULTS: A total of 12 pediatric subjects were included. The median ages at diagnosis and catheterization were 0.2 and 2.8 years, respectively. All CCFs were unilateral and single with varying degrees of coronary artery dilatation and aneurysm formation and diagnosed by echocardiography. The median follow-up periods before and after catheterization were 2.5 and 7.3 years, respectively. Seven of the CCFs originated from the left side. The drainage sites were all right hearts. Before catheterization, the median size of the proximal end of the fistula was 3.1 mm, concomitant with enlargement of conduit coronary arteries. Eleven of the 12 patients underwent transcatheter closure using coils in six and vascular plugs in five. Only one patient had a significant increase in pulmonary-to-systemic flow ratio. The size of conduit coronary artery gradually decreased and the size of ipsilateral coronary branch increased after closure. CONCLUSIONS: Transcatheter occlusion for CCFs in children is safe and effective. The morphology of CCFs varies with the degrees of dilation, tortuosity, and aneurysmal formation. After occlusion, alterations in the size of coronary arteries may be a prognostic indicator.

4.
J Pediatr ; 228: 58-65.e3, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32712283

RESUMO

OBJECTIVES: To investigate the cardiovascular features and endothelium in neonates born to mothers with preeclampsia. STUDY DESIGN: In this combined observational cohort and case-control study, neonates born to mothers with normotension and mothers with preeclampsia were recruited at a neonatal intensive care unit of a tertiary medical center. Cardiovascular measurements by echocardiography and the clinical measures upon admission were analyzed. Vascular cell adhesion molecule-1 expression in umbilical arteries and in in vitro endothelial cell stimulation with plasma were examined. Continuous data were compared using nonparametric analysis, and their relationships were analyzed using linear regression. Binary logistic regression was performed in the model of adjustment of birth body weight and for multivariate analysis. RESULTS: In the cohort, almost all cardiovascular segments positively correlated to birth weight. Notably, neonates (n = 65) of mothers with preeclampsia had significantly larger coronary arteries at birth than neonates of mothers with normotension (n = 404) (median size of left main coronary artery 1.36 mm versus 1.08 mm, p <0.001; median size of right coronary artery, RCA 1.25 mm versus 1.0 mm, p <0.001). The size of the right coronary artery positively correlated to the maternal antepartum diastolic blood pressure (r = 0.298, P = .018) and was associated with in-hospital death (P < .001). Meanwhile, endothelial vascular cell adhesion molecule-1 expression was significantly increased in the umbilical arteries of the preeclamptic group and following preeclamptic cord-plasma stimulation. The latter also correlated with their relative coronary sizes. CONCLUSIONS: Neonates of mothers with preeclampsia had distinctive coronary dilatation at birth. Coronary size might be useful as a severity index of neonatal endothelial inflammation as a result of maternal preeclampsia.


Assuntos
Doença da Artéria Coronariana/etiologia , Vasos Coronários/fisiopatologia , Endotélio Vascular/fisiopatologia , Inflamação/diagnóstico , Pré-Eclâmpsia/diagnóstico , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Dilatação Patológica/diagnóstico , Dilatação Patológica/etiologia , Dilatação Patológica/fisiopatologia , Endotélio Vascular/diagnóstico por imagem , Feminino , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Inflamação/fisiopatologia , Masculino , Gravidez , Estudos Retrospectivos
5.
Eur J Med Chem ; 201: 112422, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32569926

RESUMO

P-Glycoprotein (P-gp) overexpression is a major mechanism by which cancer cells acquire the multidrug resistance (MDR) phenotype, and is associated with poor clinical outcome in patients. In an effort to develop MDR-reversal agents, we synthesized and evaluated a series of thiophenylbenzofuran derivatives (4-31) as P-gp inhibitors, among which compounds 4, 10, and 14 represented the optimal agent in reversing the MDR phenotype. These P-gp inhibitors were dramatically effective than verapamil in sensitizing the human ABCB1-overexpressing ABCB1/Flp-In™-293 cells and MDR KBvin cells to a series of chemotherapeutic agents, including vincristine and paclitaxel, as manifested by multi-fold decreases in the respective IC50 values to therapeutically attainable levels.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/farmacologia , Benzofuranos/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Benzofuranos/síntese química , Benzofuranos/metabolismo , Sítios de Ligação , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligação Proteica
6.
Future Med Chem ; 12(13): 1227-1237, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32432891

RESUMO

Background: Modulators of LXRα are of high pharmacological interest as LXRα regulates fatty acid metabolism, inflammatory processes and cancer. We aim to identify new LXRα modulators and to recognize a distinguishable feature of agonists. Results&methodology: The ligand self-dock and largest-cavity-size searching purposely located two appropriate ligand-binding sites to reach the two aims. One is identifying the new modulators from Maybridge library. 20 new compounds are confirmed by the in vitro reporter gene assay. The other is denoting an agonist by at least one best docking pose having one hydrogen bond to LXRα Helix12 His421. Conclusion: Based on the quality x-ray binding pocket, we can identify new LXRα modulators and distinguish between agonists and antagonists by molecular docking.


Assuntos
Receptores X do Fígado/agonistas , Compostos Orgânicos/farmacologia , Sítios de Ligação/efeitos dos fármacos , Cristalografia por Raios X , Humanos , Ligantes , Simulação de Acoplamento Molecular , Compostos Orgânicos/química
7.
Acta Cardiol Sin ; 35(3): 335-341, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31249464

RESUMO

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is widely used in patients with potentially reversible acute cardiac and/or pulmonary failure who are unresponsive to conventional treatment. Patients with profound left ventricular (LV) dysfunction under venous-arterial (V-A) ECMO may experience LV distention, pulmonary edema, and thrombus formation. It is critical to unload the left ventricle to prevent such complications. The aim of this study was to identify the risks, timing and methods of LV decompression in pediatric peripheral ECMO. METHODS: Between August 2006 and November 2017, 51 patients received peripheral ECMO support in our pediatric intensive care unit. All of them were less than 18 years of age and non-cardiotomy surgery-related. We retrospectively reviewed the patients' clinical presentations, decompression methods and outcomes. RESULTS: The overall success rate of ECMO removal was 76.5% (39/51), and the survival rate after discharge was 62.7% (32/51). The myocarditis group had the most favorable outcomes among the ECMO patients (100% survival). LV decompression was needed in 12 patients who had profound LV dysfunction under V-A ECMO. Five patients received medical treatment successfully, and the other 7 patients underwent intra-aortic balloon pump (IABP) procedures. In the IABP group, 1 patient still needed further pigtail-decompression. All of our decompression patients survived with good neurological outcomes (Glasgow Outcome Scale 5). CONCLUSIONS: The patients with profound LV dysfunction under peripheral VA ECMO were at risk of thromboembolic events and LV decompress was needed. If medical decompression fails, IABP is a feasible approach for LV decompression in pediatric peripheral ECMO.

8.
J Formos Med Assoc ; 118(1 Pt 1): 83-91, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29361384

RESUMO

BACKGROUND/PURPOSE: To investigate the correlations among endothelial function assessment parameters, asymmetric dimethylarginine (ADMA)-related biomarkers, and traditional risk factors in adipose children. METHODS: We enrolled adipose children aged 7-18 years between July 2014 and August 2016 as well as normal-weight controls from the outpatient clinic. Vascular measurements including echocardiography, carotid intima media thickness, pulse wave velocity (PWV), and flow-mediated dilation (FMD) were measured. Venous blood samples including traditional metabolic and endothelial dysfunction parameters were analyzed. Participants were grouped as adipose vs. normal-weight and as adipose with hypertension vs. adipose without hypertension. Clinical presentations, laboratory data, and cardiovascular measurement were compared. RESULTS: Of the 105 enrolled children, 85 were adipose. Adipose children had higher systolic blood pressure, larger left ventricular (LV) mass, and adverse traditional metabolic biomarkers. FMD was significantly reduced (8.25 (5.32-12.06) % vs. 12.49 (7.18-16.58) %, p = 0.018) in the adipose group. PWV was markedly increased (4.65 (4.2-5.5) m/sec vs. 3.95 (3.38-4.35) m/sec, p < 0.001) in the hypertensive adipose children. Endothelial dysfunction parameters were not significantly changed in this study. CONCLUSION: Adipose children were at higher risk of hypertension and LV hypertrophy. FMD, PWV and traditional cardiovascular biomarkers can detect subtle vascular changes. Hypertension is an important sign of arterial involvement in adipose children. Although ADMA-related biomarkers were not statistically significant, future studies are needed to confirm its correlation with adiposity and hypertension in children. The early detection and prevention of endothelial dysfunction may decrease the rate of progression to cardiovascular consequences in later life.


Assuntos
Biomarcadores/sangue , Endotélio Vascular/fisiopatologia , Hipertensão/fisiopatologia , Obesidade Infantil/fisiopatologia , Adolescente , Pressão Sanguínea , Índice de Massa Corporal , Espessura Intima-Media Carotídea , Criança , Estudos Transversais , Ecocardiografia , Feminino , Humanos , Hipertensão/complicações , Modelos Logísticos , Masculino , Obesidade Infantil/complicações , Análise de Onda de Pulso , Fatores de Risco , Taiwan
10.
Medicine (Baltimore) ; 97(50): e13747, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30558097

RESUMO

RATIONALE: Coronary artery fistulae (CAF) are uncommon heart lesions, but they are the most frequent significant hemodynamic congenital coronary anomaly. Transcatheter closure is an alternative treatment and a variety of techniques and devices were reported to use for the closure of congenital coronary fistulae. PATIENT CONCERNS: We reported a 5-year-10-month-old boy who was diagnosed as CAF at birth. Follow-up transthoracic echocardiography showed persistent CAF and progressed dilatation of the left coronary artery. DIAGNOSES: Coronary angiography showed torturous coronary vessel and CAF at the distal segment of the left circumflex artery (LCX). INTERVENTION: Antegrade approach with Amplatzer Vascular Plug was used due to the retrograde approach failed and showed a good result. OUTCOMES: During a 3-year follow-up period, the patient showed no symptoms and demonstrated good exercise ability. Follow-up coronary angiography showed the Amplatzer vascular plug was located at an adequate position without a residual shunt from the CAF, and the diameter of the left coronary artery regressed when compared to previous angiography results. LESSONS: The antegrade approach is a feasible method for closing CAF if torturous vessels are noted and fistulae occur at the distal portion of the coronary artery. A large randomized study or case series are needed to investigate the comparison of antegrade and retrograde method for the closure of CAF.


Assuntos
Anomalias dos Vasos Coronários/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Fístula Vascular/diagnóstico por imagem , Assistência ao Convalescente , Cateterismo Cardíaco/métodos , Pré-Escolar , Angiografia Coronária/métodos , Anomalias dos Vasos Coronários/patologia , Vasos Coronários/patologia , Ecocardiografia/métodos , Humanos , Masculino , Dispositivo para Oclusão Septal/normas , Resultado do Tratamento , Fístula Vascular/patologia , Fístula Vascular/cirurgia
11.
J Formos Med Assoc ; 117(2): 141-146, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28404481

RESUMO

BACKGROUND/PURPOSE: To investigate whether a palm-held ultrasonocardiographic scanner would be useful for screening and follow-up in congenital heart disease (CHD). METHODS: We retrospectively reviewed the echocardiographic images from June 1, 2014 to November 1, 2014. All patients underwent two ultrasonographic examinations including palm-held scanner examination and standard echocardiography. To compare the quality of the two instruments, we developed a diagnostic scoring system ranging from 1 point to 10 points, with 10 points indicating the best quality. Two experienced echocardiographers retrospectively reviewed all recorded images blindedly and gave each examination a score. Comparisons of diagnostic score between two equipments were performed. RESULTS: A total of 262 patients' images were reviewed. All cardiac lesions could be detected with both instruments. The mean diagnostic score of palm-held scanner and standard echocardiography were 8.20±0.53 versus 9.64±0.37 (p<0.05) in color image and 7.00±1.05 versus 8.56±1.14 (p<0.05) in gray-scale two-dimensional image, respectively. When we compared the score between the two instruments in individual CHDs, we found standard echocardiography had better quality except for detecting muscular ventricular septal defect and pulmonary regurgitation. CONCLUSION: The diagnostic sensitivity of palm-held scanner in detecting CHD was very good. Despite both instruments having a high diagnostic score in detecting CHD, standard echocardiography had better quality. Traditional echocardiography is still the standard tool for CHD evaluation. However, the palm-held scanner can support physical examination for initial screening and follow-up, and offer cardiologists an opportunity to visualize and listen to the heart at any time.


Assuntos
Ecocardiografia/instrumentação , Cardiopatias Congênitas/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Confiabilidade dos Dados , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taiwan , Adulto Jovem
12.
Eur J Med Chem ; 125: 1023-1035, 2017 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-27810590

RESUMO

Treatment of cancer patients with chemotherapeutic drugs is often associated with the occurrence of tumors with a multidrug resistance (MDR). Furthermore, the relation between overexpression of P-glycoprotein (P-gp) and resistant cancers has been well established. In this study, novel 2-aminobenzofuran derivatives were synthesized and tested for their ability to modulate P-gp mediated multidrug resistance (MDR) in vitro. The most potent compound, 43, increased P-gp inhibitory activity at 5 µM by 11.12-fold and was 3.6-fold stronger than verapamil. Furthermore, 43 can sensitize Flp-In™-293/MDR cells toward vincristine, paclitaxel and doxorubicin by 17.95-fold, 13.68-fold and 26.43-fold at 2.5 µM, respectively. 43 also can sensitize the resistant cancer cell line KBvin toward vincristine, paclitaxel and doxorubicin by 246.43-fold, 38.72-fold and 5.16-fold at 2.5 µM, respectively. In conclusion, important aspects for developing potent P-gp inhibitors have been emphasized in this study, providing a starting point for the further structural optimization of P-gp inhibitors.


Assuntos
Benzofuranos/química , Benzofuranos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/química , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Aminação , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Paclitaxel/farmacologia , Relação Estrutura-Atividade , Vincristina/farmacologia
13.
J Formos Med Assoc ; 115(7): 571-6, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26138373

RESUMO

BACKGROUND/PURPOSE: To investigate mid- to long-term outcomes in children with coronary artery fistula (CAF). METHODS: We retrospectively reviewed the medical records of patients seen between September 1996 and August 2011. We enrolled those diagnosed with CAF via echocardiography (Philips SONOS 7500 system and Philips IE33) or angiography. The mean follow time was 42.58 ± 3.4 months (range, 1-166 months). For comparative purposes, participants were grouped as acquired versus congenital, and symptomatic versus asymptomatic. We also measured the size of the coronary artery (CA) in patients with CA dilatation (CAD). RESULTS: Out of 122 CAF patients, spontaneous closure was detected in 37 patients at 21.59 ± 3.45 months after diagnosis. This timeframe did not differ between the acquired and congenital groups (21.64 ± 6.26 months vs. 21.57 ± 4.15 months; p = 0.991). Ninety patients were asymptomatic and remained so; their spontaneous closure rate was 28.89%. Moreover, 24 patients had CAD, including 17 with Kawasaki disease and seven with congenital CAF. The CAs of all congenital-CAF-plus-CAD patients were initially > 5 mm; these patients underwent percutaneous transcatheter intervention, and their CA sizes decreased significantly (6.11 ± 0.79 mm vs. 3.76 ± 0.36 mm; p = 0.002). CONCLUSION: With the advanced sensitivity of echocardiography, CAF can be detected more easily than ever before. Most patients with small CAFs are asymptomatic and may experience spontaneous closure. Therefore, management of CAF depends on symptoms; if patients are asymptomatic and have small CAFs, intervention may not be necessary, especially in acquired cases. However, if patients present with symptoms or persistent dilatation of the proximal CA, surgical or percutaneous closure should be performed.


Assuntos
Anomalias dos Vasos Coronários/complicações , Anomalias dos Vasos Coronários/diagnóstico por imagem , Fístula Vascular/complicações , Fístula Vascular/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Angiografia Coronária , Anomalias dos Vasos Coronários/cirurgia , Vasos Coronários/cirurgia , Ecocardiografia Doppler em Cores , Feminino , Seguimentos , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Estudos Retrospectivos , Taiwan , Resultado do Tratamento , Fístula Vascular/cirurgia
14.
Int Heart J ; 56(4): 428-31, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26118595

RESUMO

The aim of this study was to identify the factors that influence atrial septal occluder dislodgement in adults and children.From June 2003 to June 2013, a total of 213 patients (115 adults and 98 children) diagnosed with secundum atrial septal defects (ASD) underwent transcatheter closure of their defects with an atrial septal occluder (ASO) in our hospital. The ASO was implanted under transesophageal echocardiography (TEE) guidance. Ten patients suffered from ASO dislodgement, and the other 203 patients comprised the successful group. We compared the preprocedural data related to general demographics, defects, margins, and minor post-implantation complications between the two groups with the goal of identifying the factors that affected ASO dislodgement.Univariate logistic regression analyses identified a high Qp/Qs value, the Qp/Qs ratio > 3.13, ASO size, ASO size greater than 32 mm, ASO size/BSA ratio > 15.13 and IAS erosion, floppiness or aneurysm formation as factors with significant predictive value. Multivariate analysis revealed that a Qp/Qs ratio > 3.13, and interatrial septum (IAS) erosion, floppiness and aneurysm formation post-implantation were independent predictors of ASO dislodgement (P = 0.001 and P = 0.006, respectively) in both adults and children.Percutaneous device closure of ASDs is safe and effective in the current era. The Qp/Qs ratio > 3.13 and IAS erosion, floppiness or aneurysm formation post-implantation might be predictors of ASO dislodgement in adults and children.


Assuntos
Aneurisma Cardíaco , Comunicação Interatrial , Falha de Prótese , Implantação de Prótese , Dispositivo para Oclusão Septal , Adolescente , Adulto , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/métodos , Criança , Pré-Escolar , Ecocardiografia Transesofagiana/métodos , Análise de Falha de Equipamento , Feminino , Aneurisma Cardíaco/diagnóstico , Aneurisma Cardíaco/etiologia , Átrios do Coração/diagnóstico por imagem , Comunicação Interatrial/diagnóstico , Comunicação Interatrial/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Falha de Prótese/efeitos adversos , Falha de Prótese/etiologia , Implantação de Prótese/instrumentação , Implantação de Prótese/métodos , Retenção da Prótese/efeitos adversos , Retenção da Prótese/métodos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taiwan , Resultado do Tratamento
15.
Transl Res ; 163(1): 43-52, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24113064

RESUMO

Nitric oxide (NO) deficiency mediates oxidative stress in the kidney and is involved in the development of hypertension. NO synthesis occurs via 2 pathways: nitric oxide synthase (NOS) dependent and NOS-independent. We tested whether the development of hypertension is prevented by restoration of NO by dietary l-citrulline or nitrate supplementation in young spontaneously hypertensive rats (SHRs). Male SHRs and normotensive Wistar Kyoto control rats (WKYs)s age 4 weeks were assigned to 4 groups: untreated SHRs and WKYs, and SHRs and WKYs that received 0.25% l-citrulline for 8 weeks. In our second series of studies, we replaced l-citrulline with 1 mmol/kg/d sodium nitrate. All rats were sacrificed at age 12 weeks. We found an increase in the blood pressure of SHRs was prevented by dietary supplementation of l-citrulline or nitrate. Both treatments restored NO bioavailability and reduced oxidative stress in SHR kidneys. l-Citrulline therapy reduced levels of l-arginine and asymmetric dimethylarginine (ADMA)-an endogenous inhibitor of NOS-and increased the l-arginine-to-ADMA ratio in SHR kidneys. Nitrate treatment reduced plasma levels of l-arginine and ADMA concurrently in SHRs. Our findings suggest that both NOS-dependent and -independent approaches in the prehypertensive stage toward augmentation of NO can prevent the development of hypertension in young SHRs.


Assuntos
Citrulina/administração & dosagem , Hipertensão/prevenção & controle , Nitratos/administração & dosagem , Óxido Nítrico/metabolismo , Animais , Arginina/análogos & derivados , Arginina/sangue , Suplementos Nutricionais , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
16.
Molecules ; 18(9): 10242-53, 2013 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-23973996

RESUMO

Cancer stem cells (CSCs) are a small subset of cancer cells with indefinite potential for self-renewal and the capacity to drive tumorigenesis. Brefeldin A (BFA) is an antibiotic that is known to block protein transport and induce endoplasmic reticulum (ER) stress in eukaryotic cells, but its effects on colorectal CSCs are unknown. We investigated the inhibitory effect of BFA on human colorectal cancer Colo 205 cells. We found that BFA effectively reduced the survival of suspension Colo 205 cells (IC50 = ~15 ng/mL) by inducing apoptosis, and inhibited the clonogenic activity of Colo 205 CSCs in tumorsphere formation assay and soft agar colony formation assay in the same nanogram per milliliter range. We also discovered that at such low concentrations, BFA effectively induced endoplasmic reticulum (ER) stress response as indicated by the increased mRNA expression of ER stress-related genes, such as glucose-regulated protein 78 (GRP78), X-box binding protein 1 (XBP1), and C/EBP homologous protein (CHOP). Finally, we found that BFA reduced the activity of matrix metallopeptidase 9 (MMP-9). These findings suggest that BFA can effectively suppress the progression of colorectal cancer during the tumorigenesis and metastasis stages. These results may lead to the development of novel therapies for the treatment of colorectal cancer.


Assuntos
Antineoplásicos/farmacologia , Brefeldina A/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais , Ensaios de Seleção de Medicamentos Antitumorais , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Células-Tronco Neoplásicas/enzimologia , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/enzimologia
17.
Biomed J ; 36(1): 28-34, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23515152

RESUMO

BACKGROUND: Conventional therapy against acute pediatric cardiopulmonary failure (APCPF) caused by a variety of disease entities remains unsatisfactory with extremely high morbidity and mortality. For refractory APCPF, extracorporeal membrane oxygenation (ECMO) is one of the last resorts. METHODS: In this study, the in-hospital outcomes of pediatric patients with refractory APCPF receiving ECMO support were reviewed. RESULTS: Between August 2006 and May 2011, a single-center cohort study was performed in pediatric patients who required ECMO support due to cardiogenic shock or severe hypoxemia. A total of 22 patients with mean age of 7.0 ± 6.3 years received ECMO (male = 11; female = 11). The indications included acute fulminant myocarditis (AFM) (n = 6), congenital diaphragmatic hernia (CDH) (n = 3), acute respiratory distress syndrome (ARDS) (n = 6), enterovirus 71 (n = 3), viral sepsis (n = 2), refractory ventricular fibrillation due to long QT syndrome (n = 1), and pulmonary edema with brain herniation (n = 1). Eighteen patients received veno-arterial (VA) mode ECMO, while another four patients undertook the veno-venous (VV) mode. The duration of ECMO use and hospitalization were 6.1 ± 3.1 and 24.4 ± 19.4 days, respectively. The survival rate in patients with AFM was 100% (n = 6). Successful ECMO weaning with uneventful discharge from hospital was noted in 14 (63.6%) patients, whereas in-hospital mortality despite successful ECMO weaning occurred in 5 patients (22.7%). Failure in ECMO weaning and in-hospital death was noted in 3 patients (13.6%). CONCLUSIONS: ECMO resuscitation is an effective strategy in the clinical setting of APCPF.


Assuntos
Oxigenação por Membrana Extracorpórea , Miocardite/terapia , Síndrome do Desconforto Respiratório/terapia , Choque Cardiogênico/terapia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Hérnia Diafragmática/terapia , Hérnias Diafragmáticas Congênitas , Mortalidade Hospitalar , Humanos , Lactente , Masculino , Taxa de Sobrevida , Resultado do Tratamento
18.
Mediators Inflamm ; 2013: 421389, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23533305

RESUMO

BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor neurons in the brainstem, motor cortex, and spinal cord. Oxidative stress and neuroinflammation have been implicated in the pathophysiology of ALS. Members of the family of damage-associated molecular patterns, including reactive oxygen species, high-mobility group box 1, and eosinophil-derived neurotoxin (EDN), may participate in pathological conditions. In this study, we aim to discover new biomarker for detecting ALS. MATERIALS AND METHODS: We examined 44 patients with ALS, 41 patients with Alzheimer's disease, 41 patients with Parkinson's disease, and 44 healthy controls. The concentration of serum EDN was measured using an enzyme-linked immunosorbent assay. RESULTS: EDN levels were significantly increased 2.17-fold in the serum of patients with ALS as compared with healthy controls (P < 0.05). No correlation between the levels of serum EDN and various clinical parameters of ALS was found. Moreover, the levels of serum EDN in patients with Parkinson's disease and Alzheimer's disease and healthy controls were similar. CONCLUSION: A higher level of serum EDN was found specifically in patients with ALS, indicating that EDN may participate in the pathophysiology of ALS.


Assuntos
Esclerose Lateral Amiotrófica/sangue , Neurotoxina Derivada de Eosinófilo/sangue , Adulto , Idoso , Doença de Alzheimer/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/sangue
19.
Circ J ; 77(1): 181-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23001044

RESUMO

BACKGROUND: Nitric oxide (NO) is involved in hypertension and chronic kidney disease (CKD). NO synthase can metabolize L-arginine (ARG) to generate NO and L-citrulline (CIT). Two methylated ARG derivatives, asymmetric and symmetric dimethylarginine, are also involved in NO deficiency. Thus it was hypothesized that their combined ratios relate to blood pressure (BP) abnormalities in children with early CKD. METHODS AND RESULTS: The relationship between these ARG metabolites in plasma was examined using 24-h ambulatory BP monitoring (ABPM) profile in children and adolescents with CKD stages 1-3 (n=44). Approximately 20.4% (9/44) of children with CKD stages 1-3 were diagnosed with hypertension on clinical BP measurement, and 77.3% (33/44) had BP abnormalities on ABPM, including increased BP load, nocturnal BP non-dipping, and nocturnal hypertension. Children with CKD stages 2-3 were more prevalent with abnormal BP on ABPM, and had a higher level of CIT and CIT-to-ARG ratio than those with stage 1. Furthermore, high CIT-to-ARG ratio was significantly correlated with abnormal ABPM profile, including nocturnal hypertension, increased diastolic BP load, and nocturnal BP non-dipping. Higher CIT level was significantly correlated with increased diastolic BP load and overall ABPM profile. CONCLUSIONS: Plasma CIT-to-ARG ratio may serve as a useful marker of cardiovascular outcome in children with early CKD.


Assuntos
Arginina/sangue , Pressão Sanguínea , Citrulina/sangue , Hipertensão , Insuficiência Renal Crônica , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Humanos , Hipertensão/sangue , Hipertensão/etiologia , Hipertensão/fisiopatologia , Masculino , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia
20.
Emerg Med J ; 30(3): e17, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22523033

RESUMO

OBJECTIVE: Small-bore pigtail catheters have been found to be effective in the treatment of primary spontaneous pneumothorax (PSP) in adults. The aim of this study was to compare the effectiveness of small-bore pigtail and large-bore catheters in the treatment of PSP in young adolescents. MATERIALS AND METHODS: Young adolescents (<18 years) with initial PSP were treated with aspiration (control group), small-bore pigtail catheters or large-bore catheters. Treatment was determined on a case-by-case basis with parental consultation. Success rate, recurrence rate (within 12 months), duration of hospital stay, duration of catheter insertion, and complications were analysed. MAIN RESULTS: There were 41 patients treated: aspiration, n=8; small-bore pigtail catheters, n=10; large-bore catheters, n=23. Demographic and baseline clinical characteristics were similar between groups. The success rates were 50.0% and 65.2% in the small-bore pigtail and large-bore catheter groups, respectively. Corresponding recurrence rates were 20.0% and 56.5%. There was no difference between the small-bore pigtail and large-bore catheter groups in the duration of hospital stay in patients for whom treatment was successful; however, the duration of catheter insertion was significantly shorter in the small-bore pigtail catheter group compared with the large-bore catheter group in patients for whom treatment was successful (p<0.05). There were no major complications in either catheter treatment group and few minor complications (small-bore pigtail catheter, n=2; large-bore catheter, n=4). CONCLUSIONS: The findings suggest that small-bore pigtail catheters may be as effective as large-bore catheters for the initial treatment of PSP in young adolescents.


Assuntos
Cateterismo/instrumentação , Tubos Torácicos , Pneumotórax/cirurgia , Adolescente , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Complicações Pós-Operatórias , Recidiva , Estatísticas não Paramétricas , Resultado do Tratamento
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