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1.
Sci Rep ; 14(1): 11167, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750091

RESUMO

Xanthine oxidoreductase (XOR) contributes to reactive oxygen species production. We investigated the cytoprotective mechanisms of XOR inhibition against high glucose (HG)-induced glomerular endothelial injury, which involves activation of the AMP-activated protein kinase (AMPK). Human glomerular endothelial cells (GECs) exposed to HG were subjected to febuxostat treatment for 48 h and the expressions of AMPK and its associated signaling pathways were evaluated. HG-treated GECs were increased xanthine oxidase/xanthine dehydrogenase levels and decreased intracellular AMP/ATP ratio, and these effects were reversed by febuxostat treatment. Febuxostat enhanced the phosphorylation of AMPK, the activation of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator (PGC)-1α and PPAR-α and suppressed the phosphorylation of forkhead box O (FoxO)3a in HG-treated GECs. Febuxostat also decreased nicotinamide adenine dinucleotide phosphate oxidase (Nox)1, Nox2, and Nox4 expressions; enhanced superoxide dismutase activity; and decreased malondialdehyde levels in HG-treated GECs. The knockdown of AMPK inhibited PGC-1α-FoxO3a signaling and negated the antioxidant effects of febuxostat in HG-treated GECs. Despite febuxostat administration, the knockdown of hypoxanthine phosphoribosyl transferase 1 (HPRT1) also inhibited AMPK-PGC-1α-FoxO3a in HG-treated GECs. XOR inhibition alleviates oxidative stress by activating AMPK-PGC-1α-FoxO3a signaling through the HPRT1-dependent purine salvage pathway in GECs exposed to HG conditions.


Assuntos
Proteínas Quinases Ativadas por AMP , Células Endoteliais , Glucose , Xantina Desidrogenase , Humanos , Glucose/metabolismo , Xantina Desidrogenase/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Purinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Febuxostat/farmacologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Glomérulos Renais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
2.
PLoS One ; 19(2): e0298060, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38359058

RESUMO

Fetal growth restriction (FGR) is one of the leading causes of perinatal morbidity and mortality. Many studies have reported an association between FGR and fetal Doppler indices focusing on umbilical artery (UA), middle cerebral artery (MCA), and ductus venosus (DV). The uteroplacental-fetal circulation which affects the fetal growth consists of not only UA, MCA, and DV, but also umbilical vein (UV), placenta and uterus itself. Nevertheless, there is a paucity of large-scale cohort studies that have assessed the association between UV, uterine wall, and placental thickness with perinatal outcomes in FGR, in conjunction with all components of the uteroplacental-fetal circulation. Therefore, this multicenter study will evaluate the association among UV absolute flow, placental thickness, and uterine wall thickness and adverse perinatal outcome in FGR fetuses. This multicenter retrospective cohort study will include singleton pregnant women who undergo at least one routine fetal ultrasound scan during routine antepartum care. Pregnant women with fetuses having structural or chromosomal abnormalities will be excluded. The U-AID indices (UtA, UA, MCA, and UV flow, placental and uterine wall thickness, and estimated fetal body weight) will be measured during each trimester of pregnancy. The study population will be divided into two groups: (1) FGR group (pregnant women with FGR fetuses) and (2) control group (those with normal growth fetus). We will assess the association between U-AID indices and adverse perinatal outcomes in the FGR group and the difference in U-AID indices between the two groups.


Assuntos
Feto , Placenta , Feminino , Humanos , Gravidez , Biometria , Estudos de Coortes , Desenvolvimento Fetal , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/epidemiologia , Feto/diagnóstico por imagem , Feto/irrigação sanguínea , Idade Gestacional , Estudos Multicêntricos como Assunto , Placenta/diagnóstico por imagem , Estudos Retrospectivos , Ultrassonografia Doppler , Ultrassonografia Pré-Natal/métodos , Artérias Umbilicais/diagnóstico por imagem
3.
Int J Mol Sci ; 24(4)2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36835220

RESUMO

Xanthine oxidase (XO) is an important source of reactive oxygen species. This study investigated whether XO inhibition exerts renoprotective effects by inhibiting vascular endothelial growth factor (VEGF) and NADPH oxidase (NOX) in diabetic kidney disease (DKD). Febuxostat (5 mg/kg) was administered to streptozotocin (STZ)-treated 8-week-old male C57BL/6 mice via intraperitoneal injection for 8 weeks. The cytoprotective effects, its mechanism of XO inhibition, and usage of high-glucose (HG)-treated cultured human glomerular endothelial cells (GECs) were also investigated. Serum cystatin C, urine albumin/creatinine ratio, and mesangial area expansion were significantly improved in febuxostat-treated DKD mice. Febuxostat reduced serum uric acid, kidney XO levels, and xanthine dehydrogenase levels. Febuxostat suppressed the expression of VEGF mRNA, VEGF receptor (VEGFR)1 and VEGFR3, NOX1, NOX2, and NOX4, and mRNA levels of their catalytic subunits. Febuxostat caused downregulation of Akt phosphorylation, followed by the enhancement of dephosphorylation of transcription factor forkhead box O3a (FoxO3a) and the activation of endothelial nitric oxide synthase (eNOS). In an in vitro study, the antioxidant effects of febuxostat were abolished by a blockade of VEGFR1 or VEGFR3 via NOX-FoxO3a-eNOS signaling in HG-treated cultured human GECs. XO inhibition attenuated DKD by ameliorating oxidative stress through the inhibition of the VEGF/VEGFR axis. This was associated with NOX-FoxO3a-eNOS signaling.


Assuntos
Nefropatias Diabéticas , Xantina Oxidase , Animais , Humanos , Masculino , Camundongos , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/enzimologia , Células Endoteliais/metabolismo , Febuxostat/farmacologia , Camundongos Endogâmicos C57BL , NADPH Oxidases/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , RNA Mensageiro/metabolismo , Transdução de Sinais , Ácido Úrico/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fatores de Crescimento do Endotélio Vascular/metabolismo , Xantina Oxidase/antagonistas & inibidores
4.
Infect Chemother ; 54(3): 433-445, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35920268

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) during pregnancy is associated with increased disease severity and an increased risk of perinatal complications. However, few studies of pregnant women with COVID-19 have been conducted in Korea. The purpose of this study was to describe the clinical course and pregnancy outcomes of pregnant women admitted to our hospital with COVID-19 according to the severity. MATERIALS AND METHODS: This retrospective cohort study included women aged 18 years of age or older who were hospitalized in the Gachon University Gil Medical Center with COVID-19 during pregnancy between July 1, 2021 and January 31, 2022. COVID-19 severity was classified according to the "Criteria for severity classification by symptoms of COVID-19" presented by the Korea Disease Control and Prevention Agency. Severe cases were defined as those who required oxygen treatment administered via a high-flow nasal cannula or invasive mechanical ventilation or should be applied extracorporeal membrane oxygenation (ECMO) or continuous renal replacement therapy. RESULTS: A total of 103 pregnant women were hospitalized with COVID-19 during the study period. Their mean age was 33 (± 4.14) years, and 4 (3.9%) had been vaccinated against COVID-19. At the time of diagnosis of COVID-19, 3 (2.9%), 33 (32.0%), and 67 (65.1%) patients were in the first, second, and third trimester, respectively. The most common symptoms were cough (99 patients, 96.1%) and fever (85 patients, 82.5%). There was 1 (1.0%) asymptomatic patient. Forty patients (38.8%) required supplemental oxygen and 19 patients (18.4%) had severe disease. Of the 19 severe cases, 7 were in the 2nd trimester and 12 were in the 3rd trimester. Forty-one (39.8%) patients delivered, including two twin deliveries. Of the 41 cases of delivery, 14 were premature, 4 out of 21 (19.0%) in mild, 4 out of 12 (25.0%) in moderate, and 6 out of 8 (75.0%) in severe. Severe disease was associated with an increased rate of preterm birth (P = 0.012). Four of the 43 neonates (9.1%) received oxygen treatment. CONCLUSION: Pregnant women with COVID-19 had a high rate of severe disease and a high preterm delivery rate, especially among those with severe disease.

5.
Materials (Basel) ; 15(12)2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35744118

RESUMO

This prospective single-arm clinical study aimed to radiographically and histomorphometrically evaluate the efficacy of the lateral approach for sinus floor elevation (LSFE) using biomimetic octacalcium phosphate (OCP) synthetic bone graft (Bontree®). LSFE using Bontree® was performed on 10 patients (15 implant placement sites) willing to undergo implant surgery, followed by implant placements after 6 months of the healing period. The vertical bone height (VBH) and Hounsfield unit (HU) values at each implant placement site were evaluated radiographically using cone-beam computed tomography at baseline immediately after surgery (T1) and 6 months after surgery (T2). A histomorphometric evaluation of the bone core biopsy specimen was also performed. The mean VBH and HU changes at all sites included a decrease by 0.91 mm and a statistically significant increase by 431.86, respectively, from T1 to T2. The mean ratio of the newly formed bone (23.34% ± 10.63%) was greater than that of the residual bone graft (19.09% ± 8.74%), indicating that Bontree® is effective for new bone formation. This pilot study suggests that Bontree® is a promising bone substitute for LSFE.

6.
Trials ; 23(1): 486, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35698156

RESUMO

BACKGROUND: The 4th Industrial Revolution with the advent of the smart era, in which artificial intelligence, such as big data analysis and machine learning, is expected, and the provision of healthcare services using smartphones has become a reality. In particular, high-risk mothers who experience gestational diabetes, gestational hypertension, and prenatal and postpartum depression are highly likely to have adverse effects on the mother and newborn due to the disease. Therefore, continuous observation and intervention in health management are needed to prevent diseases and promote healthy behavior for a healthy life. METHODS: This randomized controlled trial will provide mothers 18 years of age or older with health care information collected based on evidence-based literature data using a smartphone app for 6 weeks. About 500 mothers will be selected in consideration of the dropout rate due to the characteristics of mothers. The study group and control group will be computer-generated in a 1:1 ratio through random assignment. The research group will receive health management items through the app, and health management information suitable for the pregnancy cycle is pushed to an alarm. The control group will receive the health management information of the paper. We also followed the procedure for developing mobile apps using the IDEAS framework. DISCUSSION: These results show the effectiveness of smart medical healthcare services and promote changes in health behaviors throughout pregnancy in high-risk mothers. TRIAL REGISTRATION: Clinical trial registration information for this study has been registered with WHO ICTRP and CRIS (Korea Clinical Research Information Service, CRIS). Clinical trial registration information is as follows: Study of development of integrated smart health management service for the whole life cycle of high-risk mothers and newborns based on community, KCT0007193 . Registered on April 14, 2022, prospectively registered. This protocol version is Version 1.0. April 14, 2022.


Assuntos
Aplicativos Móveis , Adolescente , Adulto , Inteligência Artificial , Atenção à Saúde , Feminino , Humanos , Recém-Nascido , Mães , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Smartphone
7.
Front Psychiatry ; 12: 684406, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305681

RESUMO

Purpose: The number of patients with alcohol-related problems is steadily increasing. A large-scale survey of alcohol-related problems has been conducted. However, studies that predict hazardous drinkers and identify which factors contribute to the prediction are limited. Thus, the purpose of this study was to predict hazardous drinkers and the severity of alcohol-related problems of patients using a deep learning algorithm based on a large-scale survey data. Materials and Methods: Datasets of National Health and Nutrition Examination Survey of South Korea (K-NHANES), a nationally representative survey for the entire South Korean population, were used to train deep learning and conventional machine learning algorithms. Datasets from 69,187 and 45,672 participants were used to predict hazardous drinkers and the severity of alcohol-related problems, respectively. Based on the degree of contribution of each variable to deep learning, it was possible to determine which variable contributed significantly to the prediction of hazardous drinkers. Results: Deep learning showed the higher performance than conventional machine learning algorithms. It predicted hazardous drinkers with an AUC (Area under the receiver operating characteristic curve) of 0.870 (Logistic regression: 0.858, Linear SVM: 0.849, Random forest classifier: 0.810, K-nearest neighbors: 0.740). Among 325 variables for predicting hazardous drinkers, energy intake was a factor showing the greatest contribution to the prediction, followed by carbohydrate intake. Participants were classified into Zone I, Zone II, Zone III, and Zone IV based on the degree of alcohol-related problems, showing AUCs of 0.881, 0.774, 0.853, and 0.879, respectively. Conclusion: Hazardous drinking groups could be effectively predicted and individuals could be classified according to the degree of alcohol-related problems using a deep learning algorithm. This algorithm could be used to screen people who need treatment for alcohol-related problems among the general population or hospital visitors.

8.
Endocr Pathol ; 32(4): 501-512, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34215996

RESUMO

Secondary hyperparathyroidism (SHPT) is characterized by excessive serum parathyroid hormone levels in response to decreasing kidney function, and tertiary hyperparathyroidism (THPT) is often the result of a long-standing SHPT. To date, several genes have been associated with the pathogenesis of primary hyperparathyroidism (PHPT). However, the molecular genetic mechanisms of uremic hyperparathyroidism (HPT) remain uncharacterized. To elucidate the differences in genetic alterations between PHPT and SHPT/THPT, the targeted next-generation sequencing of genes associated with HPT was performed using DNA extracted from parathyroid tissues. As a result, 26 variants in 19 PHPT or SHPT/THPT appeared as candidate pathogenic mutations, which corresponded to 9 (35%) nonsense, 8 (31%) frameshift, 6 (23%) missense, and 3 (11%) splice site mutations. The MEN1 (23%, 6/26), ASXL3 (15%, 4/26), EZH2 (12%, 3/26), and MTOR (8%, 2/26) genes were frequently mutated. Sixteen of 25 patients with PHPT (64%) had one or more mutations, whereas 3 (21%) of 21 patients with SHPT/THPT had only 1 mutation (p = 0.001). Sixteen of 28 patients (57%) with parathyroid adenoma (PA) had one or more mutations, whereas 3 of 18 patients (17%) with parathyroid hyperplasia (PH) had just one mutation (p = 0.003). Known driver mutations associated with parathyroid tumorigenesis such as CCND1/PRAD1, CDC73/HRPT2, and MEN1 were identified only in PA (44%, 7/16 with mutations). Our results suggest that molecular genetic abnormalities in SHPT/THPT are distinct from those in PHPT. These findings may help in analyzing the molecular pathogenesis underlying uremic HPT development.


Assuntos
Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Secundário/diagnóstico , Adulto , Idade de Início , Idoso , Análise Mutacional de DNA/métodos , Diagnóstico Diferencial , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hiperparatireoidismo Primário/epidemiologia , Hiperparatireoidismo Primário/etiologia , Hiperparatireoidismo Primário/genética , Hiperparatireoidismo Secundário/epidemiologia , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/genética , Pessoa de Meia-Idade , Mutação , República da Coreia/epidemiologia
9.
J Obstet Gynaecol Res ; 47(7): 2318-2323, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33973302

RESUMO

OBJECTIVE: Preeclampsia is clinically unpredictable and associated with adverse outcomes. Pregnant women with suspected preeclampsia require intensive monitoring or hospitalization for elevated sFlt-1 (soluble fms-like tyrosine kinase-1) to PlGF (placental growth factor) ratios before symptoms arise. We aimed to determine the sFlt-1/PlGF ratio's usefulness in predicting adverse pregnancy outcomes in preeclampsia. METHODS: From January 2017 to February 2019, we measured the sFlt-1/PlGF ratio in 73 singleton pregnant women suspected of preeclampsia and classified them into three groups: low-risk (sFlt-1/PlGF ratio < 38, n = 19), intermediate (38 ≤ ratio < 85, n = 9), and high-risk (ratio ≥ 85, n = 32). RESULTS: Although the low- and high-risk groups both experienced weight gain during pregnancy, their body mass index (BMI) differed after pregnancy (p = 0.004). The number of women who had been taking antihypertensive medications for chronic hypertension since early pregnancy was higher in the low-risk group (31.6% vs. 22.2%, 6.7%). The gestational weeks at birth were lower in the high-risk group compared to that of the low-risk group (32.0 weeks vs. 35.79 weeks, p < 0.001). In the high-risk group, the average neonatal weight was significantly lighter (p = 0.021), and the period of stay in the neonatal intensive care unit was longer than that in the low-risk group (p = 0.003). CONCLUSION: The sFlt-1/PlGF ratio is a useful indicator of preeclampsia severity and can be utilized as a prognostic marker.


Assuntos
Pré-Eclâmpsia , Biomarcadores , Feminino , Humanos , Recém-Nascido , Proteínas de Membrana , Fator de Crescimento Placentário , Valor Preditivo dos Testes , Gravidez , Prognóstico , Receptor 1 de Fatores de Crescimento do Endotélio Vascular
10.
J Clin Med ; 9(9)2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32878271

RESUMO

Several studies reported the effect of obesity on the progression of IgA nephropathy (IgAN). However, the impact of obesity on the clinicopathologic presentation of IgAN remains uncertain. This is a retrospective cross-sectional study from eight university hospitals in South Korea. Patients were categorized into three groups using the Asia-Pacific obesity classification based on body mass index (BMI). Clinical and histopathologic data at the time of renal biopsy were analyzed. Among 537 patients with IgAN, the obese group was more hypertensive and had lower estimated glomerular filtration rate and more proteinuria than other groups. The histologic scores for mesangial matrix expansion (MME), interstitial fibrosis, tubular atrophy, and mesangial C3 deposition differed significantly between the three groups. Among these histopathologic parameters, BMI was independently positively associated with MME score on multivariable linear regression analysis (p = 0.028). Using multivariable logistic regression analysis, the obese group was independently associated with higher MME scores compared to the normal weight/overweight group (p = 0.020). However, BMI was not independently associated with estimated glomerular filtration rate or proteinuria on multivariable analysis. Obesity was independently associated with severe MME in patients with IgAN. Obesity may play an important pathogenetic role in mesangial lesions seen in IgAN.

11.
Obstet Gynecol Sci ; 63(3): 231-238, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32489967

RESUMO

OBJECTIVE: We aimed to evaluate the effectiveness of cervical pessary for extending twin pregnancy in women with a short cervix. METHODS: Between January 2014 and March 2019, the use of a cervical pessary for twin pregnancy in women with a cervical length of ≤15 mm was investigated between 16 and 28 weeks of gestation. We included women with a shortened cervix after a cerclage procedure and visible fetal membranes and cervical dilatation. Thirteen patients underwent pessary insertion and were matched with a control group of 15 patients. Pregnancy and neonatal outcomes were compared between the groups. We excluded women with major fetal anomalies discovered before or after birth and known placenta previa. RESULTS: Women who underwent pessary insertion were diagnosed with a short cervix (0.65±0.47 vs. 0.66±0.51 cm in the pessary and control groups, respectively; P=0.957) at a gestational age similar to that of the controls (23.29 vs. 25.14 weeks, P=0.294). There was no significant difference in gestational age at delivery between them (33.29 vs. 27.29 weeks in the pessary and control groups, respectively, P=0.058). The pessary group had a longer interval between the diagnosis and delivery than the control group (60.7±28.3 vs. 22.6±24.5 days, P=0.001). The number of adverse neonatal outcomes was significantly lower in the pessary group (n=7; 28.0%) than in the control group (n=14; 58.3%; P=0.032). CONCLUSION: The use of a cervical pessary may prolong gestation in twin pregnancies in women with an extremely short cervix until viable gestational age.

12.
Korean J Intern Med ; 35(1): 160-170, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31648433

RESUMO

BACKGROUND/AIMS: Parathyroid hormone (PTH) is an important factor influencing immunologic dysfunction, but the effect of PTH level on infection-related outcomes remains unclear in incident dialysis. METHODS: We evaluated a multicenter prospective cohort study of 1,771 incident dialysis patients (1,260 hemodialysis and 511 peritoneal dialysis) in Korea. Patients were divided into three groups based on serum intact PTH (iPTH) level. The primary outcomes were all-cause and infection-related mortality and multivariate Cox regression analysis was performed to evaluate the role of iPTH in all-cause and infection-related mortality. RESULTS: During the follow-up period of 27.3 months, 175 patients (9.9%) died, and infection-related death represented 20% of all-cause mortality. Both all-cause mortality and infection-related mortality rates (p < 0.001 and p = 0.003, by logrank) were markedly higher in patients with serum iPTH < 150 pg/mL than in the other groups. Multivariate Cox regression analysis revealed that patients with serum iPTH < 150 pg/mL remained at higher risk for infection-related mortality than patients in the target range of 150 ≤ iPTH < 300 pg/mL, after adjusting for confounding variables (hazard ratio [HR], 2.52; 95% confidence interval, 1.06 to 5.99; p = 0.04). The HR of infection-related mortality in patients with serum iPTH < 150 pg/mL was significantly higher in patients with low serum phosphorus, low Ca × P product, low serum alkaline phosphatase and those older than 65 years. CONCLUSION: Low serum iPTH level is an independent predictor of infection-related mortality in incident dialysis patients.


Assuntos
Diálise Peritoneal , Diálise Renal , Cálcio , Humanos , Hormônio Paratireóideo , Estudos Prospectivos , Diálise Renal/efeitos adversos , República da Coreia
13.
Sci Rep ; 9(1): 17679, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776362

RESUMO

Adequate fluid management plays an important role in decreasing cardiovascular risk in peritoneal dialysis (PD) patients. We evaluated whether strict volume control monitored by bioimpedance spectroscopy (BIS) affects cardiac function in PD patients. This study is a secondary analysis of a multicentre, prospective, randomized, controlled trial. Fluid overload was assessed by the average overhydration/extracellular water (OH/ECW) at baseline, 6 months and 12 months. Patients were categorized as time-averaged overhydrated (TA-OH/ECW ≥15%) or normohydrated (TA-OH/ECW <15%), and echocardiographic parameters were compared between groups. Among a total of 151 patients, 120 patients exhibited time-averaged normohydration. Time-averaged overhydrated patients had a significantly higher left atrial (LA) diameter and E/e' ratio and a lower left ventricular (LV) ejection fraction at 12 months than time-averaged normohydrated patients. LA diameter, end-systolic volume and end-diastolic volume were decreased at 12 months compared to baseline in time-averaged normohydrated patients only. TA-OH/ECW was independently associated with ejection fraction at 12 months (ß = -0.190; p = 0.010). TA-OH/ECW, but not OH/ECW at 12 months, was an independent risk factor for LV dysfunction (odds ratio 4.020 [95% confidence interval 1.285-12.573]). Overhydration status based on repeated BIS measurements is an independent predictor of LV systolic function in PD patients.


Assuntos
Doenças Cardiovasculares/etiologia , Espectroscopia Dielétrica/métodos , Testes de Função Cardíaca/métodos , Diálise Peritoneal/efeitos adversos , Volume Sistólico , Função Ventricular Esquerda , Adulto , Idoso , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Estado de Hidratação do Organismo , Estudos Prospectivos , Desequilíbrio Hidroeletrolítico
14.
Free Radic Biol Med ; 145: 209-220, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31560952

RESUMO

Reactive oxygen species (ROS) play a pivotal role in the development of contrast-induced nephropathy (CIN). The inhibition of xanthine oxidoreductase is known to reduce levels of ROS. We investigated whether febuxostat could attenuate oxidative stress via the activation of adenosine monophosphate-activated protein kinase (AMPK) against CIN. In a mouse model of CIN, renal impairment and tubular injury substantially increased, whereas febuxostat attenuated renal injury. Plasma and kidney xanthine oxidoreductase levels were decreased by febuxostat. Febuxostat administration was accompanied by the upregulation of AMPK phosphorylation and the inhibition of nicotinamide-adenine dinucleotide phosphate oxidase (Nox)1 and Nox2, followed by the inhibition of hypoxia-inducible factor-1α (HIF-1α) and heme oxygenase-1 expressions and the suppression of transcription factor forkhead box O (FoxO)1 and FoxO3a phosphorylation. Cell survival was significantly reduced after iohexol administration and febuxostat ameliorated iohexol-induced cell death in proximal tubular (HK-2) cells. Furthermore, febuxostat enhanced AMPK phosphorylation and inhibited Nox1, Nox2, and HIF-1α expression in iohexol-exposed HK-2 cells. Finally, these processes decrease ROS in both in vivo and in vitro models of CIN. AMPK inhibition using small interfering RNA blunted the antioxidative effects of febuxostat in iohexol-treated HK-2 cells. Febuxostat attenuated CIN by modulating oxidative stress through AMPK-NADPH oxidase-HIF-1α signaling.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Meios de Contraste/efeitos adversos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , NADPH Oxidase 1/genética , Proteínas Quinases/genética , Quinases Proteína-Quinases Ativadas por AMP , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Injúria Renal Aguda/patologia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O3/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Iohexol/farmacologia , Rim/efeitos dos fármacos , Rim/lesões , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/lesões , Túbulos Renais/patologia , Camundongos , NADPH Oxidase 2/genética , Estresse Oxidativo/efeitos dos fármacos , Proteínas Quinases/efeitos dos fármacos , RNA Interferente Pequeno/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Korean J Intern Med ; 34(5): 1091-1099, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31408925

RESUMO

BACKGROUND/AIMS: Membranous nephropathy (MN) is the most common primary glomerular disease diagnosed in older patients. Few reports describe the clinical outcomes in older patients with idiopathic MN. METHODS: The outcomes of 135 patients with histologically proven MN were analyzed. 'Older' was defined as 60 years of age or older at the time of the renal biopsy. The rates of complete remission (CR), progression to end-stage renal disease (ESRD) and infection were compared between older and younger patients. RESULTS: The cumulative event rate for achieving CR was inferior (p = 0.012) and that for requiring renal replacement was higher (p = 0.015) in older patients, and they had a greater risk of infection (p = 0.005). Older age was a significant predictor of a lower rate of CR (adjusted odds ratio [OR], 0.51; 95% confidence interval [CI], 0.26 to 0.98), and was a robust predictor of infection (adjusted OR, 5.27; 95% CI, 1.31 to 21.20). Conservative treatment was associated with a lower remission rate (p = 0.036) and corticosteroid treatment was less effective in achieving CR (p = 0.014), in preventing progression to ESRD (p = 0.013) and in reducing infection (p = 0.033) in older patients. Cyclosporine treatment had similar clinical outcomes with regard to CR, ESRD progression, and infection in older patients. CONCLUSION: Older age was independently associated with inferior rates of CR and greater risk of infection. Treatment modalities affected the outcomes of older patients differently in that cyclosporine treatment is predicted to be more useful than corticosteroids.


Assuntos
Corticosteroides/uso terapêutico , Ciclosporina/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Glomérulos Renais/efeitos dos fármacos , Corticosteroides/efeitos adversos , Adulto , Fatores Etários , Idoso , Doenças Transmissíveis/etiologia , Ciclosporina/efeitos adversos , Progressão da Doença , Feminino , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/patologia , Humanos , Imunossupressores/efeitos adversos , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Glomérulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Terapia de Substituição Renal , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Seul , Fatores de Tempo , Resultado do Tratamento
16.
Obes Res Clin Pract ; 13(2): 156-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30910529

RESUMO

BACKGROUND: Considering the obesity-related complications in pregnancy and during delivery, prepregnancy central obesity may also affect pregnancy-related complications. This study aimed to assess the relationship between prepregnancy central obesity and adverse maternal outcomes in Korean women, by using the Korean National Health Insurance Service (NHIS) cohort. METHODS: In this population-based retrospective cohort study, we used data from the NHIS database, which contains information of health-care utilisation, diagnosis and prescription, and mortality for almost the whole Korean population, together with data from the NHIS health checkup database from 2005 to 2015. The NHIS health checkup data (645-280 days before childbirth) of mothers who had deliveries (total, 783,406 deliveries) from 2006 to 2015 were collected. For maternal adverse outcome data, we searched for diagnoses of maternal complications made during the period of 280 days before each delivery. The odds for maternal complications according to 8 body mass index (BMI) and 10 waist circumference (WC) categories were analysed using logistic regression. RESULTS: The incidence rates of eclampsia/preeclampsia, caesarean section, multiple gestation, and polycystic ovary syndrome (PCOS) increased according to the increase of BMI and WC. In contrast, the incidence rate of premature rupture of membrane (PROM) was inversely correlated with BMI and WC. In the low BMI (<17.5 and 17.5-19.9 kg/m2) and low WC (<60 and 60.0-64.0 cm) groups, the odds of threatened abortion were elevated. CONCLUSION: Prepregnancy WC was closely linked to some maternal complications, including eclampsia/preeclampsia, cesarean section, PCOS, and PROM, in a manner similar to prepregnancy BMI.


Assuntos
Cesárea/estatística & dados numéricos , Ruptura Prematura de Membranas Fetais/epidemiologia , Obesidade Abdominal/complicações , Síndrome do Ovário Policístico/epidemiologia , Pré-Eclâmpsia/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , Feminino , Ruptura Prematura de Membranas Fetais/etiologia , Humanos , Masculino , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/fisiopatologia , Síndrome do Ovário Policístico/etiologia , Pré-Eclâmpsia/etiologia , Gravidez , Complicações na Gravidez/fisiopatologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Aumento de Peso , Adulto Jovem
17.
J Obstet Gynaecol Res ; 45(1): 69-77, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30230126

RESUMO

AIM: Group B streptococcus (GBS) is a leading cause of life-threatening bacterial infections among newborns, and neonates born to heavily colonized women may be subject to vertical transmission. We sought to determine an appropriate detection method for genital GBS in pregnant women by comparing culture-based methods and real-time polymerase chain reaction (PCR). In addition, we performed molecular serotyping and multilocus sequence typing (MLST) on isolates. METHODS: A total of 150 pregnant women were enrolled and underwent vaginal-rectal swabbing at 16-40 weeks of gestation. GBS was identified by conventional culture and real-time PCR with or without enrichment. Molecular serotyping and MLST were performed on isolates. RESULTS: Overall genital GBS positive rate among the 150 study subjects was 17.3%. Direct culture identified 18 (12.0%) positive specimens, enrichment culture 22 (14.6%), direct PCR 24 (16.0%) and enrichment PCR 25 (16.6%). The sensitivity and specificity by direct and enrichment PCR were as follows: for direct PCR, 90.9% and 96.9%, respectively; and for enrichment PCR, 95.5% and 96.9%, respectively. Resistance rates to clindamycin and erythromycin were 33.3% and 19.1%, respectively. Serotype III-1 was the most common (26.3%), followed by serotype Ib (21.1%), III-3 (15.8%), V (15.8%), II (10.5%), IV (5.3%) and VI (5.3%). Most common sequence types (ST) were ST-1, ST-19 and ST-862 (15.8%), followed by ST-2 and ST-654 (10.5%). CONCLUSION: Direct real-time PCR using vaginal-rectal specimen could be used for detecting GBS in emergent conditions. Molecular serotypes III, Ib and V were most common. MLST analysis frequently presented ST-1, ST-19 and ST-862.


Assuntos
Genoma Bacteriano , Genômica/métodos , Complicações Infecciosas na Gravidez/microbiologia , Sorogrupo , Infecções Estreptocócicas/microbiologia , Streptococcus/genética , Adulto , Feminino , Humanos , Tipagem de Sequências Multilocus/métodos , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , República da Coreia/epidemiologia , Sorotipagem/métodos , Infecções Estreptocócicas/epidemiologia , Streptococcus/classificação
18.
J Biomater Appl ; 33(2): 196-204, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29945536

RESUMO

Background In this study, the properties of the water glass (WG, sodium-silicate glass) were utilized to control the biodegradability of the beta tricalcium phosphate materials by the WG coating on the tricalcium phosphate disc surface with various coating thickness, chemistry, and heat-treatment. Methods Four types of disc specimens were prepared. A sample group A consisted of pure hydroxyapatite (HA) as a negative resorption control; a sample group B consisted of pure beta tricalcium phosphate as a positive resorption control; a sample group C consisted of beta tricalcium phosphate coated with WG as an early resorption model; and a sample group D consisted beta tricalcium phosphate coated with WG and heat-treated at 500°C as a delayed resorption model. Using human bone marrow-derived mesenchymal stem cells, for the analysis of cellular attachment and proliferative activity, 4-6-Diamidino-2-Phenylindole fluorescence technique was used. For the analysis of osteteogenic differentiation, alkaline phospastase (ALP) activity was measured. Results The mean z-scores of four groups (A, B, C, and D) in cellular attachment at 4 h after seeding were -1.21, -0.15, 0.42, and 0.94, respectively, and statistically significantly different in all groups respectively. Seven days after seeding, the mean z-scores of cellular proliferation were 1.97, 0.71, 1.48, and 1.83 in the four groups, respectively. The mean z-scores of the ALP activity per the mean z-scores of cell numbers of respective groups on the seventh day were 0.40, -1.51, 0.12, and 0.06, respectively, in four groups. Conclusion Initial cellular attachment is better on beta tricalcium phosphate than on HA and is enhanced by WG coating, especially with sintering at the high temperature. Cellular proliferation is considered to be increased by maintaining its attachment site through reduced dissolution of beta tricalcium phosphate by WG coating. Osteogenic differentiation in in-vitro study on the WG-coated beta tricalcium phosphate is thought to be as the result of increased silicon ion release from the WG.


Assuntos
Fosfatos de Cálcio/química , Proliferação de Células , Materiais Revestidos Biocompatíveis/química , Osteogênese , Silicatos/química , Água/química , Adesão Celular , Diferenciação Celular , Células Cultivadas , Vidro/química , Humanos , Células-Tronco Mesenquimais/citologia
20.
Int J Med Sci ; 15(6): 557-563, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29725245

RESUMO

Background: We examined the relationship and combined effect of vascular calcification (VC) and left ventricular hypertrophy (LVH) on deaths and cardiovascular events (CVEs) in hemodialysis (HD) patients. Methods: Maintenance HD patients (n=341) were included. Echocardiography data and plain chest radiographs were used to assess LVH and aortic arch VC. Results: VC was found in 100 patients (29.3%). LVH was more prevalent in patients with VC compared with those without VC (70% vs. 50.2%, P=0.001). VC was independently associated with a 2.42-fold increased risk of LVH (95% CI, 1.26-4.65). In multivariate analysis, compared with patients with neither VC nor LVH, the coexistence of VC and LVH was independently associated with CVE (HR, 2.01; 95% CI, 1.09-3.72), whereas VC or LVH alone was not. Patients with both VC and LVH had the highest risk for a composite event of deaths or CVE (HR, 1.88; 95% CI, 1.15-3.06). Significant synergistic interaction was observed between VC and LVH (P for interaction=0.039). Conclusions: VC was independently associated with LVH. The coexistence of VC and LVH was associated with higher risk of deaths and CVEs than either factor alone. VC and LVH showed a synergistic interaction for the risk of deaths and CVEs.


Assuntos
Hipertrofia Ventricular Esquerda/fisiopatologia , Falência Renal Crônica/fisiopatologia , Diálise Renal/efeitos adversos , Calcificação Vascular/fisiopatologia , Idoso , Ecocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/epidemiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia
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