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1.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445110

RESUMO

Epidermal growth factor receptor (EGFR) is overexpressed in lung cancer patients. Despite treatment with various EGFR tyrosine kinase inhibitors, recurrence and metastasis of lung cancer are inevitable. Docetaxel (DTX) is an effective conventional drug that is used to treat various cancers. Several researchers have studied the use of traditional herbal medicine in combination with docetaxel, to improve lung cancer treatment. SH003, a novel herbal mixture, exerts anticancer effects in different cancer cell types. Here, we aimed to investigate the apoptotic and anticancer effects of SH003 in combination with DTX, in human non-small-cell lung cancer (NSCLC). SH003, with DTX, induced apoptotic cell death, with increased expression of cleaved caspases and cleaved poly (ADP-ribose) polymerase in NSCLC cells. Moreover, SH003 and DTX induced the apoptosis of H460 cells via the suppression of the EGFR and signal transducer and activator of transcription 3 (STAT3) signaling pathways. In H460 tumor xenograft models, the administration of SH003 or docetaxel alone diminished tumor growth, and their combination effectively killed cancer cells, with increased expression of apoptotic markers and decreased expression of p-EGFR and p-STAT3. Collectively, the combination of SH003 and DTX may be a novel anticancer strategy to overcome the challenges that are associated with conventional lung cancer therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células A549 , Inibidores da Angiogênese/farmacologia , Animais , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT3/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
2.
Int J Mol Sci ; 22(9)2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-34063207

RESUMO

Recent studies have implicated mitochondrial disruption in podocyte dysfunction, which is a characteristic feature of primary and diabetic glomerular diseases. However, the mechanisms by which primary mitochondrial dysfunction in podocytes affects glomerular renal diseases are currently unknown. To investigate the role of mitochondrial oxidative phosphorylation (OxPhos) in podocyte dysfunction, glomerular function was examined in mice carrying a loss of function mutation of the gene encoding CR6-interacting factor-1 (CRIF1), which is essential for intramitochondrial production and the subsequent insertion of OxPhos polypeptides into the inner mitochondrial membrane. Homozygotic deficiency of CRIF1 in podocytes resulted in profound and progressive albuminuria from 3 weeks of age; the CRIF1-deficient mice also developed glomerular and tubulointerstitial lesions by 10 weeks of age. Furthermore, marked glomerular sclerosis and interstitial fibrosis were observed in homozygous CRIF1-deficient mice at 20 weeks of age. In cultured mouse podocytes, loss of CRIF1 resulted in OxPhos dysfunction and marked loss or abnormal aggregation of F-actin. These findings indicate that the OxPhos status determines the integrity of podocytes and their ability to maintain a tight barrier and control albuminuria. Analyses of the glomerular function of the podocyte-specific primary OxPhos dysfunction model mice demonstrate a link between podocyte mitochondrial dysfunction, progressive glomerular sclerosis, and tubulointerstitial diseases.


Assuntos
Albuminúria/metabolismo , Proteínas de Ciclo Celular/deficiência , Proteínas de Ciclo Celular/metabolismo , Mitocôndrias/metabolismo , Podócitos/metabolismo , Esclerose/metabolismo , Albuminúria/genética , Albuminúria/patologia , Animais , Proteínas de Ciclo Celular/genética , Nefropatias Diabéticas/metabolismo , Modelos Animais de Doenças , Feminino , Fibrose , Rim/patologia , Masculino , Camundongos , Camundongos Knockout , Mitocôndrias/genética , Membranas Mitocondriais/metabolismo , Fosforilação Oxidativa , Peptídeos/metabolismo , Esclerose/genética , Esclerose/patologia
3.
Nefrologia (Engl Ed) ; 2021 May 10.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33985859

RESUMO

BACKGROUND: The maturation and patency of permanent vascular access are critical in patients requiring hemodialysis. Although numerus trials have been attempted to achieve permanently patent vascular access, little have been noticeable. Cilostazol, a phosphodiesterase-3 inhibitor, has been shown to be effective in peripheral arterial disease including vascular injury-induced intimal hyperplasia. We therefore aimed to determine the effect of cilostazol on the patency and maturation of permanent vascular access. METHODS: This single-center, retrospective study included 194 patients who underwent arteriovenous fistula surgery to compare vascular complications between the cilostazol (n=107) and control (n=87) groups. RESULTS: The rate of vascular complications was lower in the cilostazol group than in the control group (36.4% vs. 51.7%; p=0.033), including maturation failure (2.8% vs. 11.5%; p=0.016). The rate of reoperation due to vascular injury after hemodialysis initiation following fistula maturation was also significantly lower in the cilostazol group than in the control group (7.5% vs. 28.7%; p<0.001). However, there were no significant differences in the requirement for percutaneous transluminal angioplasty (PTA), rate of PTA, and the interval from arteriovenous fistula surgery to PTA between the cilostazol and control groups. CONCLUSION: Cilostazol might be beneficial for the maturation of permanent vascular access in patients requiring hemodialysis.

4.
PLoS One ; 16(4): e0250467, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33891656

RESUMO

BACKGROUND AND AIMS: Knowledge of the proper dry weight plays a critical role in the efficiency of dialysis and the survival of hemodialysis patients. Recently, bioimpedance spectroscopy(BIS) has been widely used for set dry weight in hemodialysis patients. However, BIS is often misrepresented in clinical healthy weight. In this study, we tried to predict the clinically proper dry weight (DWCP) using machine learning for patient's clinical information including BIS. We then analyze the factors that influence the prediction of the clinical dry weight. METHODS: As a retrospective, single center study, data of 1672 hemodialysis patients were reviewed. DWCP data were collected when the dry weight was measured using the BIS (DWBIS). The gap between the two (GapDW) was calculated and then grouped and analyzed based on gaps of 1 kg and 2 kg. RESULTS: Based on the gap between DWBIS and DWCP, 972, 303, and 384 patients were placed in groups with gaps of <1 kg, ≧1kg and <2 kg, and ≧2 kg, respectively. For less than 1 kg and 2 kg of GapDW, It can be seen that the average accuracies for the two groups are 83% and 72%, respectively, in usign XGBoost machine learning. As GapDW increases, it is more difficult to predict the target property. As GapDW increase, the mean values of hemoglobin, total protein, serum albumin, creatinine, phosphorus, potassium, and the fat tissue index tended to decrease. However, the height, total body water, extracellular water (ECW), and ECW to intracellular water ratio tended to increase. CONCLUSIONS: Machine learning made it slightly easier to predict DWCP based on DWBIS under limited conditions and gave better insights into predicting DWCP. Malnutrition-related factors and ECW were important in reflecting the differences between DWBIS and DWCP.


Assuntos
Água Corporal/metabolismo , Falência Renal Crônica/metabolismo , Aprendizado de Máquina , Diálise Renal , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Idoso , Peso Corporal/fisiologia , Creatinina/sangue , Impedância Elétrica , Espaço Extracelular , Feminino , Hemoglobinas/metabolismo , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Albumina Sérica/metabolismo
5.
J Am Soc Nephrol ; 32(1): 199-210, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33168602

RESUMO

BACKGROUND: Tacrolimus is used as a steroid-sparing immunosuppressant in adults with minimal change nephrotic syndrome. However, combined treatment with tacrolimus and low-dose steroid has not been compared with high-dose steroid for induction of clinical remission in a large-scale randomized study. METHODS: In this 24-week open-label noninferiority study, we randomized 144 adults with minimal change nephrotic syndrome to receive 0.05 mg/kg twice-daily tacrolimus plus once-daily 0.5 mg/kg prednisolone, or once-daily 1 mg/kg prednisolone alone, for up to 8 weeks or until achieving complete remission. Two weeks after complete remission, we tapered the steroid to a maintenance dose of 5-7.5 mg/d in both groups until 24 weeks after study drug initiation. The primary end point was complete remission within 8 weeks (urine protein: creatinine ratio <0.2 g/g). Secondary end points included time until remission and relapse rates (proteinuria and urine protein: creatinine ratio >3.0 g/g) after complete remission to within 24 weeks of study drug initiation. RESULTS: Complete remission within 8 weeks occurred in 53 of 67 patients (79.1%) receiving tacrolimus and low-dose steroid and 53 of 69 patients (76.8%) receiving high-dose steroid; this difference demonstrated noninferiority, with an upper confidence limit below the predefined threshold (20%) in both intent-to-treat (11.6%) and per-protocol (17.0%) analyses. Groups did not significantly differ in time until remission. Significantly fewer patients relapsed on maintenance tacrolimus (3-8 ng/ml) plus tapered steroid versus tapered steroid alone (5.7% versus 22.6%, respectively; P=0.01). There were no clinically relevant safety differences. CONCLUSIONS: Combined tacrolimus and low-dose steroid was noninferior to high-dose steroid for complete remission induction in adults with minimal change nephrotic syndrome. Relapse rates were significantly lower with maintenance tacrolimus and steroid compared with steroid alone. No clinically-relevant differences in safety findings were observed.

6.
Transpl Int ; 34(2): 290-301, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33258121

RESUMO

BACKGROUND: Outcomes of ABO-incompatible living donor kidney transplantation (ABOi LDKT) in older individuals have not been established. METHODS: This multicentric observational study, using data from the Korean Organ Transplantation Registry database, included 634 older patients (≥60 years) undergoing kidney transplantation. We compared clinical outcomes of ABOi LDKT (n = 80) with those of ABO-compatible LDKT (ABOc LDKT, n = 222) and deceased donor kidney transplantation (DDKT, n = 332) in older patients. RESULTS: Death-censored graft survival was similar between the three groups (P = 0.141). Patient survival after ABOi LDKT was similar to that after ABOc LDKT (P = 0.489) but higher than that after DDKT (P = 0.038). In multivariable analysis, ABOi LDKT was not risk factor (hazard ratio [HR] 1.73, 95% confidence interval [CI] 0.29-10.38, P = 0.548), while DDKT was significant risk factor (HR 3.49, 95% CI 1.01-12.23, P = 0.049) for patient survival. Although ABOi LDKT showed higher biopsy-proven acute rejection than ABOc LDKT, the difference was not significant after adjustment with covariates. However, ABOi LDKT was significant risk factor for infection (HR 1.66, 95% CI 1.12-2.45, P = 0.012). CONCLUSIONS: In older patients, ABOi LDKT was not inferior to ABOc LDKT and was superior to DDKT for patient survival. ABOi LDKT can be recommended for older patients, rather than waiting for DDKT.


Assuntos
Transplante de Rim , Sistema ABO de Grupos Sanguíneos , Idoso , Incompatibilidade de Grupos Sanguíneos , Estudos de Coortes , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Doadores Vivos
7.
Sci Rep ; 10(1): 17735, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33082368

RESUMO

Diabetic nephropathy (DN) is a major complication of diabetes mellitus. NAD(P)H:quinone oxidoreductase 1 (NQO1) is an antioxidant enzyme that has been involved in the progression of several kidney injuries. However, the roles of NQO1 in DN are still unclear. We investigated the effects of NQO1 deficiency in streptozotocin (STZ)-induced DN mice. NQO1 was upregulated in the glomerulus and podocytes under hyperglycemic conditions. NQO1 knockout (NKO) mice showed more severe changes in blood glucose and body weight than WT mice after STZ treatment. Furthermore, STZ-mediated pathological parameters including glomerular injury, blood urea nitrogen levels, and foot process width were more severe in NKO mice than WT mice. Importantly, urine albumin-to-creatinine ratio (ACR) was higher in healthy, non-treated NKO mice than WT mice. ACR response to STZ or LPS was dramatically increased in the urine of NKO mice compared to vehicle controls, while it maintained a normal range following treatment of WT mice. More importantly, we found that NQO1 can stimulate actin polymerization in an in vitro biochemical assay without directly the accumulation on F-actin. In summary, NQO1 has an important role against the development of DN pathogenesis and is a novel contributor in actin reorganization via stimulating actin polymerization.


Assuntos
Actinas/metabolismo , Nefropatias Diabéticas/metabolismo , Glomérulos Renais/metabolismo , NAD(P)H Desidrogenase (Quinona)/metabolismo , Animais , Células Cultivadas , Modelos Animais de Doenças , Humanos , Glomérulos Renais/patologia , Lipopolissacarídeos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NAD(P)H Desidrogenase (Quinona)/genética , NADP/metabolismo , Polimerização , Estreptozocina
8.
J Korean Med Sci ; 35(28): e257, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32686373

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This disease, which is quickly spreading worldwide, has high potential for infection and causes rapid progression of lung lesions, resulting in a high mortality rate. This study aimed to investigate the effects of SARS-CoV-2 infection on renal function in patients with COVID-19. METHODS: From February 21 to April 24, 2020, 66 patients diagnosed with COVID-19 at Chungnam National University Hospital were analyzed; all patients underwent routine urinalysis and were tested for serum creatinine, urine protein to creatinine ratio (PCR), and urine albumin to creatinine ratio (ACR). RESULTS: Acute kidney injury (AKI) occurred in 3 (4.5%) of the 66 patients, and 1 patient with AKI stage 3 underwent hemodialysis. Upon follow-up, all 3 patients recovered normal renal function. Compared with patients with mild COVID-19, AKI (n = 3) occurred in patients with severe COVID-19, of whom both urine PCR and ACR were markedly increased. CONCLUSION: The incidence of AKI was not high in COVID-19 patients. The lower mortality rate in SARS-CoV-2 infection compared with previous Middle East respiratory syndrome and SARS-CoV infections is thought to be associated with a low incidence of dysfunction in organs other than the lungs.


Assuntos
Injúria Renal Aguda/virologia , Albuminúria/urina , Infecções por Coronavirus/patologia , Creatinina/sangue , Pneumonia Viral/patologia , Proteinúria/urina , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/patologia , Idoso , Albuminas/análise , Betacoronavirus , COVID-19 , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Pandemias , República da Coreia/epidemiologia , SARS-CoV-2
9.
J Stroke Cerebrovasc Dis ; 29(8): 104973, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689596

RESUMO

BACKGROUND AND PURPOSE: As intraarterial thrombectomy (IAT) has been actively practiced, blood biomarkers that can predict outcomes after IAT have drawn attention. Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine and the levels are increased during inflammation or other pathological conditions of various tissues, including the brain. However, GDF-15 levels have not been reported as a biomarker for IAT outcomes. This study was performed to evaluate whether GDF-15 was related to the extent of brain damage and whether it could predict patient prognosis after IAT. METHODS: Patients who showed large arterial occlusion and significant diffusion-perfusion mismatch on imaging underwent IAT. A total of 62 patients who underwent IAT and had blood samples for GDF-15 measurements were enrolled from July 2013 to May 2015. We assessed the infarct severity by consecutive changes on the National Institutes of Health Stroke Scale (NIHSS) during admission and the size of the infarction on brain imaging. Modified Rankin Scale scores (mRS) from 0 to 2 were considered good outcomes, representing functional independence at discharge and three months later. RESULTS: The levels of GDF-15 at the time of admission were significantly correlated with the NIHSS scored at 24 hours (r = 0.306, p = 0.016), three days after IAT (r = 0.261, p = 0.041), and at discharge (r = 0.266, p = 0.037), as well as the infarct size on diffusion-weighted image taken 24 h after IAT (r = 0.452, p = 0.001), but the levels were not correlated with the initial NIHSS or the infarct size before IAT. Multiple logistic regression showed that GDF-15 levels were an independent predictor of functional independence (mRS 0 - 2) at discharge (p = 0.028) and three months after IAT (p = 0.019). Other factors that could predict prognosis were good collateral status on the initial brain angiography and rapid recanalization within six hours from symptom onset. CONCLUSION: The GDF-15 level at the time of admission showed a significant positive correlation with the severity of cerebral damage and clinical outcome after IAT. This suggests that GDF-15 can provide useful prognostic information for patients who successfully underwent IAT in an emergency setting.


Assuntos
Isquemia Encefálica/terapia , Fator 15 de Diferenciação de Crescimento/sangue , Acidente Vascular Cerebral/terapia , Trombectomia , Idoso , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Angiografia Cerebral , Imagem de Difusão por Ressonância Magnética , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Trombectomia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
10.
Endocrinol Metab (Seoul) ; 35(2): 367-376, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32615721

RESUMO

BACKGROUND: This study assessed the proportion of risk-stratified Korean patients with dyslipidemia achieving their low-density lipoprotein cholesterol (LDL-C) targets as defined by the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) (2011) guidelines while receiving lipid-modifying treatments (LMTs). METHODS: In this multicenter, cross-sectional, observational study, we evaluated data from Korean patients aged ≥19 years who were receiving LMTs for ≥3 months and had an LDL-C value within the previous 12 months on the same LMT. Data were collected for demographics, cardiovascular (CV) risk factors, medical history, and healthcare consumption. Patients were risk-stratified according to the ESC Systematic COronary Risk Evaluation (SCORE) chart and LDL-C target achievement rate was assessed. RESULTS: Guideline-based risk-stratification of the 1,034 patients showed the majority (72.2%) to be in the very high-risk category. Investigators' assessment of risk was underestimated in 71.6% compared to ESC/EAS guidelines. Overall LDL-C target achievement rate was 44.3%; target achievement was the highest (66.0%) in moderate-risk patients and the lowest (39.0%) in very high-risk patients. Overall 97.1% patients were receiving statin therapy, mostly as a single-agent (89.2%). High-intensity statins and the highest permissible dose of high-intensity statins had been prescribed to only 9.1% and 7.3% patients in the very high-risk group, respectively. Physician satisfaction with patients' LDL-C levels was the primary reason for non-intensification of statin therapy. CONCLUSION: Achievement of target LDL-C level is suboptimal in Korean patients with dyslipidemia, especially in those at very high-risk of CV events. Current practices in LMTs need to be improved based on precise CV risk evaluation posed by dyslipidemia.


Assuntos
Biomarcadores/sangue , LDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Guias de Prática Clínica como Assunto/normas , Medição de Risco/métodos , Adulto , Idoso , Estudos Transversais , Dislipidemias/sangue , Dislipidemias/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , República da Coreia/epidemiologia
11.
Transplant Proc ; 52(6): 1744-1748, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32448650

RESUMO

BACKGROUND: It is unclear whether both Kidney Donor Profile Index (KDPI) and Kidney Donor Risk Index (KDRI) scores can be applied to elderly deceased donors (DDs). This study aimed to compare the predictive values of KDRI and KDPI for the occurrence of delayed graft function (DGF) in kidney transplantation (KT) from elderly DDs. METHODS: The data for 1049 DD KTs from the database of the Korean Organ Transplant Registry were reviewed retrospectively. RESULTS: The mean age of the 1049 DDs was 50.94 ± 10.57 years. A total of 224 DDs were ≥60 years old (21.35%). The mean KDRI and KDPI were 1.24 ± 0.40 and 63.58 ± 25.16, respectively. Ninety (8.6%) recipients had DGF postoperatively. The right-skewed distributions of KDRI in both elderly and nonelderly DDs were similar. However, the KDPI curve showed a sharp increase from a KDPI score of 60 in DDs aged ≥60 years. The areas under the curve (AUCs) of receiver operator characteristics (ROC) for KDPI and KDRI were different. In DDs aged <60 years, the estimated AUCs of ROC showed significant values for KDPI (0.577, 95% confidence interval, 0.503-0.637; P = .048) and KDRI (0.576, 0.505-0.639; P = .043). However, in DDs aged ≥60 years, KDRI score, not KDPI, was a significant value: KDRI, 0.633 (0.498-0.767; P = .034); KDPI, 0.530 (0.476-0.643; P = .138). CONCLUSION: KDRI was more reliable in predicting graft outcome than KDPI in KT from elderly DDs. A longer follow-up period is needed to assess predictors for postoperative renal functions.


Assuntos
Função Retardada do Enxerto/etiologia , Seleção do Doador/estatística & dados numéricos , Transplante de Rim/efeitos adversos , Doadores de Tecidos/estatística & dados numéricos , Transplantes/estatística & dados numéricos , Adulto , Idoso , Área Sob a Curva , Seleção do Doador/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Sistema de Registros , República da Coreia , Estudos Retrospectivos , Medição de Risco
12.
J Microbiol Biotechnol ; 30(7): 1060-1066, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32270659

RESUMO

This study was focused on developing and obtaining a kimchi starter for use in commercial kimchi production. Kimchi varieties made with selected starters are of high quality, have high levels of mannitol, and extended shelf life. The starters were screened for properties such as mannitol production, low gas/acid production, and acid resistance. Finally, kimchi fermentation testing was performed using selected LAB starters. Kimchi samples were prepared with lactic acid bacteria (LAB) starters, including Leuconostoc mesenteroides PBio03 and Leuconostoc mesenteroides PBio104. The LAB starters are isolated from kimchi and can grow under pH 3.0 and low temperature conditions of 5°C. Four kimchi samples were fermented and stored for 28 days at 5°C. The kimchi samples made with starters (PBio03 and PBio104) had better quality (production of mannitol and maintenance of heterofermentative LAB dominance) than the non-starter kimchi samples. In the starter kimchi, Leu. mesenteroides was the dominant LAB, comprising 80% and 70% of total LAB counts at 7 and 21 days, respectively. Mannitol content of the kimchi with Leu. mesenteroides PBio03 was 1,423 ± 19.1 mg/ 100 g at 28 days, which was higher than that of the non-starter kimchi sample (1,027 ± 12.2 mg/100 g). These results show the possibility of producing kimchi with improved qualities using Leu. mesenteroides PBio03 and PBio104 as starters.


Assuntos
Alimentos e Bebidas Fermentados/microbiologia , Microbiologia de Alimentos , Leuconostoc mesenteroides/isolamento & purificação , DNA Bacteriano , Fermentação , Concentração de Íons de Hidrogênio , Lactobacillales/classificação , Lactobacillales/isolamento & purificação , Leuconostoc mesenteroides/classificação , Manitol/metabolismo , Paladar
13.
Ther Apher Dial ; 24(1): 42-55, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31119846

RESUMO

TRK-100STP, a sustained-release preparation of the orally active prostacyclin analogue beraprost sodium, targets renal hypoxia. This study aimed to show the superiority of TRK-100STP over placebos in patients with chronic kidney disease (with either primary glomerular disease or nephrosclerosis) to determine the recommended dose. CASSIOPEIR (Chronic Renal Failure Asian Study with Oral PGI2 Derivative for Evaluating Improvement of Renal Function) was a randomized, double-blind, placebo-controlled study conducted at 160 sites in seven Asia-Pacific countries and regions. Eligible patients (n = 892) were randomized to TRK-100STP 120, 240 µg, or placebo for a treatment period of up to 4 years. The primary efficacy endpoint was time to first occurrence of a renal composite: doubling of serum creatinine or occurrence of end-stage renal disease. No significant differences were observed in composite endpoints between TRK-100STP and placebo (P = 0.5674). Hazard ratios (95% CI) in the TRK-100STP 120 and 240 µg vs. placebo groups were 0.98 (0.78, 1.22) and 0.91 (0.72, 1.14), respectively. The overall incidence of adverse events and adverse drug reactions was comparable between treatment arms.


Assuntos
Epoprostenol/análogos & derivados , Nefroesclerose/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Vasodilatadores/administração & dosagem , Adulto , Idoso , Creatinina/sangue , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Método Duplo-Cego , Epoprostenol/administração & dosagem , Epoprostenol/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefroesclerose/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Vasodilatadores/efeitos adversos , Adulto Jovem
14.
BioDrugs ; 34(1): 99-110, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31749113

RESUMO

BACKGROUND: Darbepoetin-alfa is an erythropoiesis-stimulating agent (ESA) with a long elimination half-life that achieves better hemoglobin (Hb) stability than short-acting ESAs. OBJECTIVE: We aimed to evaluate the efficacy and safety of intravenous CKD-11101 (a biosimilar of darbepoetin-alfa) compared with those of darbepoetin-alfa in hemodialysis patients. METHODS: The study was performed in 24 centers in Korea between June 2015 and June 2017. The study subjects were randomized in a double-blind manner. The follow-up duration was 24 weeks, which consisted of 20 weeks of maintenance and 4 weeks of evaluation period. All patients underwent a stabilization period to achieve a target baseline Hb of 10-12 g/dL before randomization. Following randomization, patients received darbepoetin-alfa or CKD-11101 weekly or biweekly. RESULTS: A total of 403 patients were randomized into two groups, and a total of 325 patients (80.6%) completed the investigation. The differences between the two groups in terms of change in the average Hb level from baseline to evaluation were not significant. The average administered dose of ESA was similar between the groups. There was no difference in the proportion of patients who maintained the target Hb during the evaluation period [60.4% vs. 66.2% in the CKD-11101 and darbepoetin-alfa groups, respectively (p = 0.3038)]. In addition, the safety analysis, consisting of adverse events and adverse drug reactions, showed comparable results between the two groups. CONCLUSION: The changes in the level of Hb, dose of erythropoietin, and achievement rate of the target Hb during the study period were comparable between the groups. CKD-11101 has an equivalent efficacy and safety compared with darbepoetin-alfa in patients undergoing hemodialysis.


Assuntos
Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/uso terapêutico , Darbepoetina alfa/efeitos adversos , Darbepoetina alfa/uso terapêutico , Epoetina alfa/efeitos adversos , Epoetina alfa/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/métodos , Insuficiência Renal Crônica/metabolismo
15.
Electrolyte Blood Press ; 17(1): 16-20, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31338110

RESUMO

A 68-year-old man presented at the emergency room with sudden blindness. The day before, he had eaten sashimi and eel and drank alcohol for dinner. He experienced nausea, vomiting, and dizziness afterward. His medical history included hypertension and diabetes, and the latter was treated with metformin. Initial laboratory tests revealed severe metabolic acidosis (lactic acidosis). Massive hydration and intravenous sodium bicarbonate replacement therapies were initiated, but severe metabolic acidosis (lactic acidosis) did not resolve, in turn, leading to hemodialysis, which decreased metabolic acidosis. The patient's blindness improved, and his vision gradually recovered. As it is not easy to distinguish between blindness related to metformin-associated lactic acidosis (MALA) and blindness related to other causes, rapid correction of metabolic acidosis through hemodialysis might be helpful in differentiating this from of blindness from blindness related to other causes.

16.
Kidney Res Clin Pract ; 38(1): 116-123, 2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30743320

RESUMO

Background: Kidney transplantation is an effective renal replacement therapy for patients with end-stage renal disease (ESRD). In this study, we assessed the impact of the baseline characteristics and comorbidities of ESRD patients on the probability of deceased donor kidney transplantation (DDKT) and evaluated the morbidity and mortality during the time spent waiting. Methods: The study population consisted of 544 ESRD patients on the waiting list for DDKT at Chungnam National University Hospital in South Korea between February 2000 and October 2015. The patients were observed from the date of transplantation list registration to the date of transplantation. Baseline characteristics and comorbidities were investigated together with new-onset comorbidities that occurred during the waiting time. Results: Diabetes mellitus (39.0%), hypertension (25.2%), and glomerulonephritis (21.3%) were the three most common causes of ESRD in this study, and coronary artery disease (9.4%) was the most common comorbidity. The 115 patients (19.3%) who underwent DDKT had a mean waiting time of 1,711 days (768-2,654 days or 4.68 years [2.10-7.27]). Blood groups other than type O, peritoneal dialysis, and nondiabetic ESRD were significantly associated with a higher likelihood of DDKT. Infection was the leading cause of death and the most common comorbidity that arose during the waiting time. Patients who experienced cardiovascular events during the waiting time showed a lower transplant rate compared with those who did not. Conclusion: The prevalence of comorbidities was high in renal transplantation candidates. During the often-long waiting time, new comorbidities may occur, with long-term sequelae limiting access to kidney transplantation or resulting in death.

17.
Curr Med Res Opin ; 35(6): 1111-1118, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30569763

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of CKD-11101 (biosimilar darbepoetin-alfa, Chong Kun Dang Pharm.) compared with NESP® in treatment of anaemia in patients with chronic kidney disease not on dialysis. CLINICAL TRIAL REGISTRATION: NCT03431623. METHOD: In this multi-centre, randomized, double-blind study, patients were treated with CKD-11101 and NESP. The efficacy evaluation period (EEP) was 24 weeks, during which patients were treated every 2 weeks. All patients who completed the EEP were treated with CKD-11101 every 2 weeks for the first 4 weeks and every 4 weeks for the safety evaluation period (SEP), which was from 24 weeks to 52 weeks. The primary efficacy endpoint was the change in mean haemoglobin (Hb) level from baseline to end of EEP and mean dose needed to achieve the target Hb. RESULTS: The mean Hb level was increased in both groups during the EEP (both p < 0.001). The difference in mean Hb level change between the two groups was 0.01 g/dL (95% CI = -0.213-0.242), indicating that CKD-11101 was equivalent to NESP. The difference in mean administration dose between groups was -1.40 mcg (95% CI = -6.859-4.059) included in the equivalent range. The incidence of AEs and ADRs was not different between the two groups, and the frequency of ADRs was favourable in both groups (1.2% in CKD-11101 vs 7.7% in the NESP to CKD-11101 conversion group). CONCLUSION: CKD-11101 has an equivalent therapeutic effect as NESP in chronic kidney disease patients with renal anaemia. CKD-11101 can be safely used for long-term treatment and in patients converted from NESP.


Assuntos
Anemia/tratamento farmacológico , Medicamentos Biossimilares/uso terapêutico , Darbepoetina alfa/uso terapêutico , Diálise Renal , Insuficiência Renal Crônica/complicações , Adulto , Idoso , Medicamentos Biossimilares/efeitos adversos , Darbepoetina alfa/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/terapia
18.
Food Sci Biotechnol ; 27(2): 489-498, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30263773

RESUMO

Kimchi was prepared with different types of salts: purified salt (PS), solar salt aged for 1 year (SS1), aged for 3 years (SS3), and bamboo salt (BS). Kimchi inoculated with Leuconostoc mesenteroides P30 (starter kimchi), and control kimchi (non-starter kimchi) were prepared, and stored at - 1 °C for 20 weeks. Titratable acidity values increased slowly and reached 0.96-1.01% (pH 3.73-3.83) at 20 weeks. Proportions of coccus-type lactic acid bacteria (LAB) among total LAB were higher in SS kimchi than PS kimchi. Among non-starter kimchi, the proportions were 44.7, 41.6, 29.7, and 32.1% for SS3, SS1, BS, and PS kimchi, respectively, at 2 weeks, and 11.5, 12.8, 6.7, and 5.8%, respectively, at 20 weeks. SS kimchi had much less yeast counts than PS kimchi. Among starter kimchi, yeasts were detected from PS kimchi at 10 weeks but not detected until 18 weeks from SS1 and BS kimchi and 20 weeks from SS3 kimchi.

19.
J Microbiol Biotechnol ; 28(4): 534-541, 2018 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-29724081

RESUMO

Kimchi (a traditional Korean fermented vegetable) was prepared with a starter, Lactobacillus zymae GU240 producing γ-aminobutyric acid (GABA), and one precursor of GABA (glutamic acid, glutamic acid monosodium salt (MSG), or kelp extract). L. zymae GU240, an isolate from kimchi, can grow at 7% NaCl and low temperature. Five different kimchi samples were fermented for 20 weeks at -1°C. Kimchi with starter alone could not produce GABA. The GABA content was highest in kimchi with co-inoculation of the starter and MSG (1% (w/w)). Kimchi co-inoculated with the starter and kelp extract powder (3% (w/w)) had the second highest GABA content. Addition of glutamic acid powder (1% (w/w)) caused a reduction in the pH level of kimchi and growth inhibition of lactic acid bacteria and yeasts. Kimchi samples with MSG or kelp extract showed improvement of sensory evaluation scores. The results demonstrate the possibility to produce kimchi with improved functionality and taste by using L. zymae GU240 as a starter along with a suitable precursor such as MSG or kelp extract.


Assuntos
Fermentação , Alimentos e Bebidas Fermentados/microbiologia , Lactobacillales/metabolismo , Ácido gama-Aminobutírico/metabolismo , Técnicas de Cocultura , Contagem de Colônia Microbiana , Ácido Glutâmico/metabolismo , Concentração de Íons de Hidrogênio , Kelp/química , Lactobacillales/crescimento & desenvolvimento , Lactobacillus/crescimento & desenvolvimento , Lactobacillus/isolamento & purificação , Lactobacillus/metabolismo , Viabilidade Microbiana , República da Coreia , Salinidade , Cloreto de Sódio/metabolismo , Açúcares/metabolismo , Paladar , Temperatura , Leveduras/crescimento & desenvolvimento , Leveduras/metabolismo
20.
Dis Markers ; 2018: 1463940, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29682097

RESUMO

Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome. No biomarker to predict the long-term prognosis of IMN is currently available. Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-ß superfamily and has been associated with chronic inflammatory disease. It has the potential to be a useful prognostic marker in patients with renal diseases, such as diabetic nephropathy and IgA nephropathy. This study examined whether GDF-15 is associated with the clinical parameters in IMN and showed that GDF-15 can predict IMN disease progression. A total of 35 patients with biopsy-proven IMN, treated at Chungnam National University Hospital from January 2010 to December 2015, were included. Patients younger than 18 years, those with secondary membranous nephropathy, and those lost to follow-up before 12 months were excluded. Levels of GDF-15 at the time of biopsy were measured using enzyme-linked immunosorbent assays. Disease progression was defined as a ≥30% decline in estimated glomerular filtration rate (eGFR) or the development of end-stage renal disease. The mean follow-up was 44.1 months (range: 16-72 months). Using receiver operating curve analysis, the best serum GDF-15 cut-off value for predicting disease progression was 2.15 ng/ml (sensitivity: 75.0%, specificity: 82.1%, p = 0.007). GDF-15 was significantly related to age and initial renal function. In the Kaplan-Meier analysis, the risk of disease progression increased in patients with GDF-15 ≥ 2.15 ng/ml when compared with those with GDF-15 < 2.15 ng/ml (50.0% versus 9.7%) (p = 0.012). In the multivariate Cox regression analysis adjusted for potential confounders, only GDF-15 was significantly associated with disease progression in IMN (p = 0.032). In conclusion, the GDF-15 level at the time of diagnosis has a significant negative correlation with initial renal function and is associated with a poor prognosis in IMN. Our results suggest that GDF-15 provides useful prognostic information in patients with IMN.


Assuntos
Glomerulonefrite Membranosa/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Idoso , Biomarcadores/sangue , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite Membranosa/patologia , Humanos , Masculino , Pessoa de Meia-Idade
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