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1.
Ren Fail ; 46(2): 2375103, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38973376

RESUMO

INTRODUCTION: Cardiovascular events resulting from volume overload are a primary cause of mortality in hemodialysis patients. Bioelectrical impedance analysis (BIA) is significantly valuable for assessing the volume status of hemodialysis (HD) patients. In this article, we explore the correlation between the volume index measured by BIA and the cardiac function index assessed by echocardiography (ECG) in HD patients. METHODS: Between April and November 2018, we conducted a cross-sectional study involving randomly selected 126 maintenance HD patients. Comprehensive data on medical history and laboratory test results were collected. Subsequently, we investigated the correlation between volume indices measured by BIA and cardiac function parameters by ECG. RESULTS: We discovered a significant correlation between the volume indices measured by BIA and various parameter of cardiac function. The Left Ventricular Hypertrophy (LVH) group exhibited higher levels of the percentage of Extracellular Water (ECW%) and the percentage of Total Body Water (TBW%) compared to the Non-LVH group. Extracellular Water (ECW) and Third Interstitial Fluid Volume (TSFV) were identified as independent risk factors for Left Ventricular Mass (LVM), and both demonstrated a high predictive value for LVM. ECW% emerged as an independent risk factor for the Left Ventricular Mass Index (LVMI), with a high predictive value for LVMI. CONCLUSION: ECW and TSFV were found to be positively associated with cardiac function parameters in HD patients.


Assuntos
Ecocardiografia , Impedância Elétrica , Hipertrofia Ventricular Esquerda , Falência Renal Crônica , Diálise Renal , Humanos , Diálise Renal/efeitos adversos , Feminino , Masculino , Estudos Transversais , Pessoa de Meia-Idade , Ecocardiografia/métodos , Idoso , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/etiologia , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Falência Renal Crônica/fisiopatologia , Água Corporal , Adulto
2.
Front Med (Lausanne) ; 9: 848938, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35492337

RESUMO

Histone deacetylases (HDACs) inhibitors are promising therapeutic agents against proteinuric kidney diseases, here, we investigated the effect of MC1568, a selective inhibitor of HDAC class IIa, on the development and progression of nephrotic syndrome in a murine model induced by Adriamycin (ADR). In kidney tissues of FSGS patients, all four members of HDAC IIa were significantly upregulated in podocytes. In ADR-treated cultured human podocyte, expression of HDAC IIa were induced, meanwhile inhibition of HDAC IIa with MC1568 restored cytoskeleton structure and suppressed expression of desmin and α-SMA. In mice, administration of MC1568 at 14 days after ADR ameliorated proteinuria and podocyte injury, also decreased expression of Fibronectin and α-SMA. Mechanistically, MC1568 inhibited ADR induced ß-catenin activation in vitro and in vivo. Together, these finding demonstrate that HDAC IIa inhibition ameliorates podocyte injury and proteinuria, which provide a possibility that MC1568 may be used in nephrotic syndrome.

3.
Ther Apher Dial ; 26(1): 71-84, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34038022

RESUMO

Cardiovascular diseases (CVD) are common in maintenance hemodialysis (MHD) patients, and vascular calcification is associated with the incidence of CVD. Malnourished MHD patients are particularly prone to CVD events. Thus far, there is no clear explanation for the relationship of nutrition status with vascular calcification; therefore, we investigated the relationship between malnutrition and vascular calcification. One hundred thirty-one patients underwent laboratory testing, assessment of vascular calcification, modified quantitative subjective global assessment (MQSGA), bioelectrical impedance analysis (BIA), and anthropometric measurements. The patients were divided into two groups based on the presence or absence of coronary artery calcification (CAC), and nutritional statuses were compared between the two groups. The MQSGA score was higher in the CAC group (mean 10.9 ± 1.81) than in the no-CAC group (mean 10.2 ± 1.51); in addition, the mean phase angle (PA) value was significantly lower in the CAC group than in the no-CAC group. Stratification according to CAC score showed that age, Kt/V, incidence of valve calcification, incidence of abdominal aortic calcification, MQSGA score, and blood cell mass were related to the severity of CAC. In addition, quartile analysis revealed that MQSGA score and PA value were related to the incidence and severity of vascular calcification. Binary regression analysis showed that MQSGA score, age, hemoglobin level, and high-density lipoprotein level were independent risk factors for dialysis-related CAC. Patients on MHD who exhibited malnutrition were more likely to have vascular calcification, especially CAC. Namely, the higher the MQSGA score, the lower the PA, and the more likely the occurrence of CAC.


Assuntos
Doença da Artéria Coronariana/epidemiologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Desnutrição/epidemiologia , Diálise Renal/métodos , Calcificação Vascular/epidemiologia , Adulto , Idoso , China/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Fatores de Risco , Adulto Jovem
4.
J Cell Mol Med ; 26(2): 507-514, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34889045

RESUMO

Lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (SA-AKI) is a model of clinical serious care syndrome, with high morbidity and mortality. Tacrolimus (TAC), a novel immunosuppressant that inhibits inflammatory response, plays a pivotal role in kidney diseases. In this study, LPS treated mice and cultured podocytes were used as the models of SA-AKI in vivo and in vitro, respectively. Medium- and high-dose TAC administration significantly attenuated renal function and renal pathological manifestations at 12, 24 and 48 h after LPS treatment in mice. Moreover, the Toll-like receptor 4 (TLR4)/myeloid differential protein-88 (MyD88)/nuclear factor-kappa (NF-κB) signalling pathway was also dramatically inhibited by medium- and high-dose TAC administration at 12, 24 and 48 h of LPS treatment mice. In addition, TAC reversed LPS-induced podocyte cytoskeletal injury and podocyte migratory capability. Our findings indicate that TAC has protective effects against LPS-induced AKI by inhibiting TLR4/MyD88/NF-κB signalling pathway and podocyte dysfunction, providing another potential therapeutic effects for the LPS-induced SA-AKI.


Assuntos
Injúria Renal Aguda , Receptor 4 Toll-Like , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Animais , Lipopolissacarídeos/farmacologia , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Tacrolimo/farmacologia , Receptor 4 Toll-Like/metabolismo
5.
Nephron ; 145(5): 553-567, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34126619

RESUMO

BACKGROUND: Early acute kidney injury (AKI) predicts a high mortality rate in severely burned patients. However, the pathophysiology of early AKI induced by severe burn has not been well-defined. This study was designed to examine the protective effects of calcium dobesilate (CaD) against severe burn-induced early AKI in mice and explore the mechanism. METHODS: The shaved backs of mice were immersed in 100°C water for 10 s to make severe burn (40% of the total body surface area). CD-57 male mice were randomly divided into sham, burn, burn + vehicle, and burn + CaD groups. Renal function, reactive oxygen species generation, tubular necrosis, and phosphorylation of mitogen-activated protein kinase, protein kinase B (Akt), and nuclear factor (NF)-κB were measured at 24 and 48 h after the burn. Renal histology, ELISA, qRT-PCR, and Western blotting were performed on the renal tissue of mice to examine the effects and mechanisms at 24 and 48 h after the burn. RESULTS: Tubular damage, cast formation, and elevations of serum creatinine, BUN, and renal tissue kidney injury molecule 1 levels were all observed in the burned mice, and these were all alleviated in the mice with CaD treatment. In addition, the levels of oxidation-reduction potential and malondialdehyde were decreased, while the activities of the endogenous antioxidative enzymes were increased in the kidney tissues from the mice after CaD treatment. Furthermore, the activities of Akt, p38, extracellular sign-regulated kinase, Jun N-terminal kinase, and NF-κB signaling were increased in the kidney of burned mice and normalized after CaD treatment. CONCLUSION: This study has established, for the first time, the protective effect of CaD against early AKI in severely burned mice. CaD may exert its protective effect through alleviating oxidative stress, apoptosis, and inflammation, as well as modulating some signaling pathways in the kidney.


Assuntos
Injúria Renal Aguda/prevenção & controle , Queimaduras/complicações , Dobesilato de Cálcio/uso terapêutico , Injúria Renal Aguda/complicações , Injúria Renal Aguda/etiologia , Animais , Apoptose/efeitos dos fármacos , Dobesilato de Cálcio/farmacologia , Creatinina/sangue , Masculino , Camundongos , NF-kappa B/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos
6.
Ther Apher Dial ; 23(6): 562-569, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30843338

RESUMO

Our aim was to analyze the practice pattern of vascular access use and complication rates in patients receiving continuous renal replacement therapy from a large Chinese urban medical center. Patients who had received continuous renal replacement therapy (CRRT) from April to October 2014 in our center were included in this study. Demographic data, primary disease, department for hospitalization, blood pressure, heart rate, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE II) score, presence of mechanical ventilation, CRRT modalities, choice of functioning vascular access, site and duration of catheter insertion, presence of recatheterization, cumulative catheter indwelling time, catheter malfunction and catheter-related infections, as well as laboratory test results, were collected. A total of 292 patients were enrolled in our study, including 175 males (59.9%) and 117 females (40.1%), aged 50.8 ± 18.6 years (range, 12 to 94 years). Acute kidney injury, multiple organ dysfunction syndrome, and systemic inflammatory response syndrome were the main indications for treatment with CRRT. Initial vascular access was non-cuffed temporary catheters in 280 patients and was preferentially obtained in the right internal jugular vein (54.3%). There were 32 (11.4%) patients requiring re-catheterization. Catheter malfunction occurred in 7.14% of all patients, and the median time of catheter malfunction was found at the 5th day. By multivariate analysis, it was found that the main risk factors of catheter malfunction were cumulative treatment time of CRRT and the level of hemoglobin. The average time of catheter-related infections was 10.7 days after insertion and the catheter-related infections occurred at a rate of 7.19 per 1000 catheter days. The main risk factors for catheter-related infections were cumulative time of catheterization and the level of serum albumin. In this cohort of critically ill patients, the main risk factors for catheter malfunction were cumulative CRRT time and the level of hemoglobin. In addition, the main risk factors for catheter-related infections were cumulative time of catheterization and the level of serum albumin.


Assuntos
Infecções Relacionadas a Cateter/epidemiologia , Cateterismo/métodos , Cateteres de Demora , Terapia de Substituição Renal Contínua/métodos , APACHE , Injúria Renal Aguda/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China , Estudos de Coortes , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Fatores de Risco , Fatores de Tempo , Adulto Jovem
7.
Clin Sci (Lond) ; 133(1): 9-21, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30523047

RESUMO

Recently, a novel heterozygous missense mutation c.T1421G (p. L474R) in the PODXL gene encoding podocalyxin was identified in an autosomal dominant focal segmental glomerulosclerosis (AD-FSGS) pedigree. However, this PODXL mutation appeared not to impair podocalyxin function, and it is necessary to identify new PODXL mutations and determine their causative role for FSGS. In the present study, we report the identification of a heterozygous nonsense PODXL mutation (c.C976T; p. Arg326X) in a Chinese pedigree featured by proteinuria and renal insufficiency with AD inheritance by whole exome sequencing (WES). Total mRNA and PODXL protein abundance were decreased in available peripheral blood cell samples of two affected patients undergoing hemodialysis, compared with those in healthy controls and hemodialysis controls without PODXL mutation. We identified another novel PODXL heterozygous nonsense mutation (c.C1133G; p.Ser378X) in a British-Indian pedigree of AD-FSGS by WES. In vitro study showed that, human embryonic kidney 293T cells transfected with the pEGFP-PODXL-Arg326X or pEGFP-PODXL-Ser378X plasmid expressed significantly lower mRNA and PODXL protein compared with cells transfected with the wild-type plasmid. Blocking nonsense-mediated mRNA decay (NMD) significantly restored the amount of mutant mRNA and PODXL proteins, which indicated that the pathogenic effect of PODXL nonsense mutations is likely due to NMD, resulting in podocalyxin deficiency. Functional consequences caused by the PODXL nonsense mutations were inferred by siRNA knockdown in cultured podocytes and podocalyxin down-regulation by siRNA resulted in decreased RhoA and ezrin activities, cell migration and stress fiber formation. Our results provided new data implicating heterozygous PODXL nonsense mutations in the development of FSGS.


Assuntos
Códon sem Sentido , Glomerulosclerose Segmentar e Focal/genética , Podócitos/metabolismo , Sialoglicoproteínas/genética , Adulto , Idoso , Animais , Povo Asiático/genética , Estudos de Casos e Controles , China , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/etnologia , Glomerulosclerose Segmentar e Focal/metabolismo , Células HEK293 , Hereditariedade , Heterozigoto , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Linhagem , Fenótipo , Podócitos/patologia , Proteinúria/etnologia , Proteinúria/genética , Proteinúria/metabolismo , Estabilidade de RNA , Insuficiência Renal/etnologia , Insuficiência Renal/genética , Insuficiência Renal/metabolismo , Fatores de Risco , Sialoglicoproteínas/metabolismo , Adulto Jovem , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP
8.
Ren Fail ; 40(1): 273-279, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29619899

RESUMO

BACKGROUND: TLR4 signaling is known to be involved in podocyte injury. We have previously shown that Salvia przewalskii extract of total phenolic acids (SPE) and its active monomer salvianolic acid B (SalB) and rosmarinic acid (RA) protect podocytes from injury induced by PAN. In the present study, we test whether SPE inhibits TLR4 signaling. METHODS: The conditionally immortalized mouse podocytes were treated with SPE, SalB, RA, SalB + RA or tacrolimus for 30 min, followed by PAN (100 µg/mL) for 24 h. The F-actin staining with phalloidin was used to assess cytoskeletal injury in the podocytes. Western blotting and semi-quantitatives RT-PCR were used to assess the changes of the components in the TLR4 signaling pathway. RESULTS: (1) The F-actin stress fibers of podocytes were almost completely disrupted after PAN treatment for 24 h, and the disruption was significantly alleviated by SPE; (2) the PAN-induced elevation of mRNA levels of TLR4, MyD88 and p65 were inhibited except p65 with high-dose SalB; (3) consistently, the protein levels of TLR4, MyD88 and pp65 were significantly elevated by PAN, and SPE, SalB, RA and admixture, respectively, attenuated the elevations of TLR4 and pp65 proteins; (4) SPE and tacrolimus have a similarly strong effect on inhibition of the expression of TLR4 signaling components. CONCLUSIONS: SPE protects podocytes from PAN-induced injury at least partly through inhibiting TLR4 signaling. SPE is as strong as tacrolimus in inhibiting TLR4 signaling in podocytes.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Podócitos/efeitos dos fármacos , Salvia/química , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Benzofuranos/farmacologia , Linhagem Celular , Cinamatos/farmacologia , Depsídeos/farmacologia , Medicamentos de Ervas Chinesas/química , Camundongos , Podócitos/patologia , Puromicina Aminonucleosídeo/toxicidade , Ácido Rosmarínico
9.
Ther Apher Dial ; 22(1): 22-30, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29214739

RESUMO

Although intra-dialytic hypertension (IDH) has been noted in clinical settings for many years, its pathogenesis remains unclear. In this cross-sectional study, we analyzed IDH incidence in our center and the correlation between postdialysis volume state and IDH. One hundred thirty-one maintenance hemodialysis (MHD) patients were enrolled in our study, and bioelectrical impedance (BIA) and echocardiography (ECG) were recorded. In addition, demographic data were collected, and laboratory examinations were conducted. The patients were grouped into four groups according to the change in systolic blood pressure (SBP) between predialysis and postdialysis. The incidence of IDH was 10.7%. The proportion of extracellular water to total body weight (ECW/TW), as evaluated by BIA, was significantly higher in the IDH group than in the other three groups both in pre-and post-dialysis. In particular, postdialysis SBP was highest in the highest tertile interval of ECW/TW. In addition, among the four groups, left ventricular volume (LVV) was highest in the IDH group. Binary logistic analyses revealed that predialysis SBP, postdialysis ECW/TW and LVV were independent risk factors of intradialytic hypertension. When predicting IDH, the AUC of the ROC curve was higher for ECW/TW combined with LVV (0.752, 95% CI 0.613-0.896) than for either LVV or ECW/TW alone. Our study further showed that post-dialysis volume expansion is an important factor for the development of IDH.


Assuntos
Ecocardiografia/métodos , Impedância Elétrica , Hipertensão/complicações , Hipertensão/diagnóstico , Falência Renal Crônica/complicações , Diálise Renal , Adulto , Idoso , Água Corporal , Peso Corporal , Estudos Transversais , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores de Risco , Adulto Jovem
10.
Pharm Biol ; 55(1): 2153-2160, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29025319

RESUMO

CONTEXT: Salvia przewalskii Maxim. (Lamiaceae) is a Chinese herbal medicine that has long been used for the treatment of cardiovascular disease. OBJECTIVE: The study investigated the therapeutic efficacy of S. przewalskii total phenolic acid extract (SPE) on immune complex glomerulonephritis (ICG) in rats. MATERIALS AND METHODS: Sixty-two Wistar rats were randomized into six groups. ICG was induced in all groups except normal control group. SPE was administered intragastrically at 24 h intervals for 40 consecutive days. Urine protein (UP), total serum protein (TSP), serum albumin (SA), serum cholesterol (SC) and serum urea nitrogen (SUN) were measured one day before, on day 20 and 40 after SPE administration. On day 40 after SPE administration, the kidneys were removed and prepared into pathologic sections. In addition, kidney wet mass was measured for calculating the kidney wet mass coefficient (KWMC). RESULTS: UP excretion was reduced significantly on day 20 after SPE administration in all three SPE groups as compared with that in medium group, and this effect was observable continuously until 40 days after SPE administration. Compared with medium group, TSP and SA were increased in all three SPE groups after 40 days treatment, while SC and SUN were decreased. KWMC was decreased significantly in 100 mg/kg SPE group after 40 days treatment compared with that in medium group. Histopathologic analyses showed that renal inflammatory infiltration and kidney intumesce were alleviated in all three SPE groups. CONCLUSIONS: SPE may be a potential therapeutic drug for glomerulonephritis.


Assuntos
Glomerulonefrite/tratamento farmacológico , Hidroxibenzoatos/uso terapêutico , Doenças do Complexo Imune/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Salvia , Animais , Glomerulonefrite/metabolismo , Doenças do Complexo Imune/metabolismo , Extratos Vegetais/isolamento & purificação , Raízes de Plantas , Distribuição Aleatória , Ratos , Ratos Wistar , Rizoma , Resultado do Tratamento
11.
Nephron ; 134(4): 253-271, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27529846

RESUMO

BACKGROUND: Oxidative stress is a leading cause of puromycin aminonucleoside (PAN)-induced nephrosis. As the inhibition of oxidative stress may improve injury of podocyte, we aimed at examining the effect of total phenolic acid extract of Salvia przewalskii (SPE) on PAN-induced oxidative stress in vivo and in vitro. METHODS: Seventy-two male Sprague-Dawley rats were randomly assigned into 6 groups (n = 12), PAN alone, tacrolimus (TAC), SPE (50, 100 and 200 mg/kg) and normal control group. Salvianolic acid B (SalB, 5.52%) and rosmarinic acid (RA, 31.58%) were isolated from SPE. The intensities of 8-oxo-2'-deoxyguanosine (8-OHdG) were evaluated by immunofluorescence. In vitro, the podocytes were assigned into groups of control, PAN alone, TAC (1 µg/ml), SPE (158, 316 µg/ml), SalB (8.5, 17 µg/ml) and RA (25, 50 µg/ml). The intracellular reactive oxygen species (ROS) production and cell apoptosis rate were measured by flow cytometry. Form factor and aspect ratio were calculated to assess mitochondrial morphology. RESULTS: In vivo, PAN increased the intensity of 8-OHdG in the renal tissue in the PAN group (p < 0.05). The high-dose SPE reduced 8-OHdG significantly at levels comparable to TAC alone (p > 0.05) on day 15. The intracellular ROS production, podocytes apoptosis rate and mitochondrial fragmentation increased significantly following PAN exposure in podocytes (p < 0.05). Treatment with high-dose SalB significantly ameliorated the increase in the expression of ROS and revised the structure of mitochondria. The percentage of apoptotic cells was decreased compared with the PAN group after SPE, SalB, RA, and TAC treatment for 24 h (p < 0.05). CONCLUSION: These findings suggest that high-dose SPE significantly attenuated 8-OHdG in PAN nephrosis. Antioxidative stress effects of high-dose SPE, SalB against PAN-stimulated cultured podocyte via mechanisms include suppression of ROS expression and mitochondria fission. In addition, SPE, SalB and RA can suppress PAN-induced apoptosis.


Assuntos
Antioxidantes/farmacologia , Podócitos/efeitos dos fármacos , Podócitos/metabolismo , Salvia , 8-Hidroxi-2'-Desoxiguanosina , Citoesqueleto de Actina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Puromicina Aminonucleosídeo/toxicidade , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
12.
Ren Fail ; 38(3): 364-71, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26738817

RESUMO

BACKGROUND: Sarcopenia is a degenerative syndrome mainly characterized by the atrophy of skeletal muscle, along with the decrease of muscle strength and function. However, there are currently few studies concerning sarcopenia in patients undergoing maintenance hemodialysis dialysis (MHD). This study was aimed to investigate the incidence of sarcopenia in MHD patients and its influencing factors, as well as its impact on survival risk. METHOD: All 131 MHD patients enrolled in our study were tested with bioelectrical impedance analysis (BIA) and grip strength. Demographic data was collected and anthropometric measurement and laboratory examination were conducted. RESULTS: The total incidence of sarcopenia within the 131 MHD patients was 13.7% and the incidence of sarcopenia in patients over 60 years was 33.3%. The dialysis duration, with or without diabetes, serum phosphorus and pre-albumin levels of sarcopenic patients were significantly different from those of non-sarcopenicones; the modified quantitative subjective global assessment (MQSGA) scores of sarcopenic patients were higher than those without sarcopenia. Multivariate analysis showed that dialysis duration, diabetes and serum phosphorus level were independent risk factors for sarcopenia in MHD patients. Kaplan-Meier survival analysis showed a one-year survival of 88.9% in sarcopenic patients, which was significantly lower than non-sarcopenic patients. CONCLUSION: The incidence of sarcopenia in MHD patients was high and increased gradually with age. Dialysis duration, diabetes, serum phosphorus level and malnutrition predisposed the patients to sarcopenia. One-year follow-up found that the mortality risk of sarcopenic patients was higher than that of non-sarcopenic patients.


Assuntos
Complicações do Diabetes , Desnutrição/complicações , Músculo Esquelético/fisiopatologia , Fósforo/sangue , Diálise Renal/efeitos adversos , Sarcopenia/mortalidade , Adulto , Idoso , Composição Corporal , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Adulto Jovem
13.
Biomater Sci ; 4(3): 522-32, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26797493

RESUMO

Natural polycations, such as poly(l-lysine) (PLL) and chitosan (CS), have inherent superiority as non-viral vectors due to their unparalleled biocompatibility and biodegradability. However, the application was constrained by poor transfection efficiency and safety concerns. Since previous modification strategies greatly weakened the inherent advantages of natural polycations, developing a strategy for functional group introduction with broad applicability to enhance the transfection efficiency of natural polycations without compromising their cationic properties is imperative. Herein, two uncharged functional diblock oligomers P(DMAEL-b-NIPAM) and P(DMAEL-b-Vlm) were prepared from a lactose derivative, N-iso-propyl acrylamide (NIPAM) as well as 1-vinylimidazole (Vlm) and further functionalized with four small ligands folate, glutathione, cysteine and arginine, respectively, aiming to enhance the interactions of complexes with cells, which were quantified utilizing a quartz crystal microbalance (QCM) biosensor, circumventing the tedious material screening process of cell transfection. Upon incorporation with PLL and DNA, the multifunctional oligomers endow the formulated ternary complexes with great properties suitable for transfection, such as anti-aggregation in serum, destabilized endosome membrane, numerous functional sites for promoted endocytosis and therefore robust transfection activity. Furthermore, different from the conventional strategy of decreasing cytotoxicity by reducing the charge density, the multifunctional oligomer incorporation strategy maintains the highly positive charge density, which is essential for efficient cellular uptake. This system develops a new platform to modify natural polycations towards clinical gene therapy.


Assuntos
Cátions/química , Quitosana/química , DNA/química , Endocitose/genética , Peptídeos/química , Polilisina/administração & dosagem , Polilisina/química , Quitosana/metabolismo , DNA/metabolismo , Técnicas de Transferência de Genes , Terapia Genética , Vetores Genéticos , Células HeLa , Humanos , Imidazóis/química , Peptídeos/metabolismo , Polilisina/metabolismo , Transfecção
14.
Carbohydr Polym ; 137: 222-230, 2016 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-26686124

RESUMO

A novel non-viral gene carrier based on N,N,N-trimethylchitosan (TMC) has been fabricated. First, well-defined copolymer P(PEGMA-co-DMAEMA) was synthesized through reversible addition fragmentation chain transfer (RAFT) polymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA) and N,N-(2-dimethylamino)ethyl methacrylamide (DMAEMA). Then allyl group grafting N,N,N-trimethylchitosan (Allyl-TMC) was synthesized via the reaction between allyl bromide and hydroxyl of TMC. Finally, P(PEGMA-co-DMAEMA) and folate were ordinally grafted onto Allyl-TMC to obtain TMC-g-P(PEGMA-co-DMAEMA)-FA. In comparison with pristine chitosan, TMC-g-P(PEGMA-co-DMAEMA)-FA has achieved both better water solubility and stronger pDNA packaging ability, which can contribute to improving gene transfection. Gene delivery efficiency of a series of TMC based functional polymers with different chitosan molecular weights has been tested. The results show that 20k-TMC-g-P(PEGMA-co-DMAEMA)-FA/pDNA complex at the weight ratio of 20 achieve the highest transfection efficiency in 293 T cells. This work presents a new strategy to modify chitosan efficiently as gene carrier material.


Assuntos
Quitosana/química , Polímeros/química , Linhagem Celular , Vetores Genéticos/química , Humanos , Metacrilatos/química
15.
Am J Nephrol ; 42(3): 216-27, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26439819

RESUMO

BACKGROUND: To determine the effect of Salvia przewalskii extract (SPE) from total phenolic acids on puromycin aminonucleoside (PAN)-induced rat podocyte injury. METHODS: The rats were divided into groups that were treated with either PAN only or PAN followed by tacrolimus or SPE. We evaluated the effects of SPE on podocyte injury 5, 10, 15 and 21 days following treatment. RESULTS: (1) Proteinuria was observed starting on day 5 in all groups. The peak levels of proteinuria differed among the groups with tacrolimus and high-dose SPE, which significantly decreased proteinuria relative to the PAN and low- and medium-dose SPE groups. The proteinuria in each group decreased by day 15 and returned to a normal level by day 21. (2) H&E and PAS staining revealed no abnormality in glomerular morphology. With electron microscopy, we observed foot process effacement in the rats of all groups starting on day 5, but rats in the tacrolimus and high-dose SPE groups exhibited a lower degree. (3) IHC staining of nephrin and podocin revealed unaffected expression and better linear distributions in the high-dose SPE and tacrolimus groups. Western blot analysis confirmed that SPE could improve the expression of proteins. (4) The mRNA levels of nephrin and podocin in the tacrolimus and high-dose SPE groups were significantly higher than that in the others. CONCLUSION: In our study, we first demonstrated the ability of SPE to reduce proteinuria, preserve the morphology and structure of podocytes and retain the levels of slit diaphragm proteins on PAN-induced rat podocytes injury.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Podócitos/efeitos dos fármacos , Proteinúria/prevenção & controle , Saliva , Animais , Canfanos , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Rim/metabolismo , Rim/patologia , Masculino , Proteínas de Membrana/metabolismo , Panax notoginseng , Proteinúria/induzido quimicamente , Proteinúria/metabolismo , Proteinúria/patologia , Puromicina , Ratos Sprague-Dawley , Salvia miltiorrhiza , Tacrolimo
16.
BMC Nephrol ; 16: 142, 2015 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-26283194

RESUMO

BACKGROUND: Burn patients with AKI have a higher mortality, rapid diagnosis and early treatment of AKI are necessary. Recent studies have demonstrated that urinary KIM-1 and IL-18 are potential biomarkers of early-stage AKI, however, changes in urinary KIM-1 and IL-18 levels are unclear in patients with burns. The aim of our study was to determine whether combined KIM-1 and IL-18 are more sensitive than traditional markers in detecting kidney injury in patients with burns. METHODS: Ninety-five burn patients hospitalized at the Burns and Plastic Surgery Center of our hospital from April 2013 to September 2013 were enrolled into this prospective study and divided into mild- (n = 37), moderate- (n = 30) and severe-burn groups (n = 28) by burn injury surface area. In the moderate- and severe-burn groups, patients were subcategorized to either the acute kidney injury (AKI) group, in which serum creatinine (Scr) increased to ≥ 26.5 µmol/L within 48 h, or the non-AKI group. Fifteen healthy subjects were selected as a control group. Blood specimens were collected to determine blood urea nitrogen (BUN), Scr, and other biochemical indicators. Urine samples collected at admission and 48 h after admission were analyzed for KIM-1 and IL-18. Correlations among urinary KIM-1 and IL-18, burn degree, and clinical biochemical indicators were investigated. RESULTS: AKI occurred in 11.2 % of burn patients (none in the mild-burn group). AKI developed 48 h after admission in 10.0 % of the moderate- and 28.6 % of the severe-burn groups. Urinary KIM-1 concentration in the moderate- and severe-burn groups was significantly higher than that in the control group; urinary IL-18 concentrations did not differ significantly among the burn and control groups. The AKI group had significantly higher concentrations of urinary KIM-1 and IL-18 than the non-AKI group, both at admission (p = 0.001 and p < 0.001, respectively) and 48 h later (p = 0.001 and p < 0.001, respectively). Both urinary KIM-1 and IL-18 increased before Scr. Receiver operating-curve (ROC) analysis demonstrated that KIM-1 combined with IL-18 predicted AKI with 72.7 % sensitivity and 92.8 % specificity. The area under the ROC curve was 0.904. CONCLUSIONS: Our results suggest that urinary KIM-1 and IL-18 may be used as early, sensitive indicators of AKI in patients with burns of varying degrees and provide clinical clues that can be used in early prevention of AKI.


Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/urina , Queimaduras/urina , Interleucina-18/urina , Glicoproteínas de Membrana/urina , Injúria Renal Aguda/etiologia , Adulto , Área Sob a Curva , Biomarcadores/urina , Nitrogênio da Ureia Sanguínea , Superfície Corporal , Queimaduras/classificação , Queimaduras/complicações , Estudos de Casos e Controles , Creatinina/sangue , Feminino , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Receptores Virais , Índices de Gravidade do Trauma , Adulto Jovem
17.
J Mater Chem B ; 2(33): 5387-5396, 2014 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32261759

RESUMO

Two kinds of novel oligomers were prepared by reversible addition fragmentation chain transfer (RAFT) polymerization and incorporated into the polyethyleneimine (PEI) gene delivery system through non-electrostatic assembly to improve gene transfection efficiency. The non-electrostatic assembly process was first investigated via probing the interactions of the oligomers with plasmid DNA (pDNA), PEI and AD-293 cells using a quartz crystal microbalance (QCM). The results show that the prepared oligomers almost had no interaction with pDNA while they had much stronger interactions with PEI and AD-293 cells. Meanwhile, we found that the two kinds of oligomers had different interactions with AD-193 cells, which caused different effects on gene transfection. The data of QCM tests combined with the in vitro transfection results can be used to explain what effects the oligomers have on improving gene transfection. The results also indicate that the strategy of detecting the interactions of oligomers with pDNA, polycations and cells will contribute to predetermine whether the prepared oligomer is efficient in improving gene transfection.

18.
Int J Nephrol ; 2013: 835465, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24187620

RESUMO

Objective. To identify the relationship between microinflammation, oxidative stress, and carotid arterial stiffness in hemodialysis patients. Methods. The CAS ß and PWV obtained by ultrasound technology were used to assess carotid arterial stiffness. We divided the patients into either the CAS group or the non-CAS group based on the presence or absence of CAS. The parameters of ALB, Ca, P, TC, HDL, LDL, TG, glucose, creatinine, and hs-CRP levels were routinely tested in both groups of patients. The levels of TNF- α , IL-6, and 8-isoprostane F2 α were measured by ELISA. Results. A total of 42 patients were enrolled in the CAS group and 20 patients were enrolled in the non-CAS group. No significant differences between the CAS group and the non-CAS group were observed with respect to age, dialysis duration, DBP, BUN, Cr, TC, TG, HDL, LDL, and Hb. However, SBP , pulse pressure, and 8-isoprostane levels of the CAS group were higher than those of the non-CAS group. The hs-CRP, TNF- α , and IL-6 levels were elevated in both groups but showed no significant differences. Conclusions. Maintenance of hemodialysis patients exhibits a microinflammatory state that may lead to atherosclerosis. The roles of hypertension and oxidative stress may be more important.

19.
World J Emerg Med ; 2(2): 137-40, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-25214999

RESUMO

BACKGROUND: Carotid intima media thickness (CIMT) and stiffness are taken as useful surrogate markers of atherosclerosis. In China, the number of elderly patients undergoing hemodialysis has increased year by year, with the increase of dialysis-related cardiovascular events. This study was undertaken to examine carotid stiffness in elderly hemodialysis patients by the ultrasound techniques in order to find out the possible risk factors. METHODS: From January 2006 to February 2010, a total of 87 patients (41 males and 46 females) treated with routine hemodialysis at the 97th Hospital of People's Liberation Army were enrolled in this study. The distensibility coefficient (DC) of the carotid artery was detected by Doppler ultrasonic diagnosis apparatus (Philips HBI5000, frequency 12 MHz) for evaluation of arterial stiffness. Serum albumin, total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglyceride (TG), glucose, creatinine, calcium, phosphorus, and intact parathyroid hormone (iPTH) were examined with standard methods. The liner correlation and multiple stepwise regression analysis were used to find correlations between them. RESULTS: In this study, the systolic blood pressure was 153.33±25.98 mmHg, DBP 84.22± 10.39 mmHg, TC 4.39±1.05 mmol/L, TG 1.36±0.72 mmol/L, LDL 2.47±0.77 mmol/L, Cr 889.82± 207.38 Mmol/L, Glu 5.36±1.87 mmol/L, Ca I 2.00±2.19±0.21 mmol/L, and DC 13.39±5.32×10(-3)/kPa. DC was associated with age (r=-0.459, P<0.001), SBP (r=-0.527, P<0.001), and serum calcium (r=-0.273, P=0.011). The multiple stepwise regression analysis showed that SBP, age, increased serum calcium level, and diabetes were independent risk factors for decreasing DC. CONCLUSION: Systolic blood pressure, age, increased serum calcium level and diabetes in elderly hemodialysis patients are independent risk factors for increased carotid arterial stiffness.

20.
Am J Nephrol ; 25(6): 579-85, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16254409

RESUMO

OBJECTIVE: It was the aim of this study to evaluate the distribution and expression of vascular endothelial growth factor (VEGF) in kidneys of patients with preeclamptic nephropathy and their relationship with clinical and pathological manifestations. METHODS: From May 1993 to August 2004, 19 patients with a mean age of 28.1 +/- 4.53 years (range 23-40), diagnosed with preeclamptic nephropathy by renal biopsy, were enrolled in this study. Fifteen were nulliparous and 4 multipara. Their renal tissues were subjected to immunohistochemical staining by a four-layer peroxidase-antiperoxidase method using monoclonal anti-VEGF. Residual normal renal tissue obtained at nephrectomy served as control. The relationship between the expression pattern of VEGF and clinicopathological features was also investigated. RESULTS: The expression of VEGF markedly increased in renal tissues of patients with preeclamptic nephropathy at the early stage of gestation termination in comparison with normal controls. However, over time, it gradually decreased and reached the level of normal controls (100 vs. 71.43 vs. 20%, p < 0.05). The degree of endothelial proliferation in the glomeruli was closely related to the expression of VEGF, which was stronger in patients with diffuse endothelial proliferation than in those with segment proliferation (p < 0.05). In addition, there was a proportional relationship between the expression of VEGF and the level of urinary protein excretion (p < 0.05). CONCLUSION: The patients with preeclamptic nephropathy showed strong expressions of VEGF in glomeruli, which were closely associated with glomerular endothelial lesions and proteinuria, and over time, gradually weakened to normal level after gestation termination.


Assuntos
Nefropatias/metabolismo , Rim/metabolismo , Pré-Eclâmpsia/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese , Adulto , Proliferação de Células , Endotélio/fisiopatologia , Feminino , Humanos , Rim/patologia , Nefropatias/patologia , Nefropatias/urina , Pré-Eclâmpsia/patologia , Pré-Eclâmpsia/urina , Gravidez , Proteinúria/metabolismo
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