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1.
BMJ Open ; 11(12): e050605, 2021 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-34907051

RESUMEN

INTRODUCTION: Cognitive impairment (CI) is the common complications in maintenance haemodialysis (MHD) patients. Recently, the pathogenesis of CI has been discussed and oxidative stress is one of the main mechanisms in these patients. Thiamine and folic acid, which play an important role in relieving the production of reactive oxygen species, reducing homocysteine levels, improving oxidative stress in the nervous system. In pilot study, cognitive function was significantly improved in the group with thiamine and folic supplementation. Based on this result, we hypothesise that thiamine combined with folic acid supplementation may improve cognitive function in patients with MHD. METHODS AND ANALYSIS: In this prospective, randomised, placebo-controlled, double-blind, multicentre study, we will enrol patients undergoing haemodialysis who has the Montreal Cognitive Assessment score lower than 26 to treatment group (thiamine 90 mg/day combined with folic acid 30 mg/day) or control group (thiamine placebo 90 mg/day combined with folic acid placebo 30 mg/day). All subjects will be followed up for 96 weeks. The primary endpoint is the comparison of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score between treatment group and control group at 96 weeks of follow-up. The secondary endpoints include serum thiamine, folate, homocysteine levels, cranial functional MRI and survival. The central randomisation method will be adopted and the principles of placebo-controlled, double-blind randomised control will be followed. The comparisons among ADAS-Cog scores and other secondary endpoints over time within subjects is conducted by using repeated measure analysis of variance (ANOVA) or generalised estimating equations (GEE). Pairwise t-test with Bonferroni adjustment is performed for multiple comparisons. On the other hand, for comparisons between treatment and control group, simple one-way ANOVA, GEE or Wilcoxon rank sum test is used. The χ2 method is used for statistical analysis of the categorical data. Kaplan-Meier survival curve is used for survival analysis. A p<0.05 is considered statistically significant difference. ETHICS AND DISSEMINATION: This trial has been approved by Shanghai Jiao Tong University School of Medicine, Renji Hospital Ethics Committee (KY2019-199). After publication of study results, trial report will be published in peer-reviewed journals and/or in national or international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000029297.


Asunto(s)
Disfunción Cognitiva , Ácido Fólico , China , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Método Doble Ciego , Ácido Fólico/uso terapéutico , Humanos , Estudios Multicéntricos como Asunto , Proyectos Piloto , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal , Tiamina/uso terapéutico
2.
Ann Palliat Med ; 9(6): 3885-3898, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33222468

RESUMEN

BACKGROUND: Diabetic nephropathy (DN) is the main cause of end-stage renal failure (ESRF) in diabetic patients. Chinese medicine plays an extremely important role in controlling the symptoms of DN. At present, the efficacy and safety of Bailing capsules in the treatment of type 2 DN are still unclear. Therefore, the aim of this meta-analysis was to evaluate the clinical efficacy and safety of Bailing capsules in the treatment of type 2 DN. METHODS: A literature search on type 2 DN was conducted using Chinese and English databases. The Chinese databases searched were the CNKI database, Wanfang database, and Weipu database using the following search terms: Bailing capsule and DN. The English databases were PubMed, Embase, and Web of Science using the following search terms: type 2 diabetes mellitus, type II diabetes mellitus, and Bailing capsule. The quality of the literature was evaluated using RevMan 5.3 software. The meta-analysis was performed using the R3.5.1 software meta package. RESULTS: Twenty-four articles with a total of 985 patients in the treatment group and 956 patients in the control group were found. The total effective rate of Bailing capsules in the treatment group was 1.24 times that of the control group [95% confidence interval (CI): 1.11-1.38]. Reductions in 24-h urine total protein, urine albumin excretion rate (UAER), serum creatinine (Scr), and blood urea nitrogen (BUN) levels before and after treatment in the treatment group were significantly lower than that of the control group, with standard mean differences (SMD) of 0.61 (95% CI: -1.01 to -0.22), -1.56 (95% CI: -2.34 to -0.78), -0.58 (95% CI: -0.89 to -0.27), and -0.73 (95% CI: -1.16 to -0.29), respectively. However, there was no significant change in serum potassium between the two groups (P>0.05). No publication bias was found in the metaanalysis (P>0.05). CONCLUSIONS: For type 2 DN patients, the use of Bailing capsules in routine treatment demonstrated higher clinical efficacy and was found to improve the kidney function. However, high-quality randomized controlled trials are required to further explore the safety of Bailing capsules.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Medicamentos Herbarios Chinos , Nitrógeno de la Urea Sanguínea , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/efectos adversos , Humanos
3.
Cell Physiol Biochem ; 37(4): 1491-502, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26509423

RESUMEN

BACKGROUND/AIMS: Hyperuricemia is an independent risk factor for chronic kidney disease and cardiovascular disease. Here, we examined the combined protective effects of Chinese herbal formula Si-Wu-Tang and Er-Miao-San on hyperuricemia and renal impairment in rats. METHODS: Rats were randomly divided into normal rats, hyperuricemic rats, and hyperuricemic rats orally administrated with benzbromarone (4.5 mg·kg⁻¹·d⁻¹), Si-Wu-Tang (3.78 g·kg⁻¹·d⁻¹) and Si-Wu-Tang plus Er-Miao-San (6.48 g·kg⁻¹·d⁻¹) for 4 weeks. Hyperuricemic rats were orally gavaged with adenine (0.1 g·kg⁻¹·d⁻¹) and potassium oxonate (1.5 g·kg⁻¹·d⁻¹) daily for 4 weeks. Serum uric acid, creatinine, total cholesterol (TCH), triglyceride and blood urea nitrogen (BUN) concentrations, as well as urinary uric acid and microalbuminuria were measured weekly. Serum xanthine oxidase (XOD) activity and renal histopathology were also evaluated. The renal expression of organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) was detected by western blot. RESULTS: Si-Wu-Tang plus Er-Miao-San lowered serum uric acid, creatinine, triglyceride and BUN levels to a greater degree than did Si-Wu-Tang alone. Si-Wu-Tang plus Er-Miao-San ameliorated microalbuminuria and renal histopathology, as well as decreased serum TCH concentration and XOD activity in hyperuricemic rats. Combination of Si-Wu-Tang and Er-Miao-San also led to a greater increase in OAT1 and OAT3 expression than did Siwutang alone. CONCLUSION: Si-Wu-Tang and Er-Miao-San synergistically ameliorated hyperuricemia and renal impairment in rats through upregulation of OAT1 and OAT3.


Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Hiperuricemia/tratamiento farmacológico , Adenina/toxicidad , Administración Oral , Animales , Benzbromarona/farmacología , Creatinina/sangre , Sinergismo Farmacológico , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/metabolismo , Medicamentos Herbarios Chinos/farmacología , Hiperuricemia/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Masculino , Proteína 1 de Transporte de Anión Orgánico/metabolismo , Transportadores de Anión Orgánico Sodio-Independiente/metabolismo , Ácido Oxónico/toxicidad , Exudados de Plantas/administración & dosificación , Exudados de Plantas/farmacología , Ratas , Ratas Sprague-Dawley , Ácido Úrico/sangre , Ácido Úrico/orina , Xantina Oxidasa/sangre
4.
Artículo en Inglés | MEDLINE | ID: mdl-23853656

RESUMEN

This study investigated the anti-inflammatory effects of astragaloside IV(AS-IV) on ischemia/reperfusion (IR) induced acute kidney injury (AKI) in rats. Experimental model of ischemic AKI was induced in rats by bilateral renal artery clamp for 45 min followed by reperfusion of 12 h and 24 h, respectively. AS-IV was orally administered once a day to rats at 10 and 20 mg·kg(-1)·d(-1) for 7 days prior to ischemia. AS-IV pretreatment significantly decreased serum urea, creatinine, and cystatin C levels at 12 h and 24 h of reperfusion in AKI rats. AS-IV pretreatment also ameliorated tubular damage and suppressed the phosphorylation of p65 subunit of NF- κ B in AKI rats. Moreover, NF- κ B and MPO activity as well as serum and tissue levels of TNF- α , MCP-1, and ICAM-1 were elevated in AKI rats. All of these abnormalities were prevented by AS-IV. Furthermore, AS-IV downregulated the mRNA expression of NF- κ B, TNF- α , MCP-1, and ICAM-1 in AKI rats. These results suggest that AS-IV might be developed as a novel therapeutic approach to prevent ischemic AKI through inhibition of NF- κ B mediated inflammatory genes expression.

5.
Cytokine ; 61(3): 970-7, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23434274

RESUMEN

Accumulating evidence suggests that inflammatory processes are involved in the development of diabetic nephropathy (DN). However, there are no effective interventions for inflammation in the diabetic kidneys. Here, we tested the hypothesis that Astragaloside IV(AS-IV), a novel saponin purified from Astragalus membranaceus (Fisch) Bge, ameliorates DN in streptozotocin (STZ)-induced diabetic rats through anti-inflammatory mechanisms. Diabetes was induced with STZ (65 mg/kg) by intraperitoneal injection in rats. Two weeks after STZ injection, rats were divided into three groups (n=8/each group), namely, diabetic rats, diabetic rats treated with AS-IV at 5 and 10 mgkg(-1)d(-1), p.o., for 8 weeks. The normal rats were chosen as nondiabetic control group (n=8). The rats were sacrificed 10 weeks after induction of diabetes. AS-IV ameliorated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. Renal NF-κB activity, as wells as protein and mRNA expression were increased in diabetic kidneys, accompanied by an increase in mRNA expression and protein content of TNF-α, MCP-1 and ICAM-1 in kidney tissues. The α1-chain type IV collagen mRNA was elevated in the kidneys of diabetic rats. All of these abnormalities were partially restored by AS-IV. AS-IV also decreased the serum levels of TNF-α, MCP-1 and ICAM-1 in diabetic rats. These findings suggest that AS-IV, a novel anti-inflammatory agent, attenuated DN in rats through inhibiting NF-κB mediated inflammatory genes expression.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Regulación de la Expresión Génica , Inflamación/genética , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/genética , FN-kappa B/metabolismo , Saponinas/uso terapéutico , Triterpenos/uso terapéutico , Albuminuria/sangre , Albuminuria/complicaciones , Albuminuria/tratamiento farmacológico , Albuminuria/patología , Animales , Biomarcadores/sangre , Quimiocina CCL2/sangre , Quimiocina CCL2/genética , Colágeno Tipo IV/genética , Colágeno Tipo IV/metabolismo , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/genética , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/sangre , Inflamación/complicaciones , Molécula 1 de Adhesión Intercelular/sangre , Molécula 1 de Adhesión Intercelular/genética , Enfermedades Renales/sangre , Enfermedades Renales/complicaciones , Masculino , Podocitos/efectos de los fármacos , Podocitos/metabolismo , Podocitos/patología , Podocitos/ultraestructura , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Saponinas/farmacología , Triterpenos/farmacología , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética
6.
Apoptosis ; 18(4): 409-22, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23325448

RESUMEN

Oxidative stress and apoptosis play key role in the pathogenesis of acute kidney injury (AKI). We hypothesize that Astragaloside IV(AS-IV) prevents AKI through inhibiting oxidative stress and apoptosis. The rats were divided into sham control, saline-,vehicle-, or AS-IV-treated groups. AS-IV (20 mg/kg) was orally administered once daily to the rats for 7 consecutive days before terminating the experiments. In ischemia-induced AKI model, experimental rats were subjected to bilateral clamping of the renal arteries for 45 min, followed by reperfusion for 24 h. In contrast-induced AKI model, iopamidol (2.9 g iodine/kg) was administered intravenously into the rats. Renal function, histopathology, oxidative stress and apoptosis were evaluated in these models. Pretreatment with AS-IV significantly decreased blood urea nitrogen, serum creatinine, cystatin C and neutrophil gelatinase-associated lipocalin levels, as well as urinary kidney injury molecule-1 level and tubular injury. AS-IV also reduced oxidative stress and tubular cell apoptosis. The p38 mitogen-activated protein kinase phosphorylation and caspase-3 activity were elevated in kidney tissues from AKI rats, accompanied by an increase in Bax expression and a decrease in Bcl-2 expression at mRNA and protein levels. These changes were prevented by AS-IV pretreatment. Therefore, AS-IV can be developed as a novel therapeutic approach to prevent AKI through targeting inhibition of oxidative stress and apoptosis pathways.


Asunto(s)
Lesión Renal Aguda/prevención & control , Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Riñón/irrigación sanguínea , Estrés Oxidativo/efectos de los fármacos , Saponinas/uso terapéutico , Triterpenos/uso terapéutico , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/cirugía , Proteínas de Fase Aguda , Animales , Caspasa 3/metabolismo , Moléculas de Adhesión Celular/orina , Cistatina C/sangre , Medicamentos Herbarios Chinos/farmacología , Isquemia/cirugía , Riñón/efectos de los fármacos , Riñón/cirugía , Pruebas de Función Renal , Lipocalina 2 , Lipocalinas/sangre , Masculino , Modelos Animales , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas/sangre , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Arteria Renal/cirugía , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Saponinas/farmacología , Triterpenos/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
7.
World J Gastroenterol ; 8(1): 74-8, 2002 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11833075

RESUMEN

AIM: To conduct a randomized trial to evaluate the role of using high-dose iodized oil transcatheter arterial chemoembolization (TACE) in the treatment of large hepatocellular carcinoma (HCC). METHODS: From January 1993 to June 1998, 473 patients with unresectable hepatocellular carcinoma were divided into two groups: 216 patients in group A received more than 20 mL iodized oil during the first TACE treatment; 257 patients in group B received 5-15 mL iodized oil in the same way. The Child's classification and ICG-R15 for evaluating the liver function of the patients were done before the treatment. During the TACE procedure the catheters were inserted into the target artery selectively and the tumor vessels were demonstrated with contrast medium in the hepatic angiography.The anticancer drugs mixed with iodized oil (Lipiodol) were Epirubicin and Mitomycin. In group A, 112 cases received 20-29 mL Lipiodol in the first procedure, 85 cases 30-39 mL, 19 cases more than 40 mL. The largest dose was 53 mL and the average dose was 28.3 mL. In group B, 119 cases received 5-10 mL Lipiodol,138 cases received 11-15 mL and the average dose was 11.8 mL. RESULTS: High-dose Lipiodol chemoembolization had tolerable side effects and a little hurt to the liver function in the patients with Child's A or ICG-R15<20. But the patients with child's B or ICG-R15>20 had higher risk of liver failure after high-dose TACE. More type I and type II in CT scan after 4 weeks of TACE were seen in the patients of group A than those in the patients of group B (P<0.01). The resection rate and complete tumor necrosis rate of group A were higher than those of group B (P<0.05). The 1-,2-, 3-year survival rates of group A patients with Child's A were 79.2 , 51.8 and 34.9 , respectively, better than those of group A (P<0.001). CONCLUSION: High-dose Lipiodol can result in more complete tumor necrosis by blocking both arteries and small portal vein of the tumor. High-dose TACE for treatment of large and hypervascular hepatocellular carcinoma is practically acceptable with the better effect than the routine dose. For the patients with large and hypervascular tumor of Child grade A liver function or ICG-R15 less than 20%, oily chemoembolization with 20-40 mL Lipiodol is recommended.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Medios de Contraste/administración & dosificación , Aceite Yodado/administración & dosificación , Neoplasias Hepáticas/terapia , Adulto , Anciano , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Medios de Contraste/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Aceite Yodado/efectos adversos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
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