RESUMEN
OBJECTIVE: Peritoneal dialysis-related peritonitis (PDRP) presents a significant challenge for nephrologists. Continuous intraperitoneal cefazolin and ceftazidime are recommended for the treatment of peritonitis. However, some pharmacokinetic studies have shown that doses of 15-20 mg/kg/d may not achieve sufficient therapeutic levels. In this study, we investigated the pharmacokinetics of ceftazidime and cefazolin in patients with continuous ambulatory peritoneal dialysis-related peritonitis and compared the pharmacokinetic characteristics between traditional and modified treatment groups. METHODS: From February 2017 to December 2019, 42 PDRP patients (17 males, 25 females; mean age: 50.7 ± 12.1 years; mean body weight: 60.9 ± 11.8 kg) were recruited for the study, all participants were anuric. Twenty patients were enrolled in the traditional group and treated with cefazolin (1.0 g) and ceftazidime (1.0 g) via intraperitoneal administration once daily for 14 days. Twenty-two patients were enrolled in the modified group and received the same dose of antibiotics twice daily for the initial five days, followed by once daily for the subsequent nine days. Serum and dialysate samples were collected after days 1, 2, 3, 5, 7, 10, and 14 and analyzed via liquid chromatography-mass spectrometry. RESULTS: In the traditional group, the highest and lowest serum concentrations of ceftazidime were 35.9 and 21.7 µg/mL, respectively. The highest concentration of cefazolin was 54.6 µg/mL on day 5 and the lowest concentration was 30.4 µg/mL on day 1. In the modified group, the highest and lowest serum concentrations of ceftazidime were 102.2 and 54.8 µg/mL, respectively. The highest concentration of cefazolin was 141.7 µg/mL and the lowest concentration was 79.8 µg/mL. All antibiotic concentrations were above the minimum inhibitory concentration (MIC) level (8 µg/mL of ceftazidime and 2 µg/mL of cefazolin) throughout the treatment period. However, on day 1, the concentration of ceftazidime in the third bag of dialysate effluent from the traditional group fell below the MIC level. Despite remaining above the MIC, cefazolin concentration was consistently lower in the third bag of dialysate effluent from the traditional group throughout the treatment period. CONCLUSIONS: Intraperitoneal administration of cefazolin and ceftazidime at a dose of 1 g twice daily for 5 days and then once daily for the rest of the treatment period ensured adequate therapeutic levels of antibiotics for treating anuric PDRP patients.
Asunto(s)
Anuria , Diálisis Peritoneal Ambulatoria Continua , Peritonitis , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Cefazolina , Ceftazidima/farmacocinética , Ceftazidima/uso terapéutico , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Diálisis Peritoneal Ambulatoria Continua/métodos , Estudios Prospectivos , Antibacterianos/uso terapéutico , Peritonitis/tratamiento farmacológico , Peritonitis/etiología , Soluciones para Diálisis , Anuria/etiologíaRESUMEN
BACKGROUND/AIMS: The purpose of this study is to analyze the expression and biological function of lncRNA ANRIL, microRNA-199a, TLR4, and nuclear factor-kappa B (NF-κB) in acute renal injury (AKI) induced by lipopolysaccharide (LPS). METHODS: The levels of ANRIL and microRNA-199a in mouse cells and kidneys were detected by quantitative-polymerase chain reaction. Western blot analysis was used for the NF-κB pathway protein. MTT assay was used for cell viability. Enzyme-linked immunosorbent assay was used for the secretion of inflammatory factors in mouse kidney tissue. Apoptosis was measured by flow cytometry and Western blotting. The potential binding region between ANRIL and miR-199a was verified by luciferase reporter assay. RESULTS: The upregulation of ANRIL can reduce the expression of microRNA-199a and increases the number of apoptotic cells. The expression levels of ANRIL in LPS-induced AKI mice and LPS-treated HK2 cells were upregulated compared with the control group. Overexpression of ANRIL increased apoptosis and promoted TLR4 (Toll-like receptor 4), NF-κB phosphorylation, and downstream transcription factor production. CONCLUSION: ANRIL/NF-κB pathway in LPS-induced apoptosis provided theoretical guidance for ANRIL in the treatment of AKI.
Asunto(s)
Lesión Renal Aguda/genética , Lipopolisacáridos/metabolismo , FN-kappa B/metabolismo , ARN Largo no Codificante/genética , Receptor Toll-Like 4/metabolismo , Animales , Apoptosis , Modelos Animales de Enfermedad , Humanos , Masculino , RatonesRESUMEN
Cytochrome P450 (CYP) epoxygenases can metabolize arachidonic acids to epoxyeicosatrienoic acids (EETs), which play a protective role in the renal system, but their involvement in ischemia/reperfusion (I/R)-induced acute kidney injury remains unknown. Here, using a rat model, we demonstrated that forced CYP2J2 expression attenuated I/R-induced renal dysfunction and protected histological integrity. We showed that CYP2J2 significantly decreased I/R-induced upregulation of blood urea nitrogen and serum creatinine and enhanced autophagy during I/R treatment. In addition, we determined the protective effect of CYP2J2 against I/R-caused apoptosis. We demonstrated that CYP2J2 overexpression attenuated the downregulation of SIRT1 and FoxO3a by I/R-induced injury. Moreover, exogenous 11,12-EET addition obviously promoted I/R-induced autophagic flux and suppressed I/R-induced apoptosis through SIRT1-FoxO3a signaling activation. Our data indicate that CYP2J2-produced EETs improve I/R-caused kidney injury by activating the SIRT1-FoxO3a signaling pathway, which protects from renal I/R injury.
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Lesión Renal Aguda/etiología , Sistema Enzimático del Citocromo P-450/metabolismo , Eicosanoides/metabolismo , Proteína Forkhead Box O3/metabolismo , Daño por Reperfusión/complicaciones , Transducción de Señal , Sirtuina 1/metabolismo , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Animales , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Citocromo P-450 CYP2J2 , Riñón/patología , Masculino , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismoRESUMEN
BACKGROUND: Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) and also a major cause of end-stage renal disease (ESRD). Olmesartan medoxomil (OM) is an angiotensin II receptor blocker (ARB) and has been shown to exhibit renoprotective effects on a streptozotocin (STZ)-induced diabetic rat model. Yet, whether OM affects DN progression and renal injury in db/db mice, a type 2 diabetic murine model, has not been established. METHODS: Wild-type (n = 15) and db/db mice (n = 15) were treated with control saline or OM via oral gavage. The physiological and biochemical parameters were evaluated and histological examinations of kidney specimens were performed. RESULTS: Compared with saline-treated db/db mice, db/db mice administered with OM showed ameliorated diabetic physiological and biochemical parameters. In addition, OM decreased urinary albumin excretion and plasma creatinine level in db/db mice. Moreover, histologically, OM reduced glomerular hypertrophy and injury, and also ameliorated tubular injury, thus suggesting that OM improves renal function and minimizes renal pathological deterioration in db/db mice. CONCLUSION: Our study reveals a beneficial role of OM in ameliorating DN in db/db mice, which is associated with its renoprotective function.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Olmesartán Medoxomilo/farmacología , Albuminuria/tratamiento farmacológico , Animales , Creatinina/sangre , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/fisiopatología , Progresión de la Enfermedad , Masculino , RatonesRESUMEN
PURPOSE: Kidney cancer is responsible for a significant number of deaths worldwide. This cancer is often diagnosed at advanced stages and there are frequent relapses following chemotherapy. Target therapies are used now for kidney cancer, while the use of chemotherapy declines. The currently used chemotherapeutic drugs have a number of adverse effects. Herein, we examined the anticancer effects of Astragalin against a panel of kidney cancer cells. METHODS: CellTiter-Glo Luminescent Cell Viability Assay Kit was used to examine the anti-proliferative effects of Astragalin. Acridine orange (AO)/ethidium bromide (EB), DAPI and annexin V/promidium iodide (PI) staining assays were used to examine the apoptotic cell death. Cell cycle analysis was performed by flow cytometry. The mRNA expression was checked by qRT-PCR and protein expression was examined by western blotting. RESULTS: Astragalin inhibited the growth of the all kidney cancer cell lines with IC50 ranging between 20 to 50 µM. Of note, Astragalin had low cytotoxic effects on the normal kidney cells with an IC50 of 110 µM. The experiments have shown that Astragalin exerts antiproliferative effects on the A498 kidney cancer cells by apoptotic cell death. This effect was concomitant with upregulation of apoptotic proteins such as caspase 3 and 9 and Bax. Astragalin also induced arrest of the A498 cells at the G2/M checkpoint of the cell cycle. Also, Astragalin could upregulate the expression of tumor-suppressive microRNAs. CONCLUSIONS: These results suggest that Astragalin exerts potent anticancer effects on kidney cancer cells and could pave the way in the management of kidney cancer provided clinical studies are carried out.
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Carcinoma de Células Renales/inducido químicamente , Quempferoles/efectos adversos , MicroARNs/metabolismo , Apoptosis , Carcinoma de Células Renales/patología , Puntos de Control del Ciclo Celular , Muerte Celular , Línea Celular Tumoral , Humanos , Quempferoles/farmacología , MitocondriasRESUMEN
Increasing research indicates that hyperglycemia plays a crucial role in the progression of diabetic nephropathy (DN); however, effective treatment for preventing or slowing DN progression are seriously lacking. Although salidroside (SAL) has been demonstrated to have a positive anti-diabetic effect, the cellular mechanisms remain unclear. FG-4592, a novel prolyl hydroxylase inhibitor, was used to regulate HIF-1α and HIF-2α expression. The present study aimed to explore the underlying mechanisms of SAL and FG-4592 on high glucose (HG)-induced rat glomerular endothelial cells (rGECs) injury. HG-cultured rGECs were used to induce a diabetic environment. An MTT assay, RT-qPCR, Western blot, flow cytometry, and immunofluorescent staining were performed to investigate the effects of SAL on HG-induced rGECs injury. FG-4592 and SAL protected rGECs against HG-induced injury by increasing cellular viability and reducing the cell apoptosis rate. SAL and FG-4592 downregulated PHD-2 expression and upregulated HIF-1α and HIF-2α expression. In conclusion, our findings suggest that SAL and FG-4592 ameliorate HG-induced rGEC injury by upregulating HIF expression, indicating that SAL and FG-4592 might be favorable for further DN-treatment.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/biosíntesis , Células Endoteliales/efectos de los fármacos , Glucosa/toxicidad , Glucósidos/farmacología , Glicina/análogos & derivados , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Isoquinolinas/farmacología , Glomérulos Renales/efectos de los fármacos , Fenoles/farmacología , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Células Endoteliales/metabolismo , Células Endoteliales/patología , Glucósidos/administración & dosificación , Glicina/administración & dosificación , Glicina/farmacología , Isoquinolinas/administración & dosificación , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Fenoles/administración & dosificación , Estabilidad Proteica , Ratas , Regulación hacia ArribaAsunto(s)
Hiperparatiroidismo Secundario/complicaciones , Hiperparatiroidismo Secundario/cirugía , Paratiroidectomía/métodos , Uremia/complicaciones , Humanos , Hormona Paratiroidea/sangre , Hormona Paratiroidea/uso terapéutico , Complicaciones Posoperatorias/epidemiología , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: Renal fibrosis is a common pathway through which a variety of chronic kidney diseases progress to end-stage renal disease. Epithelial-mesenchymal transition (EMT) of renal proximal tubular cells is one of the most important factors in renal fibrosis. This study investigates if fasudil could influence EMT of renal proximal tubular cells. METHODS: HK-2 cells in passage 3-4 were used for all experiments. The cells were divided into five groups and treated with different concentrations of PTH and then observe cellular morphological changes at 0, 24 and 48 h using an inverted microscope and investigate the expression of the epithelial cell marker E-cadherin and the renal fibroblast marker α-smooth muscle actin (α-SMA). RESULTS: PTH significantly induced EMT, fasudil-inhibited EMT induced by PTH to different degrees, and the inhibitory effect of fasudil was most pronounced at 20 µmol/L. CONCLUSION: Monitoring PTH levels, early prevention and control of hyperparathyroidism and reducing the concentration of PTH are important means to improve prognosis and delay the progression of chronic kidney disease. Fasudil can restrain EMT induced by PTH; this conclusion provides experimental data for the application of fasudil in the clinical prevention and treatment of renal fibrosis.
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Células Epiteliales/fisiología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Túbulos Renales Proximales/fisiología , Inhibidores de Proteínas Quinasas/farmacología , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , Actinas/metabolismo , Antígenos CD , Cadherinas/metabolismo , Línea Celular , Progresión de la Enfermedad , Células Epiteliales/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/fisiología , Fibrosis , Humanos , Riñón/patología , Fallo Renal Crónico/patología , Fallo Renal Crónico/prevención & control , Túbulos Renales Proximales/citología , Microscopía , Hormona Paratiroidea/farmacología , Transducción de Señal/efectos de los fármacos , Quinasas Asociadas a rho/antagonistas & inhibidoresRESUMEN
Cultural factors influencing high yield and good quality Linum usitatissimum (Tianya 9) were investigated. The correlations between these factors and its yield were analyzed. Path coefficient and principal component analysis were conducted, adopting uniform design of the 8 cultivating factors, i.e. planting density (X1), base nitrogen quantity (X2), base phosphorus quantity (X3), base potassium quantity (X4), foliar fertilizer (potassium dihydrogen phosphate, X5), foliar fertilizer (boron fertilizer, X6), growth regulator (multi-effect azole, X7) and growth duration irrigation amount (X8), aiming at exploring better cultivating plan of L. usitatissimum for Gansu Province. The results indicated that the factors influencing the yield of L. usitatissimum were X1, X7, X2, X3, X5 and X4 in a descending order. Simulation and optimization of the highest yield was further implemented. Frequency analysis showed that the cultivating factors resulting in yield higher than 173.58 kg . hm-2 were 4. 68 - 4. 92 kg . hm-2 (X1) , 11. 59 - 14. 75 kg . hm-2 (X2), 17.26- 21.95 kg . hm-2 (X3), 7.00-12.50 kg . hm-2 (X4) , 1.41-1.81 kg . hm-2 (X5) and 751.74- 954.04 g . hm-2 (X7).
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Agricultura/métodos , Fertilizantes , Lino/crecimiento & desarrollo , Fósforo/análisis , Potasio/análisisRESUMEN
Hypocalcemia and hypophosphatemia are common complications after parathyroidectomy (PTX). Sudden removal of high circulating levels of parathyroid hormone (PTH) causes decreased osteoclastic resorption resulting in a decreased bone remodeling space. These phenomena are likely due to an increased influx of calcium and phosphorus into bone. However, there are currently no data to support this hypothesis. In this study, we found that PTX significantly reduced levels of PTH, calcium and phosphate. Compared with preoperative levels, after 1 year, postoperative PTH, calcium and phosphate levels were 295.6 ± 173.7 pg/mL (P < 0.05), 86.62 ± 15.98 mg/dL (P < 0.05) and 5.56 ± 2.03 mg/dL (P < 0.05), respectively. We investigated continuous bovine PTH administration as well as withdrawal of bovine PTH stimulation in the mouse osteoblast precursor cell line MC3T3-E1. MC3T3-E1 cells were cultured with continuous bovine PTH treatment for 20 days or with transient bovine PTH treatment for 10 days. High doses of continuous bovine PTH exposure strongly reduced cell proliferation, alkaline phosphatase activity and the number of mineralized calcium nodules. However, withdrawal of bovine PTH (100 ng/mL) significantly increased the number of mineralized calcium nodules and caused a rapid decline in calcium and phosphorus content of culture medium. In conclusion, continuous exposure to bovine PTH inhibited osteoblast differentiation and reduced the formation of mineralized nodules. However, this inhibition was removed and mineralized nodule formation resumed with withdrawal of bovine PTH. According to the results of our clinical examinations and in vitro experiments, we hypothesize that the sudden removal of high levels of PTH may cause an increased influx of calcium and phosphorus into bone after PTX.