Blood Urine Nitrogen Research Articles

Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-\u03baB pathway

BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal failure, contributing to severe morbidity and mortality in diabetic patients. Berberine (BBR) has been well characterized to exert renoprotective effects in DN progression. However, the action mechanism of BBR in DN remains to be fully understood.MethodsThe DN rat model was generated by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) while 30 mM high glucose (HG)-treated podocytes were used as an in vitro DN model. The fasting blood glucose level and ratio of kidney weight to body weight were measured after BBR treatment (50, 100, or 200 mg/kg) in STZ-induced DN rats. The renal injury parameters including 24-h urinary protein, blood urea nitrogen and serum creatinine were assessed. qRT-PCR was performed to detect the transcript amounts of inflammatory factors. The concentrations of inflammatory factors were evaluated by ELISA kits. Western blot analysis was conducted to measure the amounts of TLR4/NF-κB-related proteins. The apoptotic rate of podocytes was analyzed by flow cytometry using Annexin V/propidium iodide.ResultsBerberine reduced renal injury in STZ-induced DN rat model, as evidenced by the decrease in fasting blood glucose, ratio of kidney weight to body weight, 24-h urinary protein, serum creatinine, and blood urine nitrogen. BBR attenuated the systemic and renal cortex inflammatory response and inhibited TLR4/NF-κB pathway in STZ-induced DN rats and HG-induced podocytes. Also, HG-induced apoptosis of podocytes was lowered by BBR administration. Furthermore, blockade of TLR4/NF-κB pathway by resatorvid (TAK-242) or pyrrolidine dithiocarbamate aggravated the inhibitory effect of BBR on HG-induced inflammatory response and apoptosis in podocytes.ConclusionsBerberine ameliorated DN through relieving STZ-induced renal injury, inflammatory response, and podocyte HG-induced apoptosis via inactivating TLR4/NF-κB pathway.

Ellagic acid mitigates sodium arsenite-induced renal and hepatic toxicity in male Wistar rats.

The aim of this study was to investigate the effect of ellagic acid (EA) on arsenic-induced renal and hepatic toxicity in rats. A total number of 35 male Wistar rats were randomly divided into five experimental groups. Group 1 received normal saline (po). Group 2 received sodium arsenite (SA, 10mg/kg, po) for 21days. Group 3 received EA (30mg/kg, po) for 14days. Groups 4 and 5 received SA 7days prior to EA (10 and 30mg/kg respectively) treatment and continued up to 21days simultaneous with SA administration. Various biochemical, histological and molecular biomarkers were measured in kidney and liver. Treatment with EA (more potently at dose of 30mg/kg) restored the SA-induced alterations in serum creatinine (Cr) and blood urine nitrogen (BUN) levels as well as the changes in aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations (all p<0.001). Elevated levels of malondialdehyde (MDA) and nitric oxide (NO) in renal and hepatic tissue was reduced by EA treatment (all p<0.001). Treatment with EA enhanced the glutathione (GSH) content in liver (p<0.001) and up-regulated renal and hepatic superoxide dismutase (SOD) and glutathione peroxidase (GPx) mRNA expression (all p<0.001). The SA-induced histopathological alterations in kidney and liver were reduced by EA treatment. In conclusion, the presence of EA with SA alleviated its toxic effects and EA treatment might be an effective strategy for the management of arsenic-induced renal and hepatic damage.

Cordycepin, a Characteristic Bioactive Constituent in Cordyceps militaris, Ameliorates Hyperuricemia through URAT1 in Hyperuricemic Mice.

Recently, we've reported the anti-hyperuricemic effects of Cordyceps militaris. As a characteristic compound of C. militaris, we hypothesized that cordycepin may play a role in preventing hyperurecimia. Remarkably, cordycepin produced important anti-hyperuricemic actions, decreasing SUA (serum uric acid) to 216, 210, and 203 μmol/L (P < 0.01) at 15, 30, and 60 mg/kg in comparison of hyperuricemic control (337 μmol/L), closing to normal control (202 μmol/L). Elisa, RT-PCR and western blot analysis demonstrated that the actions may be attributed to its downregulation of uric acid transporter 1 (URAT1) in kidney. Serum creatinine levels and blood urine nitrogen and liver, kidney, and spleen coefficients demonstrated that cordycepin may not impact liver, renal, and spleen functions. In addition, we used computational molecular simulation to investigate the binding mechanism of cordycepin. Of which, van der Waals interaction dominated the binding. Residues TRP290, ARG17, ALA408, GLY411, and MET147 contributed mainly on nonpolar energy. This provided the theoretical guidance to rationally design and synthesis novel URAT1 inhibitors.

The relationships among hyperuricemia, body mass index and impaired renal function in type 2 diabetic patients.

Chronic kidney disease (CKD) is a common chronic microvascular complication and the major cause of death in diabetic patients. This study was conceived to explore the possible mechanisms of how hyperuricemia and obesity contribute to renal function impairment in type 2 diabetic (T2DM) patients. A cross-sectional study in 609 participants recruited from a T2DM population in North China was conducted. The multiplicative interaction between body mass index (BMI) and uric acid (UA) level was assessed using an interaction term in a logistic regression analysis. Our results indicate that male T2DM patients having higher BMI (OR 1.711, p = 0.038), blood urine nitrogen (BUN) (OR 1.100, p = 0.034), and 24-hour urinary micro-albumin levels (OR 1.004, p = 0.021) were much more likely to have high UA. Whereas, for female T2DM patients, the OR of BMI, BUN, and triglyceride were 1.169 (p = 0.001), 1.337 (p = 0.000), and 1.359 (p = 0.006), respectively. In this study population, obesity and elevated UA work together to increase the risk of renal injury. In vitro experiments indicate that reactive oxygen species (ROS) production increased with UA treatment in human renal glomerular endothelial cells (HRGECs), while endothelial nitric oxide synthase (eNOS) production level dropped. UA also increased monocyte chemotactic protein-1 (MCP-1) expression and nuclear factor kappa B (NF-κB) activation. Taken together, our results indicate that high concentrations of UA lead to endothelial dysfunction through the activation of the inflammatory response and induction of oxidative stress, even in non-obese T2DM patients.

Efficacy of Probiotics Supplementation On Chronic Kidney Disease: a Systematic Review and Meta-Analysis

Background/Aims: Dysbiosis of the intestinal microbiota may accelerate the progression of chronic kidney disease (CKD) by increasing the levels of urea toxins. In recent years, probiotics have been recognized to maintain the physiological balance of the intestinal microbiota. In this study, we aim to assess the therapeutic effects of probiotics on CKD patients with and without dialysis via meta-analysis. Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) by searching the databases of Pubmed, EMBASE and Cochrane Library (No. CRD42018093080). Studies on probiotics for treatment of CKD adults lasting for at least 4 weeks were selected. The primary outcomes were the levels of urea toxins, and the second outcomes were the levels of interleukin (IL)-6, C-reactive protein (CRP) and hemoglobin (Hb). The risk of bias was assessed by Cochrane Collaboration’ tool, and the quality of evidence was appraised with the Grading of Recommendation Assessment. Means and standard deviations were analyzed by random effects analysis. Stratified analysis was done and sensitivity analysis was performed when appropriate. Results: Totally, eight studies with 261 patients at CKD stage 3 to 5 with and without dialysis were included. We found a decrease of p-cresyl sulfate (PCS) of 3 studies with 125 subjects (P = 0.01, SMD -0.57, 95% CI, -0.99 to -0.14, I² = 25%) and an increase of IL-6 in 3 studies with 134 subjects (P = 0.03, 95% CI, SMD 0.37, 0.03 to 0.72, I² = 0%) in the probiotics groups. Analysis of serum creatinine (P = 0.47), blood urine nitrogen (P = 0.73), CRP (P = 0.55) and Hb (P = 0.49) yielded insignificant difference. Conclusion: Limited number of studies and small sample size are limitations of our study. Probiotics supplementation may reduce the levels of PCS and elevate the levels of IL-6 whereby protecting the intestinal epithelial barrier of patients with CKD.

Risk factors of in-hospital mortality among patients with upper gastrointestinal bleeding and acute myocardial infarction.

Background/Aims:Patients with simultaneous upper gastrointestinal bleeding (UGIB) and acute myocardial infarction (AMI) have higher mortality than patients with either GIB or AMI. We aimed to assess the incidence and risk factors of in-hospital mortality in patients with UGIB and AMI.Patients and Methods:A total of 243 patients with UGIB and AMI were enrolled during 2012–2017. Clinical and laboratory data were collected and analyzed for clinical characteristics and potential risk factors of in-hospital mortality.Results:Among the 243 patients, 60 in-hospital deaths were observed (in-hospital mortality rate of 24.7%). Patients who died were older than the survivors (78.7 ± 6.6 vs. 72.6 ± 10.5 years, P < 0.001). Compared with survivors, patients who died showed increased peak white blood cell (WBC) count (9.74 ± 4.72 vs. 7.60 ± 2.91 × 109/L, P = 0.002), serum creatinine levels [134 (106, 190) vs. 97 (79, 125) mmol/L, P = 0.014], peak blood urine nitrogen levels (16.31 ± 8.48 mmol/L vs. 9.86 ± 6.33 mmol/L, P < 0.001), and peak brain natriuretic peptide (BNP) amounts [13,250 (6071, 30,000) vs. 3598 (728, 12,842) pg/mL, P < 0.001]. Meanwhile, patients who died also displayed lower minimum hemoglobin levels (78.3 ± 21.1 vs. 86.3 ± 22.3 g/L, P = 0.018) and minimum platelet counts (184.3 ± 79.1 vs. 214.6 ± 80.1 × 109/L, P = 0.013). In multivariable logistic analysis, age [OR (95% CI) =1.118 (1.053–1.186), P < 0.001], peak WBC count [OR (95% CI) =1.252 (1.113–1.407), P < 0.001], minimum platelet count [OR (95% CI) = 0.994 (0.989–1.000), P = 0.032], and peak BNP levels [OR (95% CI) =3.880 (1.761–8.550), P = 0.001] were independent predictors of in-hospital mortality.Conclusions:Patients with UGIB and AMI had a high in-hospital mortality, which was independently associated with age, peak WBC count, minimum platelet count, and peak BNP levels.

Study of the Determinant Factors in Seizure Following Gastroenteritis in Children Admitted in Tabriz Children's Hospital during 2001 to 2016

Background: One of the common side effects of gastroenteritis in children is seizure, which is one of the causes of fever, electrolyte disturbances, and meningitis. This study was aimed to investigate the determinant factors in seizure in children with gastroenteritis and seizure admitted in Tabriz Children's Hospital from 2001 to 2016. Materials and Methods: This is a descriptive study. The study population included all children admitted with diagnosis of gastroenteritis and seizure in Tabriz Children's Hospital during the years 2001 to 2016. The data of admitted patients including electrolyte disturbances, age, gender, blood-venous analysis, Blood urine nitrogen (BUN), and creatinine tests were extracted from hospital records by a resident and intern of this hospital using a questionnaire designed for this research. Results: A total of 84 patients were included in the study. The patients included 44 males (52.4%) and 40 females (47.6%). The mean age of the patients was 9.31 ± 7.13 years. Forty-six (55.42%) patients suffered from electrolyte impairment, 24 of which (52.2%) were male and 22 (47.8%) were female; and hyponatremia was the most common disorder (24.10%). Accordingly, only BUN of has proven to be a strong predictor of the likelihood of seizure; also despite of non-significant p-value of PH, it had a potentially strong association with seizure. Conclusion According to the results of this study, electrolyte impairment is fairly common in children with acute gastroenteritis. Education about the management of children with seizure to is an important factor in this regard.

Chronologic Changes and Correlates of Loop Diuretic Dose in Patients with Left Ventricular Assist Device.

No study has systematically evaluated the prevalence and dosages of diuretic use for patients after left ventricular assist device (LVAD) implantation. The primary objective was to characterize chronologic change in prevalence and doses of loop diuretics after LVAD placement. The secondary objective was to identify correlates of actual doses of loop diuretics. We retrospectively reviewed medical records of adult patients with LVAD implantation at the University of Kentucky. Prevalence of diuretic use and furosemide equivalent dose were assessed before LVAD implantation and at seven time points thereafter: 1 week, 1 month, 3 months, 6 months, 1 year, 18 months, and 2 years. Correlation analyses and linear mixed modeling were used to identify correlates of diuretic dose before and after LVAD implantation. Eighty-two consecutive eligible patients were reviewed. The prevalence of loop diuretic use was 95% at baseline but significantly lower than that at all subsequent time points (p < 0.048 for all). Nevertheless, more than half of patients on whom we had such follow-up data were on loop diuretics 2 years after LVAD implantation. Average furosemide equivalent dose was significantly lower at every time point after implantation compared with baseline (p < 0.006 for all). Blood urine nitrogen (BUN) was the most robust predictor of dose after LVAD implant. The prevalence and average furosemide equivalent dose were significantly reduced after LVAD implantation, but the use of loop diuretic remained more than 50% for up to 2 years. Consistent association with BUN may indirectly indicate overuse of diuretics post-LVAD implant.

The role of oxidative stress in acute renal injury of newborn rats exposed to hypoxia and endotoxin.

Neonatal kidney injury is a frequent pathology, especially among premature infants. The search for effective nephroprotection requires the creation of adequate experimental models of nephropathy in newborns. In this study, we explored the development of acute kidney injury (AKI) in neonatal rats during hypoxia or administration of endotoxin. We found that 2-h hypoxia (8% O2 ) and the intraperitoneal injection of 4 mg·kg-1 lipopolysaccharide (LPS) causes the appearance of AKI markers, such as kidney injury molecule-1 (КIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the rat urine after 24 and 72 h of exposure. On the other hand, the levels of blood urine nitrogen under the same conditions rise only slightly. The damaging effects of hypoxia and endotoxin were accompanied by histological changes in the renal tissue and a significant decrease in the proliferation marker, (proliferating cell nuclear antigen). It is revealed that 3 h after the introduction of LPS, levels of reactive oxygen species in the kidney were significantly increased, and the injection of the antioxidant N-acetylcysteine afforded protection from AKI, evaluated by urine КIM-1 and NGAL levels. Thus, the simulation of AKI in newborn rat pups can be employed in screening for potential nephroprotective drugs, particularly among antioxidative compounds to be used in neonatology.

Atractylenolide Ⅰ protects against lipopolysaccharide-induced disseminated intravascular coagulation by anti-inflammatory and anticoagulation effect.

To investigate whether atractylenolide Ⅰ (ATL-Ⅰ) has protective effect on lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) invivo and invitro, and explore whether NF-κB signaling pathway is involved in ATL-Ⅰ treatment. New Zealand white rabbits were injected with LPS through marginal ear vein over a period of 6hat a rate of 600μg/kg (10mL/h). Similarly, in the treatment groups, 1.0, 2.0, or 5.0mg/kg ATL-Ⅰ were given. Both survival rate and organ function were tested, including the level of alanine aminotransferase (ALT), blood urine nitrogen (BUN), and TNF-α were examined by ELISA. Also hemostatic and fibrinolytic parameters in serum were measured. RAW 264.7 macrophage cells were administered with control, LPS, LPS+ATL-Ⅰ and ATL-Ⅰ alone, and TNF-α, phosphorylation (P)-IκBα, phosphorylation (P)-NF-κB (P65) and NF-κB (P65) were determined by Western blot. The administration of LPS resulted in 73.3% mortality rate, and the increase of serum TNF-α, BUN and ALT levels. When ATL-Ⅰ treatment significantly increased the survival rate of LPS-induced DIC model, also improved the function of blood coagulation. And protein analysis indicated that ATL-I remarkably protected liver and renal as decreasing TNF-α expression. Invitro, ATL-I obviously decreased LPS-induced TNF-α production and the expression of P-NF-κB (P65), with the decrease of P-IκBα. ATL-Ⅰ has protective effect on LPS-induced DIC, which can elevate the survival rate, reduce organ damage, improve the function of blood coagulation and suppress TNF-α expression by inhibiting the activation of NF-κB signaling pathway.

Simple Risk Factors to Predict Urgent Endoscopy in Nonvariceal Upper Gastrointestinal Bleeding Pre-endoscopically

The goal of this study is to evaluate how to predict high-risk nonvariceal upper gastrointestinal bleeding (NVUGIB) pre-endoscopically. A total of 569 NVUGIB patients between Match 2011 and January 2015 were retrospectively studied. The clinical characteristics and laboratory data were statistically analyzed. The severity of NVUGIB was based on high-risk NVUGIB (Forrest I–IIb), and low-risk NVUGIB (Forrest IIc and III). By logistic regression and receiver-operating characteristic curve, simple risk score systems were derived which predicted patients’ risks of potentially needing endoscopic intervention to control bleeding. Risk score systems combined of patients’ serum hemoglobin (Hb) ≤75 g/L, red hematemesis, red stool, shock, and blood urine nitrogen ≥8.5 mmol/L within 24 hours after admission were derived. As for each one of these clinical signs, the relatively high specificity was 97.9% for shock, 96.4% for red stool, 85.5% for red hematemesis, 76.7% for Hb ≤75 g/L, and the sensitivity was 50.8% for red hematemesis, 47.5% for Hb ≤75 g/L, 14.2% for red stool, and 10.9% for shock. When these 5 clinical signs were presented as a risk score system, the highest area of receiver-operating characteristic curve was 0.746, with sensitivity 0.675 and specificity 0.733, which discriminated well with high-risk NVUGIB. These simple risk factors identified patients with high-risk NVUGIB of needing treatment to manage their bleeding pre-endoscopically. Further validation in the clinic was required.

Preclinical evaluation of nephroprotective potential of a probiotic formulation LOBUN on Cyclosporine-A induced renal dysfunction in Wistar rats

The aim of present study was to evaluate the nephroprotective effect of probiotic formulation LOBUN on Cyclosporine A (CsA) induced renal dysfunction in Wistar rats. CsA (20 mg/kg body weight s.c) was administered for 15 days to cause renal dysfunction in Wistar rats. The probiotic formulation LOBUN was administered with the dose of 500 mg/kg body weight (p.o) for twice (TGI) and thrice a day (TGII). The samples were analyzed for the parameters like blood urine nitrogen (BUN), serum creatinine, serum uric acid, total serum protein and urine proteins, urine potassium, urine sodium. The renal functional and histopathological studies revealed that the oral administration of probiotic formulation LOBUN has provided appreciable renoprotection and possibly alleviated the symptoms of Chronic Kidney Disease (CKD) at the dose of 500 mg/kg body weight administered thrice a day and also the results were supported by histopathological findings.

Protection of resveratrol on acute kidney injury in septic rats.

The aim of the study is to investigate protective effect of resveratrol (Res) on acute kidney injury (AKI) in sepsis. Rats in sham group received sham operation; in sham + Res received sham operation and Res (3 mg/kg); in cecal ligation and puncture (CLP) established as sepsis; in CLP + Res (3 mg/kg) with sepsis and Res (3 mg/kg); and in CLP + Res (10 mg/kg) with sepsis and Res (10 mg/kg). Survival rate, serum indexes, inflammatory factors, NF-κB-P65, and SIRT1 were detected. Lipopolysaccharide (LPS) mesangial cell was with Res and SIRT1 silencing. (1) Res intervention improved survival rate of CLP rat. (2) Compared to sham, serum creatinine, blood urine nitrogen, serum cystatin C, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, tumor necrosis factor-α, interleukin-1β, IL-6, and renal injury index increased in CLP group, while decreased in CLP + Res (3 mg/kg) and CLP + Res (10 mg/kg), significantly, as dose-dependent ( p < 0.05). (3) With Res, NF-κB-P65 and de-acetylated SIRT1 decreased, while SIRT1 and de-acetylated Nuclear factor kB-p65 9 NF-κB-P65) increased, significantly ( p < 0.05). (4) SIRT1 and de-acetylated NF-κB-P65 decreased in LPS cells, while SIRT1 increased after Res intervention, significantly ( p < 0.05). After silencing SIRT1, de-acetylated NF-κB-P65 increased, significantly ( p < 0.05). Res increases the survival rate of septic rats by inhibiting inflammatory factors to ease AKI and promotes NF-κB-P65 de-acetylation by upregulating SIRT1.

Late Gadolinium Enhancement Amount As an Independent Risk Factor for the Incidence of Adverse Cardiovascular Events in Patients with Stage C or D Heart Failure.

Background: Myocardial fibrosis (MF) is a risk factor for poor prognosis in dilated cardiomyopathy (DCM). Late gadolinium enhancement (LGE) of the myocardium on cardiac magnetic resonance (CMR) represents MF. We examined whether the LGE amount increases the incidence of adverse cardiovascular events in patients with stage C or D heart failure (HF).Methods: Eighty-four consecutive patients with stage C or D HF, either ischemic or non-ischemic, were enrolled. Comprehensive clinical and CMR evaluations were performed. All patients were followed up for a composite endpoint of cardiovascular death, heart transplantation, and cardiac resynchronization therapy with defibrillator (CRT-D).Results: LGE was present in 79.7% of the end-stage HF patients. LGE distribution patterns were mid-wall, epi-myocardial, endo-myocardial, and the morphological patterns were patchy, transmural, and diffuse. During the average follow-up of 544 days, 13 (15.5%) patients had endpoint events: 7 patients cardiac death, 2 patients heart transplantation, and 4 patients underwent CRT-D implantation. On univariate analysis, LGE quantification on cardiac magnetic resonance, blood urine nitrogen, QRS duration on electrocardiogram, left ventricular end-diastolic diameter (LVEDD), and left ventricular end-diastolic volume (LVEDV) on CMR had the strongest associations with the composite endpoint events. However, on multivariate analysis for both Model I (after adjusting for age, sex, and body mass index) and Model II (after adjusting for age, sex, BMI, renal function, QRS duration, and atrial fibrillation on electrocardiogram, the etiology of HF, LVEF, CMR-LVEDD, and CMR-LVEDV), LGE amount was a significant risk factor for composite endpoint events (Model I 6SD HR 1.037, 95%CI 1.005–1.071, p = 0.022; Model II 6SD HR 1.045, 95%CI 1.001–1.084, p = 0.022).Conclusion: LGE amount from high-scale threshold on CMR increased the incidence of adverse cardiovascular events for patients in either stage C or D HF.

Actions of water extract from Cordyceps militaris in hyperuricemic mice induced by potassium oxonate combined with hypoxanthine

Ethnopharmacological relevanceCordyceps militaris was recorded in the classic traditional Chinese medicine book with the main functions of “protecting liver and enhancing kidney functions”, influencing serum uric acid levels. Aim of studyThe aim is to investigate the hypouricemic effects and possible mechanism of C. militaris in hyperuricemic mice. Materials and methodsA water extract (WECM) was prepared by decocting C. militaris directly at 80 °C in water bath, followed by lyophilization. WECM at 50, 100 and 200mg/kg was orally administered to hyperuricemic mice induced by potassium oxonate and hypoxanthine combinedly and allopurinol (5mg/kg) was served as a positive control. ResultsWECM exhibited excellent hypouricemic activity, which could decrease the serum uric acid levels of the hyperuricemic mice (306μmol/L) to 189, 184 and 162μmol/L at different doses respectively (P<0.01), approaching the levels of normal mice (184μmol/L). The urate transporter 1 (URAT1) protein levels of kidney at different doses of WECM were 28.15, 17.43, 9.03pg/mL respectively, much lower than that in the hyperuricemia group (93.45pg/mL, P<0.01); and suggested WECM may interact with URAT1. Docking simulations using modeled structure of URAT1 suggested that LYS145, ARG325, ARG477 and ASP168 of URAT1 are key functional residues of URAT1. Four active compounds in C. militaris were identified and their interaction energies with target were estimated between −200 and −400kcal/mol. ConclusionsThese findings suggested that C. militaris produced significant hypouricemic actions and the hypouricemic effects of WECM may be attributed to the inhibitive effect of WECM on URAT1 protein levels. The results of blood urine nitrogen and serum creatinine levels and liver, kidney and spleen coefficients showed that WECM have no negative impacts on liver, renal and spleen functions. The screened four active compounds using molecular docking method deserve further investigation in other work.

Simple risk factors to predict urgent endoscopy in nonvariceal upper gastrointestinal bleeding pre-endoscopically.

The goal of this study is to evaluate how to predict high-risk nonvariceal upper gastrointestinal bleeding (NVUGIB) pre-endoscopically. A total of 569 NVUGIB patients between Match 2011 and January 2015 were retrospectively studied. The clinical characteristics and laboratory data were statistically analyzed. The severity of NVUGIB was based on high-risk NVUGIB (Forrest I–IIb), and low-risk NVUGIB (Forrest IIc and III). By logistic regression and receiver-operating characteristic curve, simple risk score systems were derived which predicted patients’ risks of potentially needing endoscopic intervention to control bleeding. Risk score systems combined of patients’ serum hemoglobin (Hb) ≤75 g/L, red hematemesis, red stool, shock, and blood urine nitrogen ≥8.5 mmol/L within 24 hours after admission were derived. As for each one of these clinical signs, the relatively high specificity was 97.9% for shock, 96.4% for red stool, 85.5% for red hematemesis, 76.7% for Hb ≤75 g/L, and the sensitivity was 50.8% for red hematemesis, 47.5% for Hb ≤75 g/L, 14.2% for red stool, and 10.9% for shock. When these 5 clinical signs were presented as a risk score system, the highest area of receiver-operating characteristic curve was 0.746, with sensitivity 0.675 and specificity 0.733, which discriminated well with high-risk NVUGIB. These simple risk factors identified patients with high-risk NVUGIB of needing treatment to manage their bleeding pre-endoscopically. Further validation in the clinic was required.

CDK5 promotes renal tubulointerstitial fibrosis in diabetic nephropathy via ERK1/2/PPARγ pathway.

Cyclin-dependent kinase 5 (CDK5) has been documented in podocyte injuries in diabetic nephropathy (DN), however its role in renal tubular epithelial cells has not been elucidated. We report here that CDK5 is detrimental and promotes tubulointerstitial fibrosis (TIF) via the extracellular signal-regulated kinase 1/2 (ERK1/2)/peroxisome proliferator-activated receptor gamma (PPRAγ) pathway in DN. In high glucose cultured NRK52E cells, blocking CDK5 activity inhibited epithelial-to-mesenchymal transition (EMT) and fibrosis via ERK1/2/PPARγ pathway. In diabetic rats, CDK5 inhibitor roscovitine decreased renal fibrosis and improved renal function as demonstrated by a decrease in levels of blood urine nitrogen (BUN), serum creatinine and β2-microglobulin. Further studies revealed that improved renal fibrosis and function in diabetic rats were associated with inactivation of ERK1/2 and PPARγ signaling pathways. In late staged DN patients, the upregulation of CDK5 and p35 activated phosphorylated ERK1/2 and PPARγ, leading to decreased levels of E-cadherin but increased Vimentin and Collagen IV. Accordingly, renal fibrosis and function were worsened as revealed by decreased estimated glomerular filtration rate (eGFR) and increased serum BUN, creatinine, β2-microglobulin, 24-hour proteinuria and urine albumin to creatinine ratio (UACR). These findings demonstrate a novel mechanism that CDK5 increases tubulointerstitial fibrosis by activating the ERK1/2/PPARγ pathway and EMT in DN. CDK5 might have therapeutic potential in diabetic nephropathy.

The role of biochemical markers in predicting worsening heart failure; comparison of biomarkers / Kötüleşen kalp yetmezliğini öngörmede biyokimyasal belirteçlerin rolü; biyobelirteçlerin karşılaştırılması

Abstract Objective: Heart failure is the end stage of many cardiac disorders. Worsening heart failure causes high mortality in these patients. In the present study, we aimed to elucidate and compare the biochemical predictors of worsening heart failure. Methods: One hundred one patients with heart failure were included in this study. Patients were divided into two groups according to their functional status. N-terminal pro-brain natriuretic peptide (NT-pro BNP), troponin T, serum and urine creatinine, blood urine nitrogen (BUN), eGFR, cystatin C, neutrophil gelatinase associated lipocalin (NGAL), C - reactive protein, hepatic transaminases and thyroid stimulating hormone levels were measured. Results: NT-pro BNP, troponin T, serum creatinine, BUN, cystatin C and NGAL levels were significantly higher but urine creatinine level and eGFR was lower in decompensated heart failure patients. In univariate analysis, age, cystatin C, NGAL, NT-pro BNP and serum creatinine and eGFR predicted worsening heart failure (WHF). In multivariate analysis, cystatin C and NT-pro BNP variables were found to be significant in predicting WHF. However, eGFR were determined at the limit of significance (p=0.053) with an high odds ratio 3.173 (95% CI:0.983-10.240). Cystatin C and NT-pro BNP concentrations were predictors of worsening heart failure. In ROC analysis, cystatin C is a better predictor of decompensated heart failure compared with NT-pro BNP and other predictors, and has a sensitivity of 82% and a specificity of 63%. Conclusion: This study revealed that cystatin C and NT-pro BNP were significant predictors of WHF, and cystatin C is slightly better predictor of WHF. Further studies are needed to confirm these results.

Effect of sanhuanghuoxue decoction on the treatment of chronic renal failure

The aim of this study was to investigate the efficacy of sanhuanghuoxue decoction in the treatment of chronic renal failure by examining the changes in serum creatinine and blood urine nitrogen using rat models. Compared with the control group, which was treated by coated aldehyde oxystarch, the group treated by sanhuanghuoxue showed remarkable decrease in serum creatinine and blood urine nitrogen. The difference was found statistically significant.

Sex Differential Influence of Acute Orally-administered Silver nanoparticles (Ag-NPs) on Some Biochemical Parameters in Kidney of Mice Mus musculus

Our data on the gender effect of Ag-NPs on animals are inconclusive with mixed results. This study, therefore aimed to clarify sex differential influence of acute orally-administered Ag-NPs on some biochemical parameters (Blood Urine Nitrogen (BUN), Creatinine (Cr), Sodium and Potassium) in kidney of mice Mus musculus. A group of BALB/c mice of about 9 weeks (weighting 27.2 ± 3.0 g) were randomly divided into three groups (each with two replications): Ag-NPs (2) and the control (1) groups, each with 9 mice. Almost equal numbers of male and female mice were used in this study. Once a day at the same time, a volume of 50 microliters from the nanosilver solution (20 and 50 ppm) was administered orally at a given time. The untreated (control) group received distilled water without Ag-NPs. Samplings (n = 9) were conducted on days 2, 7 and 14. The blood was obtained directly from heart using heparinized tubes. The serum was obtained by centrifugation of the whole blood at 3000 rpm for 15 min. Ag-NPs had potential to adversely affect the kidney functions in gender-dependent manner so that obvious kidney toxicity was found in female mice. This study suggests that female mice suffer more serious kidney toxicity than male mice when treated with Ag-NPs. Our findings build up necessary knowledge on Ag-NPs in vivo distribution and mechanisms responsible for Ag-NPs meditated toxicity to organisms. Further studies are required to elucidate in depth how Ag-NPs interact and affect cellular processes.