BACKGROUNDDiabetic patients undergoing percutaneous coronary intervention (PCI) have a higher incidence of contrast-induced nephropathy (CIN) than nondiabetic patients, and no pharmacological approach has been demonstrated to offer consistent protection. Therefore, identifying individuals who are at increased risk becomes essential. This study was designed to assess the predictive role of the ratio of contrast medium volume to estimated glomerular filtration rate (CMV/eGFR) in diabetic patients undergoing elective PCI who developed CIN.

METHODSWe retrospectively investigated clinical factors associated with the development of CIN in 114 diabetic patients who had undergone elective PCI. The risk factors for CIN included age, gender, body mass index (BMI), left ventricular ejection fraction (LVEF), hemoglobin (Hb), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), volume of contrast medium, basic levels of serum creatinine (Scr), the number of treated vessels and the number of stents used. We conducted a stepwise regression analysis to evaluate the predictive role of these risk factors in the incidence of CIN.

RESULTSThe incidence of CIN was 18.4% (21/114). There were no significant differences in age, gender, BMI, LVEF, Hb, FPG, HbA1c, and incidence of hypertension and number of acute myocardial infarction (AMI) in patients between the CIN (n = 21) and the non-CIN (n = 93) groups. However, the eGFR was significantly lower ((72.0 ± 12.5) ml·min(-1)·1.73 m(-2) vs. (82.0 ± 16.5) ml·min(-1)·1.7 m(-2), P = 0.010), and the basic serum creatinine level ((1.07 ± 0.12) mg/dl vs. (0.97 ± 0.19) mg/dl P = 0.014) was significantly higher in the CIN group. In addition, the volume of contrast medium was significantly larger ((253 ± 75) ml vs. (211 ± 71) ml, P = 0.017) and the CMV/eGFR ratio was significantly greater (3.64 ± 1.26 vs. 2.70 ± 1.11, P = 0.001) in the CIN group. Stepwise regression analysis showed that the CMV/eGFR ratio was a significant independent predictor for the development of CIN (P = 0.001). At a cut-off point of > 3.1, the CMV/eGFR ratio exhibited 71% sensitivity and 70% specificity for detecting CIN.

CONCLUSIONThe CMV/eGFR ratio could be a valuable predictor of CIN for diabetic patients after elective PCI. At a cut-off point of > 3.1, the CMV/eGFR ratio was an optimal predictor for the incidence of CIN.

Aged ; Angioplasty, Balloon, Coronary ; Contrast Media ; adverse effects ; Diabetes Mellitus ; therapy ; Diabetic Nephropathies ; chemically induced ; Female ; Glomerular Filtration Rate ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors

OBJECTIVES: The thickening of the glomerular basement membrane in rats after Vacor ingestion was examined by electron microscopy. This study was performed to elucidate which biochemical components changed in the glomerular basement membrane after Vacor-induced diabetic glomerulopathy. METHODS: Immunohistochemical analyses of type IV collagen, laminin, fibronectin and chondroitin sulfate proteoglycan were performed. A single dose of Vacor (molecular weight 272), 80 mg/kg, was administered to adult male Wistar rats by orogastric canule, and the animals were sacrificed at 0.5, 1, 3, 7, 14, 28 and 56 days after administration. RESULTS: Mild thickening of the glomerular basement membrane was evident 7 days after Vacor administration, and the width of the glomerular basement membrane was more than twice that of normal controls at 28 and 56 days. Significantly increased expressions of type IV collagen, laminin, fibronectin and neutral polysaccharide in the thickened glomerular basement membrane were noted 14 to 56 days after administration, and a mildly increased expression of chondroitin sulfate proteoglycan appeared between 3 to 7 days. CONCLUSION: These abnormally increased glomerular basement membrane components might be part of what causes diabetic nephropathy after Vacor administration.
Animal ; Basement Membrane/pathology ; Basement Membrane/metabolism ; Basement Membrane/drug effects ; Diabetic Nephropathies/pathology ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/chemically induced* ; Extracellular Matrix Proteins/metabolism ; Kidney Glomerulus/pathology ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/drug effects ; Male ; Phenylurea Compounds/toxicity* ; Proteochondroitin Sulfates/metabolism ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effect of ursolic acid (UA) on the alloxan-induced kidney injury in diabetic mice and explored its possible mechanisms.

METHODSDiabetes mellitus was induced in male Kunming mice by an injection of alloxan (70 mg/kg, i.v.). After 72 hours, blood glucose levels were detected and mice with blood glucose levels over 13.9 mmol/L were considered as diabetic and selected for further experiment. Thirty mice were randomly divided into three groups: control, diabetic and diabetic + UA(35 mg/kg/d, i.g. continuously for 8 weeks). Blood glucose concentration, organ coefficient of kidney, blood urea nitrogen (BUN), creatinine (Cr) as well as renal tissue levels of superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined. Pathology of the renal tissue was measured by hematoxylin-eosin staining.

RESULTSCompared to the control group, blood glucose, organ coefficient of kidney, BUN and Cr increased significantly. In addition, SOD activities was reduced markedly and levels of MDA and inflammatory factors (TNF-α, IL-6) increased significantly. Renal cells from model group rats showed atrophy and disordered after HE staining and infiltration of inflammatory cells also appeared in renal tissue of the model group. These changes were significantly attenuated in the diabetic group treated with UA.

CONCLUSIONUA can significantly relieve renal damage in mice with diabetic nephropathy induced by alloxan, which might be related to decreased blood glucose level, antioxidation effect and inhibiting the production of inflammatory factors such as TNF-α and IL-6.

Alloxan ; adverse effects ; Animals ; Antioxidants ; metabolism ; Blood Glucose ; Blood Urea Nitrogen ; Creatinine ; metabolism ; Diabetes Mellitus, Experimental ; physiopathology ; Diabetic Nephropathies ; chemically induced ; drug therapy ; Interleukin-6 ; metabolism ; Kidney ; physiopathology ; Male ; Mice ; Superoxide Dismutase ; metabolism ; Triterpenes ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism

PURPOSE: To screen for diabetic autonomic neuropathy of the pupil using 0.5% apraclonidine and 0.1% pilocarpine and to evaluate the early diagnostic value of this pharmacologic pupillary test by assessing the relationship between pupillary and cardiovascular autonomic neuropathies. METHODS: A total of 22 diabetic patients were recruited. Baseline pupillary diameter (PD) and the difference in PD between the test eye and the control eye before and after instillation of apraclonidine and pilocarpine were measured. All patients also underwent cardiovascular autonomic function (CAF) testing. RESULTS: Baseline PD in room light correlated with duration of diabetes mellitus (DM, p=0.049) and the presence of DM retinopathy (DMR, p=0.022). Eleven patients (50%) had positive apraclonidine tests, and two patients had positive pilocarpine tests. The patients who had positive pilocarpine tests also had positive apraclonidine tests. Patients who had a positive pupillary test had a significantly higher rate of positive CAF tests (p=0.032). CONCLUSIONS: Pupillary autonomic neuropathy was related to the duration of diabetes and the degree of DMR. There was also a significant correlation between pupillary autonomic neuropathy and cardiovascular autonomic neuropathy (CAN). Also, sympathetic nerve dysfunction occurred prior to parasympathetic dysfunction in this study. A simple pharmacologic pupillary test can help manage complications in diabetic patients because patients with pupillary autonomic dysfunction have an increased risk of CAN.
Adrenergic alpha-Agonists/administration & dosage/diagnostic use ; Adult ; Aged ; Clonidine/administration & dosage/*analogs & derivatives/diagnostic use ; Diabetic Nephropathies/*diagnosis/physiopathology ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Miosis/*chemically induced/physiopathology ; Miotics/administration & dosage/diagnostic use ; Ophthalmic Solutions ; Pilocarpine/administration & dosage/*diagnostic use ; Pupil/drug effects/*physiology ; Reproducibility of Results

OBJECTIVETo investigate the effects of Shenkang pill on renal function and extracellular matrix secretion on the diabetic rats.

METHODThe diabetic rat models were induced by intraperitoneal injection of streptozotocin (STZ) and randomly divided into 3 groups' model control group; Capoten group and Shenkangwan group. Some normal other rats were used as normal control group. All rats were treated with corresponding drugs for 8 weeks. During and after the treatment, the general state, blood and urine glucose levels, excretion rate of the 24 hour urine protein and albumin, serum creatinine and blood urea nitrogen contents, kidney weight and relative kidney weight were measured. The mRNA of fibronectin(FN) in the kidney also detected by semi-quantitative reverse transcription polymerase chain reaction(RT-PCR).

RESULTDiabetes mellitus and renal lesions occurred in the three model groups. The expression of FN mRNA of the kidney in diabetic rats increased obviously. Shenkang pill could improve the general state and renal function of the diabetic rats, decrease the blood glucose levels and the excretion rate of the 24 hour urine protein and albumin, reduce the expression of FN mRNA in kidney.

CONCLUSIONShenkang pill has a certain protective effect on the diabetic kidney.

Animals ; Blood Glucose ; metabolism ; Blood Urea Nitrogen ; Diabetic Nephropathies ; chemically induced ; metabolism ; pathology ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Fibronectins ; biosynthesis ; genetics ; Glycated Hemoglobin A ; metabolism ; Kidney ; metabolism ; Male ; Plants, Medicinal ; chemistry ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Wistar ; Streptozocin

AIMTo investigate the effect of puerarin on expressions of MMP-2 and TIMP-2 in the kidney of diabetic rats.

METHODSUninephrectomized male Wistar rats were used to induce diabetes by intraperitoneal injection of streptozocin (65 mg x kg(-1)). Puerarin was given daily by intraperitoneal injection from the third day of induction of diabetes for 16 weeks. Using in situ hybridization and immunohistochemistry to detect MMP-2, TIMP-2 mRNA expressions and MMP-2, TIMP-2, collagen IV and Laminin expressions in diabetic kidneys with image analysis system, Flow cytometry was used to detect the expressions of TGFbeta1, MMP-2 and TIMP-2.

RESULTSCompared with those in kidneys of control group, expressions of MMP-2 mRNA and proteins were lower, while the expressions of both TGFbeta1 and TIMP-2 were higher in the diabetic kidney (P < 0.05). The level of MMP-2 expression was advanced, while expression of TIMP-2 was reduced by puerarin treatment (P < 0.05).

CONCLUSIONPuerarin showed some renal protective effect on diabetic nephropathy, partly through inhibition of excessive deposition of glomeruli extracellular matrix by up-regulating MMP-2 and down-regulating TIMP-2 expressions besides reducing the blood glucose.

Animals ; Collagen Type IV ; metabolism ; Diabetic Nephropathies ; chemically induced ; metabolism ; physiopathology ; Isoflavones ; pharmacology ; Kidney ; enzymology ; metabolism ; pathology ; Laminin ; metabolism ; Male ; Matrix Metalloproteinase 2 ; biosynthesis ; genetics ; Peptide Fragments ; metabolism ; Protective Agents ; pharmacology ; RNA, Messenger ; biosynthesis ; Rats ; Rats, Wistar ; Streptozocin ; Tissue Inhibitor of Metalloproteinase-2 ; biosynthesis ; genetics ; Transforming Growth Factor beta ; metabolism ; Transforming Growth Factor beta1

OBJECTIVETo investigate the reactive oxygen species (ROS) content and nuclear transcription factor-kappa B expression (NF-kappaB) in renal tissue of diabetic rats and the effect of Astragalus and Arctium in combination on them.

METHODSStreptozotocin (STZ)-induced diabetic model rats were established. Astragalus and Arctium in different dosages (low, moderate, high) were combined after orthogonal design and administered respectively to the model rats via gastrogavage for 4 or 8 weeks. Content of ROS in the renal tissue was detected by flow cytometry and expression of functional NF-kappaB p65 was assessed by Western blot at the 4th and 8th weekends (4th week and 8th week).

RESULTSROS content of renal tissue in the model rats was 36.55 +/- 7.46% at the 4th week and 31.91 +/- 5.83% at the 8th week, NF-kappaB p65 expression was 165.00 +/- 3.14 at the 4th week and 214.00 +/- 5.11 at the 8th week, all higher than those in normal rats (6.21 +/- 1.83% and 129.00 +/- 1.58 at the 4th week, 6.95 +/- 1.41% and 148.00 +/- 2.32 at the 8th week) respectively. The combined use of Astragalus and Arctium showed decreasing effects on both indexes significantly, and the decreasing effects of the combination with moderate and high dose Astragalus were better than those with low dose, with the details as follows: those of ROS at the 4th week were 11.43 +/- 2.42%, 18.37 +/- 7.58% and 22.10 +/- 4.71% for high, moderate and low dose Astragalus combination respectively (same hereinafter), at the 8th week 12.55 +/-4.40%, 19.15 +/- 6.64% and 23.48 +/- 3.13%; and for NF-kappaB p65 expression at the 8th week, 185.00 +/- 6.99, 183.00 +/- 3.89 and 194.00 +/- 4.98 respectively.

CONCLUSIONCombined use of Astragalus and Arctium may ameliorate the condition of diabetic nephropathy by inhibiting the activation of the ROS-NF-kappaB signal passage.

Animals ; Arctium ; chemistry ; Astragalus Plant ; chemistry ; Diabetic Nephropathies ; chemically induced ; drug therapy ; metabolism ; Disease Models, Animal ; Drug Therapy, Combination ; Gene Expression ; drug effects ; Humans ; NF-kappa B ; genetics ; metabolism ; Plant Extracts ; administration & dosage ; Random Allocation ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Streptozocin ; adverse effects

OBJECTIVE: To investigate the effects of centella asiatica (CA) granule on the expression of transform growth factor-β(TGF-β) and related down-stream signals in rats with early diabetic nephropathy(DN) and to clarify the molecular mechanisms of CA molecular mechanism of on preventing and curing early diabetic kidney disease DN by studying the effects of centella asiatica on TGF-β expression and related down-stream signals. METHODS: Sixty male SD rats were divided into control group(=10) and DN model group(=50). The model rats were made a right nephrectomy. One week later, diabetic nephropathy was induced by intraperitoneal injection of streptocozin(30 mg/kg) for three consecutive days. High blood glucose level of Tail vein (fasting glucose ≥ 16.7 mmol/L) and high urinary protein level(total protein level in DN group was more than twice higher than the control group) were measured to confirm early DN in rats. In the sham operation group, the right renal capsule was damaged and the corresponding amount of saline was injected. The model rats were administrated by the means of intragastric administration. The DN model group were divided into DN group, DN+fosinopril group(1.6 mg/kg·d), DN+high CA group(16.8 mg/kg·d), DN+medium CA group(11.2 mg/kg·d) and DN+low CA group(5.6 mg/kg·d), and each group was intragastric administration one time every morning last for 16 weeks. The expressions of mRNA and protein of TGF-β, TβR1, TβR2, Smad2/3, Smad7 and the level of Smad2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot. RESULTS: The expressions of mRNA and protein of TGF-β, TβR1, TβR2, Smad2/3 and the level of Smad2/3 phosphorylation were significantly increased, the expressions of mRNA and protein of Smad7 were dramatically decreased. The fosinopril and high dosage CA could reverse the effects of DN. CONCLUSIONS CA plays an important role in preventing and curing DN through regulating the TGF-β/Smad signaling pathways.
Animals ; Centella ; chemistry ; Diabetes Mellitus, Experimental ; Diabetic Nephropathies ; chemically induced ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Receptor, Transforming Growth Factor-beta Type I ; metabolism ; Receptor, Transforming Growth Factor-beta Type II ; metabolism ; Signal Transduction ; Smad2 Protein ; metabolism ; Smad3 Protein ; metabolism ; Smad7 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

We aimed to elucidate the effect of bilirubin on dyslipidemia and nephropathy in a diabetes mellitus (DM) type I animal model. Sprague-Dawley rats were separated into control, DM, and bilirubin-treated DM (Bil) groups. The Bil group was injected intraperitoneally with 60 mg/kg bilirubin 3 times per week and hepatoma cells were cultured with bilirubin at a concentration of 0.3 mg/dL. The Bil group showed lower serum creatinine levels 5 weeks after diabetes onset. Bilirubin treatment also decreased the amount of mesangial matrix, lowered the expression of renal collagen IV and transforming growth factor (TGF)-beta1, and reduced the level of apoptosis in the kidney, compared to the DM group. These changes were accompanied by decreased tissue levels of hydrogen superoxide and NADPH oxidase subunit proteins. Bilirubin decreased serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), free fatty acids, and triglycerides (TGs), as well as the TG content in the liver tissues. Bilirubin suppressed protein expression of LXRalpha, SREBP-1, SCD-1, and FAS, factors involved in TG synthesis that were elevated in the livers of DM rats and hepatoma cells under high-glucose conditions. In conclusion, bilirubin attenuates renal dysfunction and dyslipidemia in diabetes by suppressing LXRalpha and SREBP-1 expression and oxidative stress.
Animals ; Bilirubin/pharmacology/*therapeutic use ; Cell Line, Tumor ; Creatine/blood ; Diabetes Mellitus, Experimental/chemically induced/complications/*pathology ; Diabetic Nephropathies/*drug therapy/etiology ; Disease Models, Animal ; Kidney/pathology ; Lipoproteins, HDL/blood ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; NADPH Oxidase/metabolism ; Orphan Nuclear Receptors/antagonists & inhibitors/genetics/metabolism ; Oxidative Stress/drug effects ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Streptozocin/toxicity ; Triglycerides/analysis/*biosynthesis/blood