OBJECTIVE Diabetic nephropathy (DN) has been one of the most common complications of diabetes and the leading cause of end-stage renal disease. Glomerular hyperfiltrationis central in earlystage of DN and leads to the progression of renal architectonic and functional abnormalities. Salvi?anolic acid A (SalA) has been proved to protect diabetic complications such as hepatic fibrosis and neuropathy. The present study was designed to investigate the effects of SalAon glomerular endothelial dysfunctionand diabetic nephropathy. METHODS Primary glomerular endothelial cells were subjected to assess permeability under injury of advanced glycation end-products (AGEs). AGEs-induced changes of RhoA/ROCK pathway and cytoskeleton rearrangement were assessed bywestern blotandimmunoflu?orescence. The beneficial effects of SalA on diabetic nephropathy were investigated in a rat model induced by high-fat and high-glucose diet combined with low dose of streptozocin (35 mg·kg- 1, ip). Renal function and architectonic changes were evaluated by biochemical assay and PAS staining. RESULTS SalA 3μMameliorated AGEs- induced glomerular endothelial permeability (P<0.05) and suppressed rearrangement of cytoskeleton through inhibiting AGE-RAGE-RhoA/ROCK pathway. SalA 1 mg · kg- 1 markedly reduced endothelium loss (P<0.01) and glomerular hyperfiltration (P<0.05) in diabetic kidney. Subsequently,SalA 1 mg·kg-1 suppressed glomerular hypertrophy and mesangial matrix expansion, eventually reduced 24 h-urinary albumin and ameliorated renal function by decreasing blood urine nitrogen (BUN), serum creatinine (Scr) and serum n-acetyl-β-d-glucosaminidase (NAG). AGEs-RAGE-Nox4-induced oxidative stress was suppressed by the treatment of SalA 1 mg·kg-1. CONCLUSION SalA ameliorated AGEs-induced glomerular endothelial hyperpermeability, and effec?tively protected against early-stage diabetic nephropathy by reducing hyperfiltration and alleviating renal structural deterioration through inhibiting AGEs and its downstream pathway. Thus, SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Chronic Disease ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Osteomyelitis ; therapy ; Young Adult

Objective To evaluate the effects of diphenylhydantoin sodiumpolybutylcyanoacrylate nanoparticles (DPH-PBCA-NPs) and DPH-PBCA-NPs modified with Tween-80on rat models of epilepsy, and investigate the advantage of nanoparticle as the drug delivery system.Methods The rat models of acute epilepsy induced by lithium pilocarpine were established and randomly divided into 5 groups: group Ⅰ (performing injection of DPH-PBCA-NPs modified with Tween-80), group Ⅱ (performing injection of DPH-PBCA-NPs), group Ⅲ (performing injection of diphenylhydantoin sodium), group Ⅳ (performing injection of PBCA-NPs) and group Ⅴ (performing injection of physiological saline). The changes of electroencephalogram (EEG) manifestations of these rats were observed by using video-EEG monitoring; and their behavioral changes were noted too.Results The lithium pilocarpine induced rat models of acute epilepsy were successfully established and their status epilepticus were confirmed by EEG and their behaviors. The effective rate of DPH-PBCA-NPs modified with Tween-80 and DPH-PBCA-NPs was 91.67% and 54.55%, respectively;the effective rate of rats in group Ⅲ was 50%, and the effective rate of rats in group Ⅳ and Ⅴ was 0%;DPH-PBCA-NPs modified with Tween-80 enjoyed a better effect than DPH-PBCA-NPs and DPH (P＜0.05). Conclusion DPH-PBCA-NPs and DPH-PBCA-NPs modified with Tween-80 can be used to improve the behaviors of rats with acute epilepsy and modify the results of EEG of these rats.Nanoparticles as drug delivery system can help the drugs having their effects much quickly and effectively.

OBJECTIVETo discuss the treatment and mechanisim of acetabulum fracture combined with ipsilateral lower extremity fracture.

METHODSFourteen cases(9 males and 5 females) of acetabulum fracture were involved in the study with the mean age of 35 years (range, from 18 to 65 years). According to Letournel classification, 11 cases were the fracture of posterior wall and column, 3 cases were only the fracture of posterior column. All of them were treated with titanium plate internal fixation. Of three cases with ipsilateral femoral intertrochanteric fracture, one was treated with external fixiation device, other two were treated with DHS fixation; Three cases with ipsilateral femoral neck fracture were treated with compressive cannulated screw fixation; Among six cases with ipsilateral femoral shaft fracture,one was fixed with steel plate,the rest underwent intramedullary nailing fixation; Two cases with ipsilateral tibial plateau fracture were treated with anatomic plate internal fixation.

RESULTSAll patients except the died old patient were followed up from 18 months to 5 years, with mean of 30 months. According to standard of American institute of orthopaedics, 9 cases obtained excellent results, 3 good and 2 poor and the excellent and good rate was 92.3%.

CONCLUSIONMost cases of acetabulum fracture combined with ipsilateral lower extremity fracture are due to great violence, their mechanisms are complex, and easily lead to missed diagnosis, therefore the early correct diagnosis, and reasonable internal fixation should be considered.

Acetabulum ; injuries ; surgery ; Adolescent ; Adult ; Aged ; External Fixators ; Female ; Fracture Fixation, Internal ; methods ; Fractures, Bone ; surgery ; Humans ; Leg Injuries ; surgery ; Male ; Middle Aged

The aim of this study is to investigate the effects of the metformin on the formation of hepatic fibrosis in type 2 diabetic rats and discuss its mechanism of liver-protecting activity. After SD rats were fed with high-fat and high-sucrose diet for four weeks, low-dose streptozotocin (STZ) was injected intraperitoneally to make the animal mode of type 2 diabetes. Then, all diabetic rats was fed with the high-fat diet and metformin (ig, 100 mg x kg(-1)) was given orally to metformin group for four months. After the last administration, fasting blood glucose was determined. The livers were removed to calculate the hepatic coefficient and to make HE and Picro acid-Sirius red staining, immunohistochemistry (alpha-SMA and TGFbeta1) and TUNEL staining in order to evaluate the effect of metformin on the hepatic fibrosis. The animal model of type 2 diabetes with hepatic fibrosis was successfully made. Metformin can significantly alleviate the lesions of hepatic steatosis and fibrosis, markedly reduce the expressions of alpha-SMA and TGFbeta1 in liver tissue of type 2 diabetic rats. However, TUNEL staining result suggested that metformin could not reduce apoptosis of hepatocytes. The results suggest that metformin can inhibit the formation of hepatic fibrosis in type 2 diabetes.
Actins ; metabolism ; Animals ; Apoptosis ; drug effects ; Blood Glucose ; metabolism ; Body Weight ; drug effects ; Diabetes Mellitus, Experimental ; drug therapy ; etiology ; metabolism ; pathology ; Diabetes Mellitus, Type 2 ; drug therapy ; etiology ; metabolism ; pathology ; Diet, High-Fat ; Female ; Hepatocytes ; pathology ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Liver ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; drug therapy ; metabolism ; pathology ; Male ; Metformin ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo summarize the experiences in high-risk renal transplant recipients for ketter long-term survival.

METHODSFrom April 1991 to December 2008, a total of 921 kidney recipients with high-risk factors were divided into six groups as following: (1) pediatric patients (< 18 years old) (GI, n = 34); (2) retransplant recipients (GII, n = 169); (3) high sensitized patients (PRA> 30% or peak PRA > 50%)(GIII, n = 35); (4) elderly recipients (> 60 years old) (GIV, n = 297); (5) diabetic patients (GV, n = 112); (6) patients with HBV/HCV infection or HBV/HCV carrier (GVI, n = 274). Each group was compared to a control of 807 recipients without any above risk factor for patient and graft survival at 1, 3 and 5 years. Incidences of acute rejection (AR), chronic rejection (CR) and complication were analyzed and compared respectively between the studied subjects and the control group as well.

RESULTSCompared with the control group, patient/graft survivals were lower in GII, GIII and GVI (all P < 0.05), GIV had worse patient survival (P < 0.05); AR and CR incidences were greater in GI and GIII (all P < 0.05); GIV, GV and GVI had more complications.

CONCLUSIONSThis study suggests the benefits for long-term outcome in high-immunological risk renal transplant recipients of low acute selection incidence rate, and reduction of complication incidences is the key to long term results for non-immunological high risk recipients.

Adolescent ; Adult ; Aged ; Child ; Female ; Graft Rejection ; epidemiology ; Graft Survival ; Humans ; Kidney Transplantation ; statistics & numerical data ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Survival Rate ; Treatment Outcome ; Young Adult

OBJECTIVEFollowing the former report, we continue to observe the chronic renal tubular-interstitial injury induced by Radix Aristolochiae Fangchi Extract(RAFE) in rats in order to understand whether RAFE in different doses causes the renal tubular-interstitial injury or not.

METHODRAFE at the dose of 25.0 mg x kg(-1) x d(-1), 120.0 mg kg(-1) x d(-1) and 200.0 mg x kg(-1) x d(-1) and aristolochic acid (AA, 10.0 mg x kg(-1) d(-1)) was interruptedly administrated by gastric tube for 22 w and 4 w durg withdrawal. Blood, urine and kidney were taken out respectively in 17 w, 22 w and 26 w to measure the indexes of renal function. The morphology of kidney was observed, and Masson staining of kidney were made respectively to compare RAFE groups with AA group.

RESULTPathological changes of renal tissue forms were as follows: All RAFE groups and AA group could develop the pathological process of renal tubular injury-chronic renal interstitial fibrosis. The pathologic changes of RAFE were similar with AA.

CONCLUSIONRAFE at all doses administrated interruptedly by gastric tube above 13 w caused chronic renal tubulo-interstitium fibrosis. The renal injury in functions and tissue forms in rats were similar with AA closely. The results showed that AA was the main toxic composition of RAFE.

Animals ; Aristolochia ; chemistry ; toxicity ; Aristolochic Acids ; isolation & purification ; toxicity ; Blood Urea Nitrogen ; Body Weight ; drug effects ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; toxicity ; Female ; Fibrosis ; blood ; chemically induced ; pathology ; Kidney Tubules ; pathology ; Male ; Nephritis, Interstitial ; blood ; chemically induced ; pathology ; Plant Roots ; chemistry ; toxicity ; Plants, Medicinal ; chemistry ; toxicity ; Proteinuria ; chemically induced ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of Qingikailing and Shengmai injection alone or combined on the acute lung injury (AL) induced by oleic acid in rabbits.

METHODThe rabbits were randomly divided into 11 groups: oleic acid group; control group; treatment groups including low, middle and high dosage groups of Qingkailing and Shengmai injection alone and combined, respectively. ALI model was established by iv oleic acid (0.05 mL x kg(-1)) in these groups, and then iv above drugs respectively,while in control group, the same volume of normal saline was given. The respiratory amplitude and rate were observed, and blood samples were taken from cervical artery for blood-gas analysis before and at 30, 60, 120 min after oleic acid or normal saline administration. At the end of experiment, the concentration of LDH, CAT and MDA in the lung tissue were measured and pathologic changes of lung tissue were observed microscopically.

RESULTCompared with oleic acid group, the respiratory amplitude markedly enhanced (P < 0.05) in the low and high dose groups of Qingkailing and Shengmai injection. PaO2 increased significantly (P < 0.05) in the low dose group of combined Qingkailing and Shengmai injection, PaCO2 decreased markedly (P < 0.05) in the low dose groups of Qingkailing and Shengmai injection alone and combined. The level of MDA significantly decreased (P < 0.05) in the each group of Qingkailing and Shengmai injection alone, the level of MDA significantly decreased (P < 0.05) and CAT increased (P < 0.05) in the low dose group of combined Qingkailing with Shengmai injection. The low dose group of combined Qingkailing and Shengmai injection can alleviate the pathological changes induced by oleic acid.

CONCLUSIONThe curative effect of the low dose group of combined Qingkailing with Shengmai injection for the ALI induced by oleic acid was better than Qingkailing and Shengmai injection alone at the same dosage.

Animals ; Carbon Dioxide ; blood ; Catalase ; blood ; Drug Combinations ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Female ; L-Lactate Dehydrogenase ; metabolism ; Lung ; pathology ; Male ; Malondialdehyde ; blood ; Oleic Acid ; Oxygen ; blood ; Plants, Medicinal ; chemistry ; Rabbits ; Random Allocation ; Respiration ; drug effects ; Respiratory Distress Syndrome, Adult ; blood ; chemically induced ; pathology ; physiopathology

OBJECTIVETo investigate the effect of Qingkailing and Methylprednisolone (MP) injection alone or combined on the acute lung injury (ALI) induced by oleic acid in rabbits.

METHODThe rabbits were randomly divided into 11 groups: oleic acid group; control group; treatment groups including low, middle and high dosage groups of Qingkailing and MP alone and combined, respectively. ALI model was established by i.v. oleic acid (0.05 mL x kg(-1)) in these groups, and then i.v. above drugs respectively, while in control group, the same volume of normal saline was given. The respiratory amplitude and rate were observed, and blood samples were taken from cervical artery for blood-gas analysis before and at 30, 60, 120 min after oleic acid or normal saline administration. At the end of experiment, the concentration of LDH, CAT and MDA in the lung tissue were measured and pathologic changes of lung tissue were observed microscopically.

RESULTCompared with oleic acid group, the respiratory amplitude markedly enhanced (P < 0.05) and respiratory rate lowered (P < 0.05) in the low, middle and high dose groups of Qingkailing and MP injection. On the 30 min of treatment, PaO2 increased significantly (P < 0.05) in the low and middle dose groups of combined Qingkailing and MP injection; PaCO2 decreased markedly (P < 0.05) on the 120 min of treatment in each treatment group. The level of LDH significantly increased (P < 0.05), CAT and MDA decreased (P < 0.05) in the middle and high groups of Qingkailing and MP injection. The low and middle dose groups of combined Qingkailing and MP injection can alleviate the pathological changes induced by oleic acid.

CONCLUSIONThe curative effect of the low dose group of combined Qingkailing and MP for the ALI induced by oleic acid was better than Qingkailing and MP alone, while the big dose groups of Qingkailing and MP alone better than the combination at the same dosage.

Animals ; Anti-Inflammatory Agents ; therapeutic use ; Blood Gas Analysis ; methods ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; isolation & purification ; therapeutic use ; Female ; Lung ; metabolism ; pathology ; Male ; Methylprednisolone ; therapeutic use ; Oleic Acid ; Phytotherapy ; Plants, Medicinal ; chemistry ; Rabbits ; Random Allocation ; Respiratory Distress Syndrome, Adult ; chemically induced ; drug therapy ; metabolism ; Respiratory Function Tests

BACKGROUNDEnhanced external counterpulsation (EECP) improves ischemia in patients with refractory angina pectoris, but the mechanism remains unclear. To explore the mechanisms of EECP action, we detected progenitor cells presenting any of the following markers CD34(+), CD29(+), and CD106(+).

METHODSGrowth cytokines-mediated progenitor cell mobilization and associated angiogenesis potential were assessed in a porcine model of hypercholesterolemia. Twenty-four male domestic swines were randomly assigned to 4 groups: normal diet (control, n = 6), hypercholesterolemic diet (CHOL, n = 6), hypercholesterolemic diet with administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (rhG-CSF, n = 6), and hypercholesterolemic diet with EECP treatment (EECP, n = 6). EECP was applied 2 hours every other day for a total of 36 hours. Serum levels of vascular endothelial growth factor (VEGF) and granulocyte colony-stimulating factor (G-CSF), peripheral blood progenitor cell counts, level of regional angiogenesis, and expression of VEGF and stromal cell derived factor 1alpha (SDF-1alpha) in porcine myocardium were assessed, respectively.

RESULTSA porcine model of hypercholesterolemia-induced arteriosclerosis was successfully established. There was no significant difference in serum levels of VEGF among the four groups. The serum levels of G-CSF in the EECP group increased significantly at week 15 and week 18 ((38.3 +/- 5.6) pg/ml at week 15 vs (26.2 +/- 3.7) pg/ml at week 12, P < 0.05, and (46.9 +/- 6.1) pg/ml at week 18 vs (26.2 +/- 3.7) pg/ml at week 12, P < 0.01). The serum levels of G-CSF in group 3 increased also significantly after receiving rhG-CSF injection for five days ((150 +/- 13.9) pg/ml at week 18 vs (24.8 +/- 5.4) pg/ml at week 12, P < 0.01). Compared to other groups and other time points, progenitor cell counts increased significantly after 2-hour EECP treatment (108 +/- 13 vs 26 +/- 6 per 10(5) leukocytes, P < 0.01), but not at week 18. The progenitor cell counts also increased significantly after subcutaneous injection of rhG-CSF for five days compared to the week 12 (baseline) (180 +/- 21 vs 25 +/- 7 per 10(5) leukocytes, P < 0.01). There was no significant difference among the four groups at other time points. Moreover, the expression of VEGF and SDF-1alpha and the level of regional angiogenesis in myocardium increased significantly in both EECP and rhG-CSF groups.

CONCLUSIONSThe results demonstrated that EECP could facilitate angiogenesis in the myocardium of atherosclerotic swines by increasing endogenous G-CSF, inducing an enhanced mobilization of progenitor cells and augmenting myocardial expression of VEGF and SDF-1alpha.

Animals ; Arteriosclerosis ; physiopathology ; Blotting, Western ; Chemokine CXCL12 ; metabolism ; Counterpulsation ; methods ; Disease Models, Animal ; Electrophoresis, Polyacrylamide Gel ; Granulocyte Colony-Stimulating Factor ; blood ; metabolism ; Humans ; Hypercholesterolemia ; metabolism ; surgery ; Immunohistochemistry ; Male ; Myocardium ; metabolism ; Neovascularization, Pathologic ; metabolism ; surgery ; Random Allocation ; Recombinant Proteins ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cells ; cytology ; Swine ; Vascular Endothelial Growth Factor A ; blood ; metabolism