Objective:To investigate the concentrations of secreted protein acidic and rich in cysteine(SPARC)in the serum and urine of patients with IgA nephropathy and its expression in the kidney tissues.Methods:The concentrations of SPARC, tumor necrosis factor-?(TNF-?),interleukin 1?(IL-1?),and interleukin 6(IL-6)in the serum and urine were measured with enzyme-linked immunosorbent assay(ELISA).The contents of'SPARC protein in the culture medium of human mesangial cell (HMC)and human renal tubular epithelial cell(HKC),which had been treated with IL-6,were determined by ELISA.The ex- pression and distribution of SPARC in IgA nephropathy and normal kidney tissues were observed by immunohistochemistry as- say.Results:The concentrations of SPARC in serum and urine of IgA nephropathy patients were higher than those of the normal control subjects([2.43?1.22]?g/ml vs[0.69?0.21]?g/ml,[7.73?2.81]?g/ml vs[1.17?1.03]?g/ml,P

Objective To investigate the relationship between expressions of multidurg resistance associated factors and chemosensitivity of 5-fluorouracil(5-FU) in lymph node metastases(LNMs) of colon carcinoma.Methods The chemosensitivity to 5-FU was measured by MTT assay,and the expressions of P-gp,GST-?,p53,survivin,Bcl-2 and Bax were determined immunohistochemically in 48 paired primary tumor(PT) and LNMs of colon carcinoma.Results The inhibition rates of LNMs cells for 5-FU were higher than that of PT(P

Objective To investigate the effect of L-carnitine on pathological changes of myocardium and the underlying mechanism in chronic renal failure rats (CRF). Methods A total of 55 male SD rats were randomly divided into sham group (n=10),model group (n=15),low dose (300 mg/kg),medium dose (600 mg/kg) and high dose (900 mg/kg) L-carnitine group(n=10,each).5/6 subtotal nephrectomy was performed in these rats without sham group.One week after the operation,normal saline or corresponding dose L-carnitine were intragastrically administrated to sham and model group or L-carnitine groups for 17 weeks.Transthoracic echocardiography,mean arterial pressure (MAP),heart rate (HR) and heart weight/body weight were assessed.Moreover,24h urine protein,renal function,SOD,MDA,IL-6,ATP,ADP were measured at the end of the study.Additionally,pathological changes in myocardium were detected by light microscope and transmission electron microscope. Results (1) ATP (μmol/g·wt)in L-carnitine groups (2.35±0.24,3.59±0.28,3.78±0.25) was significantly higher than that in model group (1.61±0.12) (all P＜0.01).(2) Thickness of posterior wall of left ventricle (mm) in high dose L-carnitine group was thinner than that in model group (3.74±0.23 vs 4.18±0.48,P＜0.05). (3) The ratios of heart weight to body weight in both medium dose and high dose L-carnitine groups (3.92±0.27,3.65±0.2) were significantly lower compared to model group (3.99±0.27) (all P＜0.01). (4) Under light microscopy,disarrangement and hypertrophy of cardiac myocytes,increased myocardial fibrosis were observed in model group, while these changes and the pathological scores were significantly improved in both medium dose and high dose L-carnitine groups (7.14±1.07,6.13±0.99),as compared with model group (9.88±1.13) (all P＜0.01).Under electron microscopy,typical changes in cardiac hypertrophy were observed,including dissolution of myocardial fibers,increasing and swelling of mitochondria,membrane rupture as well as matrix increase in model group,while these changes were ameliorated by L-carnitine in a dose-dependent manner. (5) Seventeen weeks after the treatment,both IL-6 and MDA were decreased in all L-carnitine-treated groups than those in model group [IL-6 (ng/L):261.86±13.18,240.12±18.7,233.34±36.88 vs 596.64±81.41; MDA (nmol/L):15.23±2.01,12.41±0.6.10.97±1.9 vs 21.84±2.71).Whereas,SOD (U/ml) were increased in L-carnitine-treated groups (51.2±6.11,58.51±5.52,60.63±6.94) than that in model group(32.01 ±5.69 )(all P＜0.05).(6) No significant differences of systolic,diastolic blood pressure or MAP were found among groups. Conclusion L-carnitine can improve energy metabolism,micro-inflammation and oxidative stress in myocardium of CRF rats,which may be associated with the amelioration of cardiac hypertrophy and fibrosis.

ced glutathione in MHD patients appears to be associated with an improvement of oxidative stress.

Objective To investigate the effects of SPARC (secreated protein acidic and rich in cysteine) and its peptide on proliferation, apoptosis and cell cycle of human mesangial cells cultured in vitro, and explore the possible mechanism. Methods Mesangial cells were incubated in the media with various concentrations of SPARC and its peptide cultured in vitro. Cell proliferation was assessed by MTT colorimetric assay. Cell cycle and apoptosis index were analyzed by flow cytometry. The expression of cyclinD1 and p21Wafl proteins in response to SPARC and its peptide in HMC was determined by Western blot. Results Various concentrations of SPARC and its peptide could significantly inhibit the proliferation of mesangial cells in dose- and time-dependent manner, regulate the cell cycle at phrase G-0/G1 increased while cells phrase S reduced, and could also induce apoptosis. Under the stimulation of SPARC and its peptide, the expression of cyclinDl in HMC decreased markedly meanwhile the expression of p21Wafl increased significantly. Conclusions SPARC and its peptide can effectively inhibit HMC proliferation and regulate cell cycle progression. The mechanism may be mediated by inhibiting cyclinDl and stimulating p21Wafl expression, subsequently blocking cells passing through G-S check point, which will be useful for treating mesangial proliferative glomerulonephritis.

AIM:To observe the effect of altitude hypoxia on ?-aminobutyric (GABA) content and prepro-somatostatin mRNA (PPS-mRNA) in the rat hypothalamus. METHODS: Using altitude hypoxia model,in situ hybridization and amino acid analyzer, the number of PPS-mRNA and GABA content in rat hypothalamus was determined. RESULTS:After altitude hypoxia, the contents of GABA in hypothalamus and the number of PPS-mRNA neurons in periventricular nucleus (PeVN), paraventricular nucleus (PaVN) and arcuate nucleus (ArcN) increased significiantly. Bicuculline, a GABA receptor antagonits, could enhance PPS-mRNA expression evoked by altitude hypoxia, but had no effect on GABA content. CONCLUSION: Altitude hypoxia can induce neurotransmitter imbalance of hypothalamus.

AIM: To observe the effect of altitude hypoxia on glutamate, aspartate and nitric oxide synthase (NOS) in the rat hypothalamus. METHODS: Using altitude hypoxia model, amino acid analysis system and the NADPH-d histochemistry, we determined the content of glutamate, aspartate and the number of NADPH-d neurons in the rat hypothalamus. RESULTS: After altitude hypoxia, the contents of glutamate, aspartate in the hypothalamus of rats were increased significantly, densely and deeply stained NADPH-d neurons were seen in hypothalamic paraventricular nucleus (PVN)and supraoptic nucleus(SON). If rat were pretreated with the NMDA receptor blockers Ketamine (ip,40 mg/Kg)or AP-V(i.c.v, 10 ?g) , the number of NADPH-d neurons in the rat hypothalamic PVN and SON was markedly less than that in corresponding altitude hypoxia group. CONCLUSION: NMDA receptor may take part in the expression of hypothalamic NOS induced by altitude hypoxia.

Objective To investigate the serum cystatin C (CysC) level and explore its relationship with cytokines and atherosclerosis (AS) in maintenance hemodialysis (MHD) patients.Methods A total of 110 stable MHD patients undergoing hemodialysis for at least six months and 60 healthy control people were enrolled in the study.Serum levels of CysC and high-sensitivity Creactive protein (hsCRP) were measured by immunoturbidimetry.The serum levels of total homocysteine (tHcy),IL-1β,IL-6 and TNF-α were determined by ELISA.Prevalence of atherosclerosis was detected by carotid ultrasonography.The relationship of CysC level and cardiac geometry incidence in MHD patients was analyzed by Logistic regression model.Results The serum CysC level was significantly higher in MHD patients as compared with healthy controls [(6.19±0.95) mg/L vs (0.76±0.21) mg/L,P＜0.01],and the serum levels of hsCRP,tHcy,IL-1β,IL-6,TNF-α were significantly higher in MHD patients than those in healthy control group (P＜0.05 or P＜0.01).The serum CysC level was higher in MHD patients with carotid artery atherosclerosis compared to patients without carotid artery atherosclerosis (P＜0.05).CysC was positively correlated with hsCRP,tHcy,IL-1β,IL-6,TNF-α respectively (P＜0.05 or P＜O.01),and was positively correlated with carotid intimal medial thickness (IMT) and AS.Besides,a negative correlation was found between the serum CysC level and the serum albumin level (P＜0.05),while CysC was positively correlated with dialysis duration,systolic pressure and iPTH (P ＜0.05).Conclusion Serum CysC level is significantly higher in MHD patients and is correlated with hsCRP,tHcy,IL-1β,IL-6,TNF-α as well as carotid artery atherosclerosis,which indicates that CysC is an independent risk factor of AS in MHD patients.

Objective To investigate the effects of trimetazidine on the oxidative stress in maintenance he-modialysis (MHD) patients. Methods Eighty-six MHD patients and 30 healthy volunteers were recruited in the study. The activity of glutathione peroxidase (GSHPx) was measured by colorimetry and superoxide dismutase (SOD) in serum was measured by hydroxylamine method. The levels of serum malondialdehyde (MDA) were meas-ured by thiobarbituric acid reaction. Serum advanced oxidation protein products (AOPP) levels were measured by enzyme-linked immunosorbent assay (ELISA). All MHD patients were randomly divided into two groups, treatment group (n = 46) and control group (n = 40), who had undergone hemodialysis for at least three months before the study and were in a stable clinic status without signs of infection or disease activity. In the treatment group,20 mg of trimetazidine was taken orally three times each day for twenty-four weeks, when the parameters for oxidative stress were studied. The levels of GSHPx. SOD, MDA and AOPP in serum were measured before and after the treat-ment. Results At the initiation of the investigation, the serum levels of GSHPx [(584.37±215.70) μmol/L, (580.87±309.12) μmol/L vs (769.06±302.46) μmol/L] and SOD [(347.87±82.09) kU/L, (348.16±75.33) kU/L vs (428.34±15.23)kU/L] in the M HD patients were significantly lower than those in the normal eontrol group (P < 0.01), whereas the content of MDA [(4.94±1.32) nmol/L, (4.97±1.61) nmol/L vs (3.56±0.46)nmol/L] and AOPP [(120.95±59.24) μg/L,(121.76±69.12) μg/L vs (47.69±20.15) μg/L] in MHD patients was higher than those in the control group( P < 0.05 and P <0.01, respectively). After treatment for twelve weeks, the scores of GSHPx and SOD were significantly increased in the treatment group compared to that before treatment (P <0.01). However, the contents of the MDA and AOPP decreased. There were significant differences in the levels of GSHPx, SOD,MDA and AOPP between the two groups of MHD patients after the treatment with trim-etazidine. Conclusions Trimetazidine in maintenance hemodialysis patients appears to be associated with an im-provement of oxidative stress.

Objective To investigate the serum level of free fatty acid (FFA) and explore its relationship with cytokines and atherosclerosis (AS) in chronic kidney disease (CKD).Methods The serum level of FFA was determined with enzymatic colorimetry.IL-1 β, IL-6 and TNFα were determined with ELISA.High-sensitivity C-reactive protein (hsCRP) was measured with immunoturbidimetry.Prevalence of atherosclerosis was detected with carotid ultrasonography.We evaluated the relationship between serum levels of FFA and IL-1β,IL-6, TNFα, hsCRP as well as the renal function in 130 adult patients with CKD, stratified according to the GFR ( based on the National Kidney Foundation/Kidney Dialysis Outcomes Quality Initiatives) and in 58 hemodialytic (HD) patients.The relationship between FFA level and cardiac geometry incidence in CKD patients was analyzed with logistic regression model.Results The serum level of FFA was significantly higher in CKD patients as compared with that in the healthy controls [(492.63 ± 143.59)vs (302.65 ± 142.18) μ mol/L, P ＜ 0.01], even in the early stage of CKD.The level of FFA increased with the progression of renal dysfunction.In the non-dialytic CKD group, the level of FFA was negatively related to GFR and positively related to the proteinuria (P ＜ 0.05), while in the HD group, it was positively correlated with dialysis duration ( P ＜ 0.05 ).The serum levels of FFA were higher in CKD patients with carotid artery atherosclerosis than those in patients without ( P ＜ 0.05 or ＜ 0.01 ).However, in both groups with impairment of renal function, the levels of FFA were positively correlated with hsCRP, IL-1 β, IL-6,TNFα and TG( all P ＜ 0.05 ).A positive correlation between the level of FFA and the clinical manifestations such as carotid intimal medial thickness (IMT) and AS was also found.A negative correlation was found between the level of FFA and the serum level of albumin and GFR( P ＜ 0.05).Conclusion Serum levels of FFA are significantly higher either in non-dialytic CKD or in HD patients and it is related with hsCRP, IL-1 β, IL-6, TNFα as well as carotid artery atherosclerosis, indicating that FFA is an independent risk factor of AS in CKD.