Enhancing effect of ultrasound-mediated microbubble destruction on gene delivery into rat kidney via different administration routes

OBJECTIVE@#To investigate the efficiency of β-galactosidase gene transfer into rat kidney with ultrasound-mediated microbubble destruction via different injection routes.@*METHODS@#A total of 25 Wistar rats were randomly divided into 5 groups. Four groups received a mixture of optison microbubbles (0.2 mL) and lacz plasmids (25 μg) injection via renal artery, tail vein, anterior tibial muscle and renal parenchyma, respectively. The control group received a mixture of PBS (xx mL) and lacz plasmids (25 μg) via renal artery. Three days after the gene transfer, ultrasound with fixed frequency and power (1 MHz, xxW) was delivered to the kidneys for 3 min. The efficiency of the gene transfer and expression was evaluated on the basis of β-galactosidase expression. The side effects of this method were evaluated by immunohistological method.@*RESULTS@#β-galactosidase expression could be observed only in tubules but not in glomeruli and interstitial area. The efficiency of renal artery group was higher than that of tail vein, anterior tibial muscle and renal parenchyma group (P<0.05). Immunohistochemical analysis revealed co-expression of β-galactosidase with a roximal tubule marker, megalin, which suggested that ultrasound enhanced gene transfer into the proximal tubular epithelial cells. No β-galactosidase expression was observed in the extrarenal organs. There were no evident pathological and biochemical changes after gene transfer.@*CONCLUSIONS@#Ultrasound-mediated microbubble destruction can transfer gene into kidney via renal artery, tail vein, anterior tibial muscle and renal parenchyma. Compared with renal artery, administrating microbubbles via tail vein and anterior tibial muscle are more convenient and less vulnerarious.

Effect of triptolide on the regulation of inflammatory response and apoptosis in PBMC from IgA nephropathy patients / 中华肾脏病杂志

ObjectiveToinvestigatetheinflammatoryresponseandapoptosisof peripheral blood mononuclear cells(PBMCs) and their regulation by triptolide(TP) in IgA nephropathy(IgAN) patients.MethodsBlood samples were collected from 29 IgAN patients and 16 healthy individuals.TNF-α and IL-6 concentrations were measured by ELISA and NO concentration by Griess reagent in the plasma of samples.PBMCs were isolated from IgAN patients and cultured in vitro,and subsequently activated by PHA(10 mg/L).The cytotoxicity of different TP concentrations was assayed by MTT and two non-toxic concentrations (12.5 μg/L or 25.0 μg/L)were selected for treatment.TNF-α,IL-6 and NO concentrations were measured in the culture media collected from PBMCs cultures activated by PHA (10 mg/L) and treated with TP (12.5 μg/L or 25.0 μg/L).The PHA-activated,TP-treated cells apoptotic rate was analyzed by FACS using Annexin V-FITC staining.The expression of Bcl-2,Bax,caspase-9 and caspase-3 were detected by RT-PCR and Western blotting from lyses of PHA-activated with or without TP-treated cells.ResultsThe serum concentrations of TNF-α[(131.57±50.61) ng/L vs(30.24±18.93) ng/L,P＜0.01],IL-6[(76.36±25.21) ng/L vs(35.08±16.59) ng/L,P＜0.01] and NO[(46.36±12.93) μmol/Lvs (26.61 ±10.87) μmol/L,P＜0.01] were significantly increased in IgAN patients compared to healthy individuals.PBMCs viability in culture decreased after TP treatment in a dose-dependent manner.TP also inhibited TNF-α,IL-6 and NO levels in the media of PHA-activated PBMCs in culture and induced PBMCs apoptosis.The expression of Bcl-2 decreased markedly and Bax,caspase-9 and caspase-3 increased significantly after TP treatment (all P＜0.05).Conclusions The PBMCs from IgAN patients are in a highly activated state,and have a high apoptotic rate.TP treatment induces benificial effects in IgAN patients by inhibiting the activation of PBMCs by activating pro-apoptotic pathway.

Renoprotective effect of adiponectin through an antioxidant mechanism in streptozotocin- induced diabetic rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the renoprotective effect of adiponectin in streptozotocin (STz)-induced diabetic rats and explore its association with oxidation stress.</p><p><b>METHODS</b>Type 2 diabetes mellitus was induced in rats by high-lipids and high-sucrose feeding and intraperitoneal STZ injection. The recombinant plasmid pIRES2-EGFP-gAd expressing globular adiponectin was intraperitoneally injected in the rats mediated by liposome. Thirty-two Wistar rats were randomized into 4 groups, namely the normal control group (NC), diabetic group without any therapy (DM), diabetic group treated with pIRES2-EGFP-gAd (DA) and diabetic group treated with pIRES2-EGFP (DP). After the corresponding treatments for 8 weeks, the blood glucose, HbA1c and urine albumin excretion rate (UAER) were measured, and the kidneys were collected to determine the production of reactive oxygen species (ROS) and assess renal pathologies. Immunohistochemistry and Western blot were employed to determine the protein levels of endothelial nitric oxide synthesis (eNOS) and phosphorylated AMP-activated protein kinase (pAMPK).</p><p><b>RESULTS</b>UAER and ROS production increased significantly in DM group as compared with that in the control group (P<0.05), while no significant differences were found in UARE among the DM, DA, and DP groups (P>0.05). Blood glucose level, HbA1c and ROS were significantly decreased in DA group in comparison with those in DM group (P<0.05). Glomerular hypetrophy, mesangial expansion, basal membrane thickening, tubular epithelial cells cavitation and exfoliation, and mononuclear lymphocyte infiltration occurred in DM group, while these changes were ameliorated in gAd transfection group. The renal expression levels of eNOS and p-AMPK proteins in DM group were significantly lower than those in the control group (P<0.05) and gAd transfection group (P<0.05).</p><p><b>CONCLUSIONS</b>The renoprotective effect of adiponectin may be at least partially mediated by the activation of the AMPK signaling passway, ROS production inhibition, relief of the oxidative stress, and up-regulation of eNOS expression in the renal tissue of diabetic rats.</p>

Metabolic syndrome and chronic kidney disease in a rural adult population of Hunan province, China / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the relationship between metabolic syndrome and chronic kidney disease (CKD) in a rural adult population of Hunan province.</p><p><b>METHODS</b>1953 residents (older than 18 years) from the same village were randomly selected, using a stratified, multistage sampling method. All residents were interviewed and tested for albuminuria with morning spot urine albumin to creatinine ratio (abnormal: >/= 30 mg/g), reduced renal function with estimated glomerular filtration rate by modified MDRD equation [abnormal: < 60 ml/min (1.73 m(2))]. The associations of kidney damage indicators with demographic characteristics (age, gender, smoking status), indicators on health (diabetes, hypertension) and metabolic syndrome traits were examined.</p><p><b>RESULTS</b>Eligible data of 1709 subjects were enrolled in the study. After the adjustment of age, gender and other metabolic syndrome traits, participants with metabolic syndrome had a higher prevalence of CKD (19.3% vs. 13.2%, P < 0.001) than those without the syndrome. As the number of metabolic syndrome traits increased, so did the prevalence of CKD. There seemed to be a strong and independent association between metabolic syndrome and chronic kidney disease. For participants without hypertension and diabetes, metabolic syndrome was also associated with CKD (OR value 1.733, 95%CI: 1.20 - 2.41, P = 0.004).</p><p><b>CONCLUSION</b>In these 1709 adults under this study from a village of southern China, metabolic syndrome seemed to be associated with CKD.</p>

Construction and activity evaluation of pSUPER RNAi system that inhibits Smad3 / 中南大学学报(医学版)

OBJECTIVE@#To construct the expressing vector of siRNA which can inhibit the Smad3 activity.@*METHODS@#Sixty-four bases of 2 pair oligos for hairp in RNA expression which targeted Smad3 gene were chemically synthesized and annealed. pSUPER vector was linearized with BgL II and Hin d III treated with alkaline phosphatase (CIP). Anneled oligos were inserted into the downstream of the treated pSUPER's pol III H1 promoter to construct RNAi plasmid (pSUPER Smad3). Oligos with a scrambled sequence were used as a negative control. pSUPER Smad3 was transfected into human renal tubular epithelial cells (HKC).@*RESULTS@#Recombinant pSUPER Smad3 vector was identified by the digestion with Eco R I and Hin d III, and confirmed by the sequencing analysis with T3 primer. Sixty-four bases had been inserted into the expected site. Furthermore, the insertion sequence was exactly corrected. The activity evaluation indicated that mRNA and protein of Smad3 but not Smad2 were inhibited by pSUPER Smad3 in HKC.@*CONCLUSION@#The pSUPER Smad3 system has been constructed successfully, and has high inhibition and specificity in vitro.

Effect of mannitol on vasoactive substances / 中南大学学报(医学版)

OBJECTIVE@#To observe the changes of vasoactive substances in rabbits administered with mannitol at different dosages and to investigate the mechanism of acute renal failure (ARF) induced by massive mannitol administration.@*METHODS@#Eighteen healthy male New Zealand rabbits were randomly divided into 3 groups: a minor mannitol group (n=6, mannitol 8 g/kg within 2 hours), a control group (n=6, saline of the same volume), and a massive mannitol group with free water taking (n=6, mannitol 40~60 g/kg within 3 days). The changes of renin, angiotensin-I (ang-I), angiotensin-II (ang-II), endothelin (ET), and atrial natriuretic factor(ANF) in the serum were observed.@*RESULTS@#No significant changes in the renin, ang-I, ang-II, ET, and ANF in the serum were found between the minor mannitol group and the saline control group (P> 0.05). In the massive mannitol group with free water taking, renin, ang-I, and ang-II in the serum increased significantly compared with the other 2 groups; ET in the serum decreased significantly compared with the saline control group (P 0.05).@*CONCLUSION@#ARF induced by massive mannitol administration is associated with a significant change of vasoactive substances.

Inhibitive effect of troglitazone on TGF-beta(1) and fibronectin expression in human peritoneal mesothelial cells / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of the peroxisome proliferator activated receptor-gamma (PPAR-gamma) agonist troglitazone on TGF-beta(1) and fibronectin (Fn) expression in human peritoneal mesothelial cells (HPMCs).@*METHODS@#HPMCs were cultured from human omentum by an enzyme digestion method, growing in medium containing 30 mmol/L D-glucose. TGF-beta(1) and Fn expression were measured in HPMCs in the presence and absence of 15 micromol/L troglitazone. The mRNA expressions of PPAR-gamma,TGF-beta(1) and Fn were determined by semi-quantification reverse transcriptive PCR (RT-PCR). The protein of TGF-beta(1) was determined by enzyme-linked immunosorbent assay (ELISA) and proteins of PPAR-gamma and Fn were determined by Western blot.@*RESULTS@#The mRNA and protein expression of TGF-beta(1) and Fn were significantly increased in HPMCs stimulated with 30 mmol/L D-glucose compared with the control group with F12 media (P<0.01). Obvious decrease of TGF-beta(1) was found in troglitazone(15 micromol/L) treated group compared with group stimulated with 30 mmol/L D-glucose (P<0.05). Exposure of HPMCs to troglitazone reduced the Fn secretion (P<0.05).@*CONCLUSION@#Troglitazone reduced the expression of TGF-beta(1) in HPMCs stimulated by 30mmol/L D-glucose, and reduced Fn production. PPAR-gamma agonists may have a specific role in ameliorating the course of progressive peritoneal fibrosis under long-term peritoneal dialysis states.

Protective effect of amlodipine on the cytotoxicity induced by contrast media in human kidney cells / 中南大学学报(医学版)

OBJECTIVE@#To explore the protective effect of amlodipine on the cytotoxicity induced by contrast media (meglumine diatrizoate) in human kidney cells (HKC).@*METHODS@#An HKC line was used. The experiment was divided into 4 groups: a model group (diatrizoate 111g/L), a prevention group (diatrizoate 111g/L+amlodipine 10(-5)mol/L), an amlodipine control group (amlodipine 10(-5)mol/L), and a culture medium control group (simple none blood serum DMEM-F12 medium). Cytotoxicity induced by meglumine diatrizoate was analysed by methyl thiazolyl tetrazolium (MTT) test, lactate dehydrogenase (LDH) assay, Hochest33258 fluorescence stained cytospins, and flow cytometric DNA analysis. The protein expression of Bax was determined by Western blot, and caspase-3 activity was examined by fluorometric method.@*RESULTS@#In the prevention group, the cell viability increased significantly (P<0.05), LDH levels decreased (P<0.05), and the apoptosis was lower than that of the model group (P<0.05) .Bax protein expression and caspase 3 activity decreased (P<0.05).@*CONCLUSION@#Amlodipine can inhibit the HKC apoptosis and protect the renal tubule cell from injury induced by meglumine diatrizoate.

Nephrotoxicity of high- and low-osmolar contrast media: Protective role of fosinopril or telmisartan in a rat model / 中南大学学报(医学版)

OBJECTIVE@#To compare the nephrotoxicity of high- and low-osmolar contrast media (HOCM and LOCM), and to determine the protective role of fosinopril or telmisartan and its possible mechanism.@*METHODS@#Forty eight healthy SD rats were randomly divided into 6 groups: a normal control group, a glycerol control group, a low-osmolar contrast media (LOCM) group, a high-osmolar contrast media (HOCM) group, a fosinopril group, and a telmisartan group. Glycerine for inducing kidney damage was given to all rats except the normal control group. Twenty-four hours after the injection of glycerine, the mixed fosinopril suspension (10mg/kg) or telmisartan (5mg/kg) was poured into the stomach in the preventive group. Serum creatinine (SCr) and plasma angiotensin II (AngII) levels were detected by an automatical biochemical analyzer and radioimmunoassay; caspase-3 activity and claudin-1 expression of the renal tissue were detected by fluorometric method and immunohistochemical method. The renal injury was assessed by hematoxylin and eosin (HE) staining and terminal deoxynucleotide mediated nick and labeling (TUNEL) staining, respectively.@*RESULTS@#In diatrizoate-injected rats, SCr and AngII levels were increased (P<0.05). Expression of claudin-1 protein and caspase-3 activity in the renal tissue was upregulated. The histologic changes and percentage of apoptotic cells were milder in the LOCM rats than those in the HOCM rats. In the group pretreated with fosinopril or telmisartan, no increase in the levels of SCr and AngII was discovered. The expression of claudin-1 protein and caspase-3 activity was significantly lower than that in the HOCM group. The renal injuries induced by diatrizoate were alleviated.@*CONCLUSION@#Both HOCM and LOCM could cause cellular apoptosis in the kidney.LOCM was less toxic to rat kidney than HOCM. Nephrotoxicity induced by HOCM might be related to caspase-3, claudin-1 and AngII. Fosinopril or telmisartan may protect the renal tissue from nephrotoxicity induced by diatrizoate.

Inhibition effect of small interfering RNA of connective tissue growth factor on the expression of vascular endothelial growth factor and connective tissue growth factor in cultured human peritoneal mesothelial cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The peritoneum response to peritoneal dialysis can lead to fibrosis. The transforming growth factor beta1 (TGF-beta1) plays a key role in regulating tissue repair and remodelling after injury. Connective tissue growth factor (CTGF), a downstream mediator of TGF-beta1 inducing fibrosis, has been implicated in peritoneal fibrosis. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis that can hasten peritoneal fibrosis. In this study, we investigated the effect of small interfering RNA (siRNA) of CTGF by pRETRO-SUPER (PRS) retrovirus vector on the expression of CTGF and VEGF in human peritoneal mesothelial cells.</p><p><b>METHODS</b>Retrovirus producing CTGF siRNA were constructed from the inverted oligonucleotides and transferred into packaging cell line PT67 with lipofectamine, and the virus supernatant was used to infect human peritoneal mesothelial cell (HPMC). The cells were divided into seven groups: low glucose DMEM, low glucose DMEM + TGF-beta1 5 ng/ml, low glucose DMEM + TGF-beta1 5 ng/ml + PRS-CTGF-siRNA(1-4) and low glucose DMEM + TGF-beta1 5 ng/ml + PRS. The expression of CTGF and VEGF were measured by semiquantitative RT-PCR and Western blot.</p><p><b>RESULTS</b>Low levels of CTGF and VEGF were detected in confluent HPMCs. Following stimulation with TGF-beta1, the levels of CTGF and VEGF were significantly upregulated (P < 0.01). Introduction of PRS-CTGF-siRNA(1-4) resulted in the significant reduction of CTGF mRNA and protein, and VEGF mRNA (P < 0.01), especially in groups PRS-CTGF-siRNA1 and PRS-CTGF-siRNA4. The introduction of PRS void vector did not have these effects (P > 0.05).</p><p><b>CONCLUSIONS</b>The expression of CTGF siRNA mediated by PRS retrovirus vector can effectively reduce the level of CTGF and VEGF induced by TGF-beta1 in cultured HPMCs. This study may provide potential therapeutic strategies to prevent the peritoneal fibrosis.</p>

Effects of tacrolimus and cyclosporine on albumin secretion in cultured human hepatocyte / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effects of inflammation cytokines, (FK506) and cyclosporine (CSA) on albumin secretion, and the effects of FK506 and CSA on the IL-6 induced suppression of albumin synthesis in cultured human hepatocytes.@*METHODS@#Human hepatoma cell lines (HepG2 cells) were separately cultured with IL-6, IL-2 and IL-10 (0 approximately 10 microg/L) and FK506, CSA (0 approximately 100 microg/L) for 48 h. In another experiment, HepG2 cells were stimulated with different doses of FK506 and CSA (0 approximately 10 microg/L) in the presence of IL-6 (5 microg/L) for 48 h. Albumin levels in the supernatant of all groups were measured by radioimmunoassay (RIA). The concentration of LDH secreted by cells stimulated with FK506 and CSA were detected with spectrophotometry.@*RESULTS@#For cultured HepG2 cells, IL-6 significantly decreased albumin levels in a dose-dependent manner (P 0.05). FK506 obviously decreased LDH levels in the supernatant (P 0.05).@*CONCLUSION@#IL-6 but not IL-2 and IL-10 suppressed the production of hepatic albumin in vitro. FK506 protected against the suppression of hepatic albumin synthesis caused by IL-6, suggesting its potential role in improving hypoalbuminaemia in immune glomerulonephritis.

Etiologic and relevant factor analysis of 1,622 ESRD patients with hemodialysis in Hunan province / 中南大学学报(医学版)

OBJECTIVE@#To analyze the etiology and the relevant factors such as age, sex, blood pressure, outcomes and causes of death in end stage renal disease (ESRD) with hemodialysis (HD) in some hospitals in Hunan province.@*METHODS@#The retrospective analysis included 1,622 ESRD with HD patients. Data on the etiology, demographic and epidemiologic aspects of these patients were examined, and life expectancy and mortality rate were calculated.@*RESULTS@#In 1,622 ESRD with HD patients, the average age at the start of HD was 46.91 +/- 15.41, and the male/female ratio was 1.45/1. As the leading cause, chronic glomerulonephritis accounted for 56.43%, followed by hypertensive nephropathy (12.58%), obstructive nephropathy (9.13%) and diabetic nephropathy (8.85%). In recent years, the constituent ratio of diabetic nephropathy rose. The number of ESRD maintenance HD (MHD) patients was 581. Among them, 43.7% remained MHD, 13.0% received renal transplantation, 19.9% were transferred to other hospitals for HD, 7.2% became peritoneal dialysis, 14.8% died, and 1.4% ceased treament for economic reasons. The longest MHD was 13 years. The 1st-year, 3rd-year and 5th-year survial rate of MHD patients was 93.53%, 68.92% and 62.51%, respectively. The leading cause of death was cardiovascular incidence. In this group of ESRD with (53.6%), and then cerebrovascular disorder (21.0%).@*CONCLUSION@#HD patients, the age of starting dialysis was 30 approximately 70. The first cause was chronic glomerulonephritis. As the age increased, the constituent ratio of diabetic nephropathy rose. In MHD patients, the 1st-year, 3rd-year and 5th-year survial rate of maintenance hemodialysis patients was 93.53%, 68.92% and 62.51%, respectively. The first cause of death was cardiovascular accidence, and then cerebrovascular disorder.

Effects of high glucose on the cell proliferation, damage and cytokine in human peritoneal mesothelial cells / 中南大学学报(医学版)

OBJECTIVE@#To determine the mechanism of peritoneal fibrosis of peritoneal mesothelial cells by high glucose.@*METHODS@#The third passage human peritoneal mesothelial cells (HPMCs) from primary culture were divided into a control group (F(12)) and high glucose groups (F(12)+4% glucose) in different times (24, 48 h). The cell proliferation was assayed by the method of MTT (methylthiazoletetrazolium). The cell damage was measured by LDH (lactate dehydrogenase). The protein expression of fibronectin (FN), transforming growth factor-beta1(TGF-beta(1)) and connective tissue growth factor (CTGF) were detected by ELISA. The mRNA expression of FN, TGF-beta(1) and PAI-1 were detected by RT-PCR.@*RESULTS@#High glucose suppressed the cell proliferation. The result of MTT showed that compared with the control group, the value of OD of high glucose groups at 24 or 48 h decreased significantly (P<0.01 or 0.01); The cell damage was enhanced in high glucose groups, at 24 or 48 h compared with the control group at the same time (all P<0.01). The protein expressions of TGF-beta(1), CTGF and FN in supernate fluid of cell culture were significantly enhanced when high glucose stimulated the HPMCs in the high glucose groups at 24 or 48 h compared with the control group at the same time (P<0.05 or 0.001). The expressions of FN, TGF-beta(1) and PAI-1 mRNA were upregulated in 24 h high glucose group compared with that of 24 h control group.@*CONCLUSION@#High glucose can suppress the HPMC proliferation and damage HPMCs. Increase of TGF-beta(1), CTGF, FN and PAI-1 of HPMCs stimulated by high glucose can promote the synthesis and decreased degradation of extracellular matrix, which might be related with the mechanism of peritoneal fibrosis of peritoneal mesothelial cells by high glucose.

Effect of indomethacin on fibronectin and plasminogen activator inhibitor-1 in cultured human peritoneal mesothelial cells / 中南大学学报(医学版)

OBJECTIVE@#To determine the effect of indomethacin on high concentration glucose and lipopolysaccharide (LPS) induced fibronectin (FN) and plasminogen activator inhibitor-1 (PAI-1) secretion in cultured human peritoneal mesothelial cells.@*METHODS@#Mesothelial cells were isolated from human omental specimens by trypsin disaggregation and incubated by 2.5% glucose or LPS together with different concentrations of indomethacin. Enzyme-linked immunosorbent assay determined the quantity of FN and PAI-1 in the cultured supernatants.@*RESULTS@#Compared with the control group, the levels of FN and PAI-1 in the cultured supernatants were increased significantly exposuring to high concentration glucose and LPS (P <0.01). The different concentrations of indomethacin decreased FN and PAI-1 secretion in the 2.5% glucose or the LPS group within 24 h (P < 0.05).@*CONCLUSION@#Indomethacin can inhibit the synthesis and secretion of extracellular matrix in human peritoneal mesothelial cells, which may be effective in the gene therapy for peritoneal fibrosis.

Comparision of several different peritoneal fibrosis rat models / 中南大学学报(医学版)

OBJECTIVE@#To compare different types of peritoneal fibrosis models in rats.@*METHODS@#Thirty-four SD rats were divided into 5 groups: control group (Group 1), normal saline group (Group 2), high glucose group (4.25% peritoneal dialysate, 4.25% PDF, Group 3), high glucose + lipopolysaceharides (LPS) group (4.25% PDF + LPS, Group 4), high glucose + erythromycin group (4.25% PDF + lactobionate erythromycin, Group 5). A 2-hour peritoneal equilibration test (PET) was performed after 5 weeks. Then animals were humanely killed. Dialysate-to-plasma urea ratio (D/ Purea), glucose reabsorption (D2/D0), net ultrafiltration (UF) volume were determined. The level of fibronectin in peritoneal tissues was measured by immunohistochemical method. Peritoneal membrane histology was evaluated by light microscopy.@*RESULTS@#The D2/D0 ratio and net ultrafiltration volume in Groups 3, 4, and 5 were significantly lower than those in Groups 1 and 2 (P < 0.05) . The D/Purea ratio in Groups 3, 4 and 5 were significantly higher than that in Groups 1 and 2 (P < 0. 05 ). The level of fibronectin in Groups 3, 4 and 5 were significantly higher than that in Groups 1 and 2 (P < 0.05 ).@*CONCLUSION@#Different types of peritoneal fibrosis models in rats has been established. The best model is high clusion glucose + erythromycin.

Assessment of urinary endothelin-1 and nitric oxide levels and their relationship with clinical and pathologic types in primary glomerulonephritis

To determine the relationship between the urinary endothelin (ET-1), nitric oxide (NO) levels and the clinical, pathologic types of primary glomerulonephritis (GN) patients, urinary levels of ET-1 and NO were detected in 27 patients with biopsy-proven primary GN and 12 normal controls by radioimmunoassay and by copper-plated and cadmium column reduction assay, respectively. The results showed that urinary ET-1 levels in the patients with primary GN were significantly higher than in normal controls (p < 0.01), while the urinary ET-1 levels in patients with moderate mesangial proliferation GN were significantly higher than those in patients with mild mesangial proliferation GN (p < 0.05). Urinary ET-1 levels in patients whose clinical feature was nephrotic syndrome were found to be higher than in patients whose clinical feature was nephritic syndrome. However, urinary NO levels were to the contrary (p < 0.05). The ratio of ET-1/NO in primary GN patients was significantly higher than that in normal controls, and it positively correlated with the 24-hour urinary excretion of protein. These results suggest that urinary ET-1 levels are related to the proliferation of mesangial cells. The imbalance between ET-1 and NO may be related to the pathogenesis of primary GN and the occurrence of proteinuria.