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Rapid-growth Marchantia paleacea calluses were induced on MSK2 medium through surface sterilisation of the capsula. Ten known compounds including two steroids (1-2), six bibenzyls (3, 5-9), a flavonoid (10), and a terpenoid (4) were isolated from these calluses. The allelopathic effect of the six bibenzyls was assessed in Arabidopsis thaliana. Results revealed that bibenzyls could inhibit seedling growth in a dose-dependent manner.

The activities of glomerular intrinsic antioxidant enzymes (AOEs) were measured in a diabetic spontaneously hypertensive rat (SHR) model. The effects of antihypertensive drugs, i.e. captopril or triple therapy (hydralazine, reserpine, and hydrochlorothiazide), on glomerular intrinsic AOE activities in this model were evaluated. The effects of blood glucose control on the AOE activities were also determined. The aim of the present study was to determine whether activities of glomerular intrinsic AOEs might correlate with disease activity in diabetic SHR. This study showed a decrease of glomerular intrinsic AOE, i.e. Cu/Zn-SOD and Mn-SOD (SOD = superoxide dismutase), glutathione peroxidase, and catalase, activities in diabetic SHR. Glomerular Cu/Zn-SOD or Mn-SOD, glutathione peroxidase, and catalase activities in nondiabetic SHR were slightly lower than those in nondiabetic WKY rats. These activities in diabetic SHR were significantly improved after captopril or triple therapy or blood glucose control. The levels of urinary albumin excretion, creatinine clearance, and glomerular tuft areas in diabetic SHR were also improved after the therapy. It appears that hypertension and hyperglycemia may influence the glomerular intrinsic AOE activities, albuminuria, creatinine clearance, and glomerular tuft areas in diabetic SHR. Thus, it is indicated that control of blood pressure or blood glucose is a very important factor for preventing renal injuries in the diabetic SHR model.

Effects of benidipine hydrochloride or triple therapy (hydralazine, reserpine, and hydrochlorothiazide) on renal cortical and medullary intrinsic antioxidant enzyme (AOE) activity were evaluated in stroke‐prone spontaneously hypertensive rats (SHR‐SP) as an animal model for human essential hypertension with cerebral stroke. This study showed a significant decrease of renal intrinsic glutathione peroxidase (GSH‐Px) activity in untreated SHR‐SP. Renal GSH‐Px activity in untreated SHR‐SP was significantly lower than that in Wister Kyoto rats (WKY) as a normotensive reference strain. GSH‐Px activity in SHR‐SP was significantly improved after benidipine hydrochloride therapy. Levels of urinary albumin excretion or creatinine clearance (Ccr) in SHR‐SP were also improved after the therapy. Glomerular sclerosis index was slightly improved in SHR‐SP treated with benidipine hydrochloride according to light microscopic analysis. It appears that hypertension may influence the renal intrinsic GSH‐Px activity, albuminuria, and Ccr in SHR‐SP. Thus it is indicated that control of blood pressure may improve the GSH‐Px activity in SHR‐SP. J. Clin. Lab. Anal. 11:158–162, 1997. © 1997 Wiley‐Liss, Inc.

Data on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.The survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP140/90 mmHg and130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.The analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to140/90 mmHg and130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P0.001). When the threshold of BP130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P0.05). Using the threshold of140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P0.05).The prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

A study of albuminuria, creatinine clearance (CCr) and blood pressure of streptozotocin (STZ)-induced diabetic rats with or without treatment by a prostacyclin (PGI2) analog, beraprost sodium (BPS), is described. Glomerular prostanoid synthesis was measured by gas chromatography (GC) mass spectrometry. Renal specimens stained with hematoxylin and eosin and periodic acid-Schiff were examined by light microscopy. Mean values of albuminuria in BPS-treated diabetic rats were significantly decreased compared with those in nontreated diabetic rats. The ratio of kidney to body weight in the BPS-treated diabetic rats was significantly lower than that in the nontreated diabetic rats. Levels of CCr and blood pressure were decreased in diabetic rats after the treatment with BPS. GC mass spectrometry showed that BPS did not influence the glomerular synthesis of PGI2 and TXB2. No histologic injury in the renal tissues was observed in the diabetic rats with or without BPS treatment. We concluded that BPS (PGI2 analog) might decrease the levels of urinary albumin excretion and CCr due to its vasodilating effects in the early phase of STZ-induced diabetes in rats.

Phenylalanyl-tRNA synthetase (PheRS), a member of aminoacyl-tRNA synthetase family, was the new target of anti-tubercular drug discovery. In an attempt to fully exploit the new potential anti-tuberculosis drugs presented in micro-organisms, we developed a high-throughput screening assay against Mycobacterium tuberculosis (Mtb) PheRS and then screened a library consisting of 32,000 strains and 1500 natural product-derived compounds. One potent hit extract of Penicillium griseofulvum CPCC-400528 was identified. In this study, isopatulin (1), (+)-epiepoformin (2) and gentisyl alcohol (3), three patulin-producing intermediates, together with three indole-tetramic acids, α-cyclopiazonic acid (4), β-cyclopiazonic acid (5) and iso-α-cyclopiazonic acid (6), were isolated and identified as bioactive constituents from P. griseofulvum CPCC-400528. Their structures were elucidated on the basis of spectroscopic data. Compounds 1, 3, 4, and 5 exhibited Mtb PheRS-inhibiting activities, as well as moderate to weak anti-tuberculosis activities against Mtb H37Rv.

A new photoinduced interconversion of four naturally occurring 19-nor-7,8-secolabdane diterpenoids was discovered and analyzed. The photochemical mechanism, intramolecular diradical rearrangement reaction, was investigated by time-lapse monitoring of the end product formations with HPLC and UV, as well as detailed theoretical calculations.

In the present study, the effect of a novel derivative of riccardin D (RD-N) against cancer cell lines was investigated in vitro and in vivo. We found that RD-N accumulated in the lysosomes associated with lysosomal swelling. As a result, the destabilized lysosomes induced cathepsins to release from the lysosomes into the cytosol and induced cell death which displayed features characteristic to both apoptosis and necrosis. In vivo tumor xenograft model indicated treatment of RD-N significantly reduced size and weight of the tumor compared with vehicles. These findings suggest RD-N could be a promising candidate for treatment of cancer.

Pallambins A (1) and B (2), two novel 19-nor-7,8-secolabdane diterpenoids with unprecedented tetracyclo[4.4.0(3,5).0(2,8)]decane skeletons, along with a pair of structurally related isomers, pallambins C (3) and D (4), were isolated from the Chinese liverwort Pallavicinia ambigua. Their structures with absolute configurations were determined by means of NMR, X-ray diffraction, and CD analyses. Their preliminary cytotoxicity to human cancer cells was also tested.

Isoriccardin C (1) and riccardin D (2), isolated from the liverwort Reboulia hemisphaerica, were first characterized to be a mixture of two enantiomeric atropisomers by online chiral high-performance liquid chromatography-circular dichroism (HPLC-CD) analysis. Exemplarily for bisbibenzyls of the diarylether-biphenyl type, the absolute atropisomeric configurations of compunds 1 and 2 were determined by the analysis of their CD data coupled with quantum chemical CD calculations.

Scaparvin A (I) is isolated together with the analogues scaparvin B (IIa), C (IIb), D (IIc) and E (III).

A novel caged cis-clerodane diterpenoid, scaparvin A, possessing an unprecedented C-6/C-11 bond and a ketal ring, as well as four new cis-clerodane derivatives, scaparvins B−E, were isolated from the Chinese liverwort Scapania parva. Their absolute structures were elucidated by analysis of NMR and CD data coupled with electronic circular dichroism (ECD) calculations. It was proposed that an enzymatic intramolecular aldol reaction was the key step in the biogenetic pathway of scaparvin A.

Systemic lupus erythematosus (SLE) associated with autoimmune thyroid disease (AITD) is a complex and well recognized autoimmune disorder. Careful monitoring/surveillance of thyroid gland functioning and active treatment of SLE patients with coexisting AITD, typically using medications, are critically important. The role of apheresis in this setting remains to be fully explored. Here we examine the use of double-filtration plasmapheresis (DFPP), as an adjuvant therapy in the treatment of patients with SLE complicated with AITD and report our experiences using this apheresis methodology.We performed a retrospective chart review of 11 patients with SLE complicated with AITD who had received DFPP in our blood purification center between 2004 and 2008. Levels of thyroid hormones, antithyroid autoantibodies, SLE disease activity, proteinuria, glomerular filtration rate (GFR), and response to therapy were analyzed.AITD, SLE, and lupus nephritis improved after DFPP. Except for one patient who died of severe pneumonia in the second month after completion of DFPP, all surviving patients continued to show clinical improvements or remained stable during the follow-up periods.DFPP can effectively remove autoantibodies and may have an important adjuvant role in therapeutic options in the treatment of SLE patients with AITD complications.

Adult onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology and pathogenesis. The disease is characterized by typical spiking fever with evanescent rash, sore throat, polyarthralgias or polyarthritis, and involvement of various organs. Most of the reported cases with liver involvement occurred during the period of treatment with hepatotoxic drugs, whereas AOSD associated autoimmune hepatitis (AIH) is extremely rare. AIH may be an indicator of the poor prognosis of AOSD. Herein we describe a case of successful treatment with plasma exchange for AOSD-associated AIH.

Levels of glomerular nonenzymatic glycosylation and lipid peroxide in streptozotocin (STZ)-induced diabetic rats were examined. Isolation of glomeruli was performed using a sieving technique. The levels of nonenzymatic glycosylation in the glomeruli of these rats were measured by the thiobarbituric acid (TBA) method. Measurement of lipid peroxide, i.e., malondialdehyde (MDA), levels in the renal cortex, medulla and isolated glomeruli was performed by the TBA test. Light-microscopic and immunofluorescent examinations were also performed. An increase in nonenzymatic glycosylation in the glomeruli was observed in the early phase, i.e., after 4 and 12 weeks, in STZ-induced diabetic rats. The levels of MDA in the renal cortex of 12-week-old STZ-induced diabetic rats were also significantly increased compared with those of control rats at the same age. Levels of MDA in the glomeruli of 12-week-old STZ-induced diabetic rats were slightly increased compared with those of control rats, but there was no statistical significance. In immunofluorescence, IgG or IgM was deposited in the glomerular mesangial areas and capillary walls in 12-week-old diabetic rats. However, there was no significant change in renal tissues after 4 and 12 weeks in STZ-induced diabetic rats. It was concluded that glomerular nonenzymatic glycosylation and lipid peroxide were already increased in the early phase of STZ-induced diabetic rats prior to the appearance of marked histologic alterations.

To investigate the potentiality of mesenchymal stem cells (MSCs) to differentiate into vascular endothelia cells (ECs) in peritubular capillary (PTC) in chronic aristolochic acid nephropathy (CAAN).MSCs were isolated from a male Wistar rat. The surface markers were identified with flow cytometry. Thirty female Wistar rats were randomly divided into 3 equal groups: Group A, perfused intragastrically with decoction of Caulis Aristolochiae manshuriensis for 12 weeks to establish CAAN models, Group B, perfused intragastrically with decoction of Caulis Aristolochiae manshuriensis for 12 weeks to establish CAAN models and injected with the MSCs by caudal vein in the 12th week, and Group C, perfused intragastrically with drinking water for 12 weeks and then injected with normal saline by caudal vein to be used as normal controls. At week 16, specimens of blood and urine were collected to detect the blood urea nitrogen (BUN), serum creatinine (Scr) and urine protein, and then the rats were killed with their kidneys taken out. Sex-determining region of the Y chromosome-fluorescence in situ hybridization (SRY-FISH) test with carboxyfluorescein (FAM)- was used to detect the cells originated from the source of the male donors. Immunohistochemistry was used to detect CD34, marker antigen pf EC. HE and Masson staining and electron microscope were used to observe the pathology of the kidney. Immunohistochemistry and RT-PCR were used to detect the expression of vascular endothelial growth factor (VEGF). Correlation analysis was conducted to study the relationships among these indices.Y chromosome and CD34 double positive cells could be seen in the renal tissue of Group B. At week 16, the density of PTC and integrated optical density of VEGF of Group A were (5.3 +/- 0.8)/0.13 mm2 and (2.8 +/- 0.4) x 10(3) respectively, both significantly lower than those of Group B [(26.5 +/- 1.6)/0.13 mm2 and (14.7 +/- 1.7) x 10(3) respectively, both P0.011]. The Scr and urine protein of Group A were significantly higher than those of Group B. The expression of VEGF mRNA of Group A was significantly lower than that of Group B.MSCs can differentiate into ECs. MSCs transplantation has beneficial effects on CAAN, which is possibly related with the reduction of PTC.

To investigate the influence of atorvastatin (ATOR) on the expression of monocyte chemoattractant protein-1 (MCP-1) induced by high concentration glucose in peritoneal mesothelial cells (PMCs) and the possible mechanism thereof.Rt PMCs were isolated, cultured, passaged, and divided into 3 groups: (1) treated with glucose of the concentrations of 0.1, 1.5, 2.5, 4.25% respectively, (2) treated with 1.5% glucose for 0, 0.5, 1, 3, 12, 24, and 48 h respectively, (3) pretreated with ammonium pyrrolidinedithiocarbomate (PDTC) of the concentrations of 5, 10, 25, or 50 micromol/L for 2 h, and then treated with 1.5% glucose for 3 h; and (4) pretreated with ATOR of the concentrations of 0.1, 1, or 10 mmol/L for 24 h, and then treated with 1.5% glucose for 3 h. Western blotting was used to measure the expression of MCP-1, p65, and inhibitor of nuclear factor-kappaBalpha (IkappaBalpha). RT-PCR was used to measure the expression of MCP-1 mRNA.PMCs expressed MCP-1 in the normal condition. Glucose dose- and time-dependently reduced the protein expression of IkappaBalpha in the PMCs and increased the p65 expression in the nucleus, and accelerated the PMCs to express MCP-1 mRNA and protein (P0.05 and P0.01). PDTC dose-dependently inhibited the acceleration of expression of MCP-1 mRNA and protein in the PMCs induced by high concentration glucose (P0.05 or P0.01). ATOR dose-dependently increased the IkappaBalpha expression, decreased the p65 expression in nucleus, and decreased the expression of MCP-1 mRNA and protein (P0.05 or P0.01).High concentration glucose induces PMCs to express MCP-1 in a time- and dose-dependent manner. Nuclear factor- kappaB (NF-kappaB) takes part in this regulation. ATOR inhibits PMCs to express MCP-1 through inhibiting NF-kappaB pathway.

Based on all phase theory, this paper designed three kinds of true 2-D all phase filter bank (true 2-D APFB), which can be used to decompose and recompose image data in true 2-D directly. If quantification error of filters is ignored, the true 2-D APFBs have perfect reconstruction property. To reduce computation, they are implemented in lifting scheme. Simulation has shown that true 2-D APFBs have nicer data compression property. With the same compression rate, PSNR of IDCT AFB7.7 is less 0.7 dB at most than Daubechies9/7 wavelet's, for true 2-D APFBs adopt quadtree SPIHT coding method which is suitable for separable 2-D wavelet transform. For true 2-D filter banks, binary tree SPIHT coding should be adopted to get better performance in compression.

To investigate whether lipopolysaccharide (LPS) influence peritoneal mesothelial cells (PMCs) on their apoptosis, growth and expression of tumor necrosis factor (TNF) through IkappaBalpha, nuclear factor p65 pathway.PMCs were isolated, cultured and passaged by enzymatic disaggregation, then identified by phase contrast inverted microscope, transmission electron microscope and scanning electron microscope, with immunocytochemistry method. The PMCs were treated under conditions, which included different concentration LPS (normal control group, 0.1 mg/L, 1.0 mg/L, 10 mg/L, 50 mg/L, 100 mg/L) and different time (0, 1, 3, 6, 12, 24 hours). Hoechst 33258 fluorescence dye method was used to detect the apoptosis of PMC. The inhibitory effect of LPS on cell growth was measured with MTT method. Immunofluorescence dye was used to observe the activity of p65. Western blot method was used to detect the expression of IkappaBalpha. L929 cell line was used to detect the activity of TNF. RT-PCR was used to measure the expression of TNFalpha mRNA.LPS could inhibit growth of PMC and induce apoptosis. LPS could lead IkappaBalpha to degration and p65 into nucleus. LPS could also induce the expression of TNF. The expression of TNF-alpha mRNA reached the peak at the 1st hour and highest TNF activity at the 3rd hour.LPS inhibit the growth of PMC and induced the apoptosis. LPS induced PMC to express TNF-alpha in a dose-dependent manner. In the early state, PMC expressed a great deal of TNF-alpha, then began to fall quickly. During the period that LPS influence PMC on apoptosis, growth and expression of TNF, IkappaBalpha-NF-kappaB p65 pathway played the important role.

To investigate the effect of d-alpha-tocopherol on the expression of hexokinase (HK) induced by high glucose in cultured human peritoneal mesothelium cell (HPMC).Specimens of human omentum were obtained from consenting patient undergoing elective abdominal surgery. HPMC were isolated and subcultured by enzymatic disaggregation. Morphology and immunocytochemical method were used for identification. HPMC were divided into normal glucose group (0.1% glucose, equal to 5.5 mmol/L), high glucose group (0.5%, 1.0%, 1.5%, 2.5%, 4.25% glucose) and d-alpha-tocopherol group. After 24 h, standard G6PDH-coupled assay, temperature sensitive essay were used to detect the activity of total HK and its isozyme. Immunocytochemical staining was used for observation the intracellular location of HKII. Western blotting was used to analyze the protein expression of HKII and RT-PCR was used to detect the mRNA expression of HKII. The net glucose utilization was assayed by glucose disappearance from medium by hexokinase method.Primary cultured HPMC reacted positively for cytokeratin and vimentin and had numerous surface microvilli under electron microscope. High glucose induced HK activity in a dose-dependent manner and increased HKII isoform selectively. At concentration of 1.5%, 2.5% and 4.25% glucose for 24 h, the relative activity of total HK were 115.4%, 129.1% and 155.2%, respectively comparing with normal control (P0.05), and selectively increased HKII isoform expression. D-alpha-tocopherol blocked the activity of total HK and HKII induced by glucose. The relative activity of total HK inhibited by d-alpha-tocopherol was 82.1% (P = 0.001). After incubated with d-alpha-tocopherol, the net glucose utilization were decreased from (25.3 +/- 3.9) mmol/L to (17.3 +/- 2.1) mmol/L (P = 0.018). HKII stained light brown in cytoplasm of HPMC in normal group, accompanying with the increased concentration of glucose, the staining of HKII became strong and accumulated to nuclear. D-alpha-tocopherol made it thinning. The protein and mRNA expression of HKII were accorded with its activity.D-alpha-tocopherol inhibited the expression of HKII in activity, protein and mRNA induced by high glucose and decreased the net glucose utilization, which might become a method to improve ultrafiltration in peritoneal dialysis.

Water containing Oscillatoria agardii was cultured under controlled conditions and harvested in the late log growth phase. The objective was to determine: the contribution of algae cells and algae extracellular organic matter (EOM) to the disinfection by-products formation potential (DBPFP), and the effects of preozonation including ozone dosage and preozonation time on DBPFP of algae cells and EOM and mechanism of these effects. The results show that the main trihalomethanes from both Oscillatoria cells and EOM are chloroform and bromodichloromethane, and that the main haloacetic acids are dichloroacetic acid and trichloroacetic acid. HAAFP from algae cells and EOM themselves or after preozonation followed by coagulation is more than THMFP, which shows that more attention should be paid to the control of HAA in the treatment of algae containing water. DBPFP of EOM is reduced by preozonation, and DBPFP clearly decreases with time. Compared with traditional coagulation, the dosage of 0.975 mg/L preozonation with reaction time of 10 minntes followed by coagulation can decrease DBPFP of EOM by 31% and decrease HAAFP by 52.6%, but increase THMFP by 12.5% under this experiment's condition. This result shows the major reason preozonation can control the DBPFP of EOM is that it can control HAAFP effectively. At the same time, the DBPFP of algae cells is significantly increased by preozonation, and this increase is almost a linear function of preozonation time. It can be concluded that in the real water treatment case most of algae cells should be removed intact before preozonation to control the DBPFP.

To investigate the manifestation of impairment of peritubular capillary (PTC) in chronic aristolochic acid nephropathy (CAAN) and the influence of hypoxia caused by PTC impairment on the progression of CAAN.Fifty-four Wistar rats were randomly divided into 2 groups: Group A (n = 30, perfused intragastrically with decoction of Caulis aristolochia manchuriensis for 8 weeks) and Group B (n = 24, perfused intragastrically with drinking water for 8 weeks). At weeks 8, 12, and 16 ten rats in Group A and 8 rats in Group B were killed. Specimens of blood and urine were collected before the killing of the rats to detect the blood urea nitrogen (BUN), serum creatinine (Scr), and urine protein. HE and Masson staining and microscopy were used to observe the pathology of the kidney. Immunohistochemistry and Western blotting were used to detect the expression of hypoxia-inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), and CD34. Correlation analysis was conducted to study the relationships among these indices.Since week 8 BUN, Scr, and urine protein of Group A began to increase in comparison with Group B (all P0.05). Pathological changes of the kidney began to appear in Group A since week 8 with the decrease of PTC density. HIF-1alpha was not expressed in Group B, and in Group A HIF-1alpha expression began to increase since week 8 and became significantly higher than that of Group B since week 12. At week 16, the PTC density and VEGF-IOD of Group A were 8.10 +/- 2.28/0.13 mm(2) and (2.78 +/- 0.78) x 10(3) respectively, both significantly lower than those of Group B [(42.80 +/- 4.49)/0.13 mm(2) and (26.49 +/- 9.34) x 10(3) respectively, both P0.01], and the HIF-1alpha-IOD of Group A was (7.11 +/- 1.20) x 10(3), significantly higher than that of Group B [(0.44 +/- 0.10) x 10(3), P0.01]. CD34 was highly expressed in Group B, and the CD34 expression of Group A began to decrease since week 16. HIF-1alpha expression was positively correlated with Scr (r = -0.945, P0/01), and PTC density and VEGF expression were negatively correlated with Scr (r = -0.907, P0.01 and r = -0.690, P0.01). PTC density was negatively correlated with HIF-1alpha expression (r = -0.880, P0.01).Severe hypoxia exists following PTC injury in CAAN. Hypoxia is correlated with the progression of CAAN.

To investigate the effects of prostaglandin E1 (PGE1) on the progression of aristolochic acid nephropathy (AAN).Twenty-four patients diagnosed as AAN with serum creatinine (Scr) between 1.5 mg/dL and 4 mg/dL during September 2001 to August 2003 were randomly divided into 2 groups. All patients had ingested long dan xie gan wan containing aristolochic acid (0.219 mg/g) for at least 3 months. Twelve patients were injected with Alprostadil (10 microg/d for 10 days in one month, summing up to 6 months). Except for PGE1, the other therapy was same in both groups. Renal function was assessed using reciprocal serum creatinine levels (1/Scr).The level of Scr an d serum hemoglobin (Hgb) was similar in both groups prior to therapy. During follow-up, 1/Scr levels in PGE1 group were significantly higher than control group (P0.01), and Hgb levels in PGE1 group were significantly increased compared with control (P0.05).PGE1 can slow the progression of renal failure and increase Hgb level of AAN patient.

Background. Angiotensin-II induces nitro-oxidative stress in patients with diabetic nephropathy. Peroxynitrite and reactive oxide species can accelerate formation of advanced glycation end-products (AGEs). We investigated the effects of candesartan, an angiotensinII type 1 receptor blocker (ARB), on the formation of AGEs and nitro-oxidative stress in type 2 diabetic KK/Ta mouse kidneys. Methods. KK/Ta mice were divided into three treatment groups: an early treatment group receiving 4 mg/kg/day candesartan from 6 to 28 weeks of age, a late treatment group receiving the same candesartan dose from 12 to 28 weeks of age and a group receiving the vehicle for candesartan. BALB/c mice treated with vehicle were used as controls. We evaluated at 28 weeks the renal expressions of carboxymethyllysine, the receptor for AGE (RAGE), the p47phox component of NADPH oxidase, endothelial nitric oxide synthase (eNOS), induced nitric oxide synthase (iNOS) and 8-OHdG and nitrotyrosine by immunohistochemistry and/or by competitive RT–PCR. Results. Kidneys from KK/Ta mice showed increased formation of AGEs, nitro-oxidative stress and RAGE expression and these were attenuated by candesartan treatment. Protein and mRNA expressions of p47phox and iNOS were upregulated in KK/Ta kidneys, which also showed increased immunostaining intensities of 8-OHdG and nitrotyrosine. Treatment with candesartan attenuated all of these changes and prevented significant albuminuria. There were no significant differences in the expression of eNOS among the four groups. Conclusions. These findings suggest that candesartan, an ARB, reduces AGE accumulation and subsequent albuminuria by down-regulating the NADPH oxidase p47phox component and iNOS expression and by attenuating RAGE expression in type 2 diabetic KK/Ta mouse kidneys.

To investigate the changes of renal type IV collagen turnover in diabetic nephropathy, urinary type IV collagen was measured by a highly sensitive one‐step sandwich enzyme immunoassay (EIA). Urinary samples were obtained from 698 diabetic patients and 191 healthy adults. Among the patients, 264 had urinary albumin levels of less than 29 mg/g·creatine (Cr) (Stage I: normoalbuminuric stage), 169 had microalbuminuria from 30 to 299 mg/g·Cr (Stage II: microalbuminuric stage), 84 patients had macroalbuminuria of more than 300 mg/g·Cr and serum Cr of less than 1.1 mg/dl (Stage IIIA: macroalbuminuric stage without renal dysfunction), 97 had macroalbuminuria of more than 300 mg/g·Cr and serum Cr of more than 1.2 mg/dl (Stage IIIB: macroalbuminuric stage with renal dysfunction), and 84 had renal failure (Stage IV). The levels of urinary type IV collagen in Stages II, IIIA, IIIB, and IV were significantly higher than those in Stage I (P < 0.0001). The level of urinary type IV collagen in Stage I (5.00 ± 0.23 μg/g·Cr; mean ± SE) was also higher than that in normal adults (3.44 ± 0.11 μg/g·Cr; mean ± SE). These levels increased gradually due to progression of the clinical stage of diabetic nephropathy. It appears that the levels of urinary type IV collagen can be a useful marker for detecting renal injuries in diabetes according to our Asian multicenter trials. J. Clin. Lab. Anal. 15:188–192, 2001. © 2001 Wiley‐Liss, Inc.

The aim of this study was to determine if treatment with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor antagonists (AIIRA) might decrease urinary albumin excretion and prevent glomerular enlargement and glomerulosclerosis in subtotal (5/6) nephrectomized rats. Morphometric image analysis of glomeruli was also performed in the subtotal nephrectomized rats. The nephrectomized rats were treated with ACEI (enalapril 100mg/l), AIIRA (L-158,809 10 mg/l) or TRX (reserpine 5 mg/l, hydralazine 80 mg/l, and hydrochlorothiazide 25 mg/l) and euthanized at 16 weeks after renal ablation. Treatments were started at 2 weeks (early treatment: Group I) or 8 weeks (later treatment: Group II) after the ablation. ACEI and AIIRA treatments were equally and significantly effective in limiting albuminuria and progression of glomerular sclerosis. TRX was also as effective in decreasing urinary albumin excretion and preserving the renal function as ACEI or AIIRA in Group I. The improvement of albuminuria, glomerular enlargement and sclerosis after these treatments in Group II was significantly less than that in Group I. It appears that the early treatment with angiotensin converting enzyme inhibitor, angiotensin II receptor antagonist or reserpine, hydralazine and hydrochlorothiazide (TRX) may prevent glomerular injury in human patients with renal hypertension. J. Clin. Lab. Anal. 11:53–62. © 1997 Wiley-Liss, Inc.

The reactive oxygen species has been proposed as a key mediator of the progression of renal injury associated with essential hypertension. Among the defense systems operating against the reactive oxygen species, superoxide dismutase, glutathione peroxidase, and catalase are the most important antioxidant enzymes (AOEs). In the present study, systolic blood pressure, renal function (creatinine clearance, urinary albumin, and N-acetyl-beta D-glucosaminidase excretion), renal intrinsic AOE activities, and renal histopathology were determined in stroke-prone spontaneously hypertensive rats and Wistar Kyoto rats. The effects of a 20-week treatment using three antihypertensive drug regimens--captopril, a sulfhydryl-containing angiotensin-converting enzyme inhibitor; temocapril, a potent, non-sulfhydryl-containing angiotensin-converting enzyme inhibitor prodrug; and a conventional triple drug combination that includes a vasodilator (hydralazine, hydrochlorothiazide and reserpine)--on renal function, renal tissue, AOE activities, and renal histopathologic abnormalities were evaluated in stroke-prone spontaneously hypertensive rats. Renal function and AOE activities were lower in the stroke-prone spontaneously hypertensive rats than in the Wistar Kyoto rats. Normalization of systolic blood pressure using the antihypertensive drugs improved renal function and produced a nonuniform alteration in renal AOEs; only glutathione peroxidase activity increased significantly with the use of all three drug regimens. The mild renal histopathologic abnormality in stroke-prone spontaneously hypertensive rats was not altered by drug treatment. The improvement in renal function may be related to an increase in glutathione peroxidase activity, but no correlation was seen between renal function changes and alteration in activities of superoxide dismutase or catalase.

The purpose of this study was to determine the antioxidant enzyme activities in renal tissues of early stage ddY mice, an animal model for primary IgA nephropathy. Eight- and 40-week-old ddY female mice and normal healthy Balb/c female mice were used in this study. The levels of Cu/Zn-SOD, Mn-SOD, and GSH-PX activities in the renal cortex were significantly higher in 40-week-old ddY mice than in Balb/c control mice of the same age; no change of catalase activity was observed. There were no significant differences in the levels of Cu/Zn-SOD, Mn-SOD, GSH-PX, and catalase activities between the ddY mice and Balb/c mice at 8 weeks of age. Urinary protein was slightly higher in 40-week-old ddY mice. IgA or C3 was deposited at low levels in the glomerular mesangial areas of 8-week-old ddY mice. Marked depositions of IgA and C3 extended from the glomerular mesangial areas to the capillary walls of 40-week-old ddY mice. Expansion of glomerular mesangial matrices and mild mesangial cell proliferation was observed in 40-week-old ddY mice. Antioxidant enzyme activities in the renal cortex were already increased in the early stage IgA nephropathy in 40-week-old ddY mice. These findings suggest that measurements of antioxidant enzyme activities in the renal cortex of 40-week-old ddY mice was useful for evaluation of the pathogenesis of renal involvement in the early stage of IgA nephropathy.

Two undescribed dimeric ArC2 derivatives, cis- and trans-1,2-bis(3,4-dimethoxyphenyl)cyclobutane (1 and 2), one new monoterpenes esters, 2α,5β-dihydroxybornane-2- cis-cinnamate (3), along with eight known compounds, 2α,5β-dihydroxybornane-2- trans-cinnamate (4), perrottetin E (5), isoriccardin C (6), marchantin A (7), marchantin E (8), marchantin C (9), and isomarchantin C (10) were isolated from the liverwort Conocephalum japonicum. All the structures were established by extensive spectroscopic analysis. The isolated compounds 3–10 were evaluated for their cytotoxicity against the human KB cell line with IC50 values ranging from 16.5 to 50.2 μM.

Gene expression profile in diabetic KK/Ta mice. Background To identify susceptibility genes for diabetic nephropathy, GeneChip® Expression Analysis was employed to survey the gene expression profile of diabetic KK/Ta mouse kidneys. Methods Kidneys from three KK/Ta and two BALB/c mice at 20weeks of age were dissected. Total RNA was extracted and labeled for hybridizing to the Affymetrix Murine Genome U74Av2 array. The gene expression profile was compared between KK/Ta and BALB/c mice using GeneChip® expression analysis software. Competitive reverse transcription-polymerase chain reaction (RT-PCR) was used to confirm the results of GeneChip® for a selected number of genes. Results Out of 12,490 probe pairs present on GeneChip®, 98 known genes and 31 expressed sequence tags (ESTs) were found to be differentially expressed between KK/Ta and BALB/c kidneys. Twenty-one known genes and seven ESTs that increased in expression and 77 known genes and 24 ESTs that decreased in KK/Ta kidneys were identified. These genes are related to renal function, extracellular matrix expansion and degradation, signal transduction, transcription regulation, ion transport, glucose and lipid metabolism, and protein synthesis and degradation. In the vicinity of UA-1 (quantitative trait locus for the development of albuminuria in KK/Ta mice), candidate genes that showed differential expression were identified, including the Sdc4 gene for syndecan-4, Ahcy gene for S -adenosylhomocysteine hydrolase, Sstr4 gene for somatostatin receptor 4, and MafB gene for Kreisler leucine zipper protein. Conclusion The gene expression profile in KK/Ta kidneys is different from that in age-matched BALB/c kidneys. Altered gene expressions in the vicinity of UA-1 may be responsible for the development of albuminuria in diabetic KK/Ta mice.