Convergent gene clusters underpin hyperforin biosynthesis in St John's wort.

The meroterpenoid hyperforin is responsible for the antidepressant activity of St John's wort extracts, but the genes controlling its biosynthesis are unknown. Using genome mining and biochemical work, we characterize two biosynthetic gene clusters (BGCs) that encode the first three steps in the biosynthesis of hyperforin precursors. The findings of syntenic and phylogenetic analyses reveal the parallel assembly of the two BGCs. The syntenous BGC in Mesua ferrea indicates that the first cluster was assembled before the divergence of the Hypericaceae and Calophyllaceae families. The assembly of the second cluster is the result of a coalescence of genomic fragments after a major duplication event. The differences between the two BGCs - in terms of gene expression, response to methyl jasmonate, substrate specificity and subcellular localization of key enzymes - suggest that the presence of the two clusters could serve to generate separate pools of precursors. The parallel assembly of two BGCs with similar compositions in a single plant species is uncommon, and our work provides insights into how and when these gene clusters form. Our discovery helps to advance our understanding of the evolution of plant specialized metabolism and its genomic organization. Additionally, our results offer a foundation from which hyperforin biosynthesis can be more fully understood, and which can be used in future metabolic engineering applications.

Changes of gut microbiota in diabetic nephropathy and its effect on the progression of kidney injury.

PURPOSE: We aimed to illustrate gut microbiota and short chain fatty acid (SCFA) levels in diabetic nephropathy (DN) patients, and investigate the mechanism of sodium butyrate in diabetic mellitus (DM) rats. METHODS: Gut microbiota and serum SCFA levels were measured by 16S rDNA and GC-MS. After being built by streptozotocin (DM rats), the DM rats were administered 300 mg/kg sodium butyrate for 12 weeks (DM + BU rats). Gut microbiota, serum and fecal butyrate level were measured. RT-PCR, WB and transmission electron microscopy were performed to explore LC3mRNA or LC3B protein expression, and autophagosomes in kidney tissues. AMPK/mTOR protein expression in renal tissue were also measured. RESULTS: The gut microbial dysbiosis was found in DM and DN groups, and some SCFAs-producing bacteria were decreased in DN group. The serum butyrate concentrations were lower in SCFA-DN group compared with SCFA-HC group and SCFA-DM group in the other cohort. Serum butyrate level was positively correlated with eGFR. Sodium butyrate increased serum and fecal butyrate levels, and improved the enlargement of glomerular area and fibronectin and collagen IV expressions in renal tissues in DM + BU rats. The LC3 mRNA, LC3BII/I ratio and number of autophagosomes were increased in renal tissue of DM + BU rats. Higher p-AMPK/AMPK ratio and lower p-mTOR/ mTOR ratio were shown in renal tissue of DM + BU rats compared with DM rats. CONCLUSIONS: We found the decrease in SCFAs-producing bacteria and low SCFAs concentrations in DN patients. Oral butyrate supplementation may improve kidney injury in DM rats, possibly by increasing autophagy via activating AMPK/mTOR pathway.

Alternative Splicing: A New Cause and Potential Therapeutic Target in Autoimmune Disease.

Alternative splicing (AS) is a complex coordinated transcriptional regulatory mechanism. It affects nearly 95% of all protein-coding genes and occurs in nearly all human organs. Aberrant alternative splicing can lead to various neurological diseases and cancers and is responsible for aging, infection, inflammation, immune and metabolic disorders, and so on. Though aberrant alternative splicing events and their regulatory mechanisms are widely recognized, the association between autoimmune disease and alternative splicing has not been extensively examined. Autoimmune diseases are characterized by the loss of tolerance of the immune system towards self-antigens and organ-specific or systemic inflammation and subsequent tissue damage. In the present review, we summarized the most recent reports on splicing events that occur in the immunopathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and attempted to clarify the role that splicing events play in regulating autoimmune disease progression. We also identified the changes that occur in splicing factor expression. The foregoing information might improve our understanding of autoimmune diseases and help develop new diagnostic and therapeutic tools for them.

The clinicopathological features of drug-induced acute kidney injury-a single-center retrospective analysis.

BACKGROUND: This study aimed to analyze changes to the drug spectrum and clinicopathological features of drug-induced acute kidney injury (AKI) with recent medication habits changes. METHODS: A retrospective analysis of the characteristics of patients diagnosed with drug-induced AKI from January 2012 to October 2016 period at the First Affiliated Hospital of the Medical College of Zhejiang University was conducted. RESULTS: Between January 2012 and October 2016, 909 patients were diagnosed with AKI. Of these, 228 were diagnosed with drug-related AKI were engaged in this study, including 51 who underwent renal biopsies, 74 treated with antibacterial and antiviral drugs, and 63 who received nonsteroidal anti-inflammatory drugs (NSAIDs), and 17 who were treated with Chinese herbal medicine. AKI was most frequently associated with antibiotics and antiviral drugs, including cephalosporins, acyclovir, azithromycin, clindamycin, and levofloxacin. In those who underwent renal biopsy, 12 patients were diagnosed with allergic interstitial nephritis, 19 with interstitial nephritis, 8 with renal tubular epithelial cell injury, 2 with minimal change nephropathy, 2 with IgA nephropathy, and 2 with mild mesangial hyperplasia with glomerulosclerosis. The mean follow-up time was 437 days, ranging from 3 to 2,756 days. Among 228 patients, 165 recovered completely, 4 recovered partially, 8 did not recover, and 51 were lost to follow-up after discharge. CONCLUSIONS: The three main contributors to drug-induced AKI were antimicrobial agents, NSAIDs, and Chinese herbal medicines. The age distribution of the three different drug-induced AKI groups was significantly different. Allergic interstitial nephritis, interstitial nephritis, and tubular epithelial cell injury were the main pathological manifestations of drug-induced AKI. The novel predictive nomogram achieved a good performance of prediction recovery within 2 weeks in drug-induced AKI patients.

A Systematic Review and Meta-Analysis about the Effect of Bisphosphonates on the Risk of Skeletal-Related Event in Men with Prostate Cancer.

BACKGROUND: Although the adjuvant therapy of bisphosphonates in prostate cancer is effective in improving bone mineral density, it is still uncertain whether bisphosphonates could decrease the risk of Skeletal- Related Event (SRE) in patients with prostate cancer. We reviewed and analyzed the effect of different types of bisphosphonates on the risk of SRE, defined as pathological fracture, spinal cord compression, radiation therapy to the bone, surgery to bone, hypercalcemia, bone pain, or death as a result of prostate cancer. METHODS: A systemic literature search was conducted on PubMed and related bibliographies. The emphasis during data extraction was laid on the Hazard Ratio (HR) and the corresponding 95% Confidence Interval (CI) from every eligible Randomized Controlled Trial (RCT). HR was pooled with the fixed effects model, and preplanned subgroup analyses were performed. RESULTS: 5 RCTs (n = 4651) were included and analyzed finally after screening 51 articles. The meta-analysis of all participants showed no significant decrease in the risk of SRE when adding bisphosphonates to control group (HR = 0.968, 95% CI = 0.874 - 1.072, p = 0.536) with low heterogeneity (I2 = 0.0% (d.f. = 4) p = 0.679). There was no significant improvement on SRE neither in the subgroups with Metastases (M1) or Castration-Sensitive Prostate Cancer (CSPC) (respectively HR = 0.968, 95% CI = 0.874 - 1.072, p = 0.536, I2 = 0.0% (d.f. = 4) p = 0.679; HR = 0.954, 95% CI = 0.837 - 1.088, p = 0.484, I2 = 0.0% (d.f. = 3) p = 0.534). CONCLUSION: Our study demonstrated that bisphosphonates could not statistically significantly reduce the risk of SRE in patients with prostate cancer, neither in the subgroups with M1 or CSPC.

Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China.

BACKGROUND: FG-4592 (roxadustat) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (HIF-PHI) promoting coordinated erythropoiesis through the transcription factor HIF. Two Phase 2 studies were conducted in China to explore the safety and efficacy of FG-4592 (USAN name: roxadustat, CDAN name: ), a HIF-PHI, in patients with anemia of chronic kidney disease (CKD), both patients who were dialysis-dependent (DD) and patients who were not dialysis-dependent (NDD). METHODS: In the NDD study, 91 participants were randomized to low (1.1-1.75 mg/kg) or high (1.50-2.25 mg/kg) FG-4592 starting doses or to placebo. In the DD study, 87 were enrolled to low (1.1-1.8 mg/kg), medium (1.5-2.3 mg/kg) and high (1.7-2.3 mg/kg) starting FG-4592 doses or to continuation of epoetin alfa. In both studies, only oral iron supplementation was allowed. RESULTS: In the NDD study, hemoglobin (Hb) increase ≥1 g/dL from baseline was achieved in 80.0% of subjects in the low-dose cohort and 87.1% in the high-dose cohort, versus 23.3% in the placebo arm (P < 0.0001, both). In the DD study, 59.1%, 88.9% (P = 0.008) and 100% (P = 0.0003) of the low-, medium- and high-dose subjects maintained their Hb levels after 5- and 6-weeks versus 50% of the epoetin alfa-treated subjects. In both studies, significant reductions in cholesterol were noted in FG-4592-treated subjects, with stability or increases in serum iron, total iron-binding capacity (TIBC) and transferrin (without intravenous iron administration). In the NDD study, hepcidin levels were significantly reduced across all FG-4592-treated arms as compared with no change in the placebo arm. In the DD study, hepcidin levels were also reduced in a statistically significant dose-dependent manner in the highest dose group as compared with the epoetin alfa-treated group. Adverse events were similar for FG-4592-treated and control subjects. CONCLUSIONS: FG-4592 may prove an effective alternative for managing anemia of CKD. It is currently being investigated in a pivotal global Phase 3 program.

Effect of uric acid-lowering therapy on blood pressure: systematic review and meta-analysis.

BACKGROUND: The purpose of this meta-analysis was to determine if uric acid-lowering therapy is associated with a decrease in blood pressure (BP) and serum creatinine levels. MATERIALS AND METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 29 June 2016, with keywords: uric-acid-lowering therapy, allopurinol, febuxostat, uricosuric, and BP. Only randomized controlled trials were included. The primary outcomes were reduction in systolic BP (SBP) and diastolic BP (DBP), and secondary was reduction in serum creatinine level. RESULTS: Patients treated with allopurinol had greater reduction in SBP (standardized difference in means [SDM] = 0.321, 95% confidence interval [CI]: 0.145-0.497, p < 0.001), DBP (SDM = 0.260, 95% CI: 0.102 to 0.417, p = 0.001), and creatinine level (SDM = 0.312, 95% CI: 0.008 to 0.615, p = 0.044) than control patients. Subgroup analysis showed that allopurinol significantly decreased SBP whether or not antihypertensive drugs were being administered; a decrease in DBP was only seen in patients receiving antihypertensive drugs. Low-dose allopurinol (≤300 mg/day) was more effective at reducing SBP than high-dose (>300 mg/day) in patients receiving antihypertensive drugs. CONCLUSIONS: These results support that allopurinol decreases BP and creatinine levels in patients with hyperuricemia. KEY MESSAGES Allopurinol decreases SBP and DPB, and creatinine levels in patients with hyperuricemia. Allopurinol resulted in a significant decrease in SBP in patients with or without treatment of antihypertensive drugs. A dose of allopurinol of ≤300 mg per day might be more effective than a higher dose.

Astilbin improves potassium oxonate-induced hyperuricemia and kidney injury through regulating oxidative stress and inflammation response in mice.

Astilbin is a flavonoid compound derived from the rhizome of Smilax china L. The effects and possible molecular mechanisms of astilbin on potassium oxonate-induced hyperuricemia mice were investigated in this study. Different dosages of astilbin (5, 10, and 20mg/kg) were administered to induce hyperuricemic mice. The results demonstrated that the serum uric acid (Sur) level was significantly decreased by increasing the urinary uric acid (Uur) level and fractional excretion of urate (FEUA) with astilbin, related with suppressing role in meditation of Glucose transporter 9 (GLUT9), Human urate transporter 1 (URAT1) expression and up-regulation of ABCG2, Organic anion transporter 1/3 (OAT1/3) and Organic cation transporter 1 (OCT1). In addition, kidney function parameters, including serum creatinine (Scr) and blood urea nitrogen (BUN) were restored in astilbin-treated hyperuricemic rats. Further investigation indicated that astilbin prevented the renal damage against the expression of Thioredoxin-interacting protein (TXNIP) and its related inflammation signal pathway, including NLR pyrin domain-containing 3/Nuclear factor κB (NLRP3/NF-κB), which is associated with the up-regulation of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), and also presented a renal protective role by suppression oxidative stress. Moreover, astilbin inhibited activation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) cascade and over-expression of suppressor of cytokine signaling 3 (SOCS3) in the kidneys of potassium oxonate-induced mice. These findings provide potent evidence and therapeutic strategy for astilbin as a safe and promising compound in the development of a disease-modifying drug due to its function against hyperuricaemia and renal injury induced by potassium oxonate.

Comparison of tripterygium wilfordii multiglycosides and tacrolimus in the treatment of idiopathic membranous nephropathy: a prospective cohort study.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome among adults. Considering the natural course of IMN, when to treat and with which immunosuppressive treatment need to be carefully considered in such patients. A combination of tripterygium wilfordii multiglycosides (TWG) and prednisone may be an effective option for treating patients with IMN. METHODS: In this prospective cohort study, we enrolled patients with biopsy-proven IMN at our kidney centre. One cohort received TWG combined with prednisone, whereas another cohort received tacrolimus (TAC) combined with prednisone, for 36 weeks. The primary outcome was the remission rate, whereas the secondary outcomes included the time to remission, relapse rate, changes in serum albumin levels and daily urinary protein levels, estimated glomerular filtration rate, and adverse events. RESULTS: A total of 53 patients with IMN met the criteria for enrollment, and all patients completed the therapy. At the end of the 36-week therapy, remission (either partial remission [PR] or complete remission [CR]) was observed in 20 patients (86.9 %) receiving TWG and in 27 patients (90.0 %) receiving TAC (p > 0.05), whereas CR was noted in 12 patients (52.2 %) receiving TWG and 14 patients (46.7 %) receiving TAC (p > 0.05). The probability of remission was similar for both the TWG and TAC groups (p > 0.05, by log-bank test). The mean time for achieving remission was 11.8 ± 12.5 weeks in the TWG group and 8.5 ± 9.1 weeks in the TAC group (p > 0.05). CONCLUSIONS: The combination of TWG and predisone is an effective and safe therapy for IMN.

The role of an integrated care model for kidney disease in the development of peritoneal dialysis: a single-center experience in China.

Peritoneal dialysis plays a crucial role in the integrated care of patients with end-stage renal disease (ESRD). In this paper, we retrospectively analyzed the quality indicators of peritoneal dialysis (PD) in 712 patients from our center who underwent PD between 2004 and 2011. In 43% of patients, follow-up was undertaken every 3 months at our outpatient department, and 54% patients were followed up by both our hospital and other local hospitals. The patient survival rate at 1, 3 and 5 years was 96.3%, 85.4% and 76.2%, respectively. The technique survival (excludes death/transplantation) at 1, 3 and 5 years was 95.1%, 87.7% and 79.6%, respectively. Fluid overload occurred in 29.2% of patients and was one of the major reasons for discontinuing PD. The peritonitis rate in our center decreased to 0.16 episodes/year in 2011. In addition, since our center is one of the largest integrated-treatment centers for ESRD in China, we have developed a multilevel care program in Zhejiang Province, which resulted in rapid growth of PD in our province in recent years.

Vitamin D status in chronic dialysis patients with depression: a prospective study.

BACKGROUND: Depression is the most widely acknowledged psychological problem among end-stage renal disease (ESRD) patients. Depression may be associated with VD deficiency. The aims of this study are to (a) elucidate the prospective association between HsCRP, VD contents and depressive symptoms in the dialyzed population, and (b) find the effect of calcitriol supplementation on depression in dialyzed patients. METHODS: In this prospective study, 484 dialysis patients (382 hemodialysis [HD] cases and 102 peritoneal dialysis [PD] cases; aged 18-60 years) from two hospitals in southeast China were included. The depression in these patients was evaluated using the Chinese version of Beck's Depression Inventory (BDI). All subjects answered the BDI-I questionnaire for assessment of depression levels in summer. A cut-off value of 16 was set to include dialysis patients with depression. All patients were divided into two groups depending on the absence (Group 1) or presence (Group 2) of depression. The two groups took 0.5 µg/day 1,25-Dihydroxyvitamin D orally for one year. BDI Scores were recalculated for all patients. Sociodemographic, clinical data, and serum VD contents were also collected. RESULTS: A total of 484 participants (247 men [51.0%] and 237 women [49.0%]) were surveyed. Depressive symptoms were found in 213 (44.0%) patients. The baseline serum VD level (VD2 + VD3) was 17.6 ± 7.7 nmol/L. Patients with depressive symptoms have significantly higher serum HsCRP level and significantly lower serum VD level compared with the control group. After one-year follow-up, the supplementation of 0.5 µg/day calcitriol slightly improved the microinflammatory state such as lowering mean serum HsCRP level and improving serum VD level, but not in significantly enhancing the depressive symptoms. CONCLUSIONS: Calcitriol supplementation did not significantly enhance the depressive symptoms in our dialyzed population although patients with low levels of serum VD were more depressed. Therefore, more prospective randomized controlled trials are necessary to reveal the exact cause-and-effect relationship between VD status and depressive symptoms or VD status related to some specific subtypes in dialyzed patients.

Sevelamer carbonate lowers serum phosphorus effectively in haemodialysis patients: a randomized, double-blind, placebo-controlled, dose-titration study.

BACKGROUND: Hyperphosphataemia in patients with advanced chronic kidney disease (CKD) is associated with adverse outcomes, including vascular calcification and higher mortality rates. While phosphate lowering is an integral aspect of CKD management, the efficacy and safety of phosphate binders in a contemporary cohort of Chinese haemodialysis patients (who have different genetics and dietary patterns than other populations) has not been previously described. Moreover, sparse data are available on strategies for optimal dose titration when transitioning from a calcium-based to a polymer-based phosphate binder. METHODS: This randomized, double-blind, dose-titration study compared sevelamer carbonate (starting dose 800 mg three times daily) with placebo over 8 weeks' duration in Chinese CKD patients on haemodialysis. Patients were required to be using calcium-based binders prior to study start. RESULTS: In all, 205 patients were randomized (sevelamer, n = 135; placebo, n = 70); mean age was 48.6 years, 61% were male and the mean time on dialysis was 4.4 years. The mean serum phosphorus decreased significantly in patients treated with sevelamer carbonate [change -0.69 ± 0.64 mmol/L (-2.14 ± 1.98 mg/dL)] but remained persistently elevated with placebo [change -0.06 ± 0.57 mmol/L (-0.19 ± 1.76 mg/dL)] (P < 0.0001). When compared with placebo, sevelamer carbonate treatment resulted in statistically significant greater mean reductions from baseline in serum total (-17.1 versus -3.3%) and low-density lipoprotein cholesterol (-33.5 versus-7.6%) (P < 0.0001 for both). Sevelamer carbonate was well tolerated with 96% adherence compared with 97% adherence in the placebo arm. Overall, adverse events experienced by patients in the sevelamer carbonate and placebo treatment groups were similar and consistent with their underlying renal disease. CONCLUSIONS: This study demonstrated that hyperphosphataemia developed quickly following the cessation of phosphate binders and remained persistently elevated in end-stage CKD in the placebo-treated group. Gradually titrating up sevelamer carbonate from an initial dose of 2.4 g/day to an average daily dose of 7.1 ± 2.5 g/day was well tolerated, safe and efficacious in contemporary Chinese haemodialysis patients.

Mineral and bone disorder in Chinese dialysis patients: a multicenter study.

BACKGROUND: Mineral and bone disorder (MBD) in patients with chronic kidney disease is associated with increased morbidity and mortality. Studies regarding the status of MBD treatment in developing countries, especially in Chinese dialysis patients are extremely limited. METHODS: A cross-sectional study of 1711 haemodialysis (HD) patients and 363 peritoneal dialysis (PD) patients were enrolled. Parameters related to MBD, including serum phosphorus (P), calcium (Ca), intact parathyroid hormone (iPTH) were analyzed. The achievement of MBD targets was compared with the results from the Dialysis Outcomes and Practice Study (DOPPS) 3 and DOPPS 4. Factors associated with hyperphosphatemia were examined. RESULTS: Total 2074 dialysis patients from 28 hospitals were involved in this study. Only 38.5%, 39.6% and 26.6% of them met the Kidney Disease Outcomes Quality Initiative (K/DOQI) defined targets for serum P, Ca and iPTH levels. Serum P and Ca levels were statistically higher (P < 0.05) in the HD patients compared with those of PD patients, which was (6.3 ± 2.1) mg/dL vs (5.7 ± 2.0) mg/dL and (9.3 ± 1.1) mg/dL vs (9.2 ± 1.1) mg/dL, respectively. Serum iPTH level were statistically higher in the PD patients compared with those of HD patients (P = 0.03). The percentage of patients reached the K/DOQI targets for P (37.6% vs 49.8% vs 54.5%, P < 0.01), Ca (38.6% vs 50.4% vs 56.0%, P < 0.01) and iPTH (26.5% vs 31.4% vs 32.1%, P < 0.01) were lower among HD patients, compared with the data from DOPPS 3 and DOPPS 4. The percentage of patients with serum phosphorus level above 5.5 mg/dL was 57.4% in HD patients and 47.4% in PD patients. Age, dialysis patterns and region of residency were independently associated with hyperphosphatemia. CONCLUSIONS: Status of MBD is sub-optimal among Chinese patients receiving dialysis. The issue of hyperphosphatemia is prominent and needs further attention.

Ginsenoside Rg3 inhibits CXCR4 expression and related migrations in a breast cancer cell line.

BACKGROUND: Ginsenoside Rg3 is an extract from the natural product ginseng. Previous studies have linked Rg3 with anti-metastasis of cancer in vivo and in vitro. CXC receptor 4 (CXCR4) is a vital molecule in migration and homing of cancer to the docking regions. METHODS: In this study, the effects of Rg3 on CXCR4 expression were investigated in a breast cancer cell line. Immunohistochemistry, chemotaxis and wound healing mobility assays were performed in cultured MDA-MB-231 cells. RESULTS: At a dosage without obvious cytotoxicity, Rg3 treatment elicits a weak CXCR4 stain color, decreases the number of migrated cells in CXCL12-elicited chemotaxis and reduces the width of the scar in wound healing. CONCLUSION: This work suggests that Rg3 is a new CXCR4 inhibitor from a natural product.

Angelica stimulates proliferation of murine bone marrow mononuclear cells by the MAPK pathway.

Murine bone marrow mononuclear cells (MNC) were isolated and co-incubated with Angelica to investigate its effects on bone marrow cells and the underlying mechanism of action. Angelica stimulates MNC proliferation as determined by the 3-(4, 5-dimethythiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Our results also suggest that the mechanism of action involves the phosphorylation of ERK1/2 and P38, two key proteins in the MAPK pathway. MAPK inhibitors, PD 98059 and SB 203580, block MNC proliferation caused by Angelica. Taken together, our results show that Angelica induces the proliferation of murine MNC by activating ERK1/2 and P38 MAPK proteins.

[Clinical observation on treatment of chronic allograft nephropathy with bailing capsule].

OBJECTIVE: To observe the effects of Bailing Capsule (BLC, a dry powder-formed preparation of Cordyceps sinensis mycelia) on chronic allograft nephropathy (CAN). METHODS: A comparative synchronous study was conducted between 36 CAN patients treated with BLC 9.0 g/d (treated group) for 12 weeks and 15 CAN patients treated without BLC (control group). The changes of renal function, endogenous creatinine clearance rate, volume of urinary protein and urinary protein components, including immune globulin (Ig) and albumin (Alb), urinary retinol binding protein (RBP) and beta2-microglobulin (beta2-MG), as well as the incidence rate of leucopenia before and after treatment in the two groups were compared. RESULTS: Compared with the control group, BLC showed more significant effects in lowering urinary protein (0.89 +/- 0.53 g/d in the treated group vs 1.31 +/- 0.59 g/d in the control group after treatment, the same below), serum creatinine (206.48 +/- 30.61 micromol/L vs 240.17 +/- 29.55 micromol/L), relieving glomerular and tubular proteinuria represented by levels of Ig, Al, RBP and beta2-MG in urine, increasing endogenous creatine clearance rate (37.33 +/- 9.91 ml/min vs. 31.92 +/- 10.95 ml/min), and reducing the incidence rate of leucopenia (2.8% vs 13.3%) in CAN patients. CONCLUSION: BLC has certain therapeutical effect on CAN. It could relieve injury in glomerulus and tubular interstitium and has preventive and therapeutical effect on leucopenia.

[Effects of Tangshenling Mixture and benazepril on rats with diabetic nephropathy and its mechanism].

OBJECTIVE: To investigate the effects of Tangshenling Mixture (TSLM) and benazepril on rats with diabetic nephropathy (DN) and its mechanism. METHODS: Diabetic nephropathy was induced in rats by intraperitoneal injection of streptozotocin. Fifty-eight rats with DN were randomly divided into four groups: untreated group, TSLM-treated group, TSLM plus benazepril-treated group and benazepril-treated group. Another seven normal rats were included in normal control group. Then, rats in each group were accordingly given normal saline, TSLM, TSLM plus benazepril and benazepril orally for six weeks respectively. Blood and urine biochemical indexes, plasma atrial natriuretic factor (ANF), pathomorphology of renal tissue, transforming growth factor beta1 (TGF-beta1) and glucose transporter 1 (GLUT1) mRNAs in renal tissue were observed. RESULTS: Both TSLM and benazepril could decrease urinary albumin excretion rates, creatinine clearance and ratio of kidney weight to body weight of the rats with DN as well as reduce the pathological damages of the renal tissues. TSLM could reduce the level of plasma ANF and the expression of GLUT1 mRNA, but had no significant effect on the expression of TGF-beta1 mRNA. Benazepril could reduce the expression of TGF-beta1 mRNA, but had no significant effect on plasma ANF and the expression of GLUT1 mRNA. CONCLUSION: TSLM can reduce the pathological damages of renal tissues in rats with early-stage DN, and its mechanism may relate to decreasing the level of plasma ANF and the expression of GLUT1 mRNA which is different from that of benazepril. It seems that TSLM has synergetic effect with benazepril.

Tests of the pharmacodynamics and toxicity of Duliang capsule.

OBJECTIVE: To study the analgesic efficacy, toxicity and impact of Duliang capsule (DLC) and Duliang pill (DLP), different dosage forms of a patent Chinese herbal medicine, on the hemodynamics in mice and rats. METHODS: In hotplate and writhing tests in mice, the effects of both drugs on the latency of paw-licking response and the writhing number of times were observed. The changes of blood viscosity in rat models of blood stasis were measured with Viscometer-R80, and acute and chronic toxicity of DLC observed. RESULTS: DLP at the dose of 5 g/kg.b.w. and DLC at 10, 5 or 3 g/kg.b.w. significantly prolonged the latency of paw-licking response and reduced writhing times. The analgesic effects of DLC and DLP occurred 0.5 and 1 h respectively after the administration, and they could both lower the viscosity of the whole blood and hematocrit level in the blood-stasis rat models. Toxicity of the drug was not observed in acute or chronic toxicity tests. CONCLUSIONS: Both DLC and DLP possess strong analgesic effect and can lower blood viscosity and hematocrit, but DLC takes effect sooner than DLP as analgesics and can be effectively and safely applied clinically.