Analysis of chronic kidney disease staging with different estimated glomerular filtration rate equations in Chinese centenarians / 中华医学杂志(英文版)

BACKGROUND@#Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations for staging CKD in a large sample of centenarians. Thus, this study aimed to investigate the differences in CKD staging with the most commonly used equations and to analyze sources of discrepancy.@*METHODS@#A total of 966 centenarians were enrolled in this study from June 2014 to December 2016 in Hainan province, China. The GFR with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study 1 (BIS1) equations were estimated. Agreement between these equations was investigated with the κ statistic and Bland-Altman plots. Sources of discrepancy were investigated by partial correlation analysis.@*RESULTS@#The κ values of the MDRD and CKD-EPI equations, MDRD and BIS1 equations, and CKD-EPI and BIS1 equations were 0.610, 0.253, and 0.381, respectively. Serum creatinine (Scr) explained 10.96%, 41.60% and 17.06% of the variability in these three comparisons, respectively. Serum uric acid (SUA) explained 3.65% and 5.43% of the variability in the first 2 comparisons, respectively. Gender was associated with significant differences in these 3 comparisons (P < 0.001).@*CONCLUSIONS@#The strengths of agreement between the MDRD and CKD-EPI equations were substantial, but those between the MDRD and BIS1 equations and the CKD-EPI and BIS1 equations were fair. The difference in CKD staging of the first 2 comparisons strongly depended on Scr, SUA and gender, and that of CKD-EPI and BIS1 equations strongly depended on Scr and gender. The incidence at various stages of CKD staging was quite different. Thus, a new equation that is more suitable for the elderly needs to be built in the future.

A non-invasive diagnostic model of immunoglobulin A nephropathy and serological markers for evaluating disease severity / 中华医学杂志(英文版)

BACKGROUND@#Immunoglobulin A nephropathy (IgAN) is the most common pathological type of glomerular disease. Kidney biopsy, the gold standard for IgAN diagnosis, has not been routinely applied in hospitals worldwide due to its invasion nature. Thus, we aim to establish a non-invasive diagnostic model and determine markers to evaluate disease severity by analyzing the serological parameters and pathological stages of patients with IgAN.@*METHODS@#A total of 272 biopsy-diagnosed IgAN inpatients and 518 non-IgA nephropathy inpatients from the Department of Nephrology of Chinese People's Liberation Army General Hospital were recruited for this study. Routine blood examination, blood coagulation testing, immunoglobulin-complement testing, and clinical biochemistry testing were conducted and pathological stages were analyzed according to Lee grading system. The serological parameters and pathological stages were analyzed. The receiver operating characteristic (ROC) analysis was performed to estimate the diagnostic value of the clinical factors. Logistic regression was used to establish the diagnostic model.@*RESULTS@#There were 15 significantly different serological parameters between the IgAN and non-IgAN groups (all P < 0.05). The ROC analysis was performed to measure the diagnostic value for IgAN of these parameters and the results showed that the area under the ROC curve (AUC) of total protein (TP), total cholesterol (TC), fibrinogen (FIB), D-dimer (D2), immunoglobulin A (IgA), and immunoglobulin G (IgG) were more than 0.70. The AUC of the "TC + FIB + D2 + IgA + age" combination was 0.86, with a sensitivity of 85.98% and a specificity of 73.85%. Pathological grades of I, II, III, IV, and V accounted for 2.21%, 17.65%, 62.50%, 11.76%, and 5.88%, respectively, with grade III being the most prevalent. The levels of urea nitrogen (UN) (13.57 ± 5.95 vs. 6.06 ± 3.63, 5.92 ± 2.97, 5.41 ± 1.73, and 8.41 ± 3.72 mmol/L, respectively) and creatinine (Cr) (292.19 ± 162.21 vs. 80.42 ± 24.75, 103.79 ± 72.72, 96.41 ± 33.79, and 163.04 ± 47.51 μmol/L, respectively) were significantly higher in grade V than in the other grades, and the levels of TP (64.45 ± 7.56, 67.16 ± 6.94, 63.22 ± 8.56, and 61.41 ± 10.86 vs. 37.47 ± 5.6 mg/d, respectively), direct bilirubin (DB) (2.34 ± 1.23, 2.58 ± 1.40, 1.91 ± 0.97, and 1.81 ± 1.44 vs. 0.74 ± 0.57 μmol/L, respectively), and IgA (310.35 ± 103.78, 318.48 ± 107.54, 292.58 ± 81.85, and 323.29 ± 181.67 vs. 227.17 ± 68.12 g/L, respectively) were significantly increased in grades II-V compared with grade I (all P < 0.05).@*CONCLUSIONS@#The established diagnostic model that combined multiple factors (TC, FIB, D2, IgA, and age) might be used for IgAN non-invasive diagnosis. TP, DB, IgA, Cr, and UN have the potential to be used to evaluate IgAN disease severity.

Relationship between protein-energy wasting and mineral metabolism disorders in maintenance hemodialysis patients / 中国实用内科杂志

Protein-energy wasting(PEW)and chronic kidney disease-mineral and bone disorder(CKD-MBD)are common complications in maintenance hemodialysis(MHD)patients, and they have notable correlation with the mortality of MHD patients. PEW and CKD-MBD have a common pathophysiological basis and are mutually reinforcing factors. At the same time, their therapy strategies also affect each other. Uremia status, hemodialysis treatment, chronic inflammatory, metabolic acidosis, nutrient intake and musculoskeletal pain promote the development of PEW and MBD. Improvement in the hemodialysis quality, keeping balanced diet of protein and phosphorus intake, and scientific rational physical exercise may improve both PEW and MBD, thereby reducing mortality and improving life quality in MHD patients.

Infection is Associated with Occurrence of Proteinuria in Type 2 Diabetes Patients: A Systemic Review and Meta-Analysis / 中华医学杂志(英文版)

Background@#Type 2 diabetes (T2DM) patients are susceptible to Helicobacter pylori (HP), and it has been reported that the occurrence of proteinuria is associated with HP infection in T2DM patients; however, this view remains controversial. This meta-analysis aimed to explore the association between HP infection and the occurrence of proteinuria in T2DM patients. In addition, we hope to provide some recommendations to readers in clinical or related fields.@*Methods@#Our meta-analysis was conducted with the methodology of the Cochrane Collaboration. Search strategies were formulated by relevant professionals. Case-control studies that compared the occurrence of proteinuria in T2DM patients with and without HP infection were involved in our meta-analysis. Relevant English or Chinese studies were searched on online databases before 2018, including PubMed, the Cochrane library, Medline, Google Scholar, the China National Infrastructure, and Wanfang database. The search strategies were "diabetic proteinuria, diabetic microalbuminuria, diabetic albuminuria, diabetic kidney disease, diabetic renal dysfunction, diabetic renal disease, diabetic nephropathy, diabetic complications, and diabetic mellitus, combined with HP." The quality of these involved articles was separately assessed by two investigators using the Newcastle-Ottawa Scale (NOS). Odds ratios (ORs) and associated 95% confidence intervals (CIs) were extracted and pooled using fixed-effects models.@*Results@#Seven studies involving 1029 participants were included. The quality of these seven articles was all above five stars as assessed by NOS, and there was no significant publication bias in our meta-analysis. We found that T2DM patients with HP infection had a 2.00 times higher risk of the occurrence of proteinuria than patients without HP infection (OR: 2.00, 95% CI: 1.48-2.69).@*Conclusions@#Our analysis showed that HP infection was associated with the occurrence of proteinuria in T2DM patients. HP radical surgery might be a therapeutic option for protecting kidney function in patients with T2DM.

Expression of lncRNA DLEU1 in non-small cell lung cancer and its effect on metastasis / 中国肿瘤临床

Objective: To investigate the expression pattern and clinical significance of long non-coding RNA deleted in lymphocytic leu-kemia 1 (DLEU1) in non-small cell lung cancer (NSCLC), and to further evaluate its effect on tumor metastasis. Methods: Paired cancer and adjacent tissues were obtained from 42 patients with NSCLC that underwent surgical resection of cancer in The Third Xiangya Hos-pital of Central South University from January 2008 to December 2012, at the Department of Cardiothoracic Surgery. The expression features of DLEU1 in NSCLC tissue were detected by real-time quantitative polymerase chain reaction assay. Statistical methods were used to analyze the relationship between the expression of DLEU1 and the clinicopathological features and the survival time of pa-tients with NSCLC. Effects of DLEU1 on migration and invasion of NSCLC cells were evaluated by in vitro wound healing and cell inva-sion assays, respectively. Western blot was performed to investigate the protein levels of E-cadherin, N-cadherin, and Vimentin, which are the biomarkers of epithelial to mesenchymal transition (EMT). Results: Of the 42 NSCLC samples, DLEU1 expression was up-regulat-ed in 35 samples (83.33%) and down-regulated in 7 samples (16.67%). The expression level of DLEU1 in NSCLC tissue was 2.11 times that in the adjacent tissues (P<0.05). The expression of DLEU1 in four NSCLC cell lines (A549, H1299, SPCA1, and H358) was higher than that in normal lung 16HBE epithelial cells, and of these, A549 cells had the highest DLEU1 expression (P<0.05). Highly expressed DLEU1 was positively correlated with lymph-node metastasis (P<0.05), but was not significantly associated with other parameters, in-cluding patient gender, age, smoking history, primary tumor size, histological grade, and the TNM stage. The survival time of patients with high DLEU1 expression was significantly shorter than that of patients with low DLEU1 expression (P<0.05). In vitro interference with DLEU1 expression significantly inhibited the migration and invasion of A549 and SPCA1 cells compared with that of the control group (P<0.05). Upon interference with DLEU1 expression , protein levels of E-cadherin increased, whereas those of N-cadherin and Vi-mentin decreased in A549 cells in comparison with the control group. Conclusions: The expression of DLEU1 is up-regulated in NSCLC tissues and cell lines, correlates with lymph-node metastasis and survival times in patients with NSCLC, and promotes tumor cell migra-tion and invasion by regulating EMT, suggesting that DLEU1 may be a potential therapeutic target for NSCLC.

Application of DNA ploidy analysis in diagnosis of serous cavity effusion / 国际检验医学杂志

Objective To explore the application value of automated cell DNA ploidy analysis system in the diagnosis of benign and malignant serous cavity effusion.Methods 262 cases of serous cavity effusion(169 cases of pleural effusion,78 cases of ascites,15 cases of pericardial effusion)were treated by centrifugation,2 slices of each sample were made.One of them used for dyeing Feulgen,which given automatic cell DNA ploidy analysis,another one for Papanicolaou staining,with a conventional cytology.The positive detection rate of these 2 kinds of different detection methods for malignant serous cavity effusion were compared.Results 119 cases(45.4％)of 262 cases abnormal were detected by conventional cytology of serous cavity effusion.Meanwhile,113 cases (43.1 ％)were detected abnormal by DNA ploidy analysis in the same samples.73 cases of tumor cells and suspicious tumor cells were found by conventional cytology,and different ploidy cells were found in all of these samples In conventional cells,46 cases of nuclear heterogeneous cells were found,while only 34 cases exist different ploidy cells.Conclusion Automated cell DNA ploidy analysis system is helpful to improve the positive diagnosis rate of serous cavity effusion,which can be used as an important auxiliary means of cytology.

Association between dyslipidemia and chronic kidney disease: a cross-sectional study in the middle-aged and elderly Chinese population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Dyslipidemia, a well-known risk factor for cardiovascular disease, is common in patients with kidney disease. Recent studies discerned that dyslipidemias play a critical role in renal damage progression in renal diseases, but the association between dyslipidemias and chronic kidney disease (CKD) in the general population remains unknown. Thus, we assessed whether the growing prevalence of dyslipidemia could increase the risk of CKD.</p><p><b>METHODS</b>A total of 4779 middle-aged and elderly participants participated in this study. Dyslipidemias were defined by the 2007 Guidelines in Chinese Adults. Incident CKD was defined as albuminuria and/or reduced estimated glomerular filtration rate (eGFR, < 60 ml×min(-1)×1.73 m(-2)). Regression analysis was used to evaluate the association between dyslipidemia and albuminuria/reduced eGFR.</p><p><b>RESULTS</b>Participants with hypercholesterolemia exhibited a greater prevalence of albuminuria and reduced eGFR (10.0% vs. 6.1%, P = 0.001; 4.0% vs. 2.4%, P = 0.028, respectively). Both hypercholesterolemia and low high density lipoprotein cholesterol (HDL-C) were independently associated with albuminuria (odds ratio (OR) 1.49; 95% confidence interval (CI) 1.08 - 2.07 and OR 1.53; 95%CI 1.13 - 2.09, respectively). The multivariable adjusted OR of reduced eGFR in participants with hypercholesterolemia was 1.65 (95%CI 1.03 - 2.65). As the number of dyslipidemia components increased, so did the OR of CKD: 0.87 (95%CI 0.65 - 1.15), 1.29 (95%CI, 0.83 - 2.01), and 7.87 (95%CI, 3.75 - 16.50) for albuminuria, and 0.38 (95%CI 0.21 - 0.69), 1.92 (95%CI 1.14 - 3.25), and 5.85 (95%CI 2.36 - 14.51) for reduced eGFR, respectively.</p><p><b>CONCLUSIONS</b>Our findings indicate that dyslipidemias increase the risk of CKD in the middle-aged and elderly Chinese population. Hypercholesterolemia plays an important role in reducing total eGFR. Both low HDL-C and hypercholesterolemia are associated with an increased risk for albuminuria.</p>

Persistent asthma increases the risk of chronic kidney disease: a retrospective cohort study of 2354 patients with asthma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chronic kidney disease (CKD) is a growing public health problem with well-established risk factors. Other contributing factors, however, remain to be identified. Systemic inflammation in asthma plays a significant role in the development of other diseases. We therefore initiated a study to assess whether the growing prevalence of asthma is associated with an increase in the risk of CKD.</p><p><b>METHODS</b>We conducted a retrospective cohort study using data from 3015 patients with asthma aged 14 years and older who were registered and followed up in Asthma Control Study at the Department of Respiratory Medicine of three medical centers from 2005 to 2011. History, asthma control test (ACT), and asthma stage were used to assess the traits of asthma. CKD was defined as proteinuria and/or reduced estimated glomerular filtration rate (eGFR) (<60 ml×min(-1)×1.73 m(-2)) in two consecutive follow-up surveys. We used logistic regression models, adjusting for age, sex, and other confounding factor to determine associations between the traits of asthma and CKD. Kaplan-Meier curves were used to analyze patient outcomes.</p><p><b>RESULTS</b>A total of 2354 subjects with complete data were recruited for this study with mean age (45.4±10.4) years. After 6 years of follow-up, 9.6% (n = 227) of the analytic cohort developed proteinuria and 3.1% (n = 72) progressed to eGFR <60 ml×min(-1)×1.73 m(-2). The patients with >20 years asthma history, not well-controlled or persistent asthma patients had higher incidence of proteinuria and reduced eGFR compared with patients with ≤20 years asthma history, at least well-controlled or remission asthma, respectively. The multivariable adjusted OR for proteinuria and reduced eGFR in participants with persistent asthma was 1.49; (95% confidence interval (CI) 1.17-1.91) and 2.07 (95% CI 1.34-4.42). Compared to patients with no asthma traits, there was a significant risk (OR, 3.39; 95% CI 1.36-8.73) for those who met all three traits, including asthma history >20 years, not well-controlled and persistent stage, after adjusting for potential confounding factors.</p><p><b>CONCLUSIONS</b>In this retrospective cohort study, we found that persistent asthma was associated with an increased risk of CKD, which was independent of obesity, diabetes, hypertension, and other well-established risk factors. Future studies should be directed to elucidate the mechanisms underlying the association between asthma and CKD.</p>

Different effects of isoflurane and sevoflurane on cytotoxicity / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Isoflurane, a commonly used inhaled anesthetic, induces apoptosis in primary rat cortical neurons of rat in a concentration- and time-dependent manner by an unknown mechanism. We hypothesized that isoflurane induced apoptosis by causing abnormal calcium release from the endoplasmic reticulum (ER) via activation of inositol 1, 4, 5-trisphosphate (IP(3)) receptors. Sevoflurane has a reduced ability to disrupt intracellular calcium homeostasis and is a less potent cytotoxic agent. This study examined and compared the cytotoxic effects of isoflurane and sevoflurane on rat primary cortical neurons and their relationship with disruption of intracellular calcium homeostasis and production of reactive oxygen species (ROS).</p><p><b>METHODS</b>Primary rat cortical neurons were treated with the equivalent of 1 minimal alveolar concentration (MAC) of isoflurane and sevoflurane for 12 hours. MTT reduction and LDH release assays were performed to evaluate cell viability. Changes of calcium concentration in the cytosolic space, [Ca(2+)](c), and production of ROS were determined after exposing primary rat cortical neurons to isoflurane and sevoflurane. We also determined the effects of IP(3) receptor antagonist xestospongin C on isoflurane-induced cytotoxicity and calcium release from the ER in primary rat cortical neurons.</p><p><b>RESULTS</b>Isoflurane at 1 MAC for 12 hours induced cytotoxicity in primary rat cortical neurons, which was also associated with a high and fast elevation of peak [Ca(2+)](c). Xestospongin C significantly ameliorated isoflurane cytotoxicity in primary cortical neurons, as well as inhibited the calcium release from the ER in primary cortical neurons. Isoflurane did not induce significant changes of ROS production in primary rat cortical neurons. Sevoflurane, at equivalent exposure to isoflurane, did not induce similar cytotoxicity or elevation of peak [Ca(2+)](c) in primary rat cortical neurons.</p><p><b>CONCLUSION</b>These results suggested that isoflurane induced elevation in [Ca(2+)](c), partially via elevated activity of IP(3) receptors, which rendered cells vulnerable to isoflurane neurotoxicity. ROS production was not involved in isoflurane-induced neurotoxicity. Sevoflurane, at an equivalent exposure to isoflurane, did not induce similar elevations of [Ca(2+)](c) or neurotoxicity in primary cortical neurons of rat.</p>

Comparative study on quality of Flos Lonicerae between geo-authentic and non-authentic producing areas / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the quality of Flos Lonicerae between different producing areas.</p><p><b>METHOD</b>ICP-AES, UV and HPLC were used to determine the contents of trace elements, chlorogenic acid, total flavonoids, five iridoid glucosides, hederagenin, and oleanolic acid. SAS software system was used to perform data and cluster analyses.</p><p><b>RESULT</b>The results showed that the geo-authentic crude drug was lower in the contents of Cr and Pb but higher in the contents of chlorogenic acid, total flavonoids, five iridoid glucosides, hederagenin, and oleanolic acid than the non-authentic crude drug.</p><p><b>CONCLUSION</b>The geo-authentic crude drug of Flos Lonicerae is better in quality than the non-authentic crude drug based on the modern chemical analyses, which confirms the validity of traditional geo-based classification.</p>

Comparison of the inhibitory activities of salvianolic acid B and Ginkgo biloba extract EGb 761 on neurotoxicity of beta-amyloid peptide / 药学学报

<p><b>AIM</b>To compare the effects of salvianolic acid B (Sal B) and Ginkgo biloba extract EGb 761 on beta-amyloid peptide (beta-AP) fibril formation and cytotoxicity to PC12 cells.</p><p><b>METHODS</b>The inhibitory effects of Sal B and EGb 761 on beta-AP1-40 fibril formation were determined by using fluorescence analysis with Thioflavin T (ThT) and electron microscopic image. beta-AP25-35 was aged by incubating at 37 degrees C for 7 d, then the protein was incubated with PC12 cells. The protective effects of Sal B and EGb 761 against cytotoxicity induced by aged beta-AP25-35 in PC12 cells were evaluated by MTT reduction assay and flow cytometric analysis. beta-AP25-35-induced accumulation of intracellular reactive oxygen species (ROS) was determined by fluorescence analysis.</p><p><b>RESULTS</b>Both Sal B and EGb 761 inhibited the formation of amyloid fibrils, protected PC12 cells from beta-AP25-35-induced cytotoxicity, and decreased ROS accumulation caused by beta-AP25-35. The effective doses of Sal B were far lower than those of EGb 761.</p><p><b>CONCLUSION</b>Sal B was much more efficient than EGb 761 in inhibiting beta-AP aggregation and in protecting PC12 cells from beta-AP-induced cytotoxicity.</p>

Clinical study on integrative Chinese and Western medicine in treating allergic purpura and preventing renal impairment / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the clinical effect in treatment of the recurrent allergic (Henoch-Schönlein) purpura and prevention of renal impairment by means of integrative Chinese and Western medicine (ICWM).</p><p><b>METHODS</b>One hundred and seventy-six children with allergic purpura were randomly divided into the treated group (Based on the Western routine therapy of the control group, Kangmin Xiaoban Yin, a kind of TCM decoction, was added for 7-10 days) and the control group. Levels of urinary beta2-microglobulin (beta2-MG) and serum IgA, IgE were measured before and after treatment. And clinical observation on the disappearance time (DT) of abdominal pain, arthralgia and purpura were implemented.</p><p><b>RESULTS</b>The DT of joint swelling, arthralgia, and purpura in the treated group was shorter than those in the control group, showing significant difference (P<0.01). Comparison between groups in urinary beta2-MG and serum IgA and IgE before treatment and 1 week after treatment were insignificantly different (P>0.05), but at 1 month and 6 months after treatment, the level of urinary beta2-MG in the treated group was lower than that in the control group, with significant difference (P<0.05), and levels of serum IgA and IgE at 1 month after treatment in the former were lower than those in the control group, also showing significant difference (P<0.05, P<0.01). Six-month recurreat rate in the treated group was 23.5%, while that in the control group. There was significant difference in comparison in 1/2-year recurrent rate (P<0.01).</p><p><b>CONCLUSION</b>ICWM in treating allergic purpura could reduce the repeated episodes and shorten the hospitalization time, and effectively prevent the renal impairment of the disease.</p>

Expression of Endothelin in Kidneys of Rats with Unilateral Ureteral Obstruction / 实用儿科临床杂志

Objective To determine the expression of endothelin in kidneys of rats with unilateral ureteral obstruction (UUO). Methods Rats were evenly divided into two groups. Some were subjected to complete ligation of left ureter and the others with sham operation were used as control group.Four weeks later, we examined the mRNA expressions of ET-1 in kidneys of all these rats using reverse transcription-polymerase chain reaction (RT-PCR) method.The immunohistochemistry analysis was carried out to investigate the protein level of ET-1. The urinary concentration of ET-1 was determined by radioimmunoassay.Results In UUO group, the urinary concentration of ET-1 increased substantially;both gene expression and protein level of ET-1 were much higher than those in control group. At the same time, tubulointerstitial fibrosis was present in the kidneys of rats with UUO. Conclusion ET-1 is involved in the pathogenesis of the injury of UUO.

Analyses on the trace elements of soils in geo-authentic and non-authentic production areas of Flos lonicearae / 中国中药杂志

<p><b>OBJECTIVE</b>To analyse the trace elements presented in the same germplasm of Flos Lonicerae with the soil in different producing areas of crude drugs and to investigate, the relationship between the trace elements and the characteristics of the geo-authentic Flos Lonicerae in the soil and crude drugs.</p><p><b>METHOD</b>The analyses on the trace elements of soil and crude drugs were made by ICP-AES.</p><p><b>RESULT</b>The contents of Sr, K, Na, Mg and Ca were higher in the geo-authentic areas, and the contents of Ca, Sr and Fe were higher, but the Cr and Pb were lower in the geo-authentic Flos Lonicerae. The geo-authentic crude drugs had a strong tendency to accumulate P and Cu.</p><p><b>CONCLUSION</b>There are no direct relationship between the concentrations of trace elements in Flos Lonicerae and those in their corresponding soil. There are good relationship between the absorption and accumulation of Ca and Cr, Co, Na and Fe; Zn and Co, Cr, Mn; Na and Co; Mg and Mn.</p>

Protective Effects of Bosentan on Kidney in Rats with Unilateral Ureteral Obstruction / 实用儿科临床杂志

Objective To research the effects of bosentan in on unilateral ureteral obstruction (UUO) rats. Methods Wistar rats were randomly divided into three groups. UUO group was subjected to complete ligation of left ureter, sham operation group with sham operation was used as control. Bosenten group was subjected to complete ligation of left ureter and to stomach with bosentan suspension. Three groups were killed at 5,10,15,20 d. We examined renal pathological changes and the expressions of transforming growth factor-?1 (TGF-?1) in kidney of all rats using immunohistochemistry analisis method. The plasma and ureteral obstructive kidney urinary concentration of endothelin - 1 (ET - 1) was determined by radioimmunoassay. Results In Bos and UUO groups, the urinary concentration of ET - 1 increased substantially and the expression of TGF - ?1 were much higher than those in the S group. At the same time.tubulointerstitial fibrosis was present in the kidney of rats in Bos and UUO group. But the expression of TGF- ?1 and tubu-lointerstitial fibrosis in Bos group were lower than those of UUO group. Conclusion Bosentan can effectively amelirate tubulointerstitial fibrosis in rats with UUO by ET and TGF - ?1 machanism.

Stereoselectivity in O-demethylation of trans tramadol in rat liver microsomes in vitro / 药学学报

<p><b>AIM</b>To study the stereoselectivity in O-demethylation of trans tramadol.</p><p><b>METHODS</b>With or without quinine and quinidine as inhibitors, rat liver microsomes were incubated in vitro with the enantiomers or the racemate of trans tramadol. The concentrations of the enantiomers of trans tramadol and O-demethyltramadol in the incubates were determined by high performance capillary electrophoresis. The O-demethylation processes were assayed by using the enzyme kinetic analysis method.</p><p><b>RESULTS</b>After incubation, the concentrations of (-)-O-demethyltramadol were higher than those of (+)-enantiomer in all rat liver microsomal incubates. Enzyme kinetic analysis showed that the Km of the formation of the enantiomers of O-demethyltramadol were similar; The Vmax and Clint of the formation of (-)-O-demethyltramadol were significantly higher than those of the formation of (+)-enantiomer. When the racemate of trans tramadol was used as the substrate, there was interaction between the two enantiomers. The Km of the formation of the enantiomers of O-demethyltramadol increased, the Vmax of the formation of (+)-O-demethyltramadol decreased, the Vmax of the formation of (-)-O-demethyltramadol increased slightly. The O-demethylation of the enantiomers of trans tramadol was shown to be inhibited competitively by quinine and quinidine. The Ki of quinine and quinidine were 1.6 and 10.8 mumol.L-1 to the formation of (-)-O-demethyltramadol, 0.8 and 3.4 mumol.L-1 to the formation of (+)-O-demethyltramadol, respectively. Furthermore, quinine and quinidine were found to have stereoselective inhibition on the formation of O-demethyltramadol, both mainly inhibited the formation of (+)-O-demethyltramadol.</p><p><b>CONCLUSION</b>The O-demethylation of trans tramadol was found to be stereoselective in rat liver microsomes in vitro, preferentially metabolized (-)-enantiomer. The stereoselectivity could be influenced by the interaction between the two enantiomers and the enzyme selective inhibitors.</p>