Biomedical subjects

Y Li

Publications and source records attributed to Y Li.

At least 73 records · Page 4Linked to original sources

PubMed2006

Effect of tacrolimus and cyclosporine A on suppression of albumin secretion induced by inflammatory cytokines in cultured human hepatocytes.

OBJECTIVE AND DESIGN: To investigate the effect of tacrolimus (FK506) and cyclosporine A (CSA) on albumin secretion and on the IL-6 -induced suppression of albumin synthesis in cultured human hepatocytes. METHODS: HepG2 cells were cultured separately with IL-6, IL-10 (0-10 ng/ml) and FK506, CSA (0-100 ng/ml) for 48 h. In another experiment, HepG2 cells were incubated with different amounts of FK506 and CSA (0-10 ng/ml) in the presence of IL-6 (5 ng/ml). The albumin levels in these groups of hepatic cultures were measured by radioimmunoassay. The concentration of LDH secreted by cells stimulated with FK506 and CSA was detected by spectrophotometry. RESULTS: IL-6 decreased the levels of albumin in a dose-dependent manner (P < 0.01), maximal inhibition was observed at 5 ng/ml. Neither IL-10 nor FK506 modulated albumin production. However, FK506 decreased LDH levels in the supernatant of cells (P < 0.05) and prevented the IL-6-induced suppression of albumin synthesis (P < 0.01) in a dose dependent manner. In contrast, CSA caused only a slight decrease in albumin levels (P < 0.05). In addition, CSA slightly increased the amount of LDH in HepG2 cells and did not interfere with the IL-6-induced decrease in albumin synthesis. CONCLUSIONS: These findings suggest that IL-6, but not IL- 10, may play an important role in the suppression of hepatic albumin secretion. FK506 but not CSA protects against the suppression of hepatic albumin synthesis caused by IL-6.

Albumins↗

PubMed2006

Redirecting carbon flux in Torulopsis glabrata from pyruvate to alpha-ketoglutaric acid by changing metabolic co-factors.

The nutrition conditions needed to redirect the carbon flux in Torulopsis glabrata, a pyruvate hyper-production yeast, from pyruvate to alpha-ketoglutaric acid (KG) were investigated in a stirred fermentor. A minor amount of KG (1.3 gl(-1)) was produced when NaOH was used to control the pH, while 12 g KG l(-1) was produced when CaCO(3) was used instead. When thiamine and biotin were included in the medium, 13 g KG l(-1) and 68 g pyruvate l(-1) were produced after 48 h when glucose was nearly consumed (approximately 5 gl(-1)). With fermentation continuing for a further 16 h, the concentration of pyruvate decreased to 31 gl(-1), and KG increased to 30 gl(-1). KG thus accumulated at the expense of pyruvate consumption.

Candida glabrata↗

PubMed2006

Conversion from cyclosporine to mycophenolate mofetil improves expression of A20 in the rat kidney allografts undergoing chronic rejection.

AIMS: Cytoprotective genes have shown to display potent anti-inflammatory and antiapoptotic functions in endothelial and smooth muscle cells. We investigated whether cytoprotective genes, especially A20, were involved in mycophenolate mofetil (MMF)'s ability to ameliorate transplant arteriosclerosis in an experimental chronic rejection model. METHODS: Sprague-Dawley rat renal grafts were orthotopically transplanted into Wistar rats following the procedure of Kamada with our modification. The recipients were divided into three oral treatment groups: (1) vehicle group (cyclosporine [CsA] 10 mg/kg.d x 10 d followed by vehicle), (2) CsA group (CsA 10 mg/kg.d x 10 d followed by CsA 6 mg/kg.d), (3) MMF group (converted from CsA 10 mg/kg.d x 10 d to MMF 20 mg/kg.d on day 11). At the same time points after transplantation, the rats were sacrificed to harvest the renal allografts. The expression of four cytoprotective genes, A20, heme oxygenase (HO)-1, Bcl-2, and Bcl-XL, was analyzed by quantitative reverse-transcriptase polymerase chain reaction and immunohistochemistry. RESULTS: The four-cytoprotective genes were all detected in rat kidney allografts undergoing chronic allograft nephropathy. The expression of A20 in grafted kidneys was significantly higher in the MMF than in the CsA or the vehicle group (P < .01). There was no significant difference between the CsA and the MMF groups in the expression of HO-1, Bcl-2, and Bcl-XL. CONCLUSIONS: We demonstrated that MMF improved the expression of A20 in rat kidney allografts undergoing chronic allograft nephropathy. The correlation between MMF and A20 provide an explanation for the mechanism by which MMF ameliorates transplant arteriosclerosis in an experimental animal model of chronic rejection.

Animals↗

PubMed2006

Comparison of rapamycin versus FK506 on expression of cytoprotective genes in the rat kidney allografts undergoing chronic allograft nephropathy.

AIMS: It is increasingly recognized that expression of cytoprotective genes in grafts can affect the progress of chronic allograft nephropathy (CAN). Little is known about the influence of different immunosuppressive regimens on expression of cytoprotective genes in allografts undergoing CAN. We investigate whether there is difference between rapamycin (Rapa) and FK506 in the expression of cytoprotective genes in rat kidney allografts undergoing CAN. METHODS: Sprague-Dawley rat renal grafts were orthotopically transplanted into Wistar rats following the procedure of Kamada with our modification. The recipients were divided into three oral treatment groups: group 1: vehicle group (cyclosporine [CsA] 10 mg/kg.dx 10 days followed by vehicle); group 2: Rapa group (CsA 10 mg/kg.d x 10 d followed by Rapa 0.8 mg/kg.d); group 3: FK506 group (CsA 10 mg/kg.d x 10 d followed by FK506 0.15 mg/kg.d). At the same times after transplantation, the rats were sacrificed to harvest the renal allografts. The expression of four cytoprotective genes, A20, heme oxygenase (HO)-1, Bcl-2, and Bcl-X/L were analyzed in these grafted kidneys by quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. RESULTS: Four cytoprotective genes were all detected in rat kidney allografts undergoing CAN. The expression of A20 in the Rapa group was significantly higher than that in the FK506 or the vehicle group (P < .05). There was no significant difference between the Rapa group and FK506 group in the expressions of HO-1, Bcl-2, and Bcl-X/L. CONCLUSIONS: We demonstrate that various immunosuppressive agents have different effects on the expression of cytoprotective genes.

Animals↗

PubMed2006

The effect of renal ischemia-reperfusion injury on expression of RAE-1 and H60 in mice kidney.

INTRODUCTION: NKG2D, an activating receptor, may trigger NK and CD8+ T cells. Ligands for NKG2D and major histocompability complex class I chain-related antigen (MIC) have been reported to be expressed in rejected human renal allografts. MIC-NKG2D engagement may induce natural killer (NK) cell activation providing T-cell costimulation. We hypothesized that this interaction between innate and adaptive immunity may occur during kidney ischemia-reperfusion injury (IRI). METHODS: Male C57BL/6 mice after right renal resection were subjected to 35 minutes of left renal ischemia: the ischemic group. Sham-operated mice underwent the same protocol without vascular occlusion. The sham and ischemic kidneys were removed at 2 to 7, 10, 14, or 28 days postoperatively. The normal, sham, and ischemic kidney tissues were collected for reverse-transcriptase polymerase chain reaction, and immunohistochemistry analysis of MIC homologues in mice (Rae-1 and H60). RESULTS: Compared with no expression in sham control and normal kidneys, IRI caused mRNA expression of Rae-1 from 2 to 10 days postoperatively and protein expression of Rae-1 from 2 to 14 days postoperatively in ischemic kidneys. We observed no expression of H60 mRNA or protein in any kidney. CONCLUSION: H60 transcripts have been reported to be present in the BALB/c background but not in C57BL/6. We found IRI did not cause H60 mRNA on protein expression in C57BL/6 kidneys. Rae-1 was absent in normal C57BL/6 kidneys. The IRI-induced expression of the NKG2D ligand, Rae-1, might activate NK and CD8+ T cells. Our results suggested that MIC may be an important link between innate and adaptive immunity in kidney IRI.

Animals↗

PubMed2006

Hypoxia/reoxygenation up-regulated the expression of death receptor 5 and enhanced apoptosis in human hepatocyte line.

OBJECTIVES: Ischemia-reperfusion injury (IRI) is a key factor that contributes to early and late dysfunction of liver graft. Although we have known that hepatocytes express death receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), the effects of TRAIL on hypoxia/reoxygenation (H/R)-mediated apoptosis are unclear. This study sought to examine the effects of H/R on TRAIL cytotoxicity, as a cause of primary hepatic graft dysfunction, delayed graft refunction, and chronic graft dysfunction. METHODS: Using an hepatocyte H/R model in vitro to mimic IRI in the grafted liver, normal human hepatocytes HL-7702 were exposed to hypoxia for 5 hours then reoxygenated for 0, 2, 4, 6, or 20 hours. In another experiment, hepatocytes were exposed to hypoxia for 0, 2, 4, 8, or 20 hours. Expressions of TRAIL-R2/Death receptor 5 (DR5) mRNA were measured by semiquantitative reverse-transcriptase polymerase chain reactions. After 16 hours of hypoxia, human hepatocytes were treated with TRAIL in different concentrations for 5 hours. The death of hepatocytes was confirmed by flow cytometer and methyl thiazolyl tetrazolium analysis. RESULT: After 5-hour hypoxia, the expressions of DR5 mRNA increased at all times of reoxygenation. DR5 mRNA was up-regulated from 0 hour after reoxygenation, reaching a peak value at 2 hours after reoxygenation compared with the normoxia cultured cells. Moreover, DR5 mRNA was up-regulated gradually following prolonged hypoxia. TRAIL-mediated cell killing was concentration-dependent being greater in the hypoxia treatment group compared to the normoxia group. CONCLUSIONS: H/R up-regulated the expression of DR5 and enhanced TRAIL-mediated apoptosis in an human hepatocyte line. The TRAIL pathway might play a critical role in hepatocyte apoptosis induced by IRI.

Apoptosis↗

PubMed2006

Selective depletion of activated T cells by recombinant immunotoxin containing anti-CTLA-4 single-chain fragment of variable antibody and N-terminal fragment of perforin.

We constructed a novel immunotoxin, hS83P34, by fusing the fragment containing the N-terminal 34 amino acids of human perforin to the C-terminal of humanized anti-CTLA-4 single chain fragment of variable antibody. In vitro cytotoxicity assays demonstrated that CTLA-4-positive activated human T cells and 6T-CEM were sensitive to hS83P34, while CTLA-4-negative resting T cells and endothelial cell ECV-304 were resistant to hS83P34. The IC50s of hS83P34 for activated T cells and 6T-CEM were about 0.2 micromol/L and 1.0 micromol/L, there was no obvious cytotoxicity of ECV-304 as detected at 8 micromol/L of hS83P34. In tumor graft rejection models, after treatment with 1.2 mg/kg immunotoxin every day for 12 days, the transplanted tumor cells were rescued by immunotoxin. The tumor weights of grafts of the rejection control group, nonrejection control group, and test group were 0.006 +/- 0.014 g, 0.261 +/- 0.048 g, and 0.135 +/- 0.056 g, respectively. In the early 3 days posttransplantation, there were a lot of CD4- and CD8-positive T cells infiltrating into the tumor grafts of the rejection control group, while only a few T cells were detected in the tumor grafts of the test group. According to these results, we concluded that immunotoxin hS83P34 selectively depleted activated T cells in vitro as well as in vivo in an acute rejection model.

Antigens, CD↗

PubMed2006

Comparison of cyclosporine versus mycophenolate mofetil on expression of Fractalkine and CX3CR1 in chronic allograft nephropathy.

INTRODUCTION: We sought to investigate whether there was a difference between cyclosporine (CsA) and mycophenolate mofetil (MMF) to affect the expression of Fractalkine/CX3CR1 in chronic allograft nephropathy (CAN). METHODS: The Sprague-Dawley Wistar rat accelerated kidney sclerosis model was performed as modified from the procedure of Kamada. Recipients were divided into three oral treatment groups (each group n = 8): group A was CsA 10 mg/kg . d for 10 days followed by vehicle; group B was CsA 10 mg/kg . d for 10 days followed by CsA 6 mg/kg.d; group C was CsA 10 mg/kg . d for 10 days followed by MMF 20 mg/kg . d. Pathological changes graded according to Banff 97 Standards were observed at 4, 8, and 12 weeks posttransplantation. The immunohistochemistry and quantitative real-time fluorescence polymerase chain reaction (PCR) were used to assess the distribution and expression of Fractalkine/CX3CR1 in the grafted kidney. RESULTS: Fractalkine/CX3CR1 were mostly expressed in the tubulointerstitium and tubular epithelial cell basolateral membrane. A proportion of the vessel showed positive staining for Fractalkine/CX3CR1, occasionally in glomerular parietal wall cells. The expression of Fractalkine/CX3CR1 in grafted kidneys at all the time points was significantly less in the MMF than in the CsA group or the control group (P < .05). Real-time fluorescence quantitative PCR revealed similar outcomes as immunohistochemistry. The expression of Fractalkine coincided with CX3CR1. CONCLUSION: Fractalkine/CX3CR1 may play an important role in the development of interstitial fibrosis in CAN. Different immunosuppressants have various effects on expression of the Fractalkine/CX3CR1.

Animals↗

PubMed2006

Effect of cyclosporine on expression of MIC in human hepatocytes.

OBJECTIVES: The human major histocompatibility complex class I chain-related antigen A, B (MICA, B) are believed to be "cell stress sensors," which encode stress-inducible surface proteins that bind to NKG2D, an activating receptor of NK, alpha beta and gamma delta T cells. While cyclosporine (CsA) has improved patient and graft survival rates following solid organ transplantation, its clinical use is often limited by acute and chronic toxicity. Besides ischemia-reperfusion injury, which could up-regulate the expression of MIC, the toxicity of CsA may also be another violent stress factor. The purpose of this study was to investigate whether CsA can affect the expression of MIC. METHODS: Various doses of CsA (5 or 20 microg/mL) was added to cultured human hepatocytes for 1, 3, 5, 8, or 24 hours. The expression of MIC was measured by immunofluorescence using a laser scanning confocal microscope. RESULTS: CsA (5 or 20 microg/mL) upregulated MIC protein expression in hepatocytes at 1 hour, peaking at 3 hours, and persisting until 5 hours (P < .05), returning to normal levels after 8 to 24 hours (P > .05). CONCLUSION: This study reported that CsA up-regulated MIC expression on human hepatocytes. MIC, as a "cellular stress biomarker," may play a significant role in activating NK, T, and B lymphocyte responses associated with transplantation. This study suggested that immunosuppressants produce deterioration in organ function in transplantation.

Cells, Cultured↗

PubMed2006

Expression of fractalkine, CX3CR1, and vascular endothelial growth factor in human chronic renal allograft rejection.

AIM: Fractalkine/CX3CR1 system may contribute to the pathogenesis of renal allograft chronic rejection (CR). Vascular endothelial growth factor (VEGF) is an endothelial mitogen, which shows increased expression in inflammation and vasculopathy. This study sought describe the expression and distribution of Fractalkine/CX3CR1 and VEGF, and their relationship to human renal allograft CR. METHODS: Renal tissue from 10 patients with CR was examined for Fractalkine/CX3CR1 and VEGF protein by immunohistochemistry for comparison with patients displaying hyperacute rejection (n = 10), acute rejection (n = 10), and normal kidneys (n = 10). All patients were selected based upon histologically proven diagnoses between 1992 and 2003. RESULTS: Immunohistochemistry revealed that Fractalkine/CX3CR1 were mostly expressed in the tubulointerstitium and tubular epithelial cell basolateral membrane. Some vessels showed positive staining for Fractalkine/CX3CR1 as well as occasionally glomerular parietal wall cells. Among the CR group, VEGF was mostly expressed in tubular epithelium and the tubulointerstitium. A proportion of glomeruli and vessels had positive staining for VEGF, which was up-regulated most strikingly in the interstitial compartment in CR. There was markedly increased expression of Fractalkine/CX3CR1 and VEGF protein in the interstitium of the CR compared with other groups (P < .05). VEGF colocalized with the expression of Fractalkine/CX3CR1. CONCLUSION: Fractalkine/CX3CR1 and VEGF may play an important role in the development of interstitial fibrosis via mononuclear cell-induced cytokine production and myofibroblast stimulation in CR. Further studies are necessary to identify the role in the pathogenesis of CR.

Acute Disease↗

PubMed2006

Nuclear translocation of SMAD3 may enhance the TGF-beta/SMADS pathway in high glucose circumstances.

OBJECTIVES: Posttransplant diabetes mellitus is one of the most frequent complications after kidney transplantation. It is considered to be one cause of chronic allograft nephropathy. This study sought to investigate the effects of high glucose on the expression and nuclear translocation of Smad3, which is an important signal mediator involved in the fibrotic signal pathway. METHODS: The established rat renal mesangial cell line HBZY-1 was cultured in medium with various concentrations of glucose (4.5 mg/mL, 9.0 mg/mL, or 13.5 mg/mL), which was collected at 7, 14, or 21 days. The total expression of Smad3, including both inner and outer nucleus proteins was examined by Western blot analysis. The nuclear translocated Smad3, representing only the inner nucleus protein, was detected by immunofluorescence staining observed under a laser confocal scanning microscope. RESULTS: No significant difference in the total Smad3 expression was demonstrated by Western blot analysis among the three groups of HBZY-1 cells at various concentration of glucose after 7, 14, or 21 days. There was no fluorescence detected in the nucleus at day 7 by immunofluorescence staining; however, robust positive expression of Smad3 was detected at days 14 and 21. CONCLUSION: As a restricted Smads member, Smad3 protein might not be upregulated in the presence of high glucose. However, with prolonged culture time, Smad3 translocates from cytoplasm to nucleus, which may be a pivotal step in the fibrotic signal pathway.

Animals↗

PubMed2006

The C-terminal peptide of connective tissue growth factor blocks the full molecule binding to tubular epithelial cell.

OBJECTIVES: Interstitial fibrosis is a critical pathologic change in chronic allograft nephropathy. The cytokine connective tissue growth factor (CTGF, also CCN2) plays an important role in epithelial-mesenchymal transformation (EMT) of tubular epithelial cells to renal interstitial fibrosis. The hexadeca-peptide within the C-terminal of CTGF (named P2) contains the unique binding domain of CTGF to its potential receptor, integrin alphavbeta3. This study examined whether P2 bound preferentially to the receptor and served as an inhibitor of CTGF. METHODS: All studies used an established rat kidney tubular epithelial cell line NRK-52E. Chemically synthesized P2 was purified, and some of it labeled with FITC. The affinity of CTGF or P2 to NRK-52E cells was examined by a solid-phase cell adhesion assay. Competitive binding between P2 and CTGF to NRK-52E cells was examined with flow cytometric analysis. RESULTS: Both P2 and CTGF bound to the NRK-52E cells, mediating cell adhesion. When the cells were incubated in the mixture of P2 and CTGF, P2 bound to the cells preferentially. Furthermore, when cells were preincubated with excessive CTGF, it became difficult for subsequent P2 binding to occur. CONCLUSIONS: P2 and CTGF seemed to bind to cell membranes at the same binding domain. P2 competitively blocked CTGF binding, acting as a CTGF inhibitor.

Animals↗

PubMed2006

Construction and characterization of a cDNA library from liver tissue of Chinese Banna minipig inbred line.

A xenograft that performs efficient functions is an essential premise for successful xenotransplantation. Our early study indicated that Chinese Banna minipig inbred line (BMI) was an ideal xenograft donor. However, the activities of some proteins synthesized by the BMI liver are different from the human, which could lead to functional disorders in coagulation, fibrinolysis, and anticoagulation after liver xenotransplantation. Therefore, it is important to investigate the genetic background of protein incompatibility and to provide new strategies for gene manipulation. In this study we constructed a cDNA expression library using BMI liver tissue to obtain an understanding of nucleic acid and protein differences between the two species. We extracted total RNA and purified mRNA of the liver tissue from one of the sixteenth inbred generation of BMI/JS 151 substrain. After double-strand cDNA synthesis, we fractionated it on a CHROMA APIN-400 column; ligated the longer than 500bp cDNA into a ZAP Express Vector; and performed a lambda: phage packaging reaction, library amplification, and titer. We randomly picked 12 plaques and tested the length of inserts. The titers of the primary and amplified libraries were 1.0 x 10(6) pfu/mL and 5.0 x 10(9) pfu/mL, respectively. The percentages of recombinants were 97.0% in the primary library and 98.0% in the amplified library. The lengths of most inserts were between 750 bp and 2.0 kb. Thus, we successfully constructed a cDNA expression library from BMI liver tissue. Using the library, we hope to get a full-length cDNA of some important genes and conduct further studies on porcine liver function in xenotransplantation.

Animals↗

PubMed2006

Expression of H60 on mice heart graft and influence of cyclosporine.

OBJECTIVES: It has been reported that the MHC class I chain-related antigen (MIC), a ligand of NKG2D, an activating receptor of natural killer cells, is expressed on rejected renal allografts. This study investigated whether heart transplantation induced expression of a homologue of MIC (H60) in outbred Kun Ming (KM) mice, widely used in China, and whether CsA had an influence on the process. METHODS: Forty-eight KM female mice were divided into untreated and CsA-treated groups, after cervical heart allotransplantation. Grafts were harvested 1, 3, 5, and 7 days postoperatively. H60 mRNA was analyzed by RT-PCR, and the protein detected by immunohistochemistry. RESULTS: Compared with no mRNA expression in the normal heart, H60 mRNA was observed at day 5 and upregulated on day 7 in the untreated group. It was detected on day 3, peaked on day 5, but was lower than untreated group, and decreased on day 7 in the CsA-treated group. H60 protein was detected in cardiocytes only on day 7 in the untreated group. CONCLUSION: Our study suggested that expression of the NKG2D ligand, H60, may activate natural killer cells playing a significant role in innate immunity associated with transplantation. The early expression of H60 mRNA on day 3 in the CsA-treated group might relate to the toxicity of CsA. The expression peaked on day 5 and decreased on day 7, possibly induced by CsA. The results suggested that H60 might be a new target for prevention of rejection.

Animals↗

PubMed2006

Yisheng injection decreases the expression of H60 and RAE-1 genes in ischemic mice liver.

OBJECTIVE: Major histocompatability complex class I chain-related antigen A, B (MICA, B) functions as ligands for human NKG2D receptors, which may play a role in graft rejection and cellular stress. In this study we explored the effect of ischemia/reperfusion injury (IRI) on the expression of H60 and RAE-1 (MICA, B homologues) in mice to study the protective effect of Yisheng injection (YS), an herbal preparation developed from traditional Chinese medicine. METHODS: Male BALB/c mice were divided into sham, ischemic, and YS-treated groups using 90 minutes of left liver lobe ischemia. Sham control mice underwent the same operation, but without vascular occlusion. In the treated group, YS (20 mg/kg) was given before ischemia and after reperfusion for 7 days. Liver samples collected at 7 days postoperation were used for real-time quantitative polymerase chain reaction analysis, Western blotting, and immunohistochemical assays. RESULTS: Compared with the sham group, H60 and RAE-1 mRNA levels were increased by sevenfold and 4.5-fold in the ischemic group, respectively. After YS treatment, they were reduced by 76% and 70%, respectively. Western blotting and immunohistochemical assays showed that there was absent or faint H60 and RAE-1 expression in sham liver, but they were apparently increased in ischemic liver; however, the expressions were significantly decreased in the presence of YS. CONCLUSIONS: Hepatic IRI significantly increased H60 and RAE-1 expression in mouse liver. YS treatment effectively reduced this increase, seeming to attenuate NKG2D-ligand-mediated immune responses caused by IRI. This may suggest a new concept to prevent IRI and graft rejection.

Animals↗

PubMed2006

Assessment of glomerular filtration rate in renal transplant patients using serum cystatin C.

AIM: Serum cystatin C (SCysC) has been proposed as a better marker of glomerular filtration rate (GFR) than serum creatinine (Scr). However, few data are available in renal transplant patients, especially, during the early postoperative phase. METHODS: Thirty-nine renal transplant patients (22 men/17 women) were recruited for determination of SCysC and Scr before operation, at 1 week and at 4 weeks after operation. SCysC was determined by particle-enhanced turbidimetric immunoassay. Creatinine clearance (Ccr) was calculated using the Cockcroft-Gault formula. RESULTS: SCysC and Scr levels significantly decreased with the recovery of allograft function. SCysC showed a significant correlation with Scr and Ccr. The relationship between SCysC and Scr showed a positive correlation (r = .849 preoperation, and r = .940 postoperation). The relationship between SCysC and Ccr revealed a negative correlation (r = .857 preoperation, and r = .876 postoperation). At the Ccr level of 50 to 80 mL/min/1.73 m(2), the correlation between SCysC and Ccr (r = .778) was significantly better than that between Scr and Ccr (r = .553; P = .032). The concentration of SCysC was not affected by age, gender, height, body weight, hemoglobin, serum protein, glucose, or mycophenolate mofetil or azathioprine dosage. However, corticosteroids slightly increased the level of SCysC and cyclosporine (CsA) decreased it. The area under the curve of the receiver operating characteristic curve for SCysC and Scr are 0.964 and 0.915, respectively (P < .05). CONCLUSION: Although the concentration may be slightly influenced by prednisolone and CsA, SCysC is more sensitive than Scr to detect early and moderate deterioration of GFR in adult renal transplant recipients.

Biomarkers↗

PubMed2006

Immunological advantage on small bowel graft induced by simultaneously transplanted liver in porcine auxiliary liver/small bowel transplantation.

BACKGROUND: We developed a new porcine model for auxiliary liver/small bowel transplantation (LSBT). The possible immunological advantage on small bowel graft induced by simultaneously transplanted liver in the large animal was assessed. METHODS: Thirty outbreed long-white pigs were randomized into two groups. Group A animals received LSBT without immunosuppressive treatment (n = 10). Group B animals had segmental small bowel allotransplantation without immunosuppressive treatment (n = 10). The postoperative survival time, initial acute rejection time, and pathological rejection scores were analyzed. RESULTS: There was no remarkable difference in survival time between groups A and B (10.33 days vs 12.89 days, P > .05), but the initial time of acute rejection in intestinal grafts in group A was obviously delayed when compared to group B (8.22 days vs 4.33 days, P < .05), and the rejection scores in group A were remarkably lower than those of group B (0 vs 0.44 on postoperative day (POD) 3, P < .05; 0.22 vs 1.78 on POD 5, P < .05; 1.11 vs 2.56 on POD 7, P < .05). CONCLUSIONS: An immunological advantage on intestinal graft can be induced by simultaneously transplanted liver in auxiliary LSBT. Compared to isolated segmental small bowel allotransplantation, the intestinal graft in LSBT has a delayed initial time of acute rejection and lower acute rejection scores. The liver graft may reduce the risk of intestinal rejection and thus protect the bowel graft.

Acute Disease↗

PubMed2006

Blood pressure and urinary sodium excretion in relation to the A-1984G adrenomedullin polymorphism in a Chinese population.

Adrenomedullin (ADM) is a vasodilator and inhibits salt appetite. An A-to-G substitution at position -1984 in the promoter region of the ADM gene likely increases transcription. We therefore investigated this polymorphism in relation to blood pressure and urinary sodium in a Chinese population. We genotyped 427 Chinese enrolled in a family-based population study. We measured blood pressure by conventional sphygmomanometry and ambulatory monitoring. The frequencies of the ADM AA, AG, and GG genotypes were 50.6, 38.2, and 11.2%, respectively. In adjusted analyses, G allele carriers, compared to AA homozygotes, had significantly lower conventional (45.3 versus 48.5 mm Hg, P = 0.004) and 24-h (42.6 versus 44.3 mm Hg, P = 0.03) pulse pressures and urinary sodium excretion (143.8 versus 159.4 mmol/day, P = 0.03). In parents, but not offspring, both systolic pressure and pulse pressure were significantly (P<0.01) lower in G allele carriers. The genotypic difference in sodium excretion was consistent across the age range. In 68 informative offspring, transmission of the G allele was associated with lower urinary sodium excretion (effect size, 40.1 mmol/day, P = 0.01). In 81 healthy volunteers, the plasma ADM concentration was 15.2% higher in GG homozygotes than in sex- and age-matched AA subjects (11.4 versus 9.9 pmol/l, P = 0.10). In conclusion, in Chinese, the ADM -1984G allele is associated with lower sodium excretion and in older subjects also with lower systolic pressure and narrower pulse pressure.

Adrenomedullin↗