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Hui Zhang

Publications and source records attributed to Hui Zhang.

At least 163 records · Page 9Linked to original sources

The existence of a linear system consisting of sympathetic endings in rat skin.

In a previous pilot study we suggested the novel notion that the catecholaminergic sympathetic nerve endings are non-homogeneously distributed in the rat skin. In the present study we have utilized several independent methods to determine the in vivo distribution of catecholamine-containing fibers in rat skin. Using whole body macro-autoradiography with an iodine125-labeled tyrosine, we localized the distribution of iodine-125-catecholamine in rat skin. The images on the film showed various pairs of symmetrical linear arrays running from the head through the back and to the hind limbs of the animal that we arbitrarily termed sympathetic substance lines (SSLs). The distribution of catecholamine in rat skin was also visualized by light microscopy autoradiography with tritiated tyrosine. The majority of silver grains in the sections were located among hair follicles along a band or zone. Furthermore, a modified sucrose-phosphate-glyoxilic acid (SPG) method was adapted to observe sympathetic fibers in the skin sections. Dense clusters of fluorescent nerve fibers in correspondence of arrector pili muscles (AP muscles) were located along lengthwise lines of the body, in a pattern coinciding with the linear arrays identified by macro-autoradiography. We concluded that concentrated clusters of noradrenergic nerve fibers innervate AP muscles and form a longitudinal linear system in the whole skin. These results are discussed in terms of physiological functions associated with hair follicles, sensory signal pathways and Meridians in Chinese traditional medicine.

Animals↗

Optimization of Fenton process for the treatment of landfill leachate.

The treatment of landfill leachate by Fenton process was carried out in a batch reactor. The effect of operating conditions such as reaction time, pH, H2O2 to Fe(II) molar ratio, Fenton's reagent dosage, initial COD strength, feeding mode, the type of polymer, and temperature on the efficacy of Fenton process was investigated. It is demonstrated that Fenton's reagent can effectively degrade leachate organics. Fenton process was so fast that it was complete in 30 min. The oxidation of organic materials in the leachate was pH dependent and the optimal pH was 2.5. The favorable H2O2 to Fe(II) molar ratio was 1.5, and organic removal increased as dosage increased at the favorable H2O2 to Fe(II) molar ratio. The efficacy of Fenton process was improved by adding Fenton's reagent in multiple steps than that in a single step. Furthermore, the stepwise addition of both hydrogen peroxide and ferrous iron was more effective than that of hydrogen peroxide only. Sludge settling characteristics were much improved with the addition of the proper polymer. Temperature gave a positive effect on organic removal.

Environmental Pollutants↗

Chlamydia pneumoniae burden in carotid arteries is associated with upregulation of plaque interleukin-6 and elevated C-reactive protein in serum.

OBJECTIVE: Chlamydia pneumoniae (Cpn) infection of vascular smooth muscle cells increases interleukin-6 (IL-6) secretion in vitro. In vivo, IL-6 stimulates liver C-reactive protein (CRP) production. Because serum levels of IL-6 and CRP are independent risk factors for stroke and myocardial infarction (MI), we investigated whether Cpn burden in carotid plaques might provide a link between plaque IL-6 expression and elevated serum levels of IL-6 and CRP. METHODS AND RESULTS: Consecutive patients undergoing elective carotid endarterectomy were studied. Serum levels of CRP and IL-6 were measured before surgery. Immunohistochemistry and real-time quantitative (k)RT-PCR were used to detect Cpn and the expression of IL-6 within carotid plaques. Cpn mRNA was present in 19 (37%) of 51 patients, suggesting viable infections. These patients had evidence for infection by PCR and immunohistochemistry. The Cpn burden, measured by real-time quantitative (k)-PCR using the number of organisms normalized against the number of eukaryotic cells in the tissue, was associated with plaque expression of IL-6 (Spearman R=0.55; P<0.0001), which was associated with serum levels of IL-6 (R=0.56; P<0.0001) and CRP (R=0.80; P<0.0001). CONCLUSIONS: IL-6 secretion in atherosclerotic plaques infected with Cpn could explain elevated serum inflammatory markers in individuals at risk for stroke and MI.

Aged↗

Expression and function of COX isoforms in renal medulla: evidence for regulation of salt sensitivity and blood pressure.

Expression of cyclooxygenase (COX)-2, but not COX-1, in the renal medulla is stimulated by chronic salt loading; yet the functional implication of this phenomenon is incompletely understood. The present study examined the cellular localization and antihypertensive function of high-salt-induced COX-2 expression in the renal medulla, with a parallel assessment of the function of COX-1. COX-2 protein expression in response to high-salt loading, assessed by immunostaining, was found predominantly in inner medullary interstitial cells, whereas COX-1 protein was abundant in collecting duct (CD) and inner medullary interstitial cells and was not affected by high salt. We compared mRNA expressions of COX-1 and COX-2 in CD vs. non-CD cells isolated from aquaporin 2-green fluorescent protein transgenic mice. A low level of COX-2 mRNA, but a high level of COX-1 mRNA, as determined by real-time RT-PCR, was detected in CD compared with non-CD segments. During high-salt intake, chronic infusions of the COX-2 blocker NS-398 and the COX-1 blocker SC-560 into the renal medulla of Sprague-Dawley rats for 5 days induced approximately 30- and 15-mmHg increases in mean arterial pressure, respectively. During similar high-salt intake, COX-1 knockout mice exhibited a gradual, but significant, increase in systolic blood pressure that was associated with a marked suppression of urinary PGE2 excretion. Therefore, we conclude that the two COX isoforms in the renal medulla play a similar role in the stabilization of arterial blood pressure during salt loading.

Animals↗

[Molecular mechanism of cyclooxygenase-2 inhibitor in inhibition of proliferation of colon cancer cells by modulating Stat5 signal transduction pathway].

OBJECTIVE: To investigate the role of NS398, a selective cyclooxygenase (COX)-2 inhibitor, in proliferation and apoptosis of colorectal cancer, and to reveal the mechanism of inhibiting colon cancer by NS-398 Independent of COX-2. METHODS: Human colon cancer cells of the line SW480 were cultured and then divided into 2 groups: experimental group and control group. NS398 of the concentrations of 12.5, 25, 50, 75, 100, and 125 micromol/L was added into the culture fluid of the experimental group. MTT assay was used to observe the proliferation of the cells, flow cytometry was used to test the cell cycle, RT-PCR analysis was performed to examine COX-2 mRNA expression, and Western blotting analysis was performed to detect the expression of Stat5, peroxisome proliferators-activated receptors (PPARs), cyclin D1 and Bcl-x(L). RESULTS: Expression of COX-2 mRNA was not detected in the SW480 colon cancer cells. 72 hours after the addition of NS398 75 micromol/L the proliferative level of the SW480 cells was decreased; the rate of the cells at the G(1) stage increased from 31.2% to 40.6%, and the rate of cells at the S stage decreased from 52.8% to 41.2%. The expression of Stat5, PPARdelta, cyclin D1 and Bcl-x(L) decreased along with the elongation of time of NS398 action. CONCLUSION: COX-2 inhibitor, such as NS-398 inhibits the colon cancer cell proliferation and induces apoptosis of colon cancer cells with the possible mechanism of inhibiting the proliferation and inducing the apoptosis of colon cancer cells through a pathway independent of COX-2.

Apoptosis↗

Small heat-shock proteins function in the insoluble protein complex.

Small heat-shock proteins (sHSPs) represent an abundant and ubiquitous family of molecular chaperones. The current model proposes that sHSPs function to prevent irreversible aggregation of non-native proteins by forming soluble complex. The chaperone activity of sHSPs is usually determined by the capacity to suppress thermally or chemically induced protein aggregation. However, sHSPs were frequently found in the insoluble complex particularly in vivo. In this report, it is clearly revealed that the insoluble sHSP/substrate complex is formed when sHSP is overloaded with non-native substrates, which is the very case under in vivo conditions. The proposal that sHSPs function to prevent the protein aggregation seems misleading. sHSPs appear to promote the elimination of protein aggregates by incorporating into the insoluble protein complex.

Escherichia coli↗

Synthesis and field emission characteristics of bilayered ZnO nanorod array prepared by chemical reaction.

The uniform, large-scale, and bilayered ZnO nanorod array on silicon substrate has been synthesized by a catalyst and template-free chemical reaction in a dilute solution. The effect of different precursor ZnO films on the morphology and size of the ZnO nanorod array has been investigated. Moreover, the morphology evolution of the ZnO nanorod array with the increase of reaction time indicates that the second growth is the reason for the decrease of the ZnO nanorod diameter and the formation of the bilayered ZnO nanorod array. Finally, the field emission from the ZnO nanorod array with different diameters is presented.

Journal Article↗

High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival.

Aberrant activation of Notch receptors has been shown to cause mammary tumors in mice. We therefore used in situ hybridization to analyze expression of Notch ligands and receptors in human breast cancer. High levels of JAG1 and NOTCH1 were noted in a subset of tumors with poor prognosis pathologic features (P < 0.05). We therefore used tissue microarrays to analyze the expression of these genes in a collection of breast cancers from patients representing a wide spectrum of clinical stages, and from whom associated follow-up survival data was available (n = 184). Patients with tumors expressing high levels of JAG1 or NOTCH1 had a significantly poorer overall survival compared with patients expressing low levels of these genes [5-year survival rate of 42% versus 65% and median survival of 50 versus 83 months, respectively, for JAG1(Hi vs. Lo) (P = 0.01); 49% versus 64% and 53 versus 91 months, respectively, for NOTCH1(Hi vs. Lo) (P = 0.02)]. Moreover, a synergistic effect of high-level JAG1 and high-level NOTCH1 coexpression on overall survival was observed (5-year survival rate of 32% and median survival of 40 months; P = 0.003). These data (a) identify novel prognostic markers for breast cancer, (b) suggest a mechanism whereby Notch is activated in aggressive breast tumors, and (c) may identify a signaling pathway activated in poor prognosis breast cancer which can be therapeutically targeted.

Adult↗

Chain structures in alkali metal borophosphates: synthesis and characterization of K3[BP3O9(OH)3] and Rb3[B2P3O11(OH)2].

Two new alkali metal borophosphates, K3[BP3O9(OH)3] and Rb3[B2P3O11(OH)2], were synthesized by applying solvothermal techniques using ethanol as solvent. The crystal structures were solved by means of single-crystal X-ray diffraction (K3[BP3O9(OH)3], monoclinic, C2/c (No. 15), a = 2454.6(8) pm, b = 736.3(2) pm, c = 1406.2(4) pm, beta = 118.35(2) degrees , Z = 8; Rb3[B2P3O11(OH)2], monoclinic, P2(1)/c (No. 14), a = 781.6(2) pm, b = 667.3(2) pm, c = 2424.8(5) pm, beta = 92.88(1) degrees , Z = 4). Both crystal structures comprise borophosphate chain anions. While for the rubidium compound a loop-branched chain motif is found as common for most of the chain anions in alkali metal borophosphates, the crystal structure of the potassium phase comprises the first open-branched chain with the highest phosphate content found so far in this group of compounds. Both chain anions are closely related to known anhydrous or hydrated phases, and the structural relations are discussed in terms of how the presence of OH groups and hydrogen bonds as well as number, charge, and size of charge balancing cations influence the 3D structural arrangement. The anionic entities are classified in terms of general principles of structural systematics for borophosphates.

Journal Article↗

Identification of a novel protein for memory regulation in the hippocampus.

Memory formation, maintenance, and retrieval are a dynamic process, reflecting a combined outcome of new memory formation on one hand, and older memory suppression/clearance on the other. Although much knowledge has been gained regarding new memory formation, less is known about the molecular components and processes that serve the function of memory suppression/clearance. Here, we report the identification of a novel protein, termed hippyragranin (HGN), that is expressed in the rat hippocampus and its expression is reduced by hippocampal denervation. Inhibition of HGN by antisense oligonucleotide in area CA1 results in enhanced performance in Morris water maze, as well as elevated long-term potentiation. These results suggest that HGN is involved in negative memory regulation.

Animals↗

Amelioration of intestinal ischemia-reperfusion injury with intraluminal hyperoxygenated solution: studies on structural and functional changes of enterocyte mitochondria.

BACKGROUND: The aim of this study was to investigate the effects of intraluminal hyperoxygenated solution (HOS) on enterocyte mitochondrial structure and respiratory function after intestinal ischemia-reperfusion (IR) in rabbits. MATERIALS AND METHODS: Thirty-two rabbits were divided randomly into four groups: control group in which sham operation was performed (Sham group), ischemia-reperfusion group (IR group), and two HOS treatment groups (H1 group and H2 group). Intestinal IR model was produced by clamping superior mesenteric artery (SMA) with an atraumatic vascular clamp for 1 h, followed by reperfusion for 2 h. Animals in the H1 group and H2 group received intraluminal HOS infusion for 1 h immediately after occlusion of SMA, and the rates of infusion were 10 and 20 mL/kg.h, respectively. After 2 h of reperfusion, enterocyte mitochondria morphological quantitative analysis was made with electron microscopy and biogenetics stereology, and the following parameters, including mitochondrial respiratory control ratio (RCR), intestinal O(2) extraction ratio (ER), and mucosal ATP contents, were measured, respectively. RESULTS: After IR, the mitochondria was severely swollen with broken cristae, and mean transaction area, diameter, surface density, and volume density of the mitochondria increased significantly. Meanwhile, specific surface and numeral density of the mitochondria decreased significantly. The mitochondrial RCR, intestinal O(2) ER, and mucosal ATP contents were all decreased significantly. There were no differences in all parameters between the IR group and H1 group. In the H2 group, the mitochondria were slightly swollen, and mean transaction area, diameter, surface density, and volume density of the mitochondria were all significantly lower, with the specific surface and numeral density of the mitochondria significantly higher compared with the IR group. The mitochondrial RCR, intestinal O(2) ER and mucosal ATP contents in H2 group were all significantly higher than those in IR group. CONCLUSIONS: Intraluminal HOS infusion at 20 mL/kg.h during ischemia ameliorates structural and functional changes of enterocyte mitochondria associated with intestinal IR injury, which is a safe, simple, and effective measure to protect the intestine from IR injury.

Adenosine Triphosphate↗

Apoptosis induced by one new podophyllotoxin glucoside in human carcinoma cells.

4-Demethyl-picropodophyllotoxin 7'-O-beta-D-glucopyranoside (4DPG), a new podophyllotoxin glucoside, was isolated from the rhizomes of Sinopodophyllum emodi (Wall.) Ying and showed cytotoxic effects in human carcinoma cells. Among the target cells (HeLa, A2 and SH-SY5Y), the cytotoxic effects of 4DPG showed dose- and time-dependency. Furthermore, the cervical carcinoma cell line, HeLa, was more sensitive to 4DPG. Flow cytometric analysis demonstrated the presence of apoptotic cells with low DNA content, a decrease of cell population at the G1 phase, and a concomitant increase of cell population at the G2/M phase. 4DPG also caused DNA fragmentation in HeLa cells. Treatment with 0.1 microM 4DPG increased p53 expression and Bax/Bcl-2 ratio in HeLa cells, as well as in A2 cells. These results suggested that 4DPG-induced apoptosis might be through a p53-dependent pathway.

Antineoplastic Agents, Phytogenic↗

[The prognostic significance of preoperative plasma level of osteopontin in combination with intercellular adhesion molecule-1 for patients with hepatocellular carcinoma].

OBJECTIVE: To investigate the enhanced predictive activity of preoperative plasma osteopontin (OPN) level in combination with intercellular adhesion molecule-1 (ICAM-1) for recurrence and prognosis of patients after resection of hepatocellular carcinoma (HCC). METHODS: A total of 75 patients received liver resection for HCC from August 2001 to December 2001 in authors' institute were enrolled in this study. The preoperative plasma levels of OPN and ICAM-1 were detected by ELISA, and the association of them combination with the recurrence and prognosis of HCC patients was analyzed. RESULTS: OPN and ICAM-1 could be detected in all of the plasma samples of the tested patients. A significantly higher OPN level and ICAM-1 level were found in plasma of patients who were found to have HCC recurrence during the follow-up time compared with those without recurrence (210.40 vs. 154.86 ng/ml, P = 0.001; 1011.23 vs. 747.49 ng/ml, P = 0.027). A significant difference of OS and DFS were found in different subgroups with higher or lower level of OPN (625 vs. 808 days, P = 0.0006; 433 vs. 674 days, P = 0.0003); and a similar situation was found in patients of high- and low- ICAM-1 levels (651 vs. 794 days, P = 0.0269; 489 vs. 642 days, P = 0.0248). The 2-year recurrence rates of the patients with higher and lower plasma levels of both OPN and ICAM-1 were 87.50% and 28.00% (P < 0.001), respectively; and the 2-year OS rates were 37.50% and 88.00% (P = 0.001), and the 2-year DFS rates were 12.50%, and 76.00 (P = 0.001), respectively. CONCLUSIONS: The evaluation of preoperative plasma level of OPN or ICAM-1 may be helpful to predict the recurrence and prognosis of HCC patients in advance. The assessment of OPN level in combination with ICAM-1 could stratify patients into groups with different potentials of HCC recurrence and different outcomes more accurately than OPN or ICAM-1 individually.

Adult↗

A software suite for the generation and comparison of peptide arrays from sets of data collected by liquid chromatography-mass spectrometry.

There is an increasing interest in the quantitative proteomic measurement of the protein contents of substantially similar biological samples, e.g. for the analysis of cellular response to perturbations over time or for the discovery of protein biomarkers from clinical samples. Technical limitations of current proteomic platforms such as limited reproducibility and low throughput make this a challenging task. A new LC-MS-based platform is able to generate complex peptide patterns from the analysis of proteolyzed protein samples at high throughput and represents a promising approach for quantitative proteomics. A crucial component of the LC-MS approach is the accurate evaluation of the abundance of detected peptides over many samples and the identification of peptide features that can stratify samples with respect to their genetic, physiological, or environmental origins. We present here a new software suite, SpecArray, that generates a peptide versus sample array from a set of LC-MS data. A peptide array stores the relative abundance of thousands of peptide features in many samples and is in a format identical to that of a gene expression microarray. A peptide array can be subjected to an unsupervised clustering analysis to stratify samples or to a discriminant analysis to identify discriminatory peptide features. We applied the SpecArray to analyze two sets of LC-MS data: one was from four repeat LC-MS analyses of the same glycopeptide sample, and another was from LC-MS analysis of serum samples of five male and five female mice. We demonstrate through these two study cases that the SpecArray software suite can serve as an effective software platform in the LC-MS approach for quantitative proteomics.

Amino Acid Sequence↗

[Standard treatment of liver malignancies with radiofrequency ablation].

OBJECTIVE: To investigate the role of standard treatment with ultrasound-guided radiofrequency ablation (RFA) in improving the treatment level of liver malignancies. METHODS: 302 patients with 476 liver malignancies were treated with established protocol and adjuvant measures and subjected to efficiency analysis. In the 302 patients, 181 had 282 hepatocellular carcinomas (HCC) with a mean diameter of 4.2 cm, and 121 had 194 metastatic liver carcinomas (MLC) with a mean diameter of 3.9 cm. According to UICC-TNM system 50 patients (27.6%) were in stage I/II and 131 (72.4%) in stage III/IV (including 39 patients with recurrent HCC after surgical resection). A standard protocol and an individualized protocol were used to treat the tumors based on their size, shape and special location such as the distance from diaphragm, gallbladder and gastrointestinal tract. Needle placement method and operation skill for the tumor region adjacent to important structures were described. Some adjuvant measures such as supplementary fine needle localization, local saline injection and feeding vessel ablation were used to improve RFA efficacy in tumors with different features. Local ablation of bleeding site and haemostatic administration systemically were adopted to deal with bleeding. For the patients with tumor adjacent to gastrointestinal tract, prolonged fasting after the RFA procedure was required. the patients were followed up regularly to assess the treatment efficiency, and the tumor was considered complete necrosed if no viability was found on enhanced CT or enhanced US one month after RFA. RESULTS: The tumor necrosis rate was 95.7% (270/282 tumors) for HCC, 94.8% (184/194 tumors) for MLC, 91.1% (51/56 tumors) for tumor near gastrointestinal tract, 88.5% (69/78 tumors) for tumors near diaphragm, and 94.3% (49/52 tumors) for tumor near gallbladder. The local recurrence rate was 10.3% (29/282 tumors) for HCC and 14.4% (28/194 tumors) for MLC. The 1, 2 and 3 year overall survival rates were 87.6%, 67.4% and 58.6% in the HCC patients, and 87.4%, 48.2%, 25.3% in the MLC patients respectively. The 1, 2 and 3 year survival rates of 50 HCC patients in early (I-II) stages were 90.7%, 85.9% and 73.7%, respectively. The incidence of complications was 2.2% (13/583 sessions), including 5 cases of hemorrhage, 1 case colon perforation, 8 cases of injury of adjacent structures. CONCLUSION: Application of proper protocol and adjuvant measures plays an important role in improving tumor ablation rate. Knowledge about possible complications and their control may increase the treatment efficacy and help to promote the use of RFA technique.

Carcinoma, Hepatocellular↗

Amino acid promoted CuI-catalyzed C-N bond formation between aryl halides and amines or N-containing heterocycles.

CuI-catalyzed coupling reaction of electron-deficient aryl iodides with aliphatic primary amines occurs at 40 degrees C under the promotion of N-methylglycine. Using l-proline as the promoter, coupling reaction of aryl iodides or aryl bromides with aliphatic primary amines, aliphatic cyclic secondary amines, or electron-rich primary arylamines proceeds at 60-90 degrees C; an intramolecular coupling reaction between aryl chloride and primary amine moieties gives indoline at 70 degrees C; coupling reaction of aryl iodides with indole, pyrrole, carbazole, imidazole, or pyrazole can be carried out at 75-90 degrees C; and coupling reaction of electron-deficient aryl bromides with imidazole or pyrazole occurs at 60-90 degrees C to provide the corresponding N-aryl products in good to excellent yields. In addition, N,N-dimethylglycine promotes the coupling reaction of electron-rich aryl bromides with imidazole or pyrazole to afford the corresponding N-aryl imidazoles or pyrazoles at 110 degrees C. The possible action of amino acids in these coupling reactions is discussed.

Amines↗

[Efficacy of radiofrequency ablation of 343 patients with hepatic tumor and the relevant complications].

OBJECTIVE: To investigate the treatment efficacy of radiofrequency ablation (RFA) of hepatic tumors and the relevant complications. METHODS: A total of 343 patients with 778 hepatic tumors underwent ultrasound-guided RFA (582 procedures). There were 212 cases of hepatic cellular carcinoma (HCC) with 448 tumors, and the average largest diameter was 4.0 cm. Of all the patients, 63 (29.7%) were in the stage of I-II (UICC Systems) and 149 (70.3%) in stage of III-IV (including 43 patients with tumor recurrence after surgical resection). There were 131 cases of metastatic liver carcinoma (MLC), with 330 metastases in the liver, the average diameter was 3.9 cm, and the liver metastases of 91 patients (69.5%) came from gastrointestinal tract. The patients were treated using the relatively standard protocol. Crucial attention must be paid to monitoring the abnormal changes in ultrasound images as well as the vital signs of the patients to find the possible hemorrhage and peripheral structure injury in time. The tumors were considered ablated successfully if no viability was found on enhanced CT within 24 hours or 1 month after RFA. The patients were followed up for 2-62 months. RESULTS: The ablation success rate for HCC was 95.5% (428/448 tumors), and the rate for MLC was 96.4% (318/330 tumors). The local tumor recurrence rates for HCC and MLC were 8.5% (38/448 tumors) and 11.8% (39/330 tumors), respectively. A total of 138 patients (40.2%) underwent repeated ablations for 2-11 times because of tumor recurrence or metastasis. The first, second and third years survival rates were 87.7%, 67.4% and 56.8% for HCC patients, 81.6%, 50.8% and 27.2% for MLC patients, respectively. The survival rate from 63 early-stage HCC patients were 92.9%, 82.8% and 74.5%, respectively. The major complication rate in this study was 2.4% (14 of 582 procedures). The complications which consisted of mechanical and thermal injuries usually occurred during or shortly after the RFA treatment. There were 5 hemorrhages, 1 colon perforation, 5 injuries of adjacent structures, 2 bile leakages and 1 skin burn. CONCLUSION: RFA, as a minimally invasive local treatment, has become an effective and relatively safety alternative for the patients of hepatic tumors, even of advanced live tumor, tumor recurrence, liver metastases which are unresectable or difficult to treat with traditional therapies. Knowledge about possible complications and their control may increase the treatment efficacy and help to promote the use of RFA technique.

Adult↗

Collecting duct-specific deletion of peroxisome proliferator-activated receptor gamma blocks thiazolidinedione-induced fluid retention.

The peroxisome proliferator-activated receptor subtype gamma (PPARgamma) ligands, namely the synthetic insulin-sensitizing thiazolidinedione (TZD) compounds, have demonstrated great potential in the treatment of type II diabetes. However, their clinical applicability is limited by a common and serious side effect of edema. To address the mechanism of TZD-induced edema, we generated mice with collecting duct (CD)-specific disruption of the PPARgamma gene. We found that mice with CD knockout of this receptor were resistant to the rosiglitazone- (RGZ) induced increases in body weight and plasma volume expansion found in control mice expressing PPARgamma in the CD. RGZ reduced urinary sodium excretion in control and not in conditional knockout mice. Furthermore, RGZ stimulated sodium transport in primary cultures of CD cells expressing PPARgamma and not in cells lacking this receptor. These findings demonstrate a PPARgamma-dependent pathway in regulation of sodium transport in the CD that underlies TZD-induced fluid retention.

Aldosterone↗