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Tun-Jun Tsai

Publications and source records attributed to Tun-Jun Tsai.

At least 19 recordsLinked to original sources
PubMed2006

The association of higher depressive symptoms and sexual dysfunction in male haemodialysis patients.

BACKGROUND: The prevalence of sexual dysfunction among male haemodialysis patients is high. Sexual dysfunction is composed of both physiological and psychological factors. However, the role of psychological depression is still obscure. METHODS: A multicentre cross-sectional study of 411 male haemodialysis patients was conducted to define the determinants of sexual dysfunction. Mid-week pre-dialytic biochemical and haematological parameters were obtained. All patients were required to complete three questionnaires by themselves: (i) the International Index of Erectile Function (IIEF, Chinese version); (ii) the Beck Depression Inventory (BDI, Chinese version) and (iii) the 36-item Short Form Health Survey Questionnaire (SF-36, Taiwan Standard Version 1.0). RESULTS: In total, 154 male patients completed the IIEF questionnaire. Their mean age was 50.2 +/- 10.7 years. A linear multivariable regression analysis demonstrated advanced age, diabetes and the presence of depressive symptoms to be independently associated with sexual dysfunction. Subjects with sexual dysfunction had significantly lower quality of life scores. CONCLUSIONS: The presence of depressive symptoms, highly prevalent in haemodialysis patients, is an independent factor of sexual dysfunction in male haemodialysis patients. In a comprehensive approach to the management of sexual dysfunction, a thorough evaluation of psychological depression must be included.

Cross-Sectional Studies↗
PubMed2006

Early activation of bradykinin B2 receptor aggravates reactive oxygen species generation and renal damage in ischemia/reperfusion injury.

The kallikrein/kinin system is beneficial in ischemia/reperfusion injury in heart, controversial in brain, but detrimental in lung, liver, and intestine. We examined the role of the kallikrein/kinin system in acute ischemia/reperfusion renal injury induced by 40 min occlusion of the renal artery followed by reperfusion. Rats were infused with tissue kallikrein protein 5 days before (pretreated group) or after (treated group) ischemia. Two days later, the pretreated group exhibited the worst renal dysfunction, followed by the treated group, then the control group. Kallikrein increased tubular necrosis and inflammatory cell infiltration with generation of more tumor necrosis factor-alpha and monocyte chemoattractant protein-1. Reactive oxygen species (ROS), malondialdehyde, and reduced/oxidized glutathione measurement revealed that the oxidative stress was augmented by kallikrein administration in both ischemic and reperfusion phases. The groups with more ROS generation also had more apoptotic renal cells. The deleterious effects of kallikrein on ischemia/reperfusion injury were reversed by cotreatment with bradykinin B2 receptor (B2R) antagonist, but not B1 receptor antagonist, and were not associated with hemodynamic changes. We conclude that early activation of B2R augmented ROS generation in ischemia/reperfusion renal injury, resulting in subsequent apoptosis, inflammation, and tissue damage. This finding suggests the potential application of B2R antagonists in acute ischemic renal disease associated with bradykinin activation.

Animals↗
PubMed2006

Diltiazem suppresses collagen synthesis and IL-1beta-induced TGF-beta1 production on human peritoneal mesothelial cells.

BACKGROUND: After long-term treatment with continuous ambulatory peritoneal dialysis (CAPD), some patients may develop peritoneal fibrosis. Peritoneal mesothelial cells (PMCs) participate in the inflammatory reactions in the peritoneal cavity, and transforming growth factor-beta1 (TGF-beta1) and interleukin-1beta (IL-1beta) are involved in peritoneal fibrosis. Diltiazem is used frequently in patients with CAPD to treat hypertension. The objectives of this study were to examine the effects of diltiazem on collagen- and IL-1beta-induced TGF-beta1 production on human PMCs and the signalling pathway of diltiazem in this induction. METHODS: Human PMCs were cultured from the enzymatic disaggregation of human omentum. Collagen synthesis was measured by [3H]proline incorporation into pepsin-resistant, salt-precipitated collagen. The expression of collagen I and III, and TGF-beta1 mRNA was evaluated by northern blotting. The production of TGF-beta1 by human PMCs was measured by immunoassay. The changes of intracellular calcium level after adding Fura-2-AM were measured by fluorescence spectrophotometry. Western blotting was used to assess mitogen-activated protein kinase (MAPK) signalling proteins. RESULTS: We found that diltiazem (<0.2 mM) inhibited collagen I and III mRNA expression and collagen syntheses on a dose-dependent basis. Diltiazem (0.2 mM) suppressed IL-1beta- (5 ng/ml) induced TGF-beta1 production on human PMCs at both the protein and mRNA levels. Diltiazem (0.2 mM) also inhibited IL-1beta- (5 ng/ml) induced collagen I and III mRNA expression. Intracellular calcium levels did not change after the treatment with diltiazem, IL-1beta or both. The IL-1beta-treated human PMCs increased phospho-JNK (stress-activated c-Jun N-terminal kinase) and phospho-p38 MAPK expression, while diltiazem could suppress this phenomenon. CONCLUSIONS: Diltiazem suppressed collagen synthesis of human PMCs and inhibited IL-1beta-induced TGF-beta1 production on human PMCs. This signalling transduction may be through p38 MAPK and JNK pathways instead of intracellular calcium. These results suggest diltiazem to be a potential therapeutic regimen in preventing peritoneal fibrosis and support further in vivo studies.

Analysis of Variance↗
PubMed2006

Poor renal outcome of antineutrophil cytoplasmic antibody negative Pauci-immune glomerulonephritis in Taiwanese.

BACKGROUND/PURPOSE: Pauci-immune glomerulonephritis (GN) is an important cause of crescentic GN, acute renal failure and mortality. However, data are limited on the clinical presentation and outcome in antineutrophil cytoplasmic antibody (ANCA) negative patients, especially in Asians. METHODS: This retrospective study analyzed medical records and pathology slides of patients who received renal biopsy between February 1998 and October 2004. Enzyme-linked immunosorbent assay was used routinely for ANCA testing in all patients. RESULTS: Among 637 patients with biopsy-proven GN included in this study, 88 (13.8%) had glomerular crescent formation. Among them, pauci-immune crescentic glomerulonephritis (PICGN) (42 patients, 47.2%) and lupus nephritis (25 patients, 28.4%) were the most common pathologic diagnoses. Lupus patients were younger (p = 0.028), while PICGN patients had more chronic lesions (p < 0.001), extensive glomerular crescents (p < 0.001), less severe proteinuria (p < 0.001) and poorer renal survival (p = 0.0017). Among the PICGN patients, 62.5% had a positive ANCA test, 80% had myeloperoxidase-ANCA and 20% had proteinase-3-ANCA. Subgroup analysis showed that ANCA negativity was associated with less crescent formation (p < 0.001) but more chronic glomerular lesions (p < 0.001) and a trend toward worse renal outcome (p = 0.055). CONCLUSION: This study illustrates the necessity for pathologic diagnosis of pauci-immune GN despite ANCA negativity. The poor prognosis associated with ANCA negativity in this study may be partly due to delayed diagnosis since these patients frequently lacked systemic involvement.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2005

Plasma interleukin-18 levels in hemodialysis patients: increased by dialysis process and association with interleukin-6 and tumor necrotic factor-alpha.

BACKGROUND/AIMS: This study investigated changes of interleukin-18 (IL-18) levels before and after dialysis, and the possible association with other pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). METHODS: Plasma IL-18 of healthy controls, and pre- and post-dialysis of uremic patients undergoing hemodialysis (HD) were evaluated by ELISA methodology. RESULTS: Plasma IL-18 levels were significantly increased in patients with maintenance HD (p <0.001) compared to its level in normal subjects. When compared to pre-dialysis levels, a significant increase in plasma IL-18 was measured at the end of HD (p = 0.032). There was a significant correlation among plasma IL-18, IL-6 and TNF-alpha levels in HD patients. CONCLUSION: Plasma IL-18 concentration was significantly higher in HD patients and was significantly elevated by cellulose-based HD processes. Pre-activation of immunologically active cells may contribute to the association between pre-dialysis IL-18 and post-dialysis IL-6 and TNF-alpha levels.

Aged↗
PubMed2005

YC-1-inhibited proliferation of rat mesangial cells through suppression of cyclin D1-independent of cGMP pathway and partially reversed by p38 MAPK inhibitor.

This study was designed to investigate the effect of 1-benzyl-3-(5'-hydroxymethyl-2'-furyl) indazole (YC-1), a guanylate cyclase activator, upon the proliferation of rat mesangial cells and its underlying mechanism. YC-1 inhibited cell proliferation and DNA synthesis in a dose- and time-dependent manner. Flow cytometry cell-cycle studies revealed that YC-1 prevented the entry of cells from G1 into S phase. The expression of cyclin D1 and the kinase activity of cyclin D1/cyclin-dependent kinase (CDK)4 were lower within YC-1-treated cells, revealed by Western blotting, Northern blotting and kinase assays. YC-1 did not increase the intracellular cGMP concentration in mesangial cells. Inhibitors of soluble guanylate cyclase, protein kinase G, or protein kinase A also did not reverse the inhibitory effect elicited by YC-1, while co-treatment with p38 mitogen-activated protein kinase (MAPK) inhibitor could partially reverse the suppressive effect. YC-1 inhibited proliferation of mesangial cells and induced cell-cycle arrest by the reduction of cyclin D1 synthesis and cyclin D1/CDK4 kinase activity. This effect acts partially through p38 MAPK signal transduction activation and is independent of cGMP-signaling pathways.

Animals↗
PubMed2005

Pentoxifylline attenuates tubulointerstitial fibrosis by blocking Smad3/4-activated transcription and profibrogenic effects of connective tissue growth factor.

Pentoxifylline (PTX) is a potent inhibitor of connective tissue growth factor (CTGF), but its underlying mechanism is poorly understood. Here, it was demonstrated that PTX inhibited not only TGF-beta1-induced CTGF expression but also CTGF-induced collagen I (alpha1) [Col I (alpha1)] expression in normal rat kidney fibroblasts (NRK-49F) and alpha-smooth muscle actin expression in normal rat kidney proximal tubular epithelial cells (NRK-52E). Furthermore, PTX attenuated tubulointerstitial fibrosis, myofibroblasts accumulation, and expression of CTGF and Col I (alpha1) in unilateral ureteral obstruction kidneys. The mechanism by which PTX reduced CTGF in NRK-49F and NRK-52E was investigated. Activation of Smad3/4 was essential for TGF-beta1-induced CTGF transcription, but PTX did not interfere with TGF-beta1 signaling to Smad2/3 activation and association with Smad4 and their nuclear translocation. However, PTX was capable of blocking activation of TGF-beta1-induced Smad3/4-dependent reporter as well as CTGF promoter, suggesting that PTX affects a factor that acts cooperatively with Smad3/4 to execute transcriptional activation. It was found that PTX increased intracellular cAMP and caused cAMP response element binding protein phosphorylation. The protein kinase A antagonist H89 abolished the inhibitory effect of PTX on Smad3/4-dependent CTGF transcription, whereas dibutyryl cAMP and forskolin recapitulated the inhibitory effect. In conclusion, these results indicate that PTX inhibits CTGF expression by interfering with Smad3/4-dependent CTGF transcription through protein kinase A and blocks the profibrogenic effects of CTGF on renal cells. Because of the dual blockade, PTX potently attenuates the tubulointerstitial fibrosis in unilateral ureteral obstruction kidneys.

Actins↗
PubMed2005

Plasma interleukin-18 levels in chronic renal failure and continuous ambulatory peritoneal dialysis.

BACKGROUND/AIMS: Based on associations of interleukin (IL)-18 with chronic inflammation, we investigated IL-18, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in patients with chronic renal failure (CRF) and patients undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: Plasma was evaluated by ELISA methodology in 15 healthy controls, 27 CRF and 15 CAPD patients. RESULTS: Plasma IL-18 levels in CRF (572.5 +/- 41.9 pg/ml) or CAPD (479.2 +/- 47.4 pg/ml) were significantly higher than normal (263.6 +/- 20.0 pg/ml), but there was no difference in IL-18 between CRF and CAPD patients. The IL-18 concentration negatively correlated with creatinine clearance (Ccr). However, the duration of dialysis, normalized protein nitrogen appearance, weekly Ccr, and Kt/V(urea) were not correlated with plasma IL-18 in CAPD. The plasma IL-18 concentration was positively correlated with TNF-alpha but not with IL-6 in renal failure patients with or without CAPD. CONCLUSION: Uremia is the principal origin of increased plasma IL-18 in these patients. Increased IL-18 levels may be associated with Th1 differentiation and elevated TNF-alpha.

Biomarkers↗
PubMed2005

Low-density lipoprotein cholesterol: association with mortality and hospitalization in hemodialysis patients.

BACKGROUND/AIMS: Hypocholesterolemia is a common finding in hospitalized elderly people, critically ill surgical patients, septic patients and end-stage renal disease patients. The different effect of lipid subfractions on patients with end-stage renal disease has never been demonstrated. We aim to study the effect of lipid subfractions on hospitalization and mortality in maintenance hemodialysis (MHD) patients. METHODS: Lipid subfractions, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured in 210 patients with MHD in a single dialysis center. Patients were stratified into three groups based on the tertiles of lipid levels, and differences in patient characteristics and survival were evaluated. RESULTS: Of a total of 22 deceased patients in our MHD cohort, infection-related mortality (50%) was higher than cardiovascular-related mortality (18.2%). Significant differences (p < 0.05) in the duration and frequency of hospitalization and in mortality events were observed when patients were divided into different subgroups according to the tertiles of baseline TC and LDL-C levels. Patients with lower LDL had significantly lower levels of albumin, TC and TG. The LDL-C tertiles were similar in terms of age, hypertension, diabetes, biochemical results, hematocrit, adequacy of hemodialysis and normalized protein catabolism rate. Both TC and LDL-C predicted survival (p < 0.001), but not TG and HDL-C in the Kaplan-Meier model. The Cox proportional hazard model demonstrated that baseline serum LDL-C was the best lipid subfraction in predicting all-cause death with an adjusted hazard ratio (95% confidence interval) for each 10 mg/dl of 0.752 (0.631-0.898; p = 0.002). CONCLUSIONS: We firstly demonstrated that lipid subfractions, including TC and LDL-C, predict poor outcomes in a MHD cohort with high infection-related mortality.

Adult↗
PubMed2005

Peritoneal fibrosing syndrome: pathogenetic mechanism and current therapeutic strategies.

Peritoneal dialysis (PD) has been established as a main renal replacement therapy for approximately 20 years. However, long-term peritoneal exposure to high glucose and other unphysiologic contents in the PD solution may potentiate the development of peritoneal fibrosing syndrome (PFS) in PD patients. PFS is composed of a wide spectrum of peritoneal alterations, which has been observed in PD patients. Molecular studies have shown that the fibrogenic effect of peritoneal mesothelial cells and the accompanying accumulation of extracellular matrix in the peritoneum are key events leading to PFS. In this review, we highlight the impact of PFS and its pathogenetic factors, including bioincompatible PD solution, multidisciplinary inflammatory mediators, and stimulatory cytokines in the peritoneal cavity. Current therapeutic strategies based on both clinical and basic evidence for the prevention or treatment of PFS are also reviewed.

Dipyridamole↗
PubMed2005

The renoprotective potential of pentoxifylline in chronic kidney disease.

Current interventions with proven efficacy, such as glycemic and blood pressure control, dietary protein restriction, and angiotensin II blockade, slow the progression of chronic kidney disease (CKD); however, whether long-term cessation of CKD progression is possible remains unclear. Because of the pathogenetic complexity of this condition, multidrug interventions with the least adverse effects should be investigated as the next step in attempts to stop CKD progression. Pentoxifylline, a non-selective phosphodiesterase inhibitor with indiscernible toxicity, exerts potent inhibitory effects against cell proliferation, inflammation, and extracellular matrix accumulation, all of which play important roles in CKD progression. Pentoxifylline monotherapy markedly reduces proteinuria in patients with membranous nephropathy. Moreover, limited human studies have proven pentoxifylline efficacy in reducing proteinuria in patients with diabetes receiving angiotensin-converting enzyme inhibitors, and in patients with nephrotic syndrome secondary to lupus nephritis despite immunosuppressive therapy. Further clinical trials are necessary to examine whether pentoxifylline can improve renal outcomes in patients receiving interventions of proven efficacy.

Cell Proliferation↗
PubMed2004

Health-related quality of life of hemodialysis patients in Taiwan: a multicenter study.

BACKGROUND/AIMS: Health-related quality of life (HRQOL) is an important determinant of treatment effectiveness in dialysis patients. To our knowledge, there are no reports evaluating HRQOL of hemodialysis (HD) in Chinese patients. The purpose of this study is to present our results about HRQOL using the 36-Item Short-Form (SF-36) questionnaire on Taiwanese hemodialysis patients. METHODS: HRQOL was measured by using the SF-36 questionnaire in 497 HD patients in five hospitals. RESULTS: The following attributes, male gender, age <50 years old, higher education level (HEL), marriage status, employment status (EPS), less comorbid medical condition (CMC), and non-diabetic patients (NDP) were all predicted on a better Physical Component Scale (PCS). Age <50 years old, body mass index >18.5, HEL, EPS and NDP were all predicted on a higher Mental Component Scale (MCS). Scales contributing to a summary measure of physical health, the PCS score was significantly lower in women (35.0 +/- 12.3) than in men (37.9 +/- 12.3). However, there was no difference in the MCS score between women and men. In multivariate analysis, age, CMC, diabetes, serum creatinine (SCr), and erythropoietin responsiveness were significant independent predictors of PCS. Diabetes, educational level, SCr, and erythropoietin responsiveness were significant independent predictors of MCS. All of the individual scales were lower in Taiwanese HD patients than in both the general Taiwanese and US population. Each of the individual scales and MCS scores were substantially lower in the Taiwan HD group than in the US HD cohort. However, the bodily pain of PCS was significantly higher in the Taiwan HD group, although the mean PCS scores for the Taiwan HD group and the US HD study participants were nearly equal at 36.3 and 36.1, respectively. CONCLUSION: The physical and mental aspects of quality of life are substantially lower for Taiwanese HD patients, except for higher bodily pain tolerance. A number of demographic and clinical characteristics have a significant impact on HRQOL in Taiwanese HD patients.

Adult↗
PubMed2004

Interleukin-18 is a strong predictor of hospitalization in haemodialysis patients.

BACKGROUND: Morbidity and mortality rates are high among patients with end-stage renal disease (ESRD), and recent evidence suggests that this may be linked to inflammation. Current research has also demonstrated the crucial involvement of interleukin-18 (IL-18) in inflammation. In agreement, the activity of IL-18 has been markedly up-regulated in ESRD patients. However, it has not been established whether elevated plasma IL-18 predicts outcome in haemodialysis (HD) patients. METHODS: To determine whether plasma IL-18 predicts overall hospitalization, we studied 184 ESRD patients (62% males, 58.5+/-1.0 years of age) undergoing maintenance HD treatment. The patients were followed for 12 months and were stratified by the tertiles of plasma IL-18 levels. Classic factors, such as age, body mass index, duration of HD, nutritional and inflammatory parameters, co-morbidity, dialysis adequacy, and lipid status were entered into a Cox regression model to predict hospitalization. The Kaplan-Meier method was used to analyse the cumulative proportion of hospitalization-free events. RESULTS: Significantly different hospitalization days and frequencies (P<0.05) were observed when patients were divided according to tertiles of plasma IL-18 levels. Patients were stratified according to IL-18 tertiles and analysed separately according to the hospitalization-free period. In the Kaplan-Meier model, the upper tertile of IL-18 had the highest probability of a hospitalization event during the entire follow-up period (P log rank = 0.027). In the Cox proportional hazard model, the relative risk for first hospital admission for each increase in Ln IL-18 (pg/ml) concentration was associated with a 1.709 (95% CI, 1.114 to 2.620; P = 0.014) increase in the risk for future hospitalization events. CONCLUSIONS: The present study demonstrated a strong predictive value of elevated IL-18 levels for poor outcome in HD patients.

Comorbidity↗
PubMed2004

Dual regulation of tumor necrosis factor-alpha-induced CCL2/monocyte chemoattractant protein-1 expression in vascular smooth muscle cells by nuclear factor-kappaB and activator protein-1: modulation by type III phosphodiesterase inhibition.

Monocyte/macrophage infiltration to the subendothelial space of arterial wall is a critical initial step in atherogenesis, in which CC chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1 (MCP-1) is thought to play a key role. This study investigated the effectiveness of phosphodiesterase inhibitors, including the nonselective pentoxifylline (PTX) and the selective type III (cilostamide) and type IV (denbufylline) inhibitors, on cytokine-induced CCL2/MCP-1 production in cultured rat vascular smooth muscle cells (VSMCs), and the signal transduction mechanisms whereby they act. Our results showed that tumor necrosis factor (TNF)-alpha induced a marked increase in CCL2/MCP-1 production in dose- and time-dependent manners. 2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059), 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio) butadiene (U0126) [both inhibitors of p42/44 mitogen-activated protein kinase (MAPK) kinase], and anthra[1hyphen]9-cd]pyrazol-6(2H)-one (SP600125) [an inhibitor of c-Jun NH(2)-terminal kinases (JNKs)] attenuated TNF-alpha-induced CCL2/MCP-1 production, without affecting I-kappaBalpha degradation or p65/nuclear factor-kappaB (NF-kappaB) nuclear translocation. PD98059 abolished TNF-alpha-activated p42/44 MAPK phosphorylation and c-Fos up-regulation, whereas SP600125 inhibited TNF-alpha-activated JNK and c-Jun phosphorylation. The NF-kappaB inhibitor carbobenzoxy-l-leucyl-l-leucyl-l-leucinal (MG132) attenuated TNF-alpha-induced CCL2/MCP-1 production in the presence of increased phospho-JNK and phospho-c-Jun levels. When SP600125 was added simultaneously, MG132 completely inhibited TNF-alpha-induced CCL2/MCP-1 production. Finally, the pretreatment of VSMCs with PTX or cilostamide, but not denbufylline, reduced TNF-alpha-induced CCL2/MCP-1 production, which was preceded by attenuation of p65/NF-kappaB nuclear translocation, p42/44 MAPK, and JNK-c-Jun phosphorylation, and c-Fos up-regulation. These data indicate that TNF-alpha-stimulated CCL2/MCP-1 production in rat VSMCs is dually regulated by activator protein-1 (AP-1) and NF-kappaB pathways, and inhibition of type III phosphodiesterase contributes substantially to the suppressive effect of PTX on CCL2/MCP-1 production via down-regulation of AP-1 and NF-kappaB signals.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2004

Pentoxifylline suppresses renal tumour necrosis factor-alpha and ameliorates experimental crescentic glomerulonephritis in rats.

BACKGROUND: Crescentic glomerulonephritis is a rapidly progressive form of glomerulonephritis, but treatment remains non-specific. The methylxanthine derivative pentoxifylline (PTX) is a clinically available phosphodiesterase inhibitor with anti-inflammatory and immunoregulatory activities. This study examined whether PTX has beneficial effects in a rat model of anti-glomerular basement membrane (GBM) crescentic glomerulonephritis. METHODS: Experimental crescentic glomerulonephritis was induced in Wistar rats by intravenous injection of rabbit anti-rat GBM serum and treated with either vehicle (phosphate-buffered saline) or PTX (0.1 g/kg/day) intravenously on a daily basis. Groups of six animals were euthanized at days 3, 7, 14 or 28 after induction of disease. Effects of PTX on renal function, histology and expression of cytokines, chemokines and adhesion molecules were determined. RESULTS: Compared with the vehicle-treated nephritic rats, PTX treatment beginning at the start of the nephritis significantly suppressed mRNA expression of tumour necrosis factor (TNF)-alpha, but not interleukin-1 beta, throughout the course of nephritis. Moreover, PTX decreased renal mRNAs for intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted (RANTES) and osteopontin (OPN) at all time points examined. These effects were associated with a significant inhibition of macrophage and T-cell infiltration, a reduction of 24-h urinary protein excretion (50-75%, P<0.05), an improvement of histological damage including glomerular crescent formation (60-70%, P<0.01) and a decrease of cortical mRNAs for type I (alpha 1) collagen and fibronectin. The efficacy of PTX could also be seen, though to a lesser extent, in rats with established nephritis. CONCLUSIONS: PTX is an effective anti-inflammatory and immunomodulatory agent capable of suppressing rat crescentic glomerulonephritis. Inhibition of renal TNF-alpha, ICAM-1, RANTES, MCP-1 and OPN expression may be a mechanism whereby PTX suppresses progressive renal injury in rat crescentic glomerulonephritis.

Animals↗