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Biomedical subjects

T J Tsai

Publications and source records attributed to T J Tsai.

At least 19 recordsLinked to original sources
PubMed2002

Serum soluble transferrin receptor reflects erythropoiesis but not iron availability in erythropoietin-treated chronic hemodialysis patients.

BACKGROUND: The diagnosis of iron deficiency using the current commonly used tests is usually difficult in hemodialysis patients. Soluble transferrin receptor (sTfR) has caught the attention of physicians recently as regards its use as a parameter for the evaluation of iron status. This study was conducted in order to evaluate the correlation of serum soluble transferrin receptor (sTfR) concentration with hematological parameters and iron profiles, in the role of identifying iron deficiency among dialysis patients. METHODS: Seventy-three patients having received chronic hemodialysis and stable maintenance recombinant human erythropoietin (rHuEPO) therapy were included. Iron, total iron-binding capacity, ferritin and sTfR were measured in the first week. Following this, these patients began to receive intravenous iron dextran (2 mg/kg/week) for 4 weeks. The hematocrit (Hct), hemoglobin (Hb) levels and reticulocyte counts were evaluated weekly. At the beginning of fifth week, the sTfR level was measured again. Patients were classified as belonging to one of the following groups: serum ferritin < 100 microg/L - absolute iron-deficient group; initial ferritin level > or = 100 microg/L with an increase in hemoglobin of greater than 1 g/dL at the end of the study occult iron deficiency group; others - non iron-deficient group. RESULTS: Seventy-one patients completed the study. The concentration of sTfR was positively correlated with Hct, Hb and reticulocyte index at the beginning (r = 0.236, p = 0.047; r = 0.257, p = 0.04; r = 0.401, p < 0.01, respectively) and at the end of the study (r = 0.384, p < 0.01; r = 0.338, p < 0.01; r = 0.427, p < 0.001, respectively). After 4 weeks of iron and rHuEPO therapy, the sTfR concentration increased, rather than declined, from 21.85 +/- 8.06 nM to 23.76 +/- 7.42 nM (p = 0.04) and the change was positively correlated with the changes in Hct, Hb and reticulocyte index. The administered rHuEPO doses did not differbetween the iron deficiency group (absolute deficiency, n = 3; occult deficiency, n = 10) and non-iron deficiency group (n = 58). The sTfR levels failed to identify the occult iron deficiency group because there was no difference between occult iron-deficient and non-iron-deficient patients (24.73 +/- 9.09 nM versus 21.60 +/- 7.89 nM, p = 0.34). Instead, transferrin saturation (TS) could be a differential marker between the 2 groups (19.0 +/- 10.9% versus 30.1 +/- 12.7%, p = 0.012). CONCLUSION: The serum sTfR concentration is indeed an appropriate marker for erythropoiesis. The erythropoitic effect of administered rHuEPO could mask the effect of iron status on the sTfR concentration. This might make the sTfR concentration no longer an appropriate index to identify the presence of occult iron deficiency. Thus, TS and ferritin currently remain better methods for the evaluation of iron status in rHuEPO-treated chronic hemodialysis patients.

Adolescent↗
PubMed2001

Dipyridamole inhibits human peritoneal mesothelial cell proliferation in vitro and attenuates rat peritoneal fibrosis in vivo.

BACKGROUND: Peritoneal fibrosis (PF) is one of the most serious complications after long-term continuous ambulatory peritoneal dialysis (CAPD). Proliferation of human peritoneal mesothelial cells (HPMC) and matrix over-production are regarded as the main processes predisposing to PF. Dipyridamole (DP) has been reported to have potential as an antiproliferative and antifibrotic agent. We thus investigated the effect of DP in inhibiting proliferation and collagen synthesis of HPMC. A rat model of peritonitis-induced PF was also established to demonstrate the in vivo preventive effect of DP. METHODS: HPMC was cultured from human omentum by an enzyme digestion METHOD: Cell proliferation was measured by the methyltetrazolium assay. Intracellular cAMP was measured using an enzyme immunoassay (EIA) kit. Total collagen synthesis was measured by (3)H-proline incorporation assay. Expression of collagen alpha1 (I) and collagen alpha 1 (III) mRNAs was determined by Northern blotting. The rat model of peritonitis-induced PF was developed by adding dextran microbeads (Cytodex, 8 mg/1 mL volume) to a standardized suspension (3 x 10(9)) of Staphylococcus aureus. DP was administrated via intravenous infusion (4 mg in 1 h) daily for seven days. Macroscopic grading of intraperitoneal adhesions and histological analyses of peritoneal thickness and collagen expression were performed. RESULTS: Addition of DP to HPMC cultures suppressed serum-stimulated cell proliferation and collagen synthesis. The antimitogenic and antifibrotic effects of DP appear to be predominantly mediated through the cAMP pathway, as DP increased intracellular cAMP in a dose-dependent manner. The macroscopic grade of intraperitoneal adhesion and peritoneal thickness were both significantly increased in animals treated with Cytodex plus S. aureus; on the other hand, DP attenuated these fibrotic changes with statistical significance (P < 0.01). Analysis of gene expression of collagen alpha 1 (I) and alpha1 (III) in the peritoneal tissue of experimental animals yielded similar results. CONCLUSIONS: This study suggests that dipyridamole may have therapeutic potential in treating peritoneal fibrosis.

Animals↗
PubMed2001

Dipyridamole inhibits TGF-beta-induced collagen gene expression in human peritoneal mesothelial cells.

BACKGROUND: Peritoneal matrix accumulation is characteristic of peritoneal fibrosis (PF). Continuous ambulatory peritoneal dialysis (CAPD) patients who had persistent transforming growth factor-beta (TGF-beta) in their drained effluent had an increased risk of PF. We previously reported that TGF-beta stimulates the expression of types I and III collagen mRNA in cultured human peritoneal mesangial cells (HPMCs), which may predispose them to develop PF. Pharmacological interventions to attenuate TGF-beta-stimulated matrix accumulation in HPMC may have therapeutic potential for the treatment of PF. The SMAD family and the extracellular signal-regulated protein kinase (ERK1/2, p44/p42) pathways have been shown to participate in TGF-beta signaling. Our current study identified these signal pathways in HPMCs and investigated the molecular mechanisms involved in the inhibitory effects of dipyridamole on TGF-beta-induced collagen gene expression in HPMCs. METHODS: HPMCs were cultured from human omentum by an enzyme digestion METHOD: Expression of collagen alpha1(I) mRNA was determined by Northern blotting. The SMAD proteins and the ERK1/2 activity were determined by Western blotting. RESULTS: TGF-beta-stimulated collagen alpha1(I) mRNA expression of HPMC was inhibited by dipyridamole in a dose-dependent manner. Smad2 and ERK1/2 were activated in response to TGF-beta; however, TGF-beta had little effect on the protein expression of Smad4. The addition of PD98059, which blocked activation of ERK1/2, suppressed TGF-beta-induced collagen alpha1(I) mRNA expression in a dose-dependent manner. At a concentration that inhibited collagen gene expression (17 microg/mL), dipyridamole suppressed ERK1/2 activation by TGF-beta. In contrast, the same concentration of dipyridamole had no effect on TGF-beta-induced activation of Smad2. CONCLUSION: Dipyridamole inhibits TGF-beta-induced collagen gene expression in HPMC through modulation of the ERK pathway. Our study of dipyridamole may provide therapeutic basis for clinical applications in the prevention of PF.

Cells, Cultured↗
PubMed2001

Dipyridamole inhibits PDGF-stimulated human peritoneal mesothelial cell proliferation.

BACKGROUND: It has been proposed that proliferation of human peritoneal mesothelial cells (HPMCs) accompanied by collagen synthesis may contribute to the development of peritoneal fibrosis (PF) in patients of long-term continuous ambulatory peritoneal dialysis (CAPD). However, the precise molecular mechanism regulating HPMC proliferation has never been reported. Dipyridamole has been reported to have potential as an antiproliferative and antifibrotic agent. We investigated the mechanism and effect of dipyridamole in regulation of HPMC proliferation. METHODS: HPMCs were cultured from human omentum by an enzyme digestion METHOD: Cell proliferation was measured by the methyltetrazolium assay and intracellular cAMP was measured using an enzyme immunoassay kit. Cell-cycle distribution of HPMC was analyzed by flow cytometry. Extracellular signal-regulated protein kinase (p44/p42 ERK) activity and expressions of cell-cycle proteins (cyclin D(1), CDK4, pRB and p27(Kip1)) were determined by Western blotting. RESULTS: The addition of DP suppressed PDGF-stimulated HPMC proliferation by cell-cycle arrest at the G1 phase. The antimitogenic effect of dipyridamole was mediated through the cAMP pathway. PDGF (25 ng/mL) increased the ERK1/2 activity of HPMC within 15 minutes, which maximized at 30 minutes, and the pretreatment with dipyridamole (17 microg/mL) substantially reduced the ERK response to PDGF by approximately 78.5%. PDGF induced elevated protein levels of cyclin D(1), but the CDK4 protein level did not change. Dipyridamole and DBcAMP had no effect on the levels of cyclin D(1) and CDK4 in PDGF-stimulated HPMC. PDGF decreased p27(Kip1) and induced pRB phosphorylation of HPMC. In contrast, dipyridamole prevented PDGF-induced p27(Kip1) degradation and attenuated PDGF-stimulated pRB phosphorylation. CONCLUSION: Dipyridamole appears to inhibit PDGF-stimulated HPMC proliferation through attenuated ERK activity, preservation of p27(Kip1), and decreased pRB phosphorylation. Thus, dipyridamole may have therapeutic efficacy to prevent or alleviate PF.

Bucladesine↗
PubMed2001

Comparison of infectious complications in peritoneal dialysis patients using either a twin-bag system or automated peritoneal dialysis.

BACKGROUND: Automated peritoneal dialysis (APD) and twin-bag (TB) systems are two major peritoneal dialysis (PD) modalities. Published data comparing the infectious complications of these modalities is limited. Subjects and methods. Ninety-five patients using APD (the APD group) and 117 patients using TB system (the TB group) were recruited. Among them, 35 patients used both modalities. The two groups' clinical characteristics, incidences of infectious complications, and the time intervals to first PD-related infection were compared. RESULTS: Clinical characteristics, incidence of exit-site infection (ESI), and time intervals to first ESI were similar in the TB and APD groups. The incidence of peritonitis in the APD group (1.22 episodes/100 patient-months) was significantly (P < 0.001) lower than that of the TB group (2.28 episodes/100 patient-months). Using the Cox proportional hazard model, APD was found to have a lower risk of peritonitis relative to TB systems, with marginal significance (RR 0.58, P = 0.051). CONCLUSION: APD was found to have a lower peritonitis rate than the TB system. Since reducing the peritonitis rate helps to maintain technical survival during PD, from this viewpoint, APD may be preferred for patients undergoing PD, unless contraindicated.

Adult↗
PubMed2001

High resistive index of the radial artery is related to early primary radiocephalic hemodialysis fistula failure.

Forty-nine patients who had received radiocephalic hemodialysis fistula construction were evaluated with duplex Doppler ultrasonography to characterize the Doppler indices of the feed radial arteries just proximal to the site of anastomosis. Forty-four patients had fistulas with good function, and 5 patients had fistulas with inadequate blood flow or thrombosis within 4 weeks after the operation. A preliminary study showed extensive variability in peak systolic velocity and end-diastolic velocity in the feed arteries. The resistive index dropped significantly 1 week after the operation and remained relatively constant over the following 5 weeks. In the success group, the mean resistive index measured 1 week after operation was 0.40+/-0.06. It was higher than that of the failure group (mean resistive index: 0.52+/-0.06). Among patients with well-functioning fistulas, diabetic patients had higher resistive indices than did non-diabetic patients (0.44+/-0.04 vs. 0.37+/-0.06). Our results suggest that a higher resistive index of the feed artery is closely related to early autogenous primary hemodialysis fistula failure.

Adult↗
PubMed2000

Pentoxifylline inhibits human peritoneal mesothelial cell growth and collagen synthesis: effects on TGF-beta.

BACKGROUND: Prevention or treatment of peritoneal fibrosing syndrome has become an important issue in patients on continuous ambulatory peritoneal dialysis (CAPD). Recent evidence has suggested that mesothelial stem cell proliferation and matrix over-production predispose the development of peritoneal fibrosis. We investigated whether pentoxifylline (PTX) affects human peritoneal mesothelial cell (HPMC) growth and collagen synthesis. METHODS: HPMC was cultured from human omentum by an enzymic disaggregation method. Cell proliferation was assayed using a methyltetrazolium uptake method. Cell cycle analysis was performed by flow cytometry. Collagen synthesis was measured by 3H-proline incorporation into pepsin-resistant, salt-precipitated collagen. Prostaglandins and cAMP were determined by enzyme immunoassay. Northern blot analysis was used to determine mRNA expression. RESULTS: Our data show that PTX inhibited serum-stimulated HPMC growth and collagen synthesis in a dose-dependent manner. Cell cycle analysis showed that PTX arrested the HPMCs in the G1 phase. PTX decreased the procollagen alpha1 (I) mRNA expression either stimulated by serum or transforming growth factor-beta (TGF-beta). PTX did not alter prostaglandins synthesis but dose-dependently increased intracellular cAMP level. PTX, the same as 3-isobutyl-l-methylxanthine, could potentiate prostaglandin E1 (PGE1) increased cAMP levels of HPMC. The antimitogenic and antifibrogenic effects of PTX on HPMC were reversed by N-[2]-((p-Bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide (H-89). Therefore, the mechanism of these effects may be due to the phospodiesterase inhibitory property of PTX. CONCLUSIONS: These data suggest that PTX may have a role in treating peritoneal fibrosing syndrome.

Cell Division↗
PubMed2000

Natural changes in peritoneal equilibration test results in continuous ambulatory peritoneal dialysis patients: a retrospective, seven year cohort survey.

We conducted a retrospective, 7 year cohort survey to examine the natural changes in peritoneal equilibration test (PET) results in patients with long-term uneventful continuous ambulatory peritoneal dialysis (CAPD). Thirty-two (17 males, 15 females) patients on CAPD with two or more standard PETs performed more than 6 months apart, in the absence of peritoneal insult, were included. Changes and pattern of PET results were evaluated by the dialysate to plasma ratio of creatinine (D:P-cre), the fourth h dialysate to instilled glucose ratio (D4:Do) and ultrafiltration volume (UF, ml). The subgroups included high (H), high-average (HA), low-average (LA), or low (L) transporters with the dividing ratios (D:P-cre) of >0.81, >0. 65 to 0.81, >0.5 to 0.65, and <0.5, respectively. The median D:P-cre significantly decreased (p = 0.04), but neither the D4:Do nor the final median UF significantly decreased. The change in D:P-cre was strongly and inversely correlated with the initial D:P-cre value (r = -0.68; p < 0.05). A similar relationship was found between the change in the final D4:Do and the initial D4:Do (r = -0.752; p < 0. 01) and between the change in the final UF and the initial UF (r = -0.875; p < 0.01). No correlation was found between the change in D:P-cre and the age of the patient, the time interval between PETs, monthly dialysate glucose exposure, or underlying diabetes/non-diabetes. The final peritoneal transport pattern was altered with 5 (15.6%) patients remaining in the extreme subgroups (H or L) and, by contrast, 84.4% (27/32) of the patients now in the averaged (HA or LA) groups (p < 0.01, chi2 test). We demonstrated a natural "centralization" migration of PET results after long-term uneventful CAPD, which may help to explain why patients with extreme PET characteristics, that is, H or L, continued to do well on CAPD.

Adult↗
PubMed2000

Clinical significance of microscopic tumor venous invasion in patients with resectable hepatocellular carcinoma.

BACKGROUND: Tumor venous invasion in patients with resectable hepatocellular carcinoma (HCC) is frequent and can be macroscopic and microscopic or microscopic alone. Although macroscopic invasion is a well-established prognostic indicator, the clinical significance of microscopic invasion remains unclear. METHODS: There were 322 patients enrolled who had undergone curative resection for HCC. The clinicopathologic factors and prognostic significance associated with macroscopic and microscopic venous invasion were analyzed. RESULTS: Macroscopic invasion was observed in 50 patients (15.5%) and microscopic invasion in 190 (59.0%). The larger the tumor, the more the incidence of venous invasion. There were 140 patients with microscopic invasion only (Group 1). Patients with macroscopic invasion (Group 2, n = 50) also had microscopic invasion. Compared with patients without venous invasion (Group 3, n = 132), Group 1 had a higher alpha-fetoprotein level, a larger tumor size, and more tumors without encapsulation. For group 1, the 1-, 3-, and 5-year disease-free survival rates were 65.6%, 41.6%, and 30.8%, respectively. The 1-, 3-, and 5-year overall survival rates were 87. 8%, 60.0%, and 52.7%, respectively. The survival rates of group 1 were lower than those of group 3 and higher than those of group 2 (P <.05). Multivariate analysis indicated that microscopic and macroscopic venous invasion, surgical margin, indocyanine-green retention, and tumor size and number were significant predictors of postresectional survival. CONCLUSIONS: In HCC patients, microscopic venous invasion is frequent and related independently to postresectional outcome.

Aged↗
PubMed2000

Clinical features of and risk factors for fungal peritonitis in peritoneal dialysis patients.

BACKGROUND AND PURPOSE: Fungal peritonitis (FP) is a serious complication for peritoneal dialysis (PD) patients and can result in technical failure and mortality. Catheter removal remains the mainstay of treatment. This study sought to identify the risk factors for FP in order to facilitate the prevention of this catastrophic complication. METHODS: A total of 246 patients who received long-term PD from 1985 to 1998 were included in this retrospective study. Twenty episodes of FP occurred in 19 patients. The clinical characteristics, pathogens, treatment modalities, and outcomes of the FP episodes were retrospectively reviewed. The FP incidence in various demographic and clinical groups, classified according to sex, age, education, and underlying cause of uremia, were compared with the Poisson test. RESULTS: Thirteen episodes of FP were caused by yeast, and the remaining episodes were caused by Aspergillus spp. Age, sex, and education did not affect the FP incidence. Lupus patients (969 patient-months) had a higher incidence of FP than patients with other underlying diseases (p < 0.05). The 19 FP patients also had a higher incidence of bacterial peritonitis than other PD patients (p < 0.01). Among the 20 FP episodes, 14 (70%) were preceded by antibiotic use, and eight (40%) developed during hospitalization. Steroids were used at the time of FP in five of six lupus patients. Seven patients (37%) died within 1 month after diagnosis of FP. Five patients were able to remain on PD after FP, but only three patients were able to maintain catheter placement. CONCLUSION: The risk factors for FP identified in this study include the use of antibiotics and steroids, underlying lupus, frequent occurrence of bacterial peritonitis, and hospitalization. Antifungal therapy may allow the catheter to be kept in place in a few patients, but catheter removal should be considered in patients whose FP is refractory to medical treatment.

Adult↗
PubMed2000

Incidence of exit-site infection with various exchange systems in continuous ambulatory peritoneal dialysis.

BACKGROUND AND PURPOSE: The disconnect twin-bag (TB) system was first introduced in Taiwan for use as an exchange system in continuous ambulatory peritoneal dialysis (CAPD) in 1995. Following its introduction, the incidence of CAPD-associated peritonitis declined, but the incidence of exit-site infection (ESI) increased. To determine the cause of the increase in ESI incidence after the introduction of the TB system, this study compared the incidence of ESI among patients using the O set, ultraviolet antiseptic (UV) device, and the TB system. METHODS: A total of 170 patients who had received CAPD for more than 3 months were enrolled in this study. Poisson test and Kaplan-Meier survival analysis were used to compare the ESI incidence and ESI-free catheter survival among patients using the O set, UV device, or TB system. Cox stepwise forward proportional hazard analysis was used to assess the impact of sex, education, cause of uremia, age, and type of exchange system on ESI. RESULTS: The incidences of ESI differed significantly among patients using the three exchange systems, with 20.9, 13.8, and 4.0 episodes per 100 patient-years for patients using the TB system, O set, and UV device, respectively. New patients using the TB system also had a shorter mean interval of ESI-free catheter survival than those using the UV device (26.9 vs 58.8 months, p = 0.002). In the Cox stepwise forward proportional hazard analysis, non-lupus patients had a lower risk of developing ESI than lupus patients (relative risk [RR] 0.40, p = 0.03). The RR of ESI in patients using the UV device was also lower than in those using the TB system (RR 0.15, p < 0.01). CONCLUSION: In this study, use of the TB system was associated with a higher incidence of ESI. The increased ESI incidence may be related to the heavier mini-transfer set of the TB system. Therefore, special attention should be given to fastening the mini-transfer set tightly during the exchanging procedure to prevent traction on the exit-site, which is associated with an increased incidence of subsequent ESI.

Adult↗
PubMed1999

Pentoxifylline inhibits PDGF-induced proliferation of and TGF-beta-stimulated collagen synthesis by vascular smooth muscle cells.

There is growing evidence that pentoxifylline (PTX) may have potential value as an antiproliferative and antifibrogenic agent. To assess whether this drug may be of use in the prevention of atherosclerosis or restenosis after angioplasty, we investigated the ability of PTX to inhibit proliferation and collagen synthesis in rat vascular smooth muscle cells (VSMCs) under both basal and platelet-derived growth factor (PDGF)- or transforming growth factor-beta (TGF-beta)- stimulated conditions. Intracellular cyclic AMP (cAMP) and cyclic GMP (cGMP) levels were measured in confluent cells using enzyme immunoassay kits. Cell proliferation was measured by methyltetrazolium assay. Cell cycle distribution was determined by flow cytometry. Total collagen synthesis was measured by 3H-proline incorporation assay. Expression of collagen alpha 1(I) and collagen alpha 1(III) mRNAs was detected by northern blotting. Addition of PTX to VSMC cultures suppressed both basal and PDGF-AB (25 ng/ml)-driven cell proliferation, in conjunction with a cell cycle blockade at the G1/S phase at 24 h. This effect was predominantly cAMP-dependent, as PTX increased cAMP in a dose-dependent manner (0.03 to 0.33 mg/ml) but not cGMP level, and the addition of dibutyryl-cAMP (0.2 to 2 m m) closely mimicked the effect of PTX. Furthermore, co-incubation with a selective inhibitor of cAMP-dependent protein kinase (PKA), H-89 (2.0 microm), or an N -myristoylated PKA pseudosubstrate nonapeptide, m-phi PKA (10 microm), prevented the antimitogenic effect of PTX. PTX also suppressed both basal and TGF- beta 1-augmented collagen alpha 1(I) and collagen alpha 1(III) mRNA levels beginning at 24 h, and attenuated both basal and TGF-beta 1 (5 ng/ml)-stimulated total collagen synthesis at 48 h. Co-incubation with H-89 or m-phi PKA reversed PTX-attenuated collagen alpha 1(I) and collagen alpha 1(III) mRNA levels at 24 h. These data suggest that the antimotigenic and anticollagen effects of PTX were mediated predominantly through a cAMP-PKA effector pathway. The dual effect of PTX on VSMC proliferation and collagen synthesis may form the rationale for animal or clinical trials for the treatment of vascular occlusion due to atherosclerosis and restenosis following angioplasty.

Animals↗
PubMed1999

Pneumoperitoneum caused by a perforated peptic ulcer in a peritoneal dialysis patient: difficulty in diagnosis.

Peritonitis due to viscus perforation in peritoneal dialysis (PD) patients can be catastrophic. We describe the first reported case of perforated peptic ulcer (PPU) in a PD patient. This 78-year-old man presented with a 1-day history of mild abdominal pain. He had been receiving nocturnal intermittent PD for 2 years and had ischemic heart disease and cirrhosis of the liver. Pneumoperitoneum and peritonitis were documented, but the symptoms were mild. The "board-like abdomen" sign was not noted. Air inflation and contrast radiography indicated a perforation in the upper gastrointestinal tract, and laparotomy disclosed a perforation in the prepyloric great curvature. Unfortunately, the patient died during surgery. This case illustrates that the "board-like abdomen" sign may be absent in PD patients with PPU because of dilution of gastric acid by the dialysate. Free air in the abdomen, although suggestive of PPU, is also not uncommon in PD patients without viscus perforation. Because PD has to be discontinued after laparotomy and exploratory laparotomy may be fatal in high-risk patients, other diagnostic methods should be used to confirm viscus perforation before surgery. PPU, which can be proved by air inflation and contrast radiography, should be suspected in PD patients with pneumoperitoneum and peritonitis.

Aged↗
PubMed1999

Pentoxifylline attenuates experimental mesangial proliferative glomerulonephritis.

BACKGROUND: Accumulation of glomerular macrophages, proliferation of mesangial cells (MCs), and deposition of extracellular matrix proteins are pathobiological hallmarks of glomerulonephritis. We previously reported that a clinically available nonselective inhibitor of cyclic 3',5'-nucleotide phosphodiesterase, pentoxifylline (PTX), inhibits proliferation of cultured rat MCs, as well as collagen production by these cells. In this study, we investigated the in vivo effects of PTX on rat anti-Thy1 disease, a model of mesangial proliferative nephritis. METHODS: Anti-Thy1 nephritis was induced in Sprague-Dawley rats by injecting mouse anti-rat Thy1 antibodies intravenously. Nephritic rats were randomly assigned to receive PTX (0.1 g/kg/day) or vehicle (phosphate-buffered saline) and were sacrificed at various time points. Paraffin kidney sections were stained with hematoxylin and periodic acid-Schiff reagents for glomerular histology. Frozen kidney sections were stained by monoclonal antibodies against proliferating cell nuclear antigen, ED-1, and alpha-smooth muscle actin and were visualized by color development from a horseradish peroxidase reaction. Monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and various extracellular matrix mRNAs were analyzed by Northern blotting. Urine protein concentrations were determined by Lowry's method. RESULTS: Nephritic rats treated with PTX excreted less urinary protein on day 5 of nephritis than vehicle-treated nephritic rats. In periodic acid-Schiff-stained kidneys from PTX-treated nephritic rats, there was attenuation of both glomerular cellularity and glomerular sclerosis compared with vehicle-treated nephritic rats. PTX decreased the augmented glomerular mRNA levels of MCP-1 and ICAM-1 at two hours and on day 1 of nephritis. Immunoreactive staining showed that PTX reduced the number of proliferating glomerular macrophages on days 1, 2, and 3, but not at two hours of nephritis, compared with vehicle-treated nephritic rats. On day 5, PTX decreased the number of activated proliferating MCs and attenuated the glomerular mRNA levels of type I (alpha1), type III (alpha1), and type IV (alpha1) collagen and fibronectin compared with vehicle-treated nephritic rats. CONCLUSION: The administration of PTX to rats with anti-Thy1 disease reduces accumulation and proliferation of glomerular macrophages, attenuates proteinuria, suppresses activation and proliferation of MCs, and ameliorates glomerular sclerosis. These results suggest that PTX may have a suppressive effect in acute phases or relapses of mesangial proliferative glomerulonephritis.

Animals↗
PubMed1999

GB virus C infection in hemodialysis patients: molecular evidence for nosocomial transmission.

Studies of the prevalence and clinical relevance of GB virus C (GBV-C) infection in 328 hemodialysis (HD) patients were done, and the possibility of nosocomial GBV-C transmission was explored by molecular epidemiology methods. For GBV-C viremic patients in a given HD unit, nucleotide sequences of the envelope region were analyzed by phylogenetic tree constructions. Of 328 HD patients, active hepatitis B virus, hepatitis C virus (HCV), and GBV-C infection were detected in 13%, 23%, and 17%, respectively. Except for a higher frequency of HCV coinfection, the demographic and clinical characteristics of patients with and without GBV-C infection were comparable. In contrast, patients with isolated HCV infection had significantly higher serum transaminase levels, longer time on HD, and more blood transfusions. Phylogenetic analysis showed several distinct clusters of closely related GBV-C isolates from one HD unit, suggesting the possibility of nosocomial transmission. These results suggest that GBV-C plays a minimal role in causing hepatitis in Taiwanese HD patients and in nosocomial transmission.

Adult↗
PubMed1999

Necrotizing fasciitis caused by Serratia marcescens in two patients receiving corticosteroid therapy.

Necrotizing fasciitis (NF), a devastating soft tissue infection, is rarely attributed to Serratia marcescens. We here report two patients with S. marcescens NF, both of whom had underlying renal disease and had been receiving corticosteroid therapy. The first patient, a 40-year-old man with systemic lupus erythematosus and uremia on prednisolone therapy, developed fulminant cellulitis and septic shock 1 month after a skin biopsy for cutaneous vasculitis of the left foot. The cellulitis evolved to NF, and blood and necrotic tissue cultures both grew S. marcescens. The patient completely recovered after debridement and ceftazidime therapy. The second patient, a 73-year-old man receiving prednisolone therapy for nephrotic syndrome, developed right leg cellulitis that evolved to NF. Blood and necrotic tissue cultures both grew S. marcescens. After aggressive debridement and ciprofloaxcin therapy, the NF improved. However, the patient died of aspiration pneumonia and massive gastrointestinal bleeding 1 month later. These findings illustrate that S. marcescens should be considered as a potential pathogen causing NF in susceptible hosts.

Adult↗