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Biomedical subjects

Hung-Chun Chen

Publications and source records attributed to Hung-Chun Chen.

At least 19 recordsLinked to original sources
PubMed2007

Effect of preload alterations by hemodialysis on the time interval between the onsets of early diastolic mitral inflow and annular waveforms.

BACKGROUND: The T(Ea-E), which is defined as the time interval between the peak of the R-wave and the onset of early diastolic mitral annular waveform (T(Ea)) minus the time interval between the peak of the R-wave and the onset of early diastolic mitral inflow waveform (T(E)), is recently proposed as a useful index of left ventricular (LV) relaxation. The aim of this study is to determine whether the T(Ea-E) is preload-independent. METHODS: Twenty hemodialysis (HD) patients (9 men; age 64 +/- 9 years) underwent echocardiography 1 hour before and 1 hour after HD was studied. RESULTS: After HD, the body weight (P < 0.001), early transmitral filling wave peak velocity (E) (P < 0.001), the ratio of E to late transmitral filling wave peak velocity (P = 0.011), the early diastolic mitral anuular velocity (Ea) (P = 0.002), E/Ea (P = 0.026), and T(Ea-E) (P < 0.001) decreased significantly, and the T(Ea) (P = 0.047) and T(E) (P = 0.005) increased significantly. In addition, T(Ea-E) had a significant negative correlation with Ea either before (r =-0.457, P = 0.043) or after HD (r =-0.637, P = 0.003). CONCLUSIONS: T(Ea-E), as well as Ea, was a preload-dependent relaxation index. The preload dependence of this newer Doppler parameter limited its utility in evaluating LV diastolic function in HD patients.

Aged↗
PubMed2006

Reduced podocyte expression of alpha3beta1 integrins and podocyte depletion in patients with primary focal segmental glomerulosclerosis and chronic PAN-treated rats.

Integrins attach cells to extracellular matrix (ECM) and mediate signals from ECM to cells or from cells to ECM. They regulate cell functions, including adhesion, migration, cell cycle regulation, and differentiation. Podocytes may detach from the glomerular basement membrane (GBM) and be excreted in the urine, and proteinuria is found in patients with primary focal segmental glomerulosclerosis (FSGS); both may be associated with loss of alpha3beta1integrins. In this study, we have examined the podocyte number in patients with primary FSGS and normal controls, and the alpha3- and beta1-integrin subunits expression of podocytes in patients with primary FSGS and chronic puromycin aminonucleoside (PAN)-treated rats by the morphometric, immunoperoxidase histochemical, and immunoelectron microscopic examination. We also measured their expression serially in rats that received repeated PAN injection. The results showed that the podocyte number was significantly decreased in patients with primary FSGS than in normal control (P < 0.05). The immunostaining score showed that both alpha3- and beta1-integrin subunits on podocytes in patients with primary FSGS were significantly lower than in normal controls (both P < 0.01). The number of immuno-gold particles of alpha3- and beta1-integrins at the effaced foot process area of patients with primary FSGS were also significantly decreased than that of normal controls (both P < 0.05). The immunostaining score of both alpha3- and beta1-integrin subunits was negatively correlated with the degree of glomerular sclerosing score and the amount of daily protein loss, and they were positively correlated with the number of podocytes. Chronic 12-week PAN-treated rats showed similar findings with decreased immunostaining expression and immuno-gold particles of alpha3-integrin on podocytes than in normal control (both P < 0.05). The chronic PAN-treated rats also showed a trend toward gradually decreased immunostaining expression of alpha3-integrin subunit on podocyte during the progress from normal to FSGS state. These studies indicate that podocyte expression of alpha3- and beta1-integrin subunits is significantly reduced in humans with primary FSGS and chronic PAN-treated rats, before the morphological changes of FSGS are observed. The decreased podocyte expression of alpha3beta1 integrins is closely related with podocyte depletion, glomerular sclerosis, and daily protein loss in patients with primary FSGS.

Adult↗
PubMed2006

Signaling and regulatory mechanisms of integrinalpha3beta1 on the apoptosis of cultured rat podocytes.

Integrin is the major adhesion molecule for the attachment of podocytes to the glomerular basement membrane, and integrins have been shown to play a major role in the regulation of cell survival. In this study, the authors investigated the apoptosis and its related signal pathways to integrin in cultured rat podocytes. Apoptosis was detected with the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) technique. Cytochrome c was examined by immunohistochemical stain, and Fas, Fas ligand, Bax, Bcl-2, and ERK activation (p-ERK/ERK) were analyzed by Western blotting analysis. The results demonstrated that the integrin antagonist, Gly-Arg-Gly-Asp (GRGD), increased the percentage of cells with apoptosis (from 0.9+/-0.5% to 27.2+/-9.9%, P < 0.01). Inhibition of protein tyrosine kinase with genistein also caused apoptosis of podocytes (from 0.9+/-0.5% to 26.0+/-8.7%, P < 0.01). In GRGD-treated cells, cytochrome c was found released into cytoplasm by immunohistochemical study and the Bax expression was upregulated, whereas Bcl-2 expression was not changed. Fas was not expressed in both control and GRGD-treated podocytes, although Fas ligand was upregulated in GRGD-treated cells. ERK activation was also found to be increased in GRGD-treated cells. The results indicated that alpha3beta1integrin is necessary for the prevention of the apoptosis of cultured rat podocytes, and that the signaling involves the Bax, Bcl-2, and cytochrome c pathways.

Animals↗
PubMed2006

TGF-beta1 and integrin synergistically facilitate the differentiation of rat podocytes by increasing alpha-smooth muscle actin expression.

Phenotypic changes can be found in certain glomerular diseases, and the cell origin is not defined. This study was designed to identify whether podocytes can differentiate by the expression of alpha-smooth muscle actin (alpha-SMA), under the effects of TGF-beta(1) (transforming growth factor-beta(1)) and integrin. Western and Northern blot analyses were performed to identify the protein and mRNA (messenger ribonucleic acid) expression of alpha-SMA. The number of podocytes, which express alpha-SMA, was measured by immunocytochemical staining. The results showed that TGF-beta(1) dose-dependently increased alpha-SMA protein and mRNA expression at 4 and 2 days, respectively. TGF-beta(1) also dose-dependently increased the alpha-SMA staining of podocytes. The alpha-SMA-positive podocytes showed front-end and back-end polarity. The integrinalpha3beta(1) antagonists, anti-integrinbeta(1) monoclonal antibody and Gly-Arg-Gly-Asp (GRGD), decreased the expression of alpha-SMA protein and the percentage of alpha-SMA positive cells stimulated by TGF-beta(1) (both P < 0.01). The addition of calphostin [inhibitor of protein kinase C (PKC)] and genistein [inhibitor of focal adhesion kinase (FAK)] also decreased the expression of alpha-SMA protein and the percentage of alpha-SMA positive cells stimulated by TGF-beta(1) (both P < 0.01). In conclusion, this study indicated that TGF-beta(1) may act synergistically with integrins, through activation of PKC and FAK, to induce the phenotypic changes of rat podocytes with increasing alpha-SMA expression.

Actins↗
PubMed2006

Effects of specific endothelin-1 receptor antagonists on proliferation and fibronectin production of glomerular mesangial cells stimulated with Angiotensin II.

Angiotensin II (Ang-II) is a potent vasoactive hormone, which plays an important role in the pathogenesis of glomerulosclerosis. Ang-II activates many cytokine systems in the kidney. Recent studies indicate that Ang-II is closely related to the activation of the endothelin-1 (ET-1) system. The present study was designed to measure the [H3]-thymidine uptake and fibronectin production of cultured rat mesangial cells stimulated with Ang-II, and to evaluate the effects of specific ET-1 receptor antagonists, BQ123 (type A receptor antagonist) and IRL1038 (type B receptor antagonist) on the cells. ET-1 was measured by radioimmunoassay and fibronectin by Western blot analysis. The results were as follows: (1) Ang-II enhanced ET-1 production, [H3]-thymidine uptake, number of cells, and fibronectin production of mesangial cells; (2) all the baseline [H3]-thymidine uptake, number of cells, and fibronectin production of mesangial cells can be partly suppressed by BQ123, but not by IRL1038; (3) the increment of Ang-II-enhanced number of cells can be partly suppressed by BQ123, but not by IRL1038; and (4) the increment of Ang-II-enhanced fibronectin production can be partly suppressed by both BQ123 and IRL1038. Our results indicate that Ang-II is an active stimulant for the proliferation and fibronectin production of mesangial cells, and the effect is partly suppressed mainly by ET-1 type A receptor antagonists.

Angiotensin II↗
PubMed2006

Flavonoid-induced acute nephropathy by Cupressus funebris Endl (Mourning Cypress).

Worldwide use of herbal therapy has increased dramatically in recent years. Most herbal therapies were not regulated as medicines, and their adverse effects often were underreported. We report a patient who developed acute renal failure, acute hepatic failure, autoimmune hemolytic anemia, and thrombocytopenia after oral intake of hot-water extract of Cupressus funebris Endl (Mourning Cypress), which is rich in flavonoids. Her renal biopsy showed acute tubular necrosis, interstitial nephritis, and hemoglobin casts. The clinical course and pathological findings were consistent with flavonoid-induced acute nephropathy. We emphasize that flavonoids are not harmless and may induce acute life-threatening renal damage.

Acute Kidney Injury↗
PubMed2006

Pancytopenia after low dose methotrexate therapy in a hemodialysis patient: case report and review of literature.

Methotrexate (MTX) is widely used in the treatment of rheumatoid arthritis (RA) with a side effect of pancytopenia. However, only a few cases of severe pancytopenia caused by low-dose MTX therapy have been reported, and the condition is rarely reported in uremic patients on dialysis therapy. We thereby report a hemodialysis patient who developed severe pancytopenia after oral treatment with low-dose MTX for RA. A 55-year-old woman who had been on regular hemodialysis treatment for 7 yr suffered from RA for 10 yr. She was regularly treated with celecoxib, prednisolone, and sulfasalazine in the past year. Because of the increasing arthralgia, 7.5 mg per week MTX was prescribed 3 months before admission. Stomatitis, fever, general fatigue, multiple skin carbuncles, and easy bruising developed after a cumulative dose of 90 mg. Pancytopenia was found at admission and the nadir of white blood cell count was 250/microL with 28% neutrophils, hematocrit was 22%, and platelet count was 6000/microL. Eosinophil counts increased from 11.5% initially to 26.1% on the sixth admission day. Transfusion with red blood cells and platelets, and appropriate antibiotics and folic acid were prescribed. She continued receiving regular hemodialysis and eventually recovered within 3 weeks.

Antirheumatic Agents↗
PubMed2006

Severe refeeding hypophosphatemia in a CAPD patient: a case report.

Refeeding syndrome is defined as severe electrolyte and fluid shifts associated with metabolic abnormalities in malnourished, refeeding patients. Hypophosphatemia is its predominant concern, though its occurrence is unusual in uremic patients due to the concomitant hyperphosphatemia. This case study reports a 56-year-old woman on continuous ambulatory peritoneal dialysis (CAPD) therapy who was admitted for peritonitis. Ileus and diarrhea developed during admission; enteral feeding was given initially and then shifted to total parenteral nutrition (TPN) because of poor digestion. A lower concentration of phosphate was administered in the TPN formula initially due to high initial serum phosphate level. However, severe hypophosphatemia (0.3 mg/dL) developed on the second day after TPN supplementation. Continuous intravenous phosphate (total 6 mmol of phosphate) was supplied immediately. Unfortunately, the sudden onset of conscious loss and cardiac arrest happened on the third day of TPN. It should be emphasized that severe refeeding hypophosphatemia can also develop early in uremic patients with hyperphosphatemia.

Enteral Nutrition↗
PubMed2006

Betel-quid use is associated with the risk of the metabolic syndrome in adults.

BACKGROUND: Betel-quid use has been associated with obesity and hyperglycemia in previous studies. OBJECTIVE: The aim was to test whether betel-quid use contributes to the metabolic syndrome, as defined by the National Cholesterol Education Program Adult Treatment Panel III. DESIGN: Associations between betel-quid use and the metabolic syndrome, obesity, hypertriacylglycerolemia, low HDL cholesterol, hyperglycemia, and high blood pressure after adjustment for sex, age, smoking, alcohol drinking, physical activity, and dietary intakes were studied in nonpregnant adults aged 20-64 y (n = 1986) from the Nutrition and Health Survey in Taiwan (1993-1996). RESULTS: The prevalence of the metabolic syndrome was not significantly different between the men and women (10.1% compared with 9.7%), whereas the prevalence of betel-quid use was higher in the men than in the women (31% compared with 2.3%; P < 0.001). The daily rate of betel-quid use was associated with the metabolic syndrome [odds ratio (OR) associated with a betel-quid consumption rate of 10 times/d: 1.31; 95% CI: 1.12, 1.55; P = 0.003], abdominal obesity (OR: 1.42; 95% CI: 1.2, 1.7; P = 0.001), hypertriacylglycerolemia (OR: 1.33; 95% CI: 1.02, 1.73; P = 0.037), and high blood pressure (OR: 1.2; 95% CI: 1.01, 1.4; P = 0.04). However, the daily rate of betel-quid use was not associated with low HDL cholesterol or hyperglycemia. CONCLUSION: The daily rate of betel-quid use is independently and positively associated with the metabolic syndrome in adults.

Adult↗
PubMed2006

Hypercalcemia in the emergency department.

BACKGROUND: Severe hypercalcemia can be life-threatening. However, its incidence and the underlying causes in the emergency department (ED) have not been determined. In the present study, we investigated these issues and the impacts on renal function and patients' survival. METHODS: We performed a retrospective study to analyze the patients with hypercalcemia in the ED for 1 year. Serum total calcium level greater than 10.3 mg/dL was defined as hypercalcemia. RESULTS: During the study period, 321 of 4293 patients (7.5%) were found to have hypercalcemia (serum calcium 11.7 +/- 1.6 mg/dL). Most of them had mild hypercalcemia (calcium level < 12.0 g/dL, 70.7%). Malignancy (36.4%) and uremia (32.4%) were the most common underlying causes. Normal renal function was observed in only 75 (23.4%) of all patients with hypercalcemia. The total mortality rate was 23.1%, and death was associated with male gender, higher calcium level, lower hemoglobin, and malignancy (all P < 0.05). Logistic analysis found that serum calcium and hemoglobin levels were independent risk factors for mortality. CONCLUSIONS: Severe hypercalcemia is frequently and life-threatening in the ED. Therefore routine determination of serum calcium level is recommended, and immediate therapy should be initiated to treat the patients at high risk.

Adult↗
PubMed2005

Advanced glycation end-product-induced mitogenesis and collagen production are dependent on angiotensin II and connective tissue growth factor in NRK-49F cells.

Diabetic nephropathy (DN) is characterized by glomerulopathy and tubulointerstitial expansion followed by renal fibrosis. Angiotensin II (Ang II) and connective tissue growth factor (CTGF) are involved in the pathogenesis of DN, while Janus kinase 2 (JAK2) is important in advanced glycation end-product (AGE)-induced effects in renal interstitial (NRK-49F) fibroblasts. Thus, we studied the role of Ang II, CTGF, and JAK2 in AGE-induced effects in NRK-49F cells. We found that AGE (150 microg/ml) increased mitogenesis and type I collagen production at 7 days while Ang II (10(-7)M) increased mitogenesis and type I collagen production at 3 days. We also found that AGE (150 microg/ml) increased angiotensinogen protein at 2 days, which was attenuated by AG-490 (a JAK2 inhibitor). AGE (150 microg/ml) increased CTGF mRNA and protein expression at 3 and 5 days, respectively. Ang II (10(-7)M) increased CTGF mRNA and protein expression at 1 and 2 days, respectively, which were attenuated by AG-490. Moreover, losartan (a type I angiotensin receptor blocker) and captopril (an angiotensin converting enzyme inhibitor) attenuated AGE-induced CTGF mRNA/protein expression while attenuating AGE-induced mitogenesis and type I collagen production. AG-490 and CTGF antisense (but not sense) oligodeoxynucleotide (ODN) attenuated Ang II (10(-7)M) and AGE-induced mitogenesis and type I collagen production at 3 and 7 days, respectively. We concluded that AGE (150 microg/ml)-induced mitogenesis and type I collagen production are dependent on the Ang II-JAK2-CTGF pathway in NRK-49F cells. Moreover, Ang II-induced mitogenesis and type I collagen production are dependent on the JAK2-CTGF pathway.

Angiotensin II↗
PubMed2005

Correlation of plasma homocysteine level with arterial stiffness and pulse pressure in hemodialysis patients.

Elevated plasma homocysteine, arterial stiffness, and increased pulse pressure (PP) are independently associated with higher cardiovascular risk in patients with end-stage renal disease. The aim of this study is to investigate the influence of plasma homocysteine on arterial stiffness and PP in hemodialysis (HD) patients. One hundred and nine HD patients were stratified into three groups by plasma homocysteine levels: low (11.2-20.8 micromol/L), middle (21.2-25.1 micromol/L), and high tertiles of plasma homocysteine (Hcy) group (25.2-43.9 micromol/L). Using a computerized oscillometry, we measured the arterial stiffness index (ASI) and blood pressure (BP) hemodynamic parameters in the brachial artery. The high Hcy group exhibited a higher ASI (110.4+/-129.5 versus 46.2+/-17.5, mean+/-S.E., P<0.01), PP (59.7+/-23.1 versus 43.3+/-16.3 mmHg, P<0.01), and age (57.8+/-14.1 versus 49.9+/-12.7 years, P<0.05) compared with the low Hcy group. Plasma homocysteine was significantly correlated with ASI (r=0.25, P<0.001), PP (r=0.33, P<0.001), systolic BP (r=0.31, P<0.001), and age (r=0.24, P<0.05). Serum ferritin was significantly correlated with ASI (r=0.24, P<0.05) and PP (r=0.23, P<0.05). ASI was also correlated with PP (r=0.64, P<0.001). Multiple regression analyses showed that both plasma homocysteine and serum ferritin had significant associations with ASI (beta=4.246, P=0.007 and beta=0.024, P=0.006, respectively), and with PP (beta=1.089, P=0.002 and beta=0.005, P=0.005, respectively) independent of other classic risk factors for atherosclerosis. In conclusion, plasma homocysteine, along with serum ferritin, may act as an important predictor for arterial stiffness and PP in HD patients.

Adult↗
PubMed2005

Decreased synthesis of glomerular adrenomedullin in patients with IgA nephropathy.

Adrenomedullin (AM) immunostaining and gene expression have seldom been measured in human kidneys. Because previous studies have shown that AM exerts antiproliferative effects on rat mesangial cells in vitro and that urine AM levels are decreased in patients with chronic glomerulonephritis, we measured glomerular AM and its gene expression in patients with primary IgA nephropathy (IgAN). Glomerular AM was measured by immunohistochemical staining, and glomerular AM mRNA was measured by in situ hybridization. Plasma and urine AM were measured by radioimmunoassay. The results showed that both the intensity of immunostaining for glomerular AM and the glomerular expression of AM mRNA were significantly decreased in IgAN patients compared with normal controls (both P < .05). Similar results were not observed in patients with non-IgA MsPGN. Glomerular AM immunostaining and glomerular AM mRNA expression were significantly correlated ( P < .001), and both were negatively correlated with the number of glomerular cells ( P < .05 and < .01, respectively). Both glomerular AM immunostaining and glomerular AM mRNA expression were correlated with urine AM levels (both P < .001), but not with plasma AM levels. The urine AM level was significantly lower in IgAN patients than in normal controls ( P < .01), whereas the plasma level was not different between the 2 groups. Our findings indicate that glomerular production of AM was decreased in patients with IgA nephropathy and that this lack of glomerular AM may be related to the pathogenesis of this mesangial disease.

Adrenomedullin↗