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Biomedical subjects

Mei-Chuan Kuo

Publications and source records attributed to Mei-Chuan Kuo.

14 recordsLinked to original sources

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↗

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↗

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↗

Alterations of glomerular and extracellular levels of glutathione peroxidase in patients and experimental rats with diabetic nephropathy.

To investigate the status and role of glutathione peroxidase (GPX) in diabetic nephropathy, we measured GPX in the plasma and urine of 14 patients with diabetic glomerulosclerosis (DGS) and measured glomerular GPX immunostaining in these patients and in rats with streptozotocin-induced diabetes of varying duration. Plasma GPX levels were significantly lower in DGS patients than in diabetic patients without nephropathy (P < .05) or normal controls (P < .01). Urinary GPX concentrations were also significantly lower in DGS patients than in diabetic patients without nephropathy or normal controls (both P < .05). Immunostaining of glomerular GPX was significantly less in DGS patients than in normal controls (P < .05) and was negatively correlated with the glomerular sclerosis score and the index of mesangial expansion. Serial examination of glomerular GPX in diabetic rats showed that immunostaining scores for glomerular GPX in rats were significantly lower than those in normal control rats after 1 and 3 months' duration of diabetes, and staining scores were also significantly lower in rats killed after 3 months of diabetes than in those killed after 1 week. In conclusion, our study demonstrates that GPX concentrations in plasma, urine, and glomeruli are decreased in individuals with DGS and that the immunostaining of glomerular GPX decreases progressively.

Adult↗

Increased glomerular and extracellular malondialdehyde levels in patients and rats with diabetic nephropathy.

Results from animal experiments have suggested that reactive oxygen species (ROS) play an important role in tissue damage associated with diabetes. To determine whether ROS are involved in patients with diabetic nephropathy, we measured the plasma and urinary levels of malondialdehyde (MDA), an important marker of lipid peroxidation, and assessed the immunoreactivity of MDA and superoxide dismutase (SOD) in glomeruli of patients and experimental rats with diabetic nephropathy. Both plasma and urinary MDA levels were significantly higher in patients with diabetic glomerulosclerosis (DGS) than those of diabetic patients without proteinuria, proteinuric patients without diabetes, and normal controls. In DGS patients, the plasma MDA was significantly correlated with urinary MDA (p<0.05). The urinary MDA, but not plasma MDA, was significantly correlated with the degree of glomerulosclerosis and the index of mesangial expansion (both p<0.01) in DGS patients. The immunostaining score of glomerular MDA and SOD were also significantly higher in DGS patients than in control kidneys. In rats with diabetes for more than one month, the glomerular immunostaining for both MDA and SOD were also significantly higher than in controls rats, and both were increased with the progression of diabetes. Our results suggest that oxidative stress is involved in the pathogenesis and the progression of DGS.

Adolescent↗

HCV infection complicated with nephrotic syndrome, immune complex crescentic glomerulonephritis and acute renal failure: a case report.

There is ample evidence suggesting that hepatitis C virus (HCV)-associated autoimmunity plays a role in a broad spectrum of autoimmune diseases, which are usually overlooked. We report on a case of nephrotic syndrome, palpable purpura, cryoglobulinemia, hypocomplementemia, and acute renal failure complicated by immune complex glomerulonephritis (GN). The patient is a 64-year-old man with HCV infection, who was initially considered to present only an HCV-associated cryoglobulinemic GN. However, renal biopsy revealed a "full house" immune complex crescentic GN, which led to our subsequent investigation. The attending clinicians faced what is a common dilemma, where an HCV-associated autoimmune disease inevitably switches to a lupus-like GN. Hence, we also discuss treatment.

Acute Kidney Injury↗

Allopurinol-induced severe hypersensitivity with acute renal failure.

A 62-year-old male was sent to the emergency room due to a high fever and generalized skin rash after taking allopurinol for 9 days. Physical examination was normal except for the generalized skin rash presenting with erythematous macules. Complete blood count showed leukocytosis with eosinophilia. Blood biochemistry showed impaired renal and hepatic function. Pathologic examination concluded that the skin rash was erythema multiforme. These findings met the diagnostic criteria for allopurinol-induced hypersensitivity syndrome (AHS). Our patient not only had the most common skin lesion but soon developed acute renal failure that required intermittent hemodialysis, despite rapid discontinuation of allopurinol and adequate hydration and steroid therapy. No other causes of acute renal failure were found. Renal impairment was the worst part of the patient's condition and he never completely recovered. AHS should be considered in the differential diagnosis of acute renal and hepatic failure in patients with evidence of allergy and recent use of allopurinol.

Acute Kidney Injury↗

1-alpha,25-Dihydroxyvitamin D3 regulates inducible nitric oxide synthase messenger RNA expression and nitric oxide release in macrophage-like RAW 264.7 cells.

The expression of inducible nitric oxide synthase (iNOS) expression and release of nitric oxide (NO) from macrophages are markedly increased in granulomatous infections. Activation of macrophages 1alpha-hydroxylase results in an increase of 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. However, the significance of this increased production is not completely understood. In this study, we analyzed 1,25(OH)(2)D(3) and NO production in patients with tuberculosis infection and hypercalcemia and used lipopolysaccharide (LPS) to stimulate RAW 264.7 cells in an attempt to assess iNOS expression and gaseous NO production regulated by 1,25(OH)(2)D(3). Peroxynitrite (OONO(-)) production and lactate dehydrogenase activity were also examined. Without additional stimulation, peripheral-blood mononuclear cells (PBMCs) from patients with tuberculosis converted more 25-hydroxyvitamin D(3) to 1,25(OH)(2)D(3) than did those from normal controls. These PBMCs released less NO than did those from control subjects, at baseline and in the stimulated state. We found that 1,25(OH)(2)D(3) dose-dependently inhibited iNOS messenger RNA expression of the LPS-stimulated RAW 264.7 cells and also significantly reduced the gaseous NO release and OONO(-) production. Paralleling the 1,25(OH)(2)D(3)-induced inhibition of NO release were reductions in OONO(-) and LDH production. In conclusion, 1,25(OH)(2)D(3) inhibited iNOS expression and reduced NO production by LPS-stimulated macrophages in the range of physiological doses. Inhibition of the NO surge was coupled with a reduction in OONO(-) and LDH production. Increased 1,25(OH)(2)D(3) production and decreased release of NO from the PBMCs of patients with tuberculosis and hypercalcemia were also noted. We propose that 1,25(OH)(2)D(3) production by macrophages may protect themselves against oxidative injuries caused by the NO burst. In the case of tuberculosis infection, increased 1,25(OH)(2)D(3) synthesis may further contribute to the development of an unwanted phenomenon-hypercalcemia.

Animals↗

Analysis of factors associated with successful cardiopulmonary resuscitation in non-traumatic dead-on-arrival patients in emergency department.

Out-of-hospital cardiopulmonary arrest has a dismal prognosis. Successful resuscitation of these patients depends on the "chain of survival". In Taiwan, the emergency medical services (EMS) system is under development and the links of "chain of survival" are weak and frequently broken. A 2-year retrospective study was conducted from January, 1999, to December, 2000 to evaluate the factors of successful cardiopulmonary resuscitation (CPR) in non-traumatic DOA patients in ED. Of 175 studied patients, 51 patients (29.1%) were successfully resuscitated with return of spontaneous circulation (ROSC), but only 7 patients (4%) survived to hospital discharge. Most successfully resuscitated patients (84.3%) regained their vital signs within 30 minutes. There were no significant differences in age, sex, vehicle of transportation, administration of prehospital CPR or not, EMS response interval, on-scene duration, and scene-to-hospital interval between patients with ROSC and without ROSC. Compared with asystole cardiac rhythm, patients with pulseless electrical activity (PEA) had a higher successful resuscitation rate (p = 0.001), but no significant differences existed between patients with ventricular fibrillation/ventricular tachycardia (VF/VT) and PEA or VF/VT and asystole. However, there were no significant differences in the survival discharge rate among patients with different initial cardiac rhythms in ED.

Adult↗

Eight cases of acute renal failure from Vipera russelli formosensis venom after administration of antivenom.

The six-valent antivenom from Vipera russelli formosensis in Taiwan has recently become available in Taiwan. Between June 1998 and December 2001 8 Vipera russelli formosensis snakebite victims were treated with antivenom within 24 h of snakebite. Bleeding stopped and coagulopathy improved after antivenom use, and neurotoxic symptoms were mild. Prothrombin time was prolonged on the 1st day and thrombocytopenia changed within 2 d. In the majority of cases, renal dysfunction persisted for several days after coagulation abnormalities normalized: 3 cases required hemodialysis. Although Vipera russelli formosensis antivenom is capable of preventing hemorrhage, antivenom administration may not alter the course of severe renal damage.

Acute Kidney Injury↗