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K C Mun

Publications and source records attributed to K C Mun.

24 records · Page 2Linked to original sources
PubMed2000

Cyanate as a hemolytic factor.

During advanced renal failure, and particularly in patients with end-stage renal disease, proteins are carbamylated as a result of a reaction with cyanate. If the carbamylation of proteins adversely alters their biologic activities and structures, then urea must be viewed as an uremic toxin, rather than a surrogate. Therefore, we studied in this paper the role of cyanate as a hemolytic factor of erythrocytes to explain anemia observed in patients with high blood urea levels due to inadequate dialysis. Cyanate was added to make the final concentration 150, 300 and 600 nmol to each test tube containing the final concentration of 140 x 10(6) with human erythrocytes per mL of phosphate buffered saline solution. And they were incubated at 37 degrees C for 24, 48 and 72 hours. The extent of hemolysis and carbamylation was monitored. The levels of hemolysis and carbamylated erythrocytes increased as the time of exposure to cyanate increased from 24 hours to 72 hours. Furthermore, those increased as cyanate concentration in the incubation media rose from 150 nmol to 600 nmol. Cyanate can induce hemolysis by carbamylation of erythrocytes. Urea, through cyanate, may contribute to hemolysis. If one extrapolates these results to patients with end-stage renal disease, it may help explain one of the reasons for the anemia in patients with high levels of BUN due to inadequate dialysis.

Anemia, Hemolytic↗
PubMed2000

Impaired biological activity of erythropoietin by cyanate carbamylation.

AIMS: During advanced renal failure, particularly in patients with end-stage renal disease (ESRD), proteins are carbamylated as a result of a reaction with cyanate. Some or all of the cyanate is derived from urea. If the carbamylation of proteins adversely alters their biologic activities, then urea must be viewed as an uremic toxin, rather than a surrogate. Therefore, we studied the effect of cyanate carbamylation on the erythropoietic activity of erythropoietin (EPO) in a rodent model. METHODS: EPO was carbamylated by incubation with cyanate at 37 degrees C. The extent of carbamylation was monitored using trinitrobenzenesulfonic acid. In Sprague-Dawley rats the erythrocyte count, hemoglobin concentration, and hematocrit were measured after the twice-weekly subcutaneous injection of either EPO or carbamylated EPO for 3 weeks. Two additional control groups received physiologic saline or 0.2 ml of 1 M cyanate. RESULTS: The level of carbamylated EPO was increased as the time of exposure to cyanate increased from 1 to 6 h, and as the cyanate concentration increased from 8 to 2,000 mM. EPO injections caused significantly large increases in all erythropoietic measures. Physiologic saline or 1 M cyanate-injected controls and the carbamylated EPO-injected animals demonstrated no change from baseline in erythropoietic parameters. CONCLUSION: These results support that EPO exposed to high levels of cyanate in vitro demonstrates diminished biologic activity in healthy Sprague-Dawley rats. This effect may be manifested by the carbamylation of EPO by the cyanate. Should this occur in ESRD patients, it may contribute to the suboptimal erythropoietic response to EPO therapy associated with high urea levels, especially related to inadequate dialysis. Targeting dialysis doses specifically to urea concentrations may be more important than previously considered.

Animals↗
PubMed1996

The protective effect of allopurinol on cholestatic liver injury induced by bile duct ligation.

To determine whether oxygen free radicals are responsible for the pathogenesis of the cholestasis induced by ligation of common bile duct (CBD) variables which reflect the hepatic function in the serum, the amount of superoxide radical production, and xanthine oxidase(XO) activity were studied. The activity of serum alanine aminotransferase, bilirubin level in the serum and the amount of superoxide radical production were lower in a CBD ligation with allopurinol treated group than in a CBD ligation without allopurinol treated group. Abnormalities of the microscopic structures were reduced in a CBD ligation with allopurinol treated group than in a CBD ligation without allopurinol treated group. Allopurinol, an inhibitor of XO, prevented the hepatic damage induced by CBD ligation through the inhibition of XO. These experiments demonstrate that oxygen free radicals are responsible for the pathogenesis of the cholestatic liver.

Allopurinol↗
PubMedDate not supplied

Chronic peritoneal inflammation by cyanate in rats.

OBJECTIVE: During peritoneal dialysis, the peritoneum is exposed to waste products, including urea. Urea forms cyanate spontaneously at body temperature and pH, and cyanate carbamylates amino acids, peptides, and proteins. Cyanate may contribute to peritoneal injury with morphological changes in the peritoneum. To test this hypothesis, we injected cyanate into rats. METHODS: Experiments were performed in two groups of 7 rats each. In the cyanate group, each rat received 1 mL of 1.5 micromol/L potassium cyanate dissolved in 40 mmol/L sodium bicarbonate solution intraperitoneally each experiment day. In the control group, each rat received 1 mL of 1.5 micromol/L potassium bicarbonate instead of potassium cyanate. The rats in both groups were anesthetized and killed at the 85th day after the first injection. After formalin fixation, tissue samples from abdominal walls and livers were sliced, embedded in a standard manner, and stained with hematoxylin and eosin. RESULTS: Parietal peritoneum from rats in the cyanate group showed a mild increase in the number of fibroblasts, with collagen deposits, infiltration by mononuclear cells, vascular congestion, round-shaped transformation of mesothelial cells, widening of submesothelial spaces, and abundant denudation of mesothelial cells. The visceral peritoneum from rats in the cyanate group showed collagen deposits with fibroblastic proliferation. CONCLUSIONS: Cyanate can induce chronic inflammation in the peritoneum, and exposure of the peritoneum to cyanate may contribute to peritoneal injury in patients being treated with peritoneal dialysis.

Animals↗